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UBC Theses and Dissertations

Syntheses of polypyrrolic macrocycles Danso-Danquah, Richmond Edward 1986

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SYNTHESES OF POLYPYRROLIC MACROCYCLES by RICHMOND EDWARD DANSO-DANQUAH B . S c . ( H o n o u r s ) , U n i v e r s i t y o f S c i e n c e and T e c h n o l o g y , Ghana, 1981 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE i n THE FACULTY OF GRADUATE STUDIES (Department of C h e m i s t r y ) We a c c e p t t h i s t h e s i s as c o n f o r m i n g t o the r e q u i r e d s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA AUGUST 1986 © Richmond Edward Danso-Danquah In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 ABSTRACT P e n t a p h y r i n s are p e n t a p y r r o l i c m a c r o c y c l e s c o n t a i n i n g f i v e b r i d g i n g methine groups between the f i v e p y r r o l i c s u b u n i t s . The s y n t h e s e s o f d e c a m e t h y l p e n t a p h y r i n 71_, 2 - e t h o x y c a r b o n y l - 3 , 7 , 8 , 1 2 , 1 3 , 1 7 , 1 8 , 2 2 , 2 3 -n o n a m e t h y l p e n t a p h y r i n 7 4 , 2 - e t h o x y c a r b o n y l - 3 , 7 , 8 , 2 2 , 2 3 - p e n t a m e t h y l -1 2 , 1 3 , 1 7 , 1 8 - t e t r a e t h y l p e n t a p h y r i n 7 5 , 3 , 1 2 - d i m e t h o x y c a r b o n y l e t h y l - 2 , 7 , 8 , -1 3 , 1 7 , 1 8 , 2 2 , 2 3 - o c t a m e t h y l p e n t a p h y r i n s 29 and the z i n c complexes of 71_ and 74 a r e d e s c r i b e d . The p h y s i c a l p r o p e r t i e s of the p e n t a p h y r i n s show them to be a r o m a t i c l i k e s a p p h y r i n s , p o r p h y r i n s and c o r r o l e s . T h i s a r o m a t i c i t y i s r e f l e c t e d i n the l a r g e s h i e l d i n g of the NH p r o t o n s and the d e s h i e l d i n g of the methine p r o t o n s i n the nmr s p e c t r a and by t h e i r o p t i c a l s p e c t r a , w h i c h e x h i b i t S o r e t and v i s i b l e bands s i m i l a r t o s a p p h y r i n s and p o r p h y r i n s . TABLE OF CONTENTS Page ABSTRACT 1 Table of Contents i i L i s t o f F i g u r e s i i i L i s t of A b b r e v i a t i o n s i v Nomenclature v Acknowledgements v i 1 . INTRODUCTION AND LITERATURE REVIEW 1 2 . RESULTS AND DISCUSSION 18 2 . 1 S y n t h e t i c S t r a t e g y 19 2 . 2 Syntheses of I n t e r m e d i a t e s 23 2 . 3 Syntheses of the M a c r o c y c l e s 39 3 . EXPERIMENTAL 46 3 . 1 G e n e r a l Methods 47 3 . 2 S t a r t i n g M a t e r i a l s 48 3 . 3 Syntheses of I n t e r m e d i a t e s 51 3 . 4 S y n t h e s e s o f P e n t a p h y r i n 80 4 . SPECTRAL ASSIGNMENTS 88 4 . 1 1 H nmr Data of P e n t a p h y r i n s 89 4 . 2 1 3 C nmr Data o f P e n t a p h y r i n s 95 4 . 3 Mass S p e c t r a of P e n t a p h y r i n s and D e r i v a t i v e s 100 4 . 4 E l e c t r o n i c A b s o r p t i o n S p e c t r a of P e n t a p h y r i n 110 and D e r i v a t i v e s REFERENCES 119 - i i -LIST OF FIGURES F i g u r e T i t l e Page 1 Nomenclature of T e t r a p y r r o l i c M a c r o c y c l e s 2 2 The 3 + 2 Mode of Approaches i n P e n t a p h y r i n S y n t h e s e s 19 3 I n t e r m e d i a t e s f o r t h e Syntheses of M a c r o c y c l e s 22 4 lH nmr Spectrum of 71 ™ 50% T F A - C D C A 3 91 5 lH nmr Spectrum o f 74 i n 50% T F A - C D U 3 92 6 1H nmr Spectrum o f 75 i n 50% TFA-CDCJc3 93 7 l H nmr Spectrum of 29 i n 50% TFA-CDCJt3 94 8 1 3 C nmr Spectrum of 7J_ i n TFA 96 9 1 3 C nmr Spectrum of 74 i n 30% TFA-CDCA3 97 10 1 3 C nmr Spectrum of 75 i n 30% TFA-CDCJc3 98 11 1 3 C nmr Spectrum of 29 i n TFA 99 12 Mass S p e c t r a o f 71 104 13 Mass S p e c t r a of 74 105 14 Mass S p e c t r a of 75 106 15 Mass S p e c t r a of 29 107 16 Mass S p e c t r a o f 72 108 17 Mass S p e c t r a of 73 109 18 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 71_ 112 19 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 74 113 20 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 75_ 114 21 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 29 115 22 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 72 116 23 E l e c t r o n i c A b s o r p t i o n S p e c t r a of 73 117 - i i i -ABBREVIATIONS A b b r e v i a t i o n s which may appear are ( i n random o r d e r ) 1 3 C nmr = Carbon-13 n u c l e a r magnetic resonance DMF = N,N-dimethylformamide EI = e l e c t r o n impact Et = e t h y l FAB = f a s t atom bombardment ! H nmr = p r o t o n n u c l e a r magnetic resonance Hz = H e r t z L i t = l i t e r a t u r e M . P . = m e l t i n g p o i n t M o l . Wt. = m o l e c u l a r weight Ph = phenyl PMe = m e t h o x y c a r b o n y l e t h y l p-TSOH = p a r a - t o l u e n e s u l f o n i c a c i d TFA = t r i f l u o r o a c e t i c a c i d THF = t e t r a h y d r o f u r a n TLC = t h i n l a y e r chromatography U n c o r r = u n c o r r e c t e d Uv = u l t r a v i o l e t A b b r e v i a t i o n s i n NMR Assignments S = s i n g l e t d = d o u b l e t t = t r i p l e t q = q u a r t e t m = m u l t i p l e t s bs = broad s i n g l e t - i v -NOMENCLATURE In t h i s w o r k , s e v e r a l terms of nomenclature are used i n t e r c h a n g e a b l y . Dipyrromethane = 2 , 2 ' - D i p y r r o l y l m e t h a n e T r i p y r r n e = T r i p y r r o m e t h a n e (= 2 , 5 - b i s - ( 2 - p y r r o l y l m e t h y l ) - p y r r o l e ) T r i p y r r e n e = P e n t a p h y r i n = IB 17 -V-ACKNOWLEDGMENTS I am v e r y g r a t e f u l t o P r o f e s s o r David D o l p h i n f o r h i s encouragement and guidance d u r i n g the c o u r s e of t h i s work. I t has been a r e w a r d i n g e x p e r i e n c e and my s i n c e r e t h a n k s goes t o h i m . My thanks and a p p r e c i a t i o n t o p a s t and p r e s e n t members of the D o l p h i n Group. T h e i r h e l p and f r i e n d s h i p was g r e a t . My thanks a l s o goes t o the C h e m i s t r y Department f o r t h e f i n a n c i a l s u p p o r t . The s e r v i c e s o f f e r e d t o me by t h e D e p a r t m e n t ' s NMR and Mass S p e c t r o s c o p y i s g r a t e f u l l y acknowedged. A s p e c i a l t h a n k s t o my w i f e , K a t e , and s o n , Jeremy. - v i -1 1. INTRODUCTION AND LITERATURE REVIEW 2 The i n c r e a s i n g i n t e r e s t i n p o l y p y r r o l e macro-cycles i s j u s t i f i e d by the c e n t r a l r o l e which p o r p h y r i n and i t s d e r i v a t i v e s p l a y i n s e v e r a l e s s e n t i a l b i o l o g i c a l p r o c e s s e s . A f u r t h e r i n f l u e n c e which f o s t e r e d the development of p o r p h y r i n c h e m i s t r y has been t h e i n t e r e s t 1n t h e t h e o r e t i c a l a s p e c t s of a r o m a t i c i t y such as the e x t e n t t o which m o d i f i c a t i o n and e x p a n s i o n of c y c l i c systems o f c o n j u g a t e d double bonds i s p o s s i b l e w h i l e s t i l l r e t a i n i n g a r o m a t i c c h a r a c t e r . The p o r p h y r i n which o c c u r s n a t u r a l l y as p r o s t h e t i c groups of b i o l o g i c a l m o l e c u l e s , haemoglobin and myoglobin i s a t e t r a p y r r o l i c m a c r o c y c l e w i t h the p y r r o l e u n i t s l i n k e d t o one a n o t h e r by methine b r i d g e s . The b a s i c p o r p h y r i n n u c l e u s i s shown i n f i g u r e 1. The d i h y d r o - and t e t r a h y d r o d e r i v a t i v e s of the p o r p h y r i n n u c l e u s a r e known as c h l o r i n [2) and b a c t e r i o c h l o r i n (3_) r e s p e c t i v e l y and are the p a r e n t m a c r o c y c l e s of a v a r i e t y of p l a n t pigments known as c h l o r o p h y l l s and b a c t e r i o c h l o r o p h y l l s . The c o r r i n ( 4 ) , a n o t h e r n a t u r a l l y o c c u r i n g c y c l i c t e t r a p y r r o l e w i t h one d i r e c t l i n k between two 1 2 3 Me H 5 Figure 1. Nomenclature of tetrapyrrolic macrocycles 3 p y r r o l e u n i t s , t s t h e p a r e n t m a c r o c y c l e o f t h e B 1 2 coenzyme. The t e t r a d e h y d r o d e r i v a t i v e of the c o r r i n n u c l e u s i s the c o r r o l e (5_). The extreme s t a b i l i t y o f t h e s e t e t r a p y r r o l i c m a c r o c y c l e s has been a t t r i b u t e d t o t h e i r a r o m a t i c i t y w i t h t h e e x c e p t i o n o f c o r r i n (4) which i s not a r o m a t i c . A r o m a t i c i t y may be d e f i n e d i n a number of d i f f e r e n t ways ' a n d s e v e r a l d i f f e r e n t methods have been proposed f o r the measurement o f a r o m a t i c c h a r a c t e r . C l a s s i c a l l y , a r o m a t i c i t y has been 3 c o r r e l a t e d w i t h t h e p r e s e n c e o f an " a r o m a t i c s e x t e t " , the s t a b i l i t y and the c h e m i c a l r e a c t i v i t y of t h e compound. C l e a r l y , c h e m i c a l r e a c t i v i t y i s not a ground s t a t e p r o p e r t y o f t h e compound but one dependent on t h e e n e r g y d i f f e r e n c e between the ground s t a t e and the t r a n s i t i o n s t a t e f o r the c h e m i c a l change i n v o l v e d . H u c k e l ' s r u l e 4 p r e d i c t s t h a t p l a n a r , m o n o c y c l i c c o n j u g a t e d systems of t r i g o n a l l y h y b r i d i z e d atoms h a v i n g a c l o s e d s h e l l c o n f i g u r a t i o n of (4n + 2)n - e l e c t r o n s w i l l p o s s e s s s t a b i l i t y , i . e . , w i l l be a r o m a t i c . T h u s , a r o m a t i c i t y i s a f u n c t i o n of the e l e c t r o n i c n a t u r e of t h e s y s t e m , and not a p r o p e r t y of the s t a b i l i t y or 5 6 c h e m i c a l r e a c t i v i t y . E l v i d g e and Jackman ' d e f i n e a r o m a t i c compounds as those which w i l l s u s t a i n an i n d u c e d r i n g c u r r e n t . The magnitude of t h e r i n g c u r r e n t w i l l be a f u n c t i o n o f the d e l o c a l i s a t i o n o f i t - e l e c t r o n s around t h e r i n g and t h e r e f o r e a measure o f a r o m a t i c i t y . The p o r p h y r i n m a c r o c y c l e i s a h i g h l y c o n j u g a t e d system and a number of resonance forms can be w r i t t e n f o r i t . There are 22 i t - e l e c t r o n s i n t h e carbon s k e l e t o n , but o n l y 18 of t h e s e a r e i n c l u d e d i n any one d e r e a l i z a t i o n pathway ( 6 ) . Thus the c r o s s - c o n j u g a t e d double bonds (shown by arrows a , b ) can be reduced w i t h o u t d i s t u r b i n g t h e a r o m a t i c i t y of t h e m a c r o c y c l e . C h l o r i n (2_) w i t h one (arrow a) o f t h e p e r i p h e r a l d o u b l e bonds r e d u c e d and b a t e r i o c h l o r i n w i t h two (arrows a , b ) r e d u c e d , both r e t a i n t h e i r a r o m a t i c i t y s i n c e t h e c o n j u g a t e d 18 it - e l e c t r o n system i s m a i n t a i n e d . S i m i l a r l y , t h e c o r r o l e n u c l e u s i s a r o m a t i c and one p e r i p h e r a l d o u b l e bond can be reduced w h i l e s t i l l m a i n t a i n i n g i t s a r o m a t i c i t y . However, t h e c o r r i n n u c l e u s i s n e i t h e r a r o m a t i c nor p l a n a r . Porphycene 1_, a p o r p h y r i n - l i k e m a c r o c y c l e , have been s y n t h e s i z e d and found t o be a r o m a t i c . ^ A number of p h y s i c a l methods a r e c u r r e n t l y used t o measure t h e e x t e n t of ^ - e l e c t r o n d e l o c a l i z a t i o n , and hence a r o m a t i c c h a r a c t e r . These i n c l u d e nmr s p e c t r o s c o p y , u v - v i s i b l e s p e c t r o s c o p y and x - r a y c r y s t a l l o g r a p h y . These and o t h e r t e c h n i q u e s have been t e s t e d on the 18 it - e l e c t r o n p o r p h y r i n system known t o be a r o m a t i c . One manner i n which t h e ^ - e l e c t r o n d e l o c a l i z a t i o n m a n i f e s t s i t s e l f i s i n s u s t a i n i n g of r i n g c u r r e n t s when p l a c e d i n an e x t e r n a l magnetic 5 f i e l d . Thus t h e p r e s e n c e of a r i n g c u r r e n t i s an i n d i c a t i o n o f a r o m a t i c i t y . A r o m a t i c compounds i n nmr s p e c t r o s c o p y e x h i b i t c h e m i c a l s h i f t s o f p r o t o n s such t h a t t h o s e i n s i d e the r i n g are s t r o n g l y s h i e l d e d due t o the r i n g c u r r e n t o p p o s i n g the a p p l i e d f i e l d (thus d i a m a g n e t i c ) and appear s h i f t e d u p f i e l d from p o s i t i o n e x p e c t e d on e l e c t r o n i c c o n s i d e r a t i o n s . P r o t o n s o u t s i d e the r i n g are s t r o n g l y d e s h i e l d e d , the r i n g c u r r e n t s t r e n g t h e n i n g t h e e x t e r n a l f i e l d , and t h e r e f o r e appear Q d o w n f i e l d from the e x p e c t e d f o r o l e f i n i c p r o t o n s . S t u d i e s on p o r p h y r i n s by nmr s p e c t r o s c o p y c l e a r l y i n d i c a t e the presence of a r i n g c u r r e n t . The p a r e n t p o r p h r i n U) i n t r i f l u o r o a c e t i c a c i d e x h i b i t s r e s o n a n c e s a t - 4 . 4 8 f o r the NH p r o t o n s , 9 . 9 8 f o r the e i g h t B - p r o t o n s and 11.226 f o r t h e g m e s o - p r o t o n s ( 6 = 0 ppm f o r TMS). A major d i f f e r e n c e between a r o m a t i c systems and c o n j u g a t e d c y c l i c or n o n - c y c l i c p o l y e n e s i s t h e f a c t t h a t i n the n o n - a r o m a t i c s y s t e m s , t h e c a r b o n - c a r b o n bond l e n g t h s are a l t e r n a t e l y long and s h o r t i n a c c o r d a n c e w i t h t h e a l t e r n a t e s i n g l e and double b o n d s , whereas i n the a r o m a t i c compounds, a l l t h e bonds are of the same l e n g t h - i . e . of the same bond o r d e r c h a r a c t e r . T h i s bond o r d e r i s unique ( r e s u l t i n g i n bond l e n g t h s i n t e r m e d i a t e between t h o s e f o r s i n g l e and double bonds) and not s i m p l y a r e l a t i o n s h i p between s i n g l e and d o u b l e b o n d s . In o r d e r t o o b t a i n t h i s bond o r d e r , t h e r e must be maximum o v e r l a p between the a x i a l l y o r i e n t e d p - o r b i t a l s and t h i s r e q u i r e s t h a t the r i n g be p l a n a r . X - r a y c r y s t a l l o g r a p h i c s t u d i e s on p r o p h i n e (J_) and some o t h e r p o r p h y r i n systems have shown^ 0 t h i s to be t h e c a s e . P o r p h y r i n s are h i g h l y c o l o r e d compounds h a v i n g a b s o r p t i o n bands i n t h e v i s i b l e r e g i o n (400-700 nm) w i t h v a r y i n g r e l a t i v e i n t e n s i t i e s 6 11 12 depending on t h e - p e r i p h e r a l s u b s t i t u e n t s on the n u c l e u s * , s o l v e n t 13 14 system and m o l e c u l a r a g g r e g a t i o n . One of t h e s e bands near t h e u l t r a v i o l e t r e g i o n (ca 400 nm) i s more i n t e n s e , G ^ I G ^ M - 1 cm"1 i n o r d e r of magnitude s t r o n g e r than the o t h e r v i s i b l e b a n d s . T h i s ' S o r e t ' b a n d , named a f t e r t h e d i s c o v e r e r , i s c h a r a c t e r i s t i c of the m a c r o c y c l i c c o n j u g a t i o n and t h e r u p t u r e of the m a c r o c y c l e r e s u l t s i n the d i s a p p e a r a n c e of t h i s band. The a r o m a t i c c h a r a c t e r i n p o r p h y r i n m a c r o c y c l e s has a l s o been c o n f i r m e d by 15 measurement of t h e i r h e a t s of combustion . In t h e l a b o r a t o r y , as w e l l as i n n a t u r e , p o r p h y r i n s are s y n t h e s i z e d f r o m p y r r o l e s , which i n t u r n a r e r e a d i l y o b t a i n e d f r o m a c y c l i c p r e c u r s o r s . The p o r p h y r i n m a c r o c y c l e can be c o n s t r u c t e d i n t h r e e f u n d a m e n t a l l y d i f f e r e n t w a y s . They a r e : (a) The s i n g l e s t e p c o n d e n s a t i o n of m o n o p y r r o l e s ^ . (b) The c o u p l i n g of two d i p y r r o l i c i n t e r m e d i a t e s , commonly r e f e r r e d t o as a "2 + 2" s y n t h e s i s ^ 7 , ( c ) The s t e p w i s e c o n d e n s a t i o n of i n d i v i d u a l p y r r o l e s , l e a d i n g t o a l i n e a r t e t r a p y r r o l e and 18 a f i n a l head t o t a i l c y c l i s a t i o n . Method (a) has v e r y l i m i t e d s y n t h e t i c v a l u e , p r i m a r i l y due t o the symmetric n a t u r e of t h e p o r p h y r i n s produced and a l s o due t o the l i m i t on t h e t y p e of s u b s t i t u e n t s t h a t can be i n t r o d u c e d . Methods (b) and ( c ) , t o g e t h e r f o r m t h e major r o u t e t o p o r p h y r i n s as w e l l as o t h e r r e l a t e d m a c r o c y c l e s s i n c e i t i s now p o s s i b l e t o s y n t h e s i z e systems w i t h d i v e r s e p e r i p h e r a l s u b s t i t u e n t s i n t h e r e q u i r e d r e l a t i v e o r i e n t a t i o n s . A s y n t h e t i c r o u t e of g r e a t v a l u e i n p o r p h y r i n s y n t h e s e s has been 19 20 t h a t d e v e l o p e d i n d e p e n d e n t l y by Woodward and MacDonald which i n v o l v e s t h e use of t h e w e l l - k n o w n r e a c t i o n whereby 2 - f o r m y l p y r r o l e s condense w i t h a c i d and 2 - u n s u b s t i t u t e d p y r r o l e s t o a f f o r d e f f i c i e n t l y t h e s t a b l e 7 2 , 2 ' - d i p y r r o m e t h e m i u m s a l t s . The e x t e n s i o n o f t h i s r e a c t i o n t o p o r p h y r i n s y n t h e s i s (Scheme 1) i n v o l v e s the c o u p l i n g of dipyrromethane d i a l d e h y d e 8a w i t h b i s - a - f r e e dipyrromethane 8b i n the presence of h y d r i o d i c a c i d i n a c e t i c a c i d s o l u t i o n t o produce an i n t e r m e d i a r y porphodimethene 10 which upon o x i d a t i o n g i v e s the f i n a l p o r p h y r i n 11 o r 12. The s y n t h e t i c analogue o f 8 b , t h e d i c a r b o x y d e r i v a t i v e can a l s o be used s i n c e i t d e c a r b o x y l a t e s d u r i n g a c i d c a t a l y s e d c y c l i z a t i o n . One p a r t i c u l a r c a t a l y s t which has been used i n t e n s i v e l y i s p - t o l u e n e s u l f o n i c a c i d . Using t h i s c a t a l y s t , Kenner e t 21 a l . c y c l i s e d a p o r p h y r i n i n m e t h a n o l . The a d d i t i o n o f z i n c a c e t a t e a f f o r d e d t h e i s o l a t i o n of the p r o d u c t s as the z i n c complex. The a c i d s t r e n g t h of the r e a c t i o n medium a f f e c t s rearrangement o f the b i p y r r o l i c u n i t s l e a d i n g t o i s o m e r s . T h i s rearrangement has been a v o i d e d by t h e use o f methanol-methylene c h l o r i d e (1 :30) m i x t u r e s 2 2 ( a » b » c ) » The p h y s i c a l and c h e m i c a l p r o p e r t i e s o f the p o r p h y r i n s and t h e i r r e l a t e d m a c r o c y c l e s have 12 been d e a l t w i t h e x t e n s i v e l y i n the s e r i a l volume "The P o r p h y r i n s " . The f i r s t i s o l a t i o n o f metal d e r i v a t i v e s of c o r r o l e 13 was r e p o r t e d 23 by Johnson and P r i c e . These syntheses r e s u l t e d from the r e a c t i o n o f formaldehyde and aqueous e t h a n o l i c hydrogen c h l o r i d e w i t h t h e p a l l a d i u m complex o f 5 , 5 " - B i s ( 5 ' - b r o m o - 3 , 3 ' - d i e t h y l - 4 , 4 ' - d i m e t h y l d i p y r r o m e t h e n e ) 14, 24 o r i g i n a l l y prepared by F i s h e r and S t a c h e l . However i t was shown t h a t t h i s 25 r e a c t i o n gave the m e t a l l o x o c o r r o l e s 15 i n s t e a d . 8 9 S i n c e the o r i g i n a l c l a i m f o r a c o r r o l e s y n t h e s i s had not been f u l f i l l e d , Woodward and Bauer d i r e c t e d t h e i r e f f o r t s toward such a s y n t h e s i s . To s y n t h e s i z e an a u t h e n t i c c o r r o l e , Woodward and Bauer t r e a t e d t h e f r e e base b i ( d i p y r r o m e t h e n e ) _16, o b t a i n e d by d e m e t a l l a t i o n and c a t a l y t i c h y d r o g e n a t i o n o f 1_4, w i t h f o r m i c and hydrobromic a c i d s . The p r o d u c t , a b l u e g l a s s i s o l a t e d i n low y i e l d e x h i b i t e d an i n t e n s e S o r e t band i n t h e 27 v i s i b l e spectrum a t 458 nm. However, Johnson and Kay had by now p r e p a r e d a u t h e n t i c samples of c o r r o l e s by the p h o t o c h e m i c a l c y c l i z a t i o n of d i d e o x y b i l a d i e n e s - a c J_7. The e l e c t r o n i c s p e c t r a o f the c o r r o l e s r e p o r t e d pp by Johnson showed a S o r e t band at ~400 nm c l e a r l y d i f f e r e n t from t h a t 10 o b s e r v e d f o r the " c o r r o l e " p r e p a r e d by Woodward and Bauer which l e d t o the r e i n v e s t i g a t i o n of the compound. The compound was found t o form a d i p e r c h l o r a t e s a l t , whereas c o r r o l e s underwent o n l y mono-N- p r o t o n a t i o n . The e m p i r i c a l f o r m u l a of the d i p e r c h l o r a t e s a l t proved t o be 17 c o n s i s t e n t w i t h a mono-hydrate d i p e r c h l o r a t e s a l t c o n t a i n i n g f i v e p y r r o l i c u n i t s , and not f o u r . A c c o r d i n g l y , the s t r u c t u r e of t h i s compound was c o n c l u d e d to be J 8 , and because o f the c r y s t a l l i n e form and b r i l l i a n t b l u e c o l o r ( r e m i n i s c e n t of s a p p h i r e s ) , was c a l l e d s a p p h y r i n . T h i s m a c r o c y c l e i s analogous i n s t r u c t u r e to a c o r r o l e w i t h one d i r e c t l i n k between p y r r o l e s . 11 The s a p p h y r i n m a c r o c y c l e 18 was the f i r s t p o l y p y r r o l i c m a c r o c y c l e i s o l a t e d c o n t a i n i n g more than f o u r p y r r o l e r i n g s . The presence o f a v e r y i n t e n s e S o r e t - l i k e a b s o r p t i o n band (458 nm) and r i n g - c u r r e n t induced nmr s h i f t s ( d o w n f i e l d f o r t h e e x t e r n a l methine p r o t o n s , u p f i e l d from t h e r e f e r e n c e s t a n d a r d t e t r a m e t h y l s i l a n e f o r the NH p r o t o n s ) i n d i c a t e t h a t t h e s a p p h y r i n s y s t e m , which can be f o r m a l l y w r i t t e n as c o n t a i n i n g 22 c o n j u g a t e d TT - e l e c t r o n s (4n + 2 , n = 5) i s a r o m a t i c . The f i r s t syntheses of a p e n t a p y r r o l i c m a c r o c y c l e g e n e r a t e d i n t e r e s t i n o t h e r workers f o r o t h e r m a c r o c y c l e s w i t h d i f f e r e n t s u b s t i t u e n t s and h e t e r o a t o m s . Thus i n 1972 Broadhurst e t a l . i n v e s t i g a t e d s a p p h y r i n - 1 i k e 29 m a c r o c y c l e s and r e p o r t e d the s y n t h e s i s of d i o x a s a p p h y r i n w i t h a b i f u r a n moiety r e p l a c i n g the b i p y r r o l e . The same a u t h o r s a l s o r e p o r t e d t h e s y n t h e s i s o f t h i a s a p p h y r i n , w i t h one thiophene moiety r e p l a c i n g a p y r r o l e 30 and p e n t a e t h y l s a p p h y r i n 19 a l l of which were a r o m a t i c and c o n t a i n e d t h e 31 i n t e n s e S o r e t t y p e band i n t h e i r v i s i b l e s p e c t r a . King and Woodward a l s o s y n t h e s i z e s a 22 i r - e l e c t r o n macrocycle which they c a l l e d s m a r a g d y r i n 30 (smaragdus:emerald) 2 0 . Johnson and c o - w o r k e r s a l s o attempted t o s y n t h e s i z e t h i s system which they c a l l e d n o r s a p p h y r i n . They d i d i n f a c t succeed w i t h syntheses of the d i o x a n o r s a p p h r y i n s (or d i o x a s m a r a g d y r i n s ) 21 a , b ) . A s e r i e s o f h e t e r o a t o m - b r i d g e d annulenes c o n t a i n i n g f u r a n and 32 26 t h i o p h e n e have a l s o been s y n t h e s i z e d by V o l d h a r d t . Bauer e t a l . r e p o r t e d the s y n t h e s i s of d e c a m e t h y l s a p p h y r i n 2 2 . The f o r m a t i o n of 18 was f i r s t r a t i o n a l i s e d as p r o c e e d i n g t h r o u g h the c o n d e n s a t i o n of two m o l e c u l e s o f 16 w i t h f o r m i c a c i d f o l l o w e d by a - p r o n a t i o n and bond c l e a v a g e to g i v e s a p p h y r i n . Another method o f 12 p r e p a r a t i o n u t i l i z e d J6 and 2 , 5 - d i f o r m y l - 3 , 4 - d i m e t h y l p y r r o l e . The S H H d e c a m e t h y l s a p p h y r i n 22_was a l s o s y n t h e s i z e d e f f i c i e n t l y u t i l i z i n g t h e c o u p l i n g of b l p y r r o l e d i c a r b o x a l d e h y d e 23 w i t h t r i p y r r a n e d i a c i d 24 by t h e agency of p - t o l u e n e s u l f o n i c a c i d i n oxygenated e t h a n o l (Scheme 2) a p r o c e s s analogous t o M a c D o n a l d ' s 2 + 2 c o u p l i n g of p o r p h y r i n (Scheme 1 ) . In a s i m i l a r p r o c e d u r e , h e x a m e t h y l s a p p h y r i n was p r e p a r e d f r o m 5 , 5 ' - d i f o r m y l - 2 , 2 ' - b i p y r r o l e and t r i p y r r a n e d i a c i d i n e x c e l l e n t y i e l d . M e t a l complexes of d e c a m e t h y l s a p p h y r i n 25 have a l s o been r e p o r t e d and i n some c a s e s i s o l a t e d . When a m e t h a n o l i c s o l u t i o n of 13 d e c a m e t h y l s a p p h y r i n and t h e a c e t a t e s a l t s of n i c k e l , i r o n , c a d i u m , 2 4 S C H E M E 2 manganese, c o b a l t and z i n c were heated i n t h e p r e s e n c e of sodium a c e t a t e , m e t a l complexes were formed as i n d i c a t e d by s p e c t r a l c h a n g e s . The complexes of c o b a l t and z i n c have been I s o l a t e d as c r y s t a l l i n e s o l i d s . The same p u b l i c a t i o n r e p o r t e d t h e u n s u c c e s s f u l a t t e m p t s t o s y n t h e s i z e u r a n y l and l e a d c o m p l e x e s . D e s p i t e t h e l a r g e " h o l e " i n t h e c e n t r e o f d i o x a n o r s a p p h y r i n i t was found not t o form metal complexes w i t h u r a n y l 33 i o n s which a r e known t o form p e n t a g o n a l b i p y r a m i d s . S u p e r p h t h a l o c y a n i d e 2 6 , a u r a n y l m o i e t y c o o r d i n a t e d t o f i v e s u b u n i t P e n t a k i s -34 ( 2 - i m i n o i s o i n d o l i n e ) was f i r s t r e p o r t e d by B l o o r e t a l . and i n 1974 14 Day e t a l . r e p o r t e d t h e s y n t h e s i s o f t h e same compound w i t h improved c h e m i c a l a n a l y s i s . Attempts t o d i s p l a c e t h e u r a n y l i o n w i t h a c i d or o t h e r m e t a l i o n s i n v a r i a b l y r e s u l t e d i n c o n t r a c t i o n of t h e m a c r o c y c l e . The s u c c e s s of t h e Harvard group i n t h e i r s y n t h e s e s o f t h o s e s a p p h y r i n m a c r o c y c l e s and t h e metal d e r i v a t i v e s encouraged them t o u n d e r t a k e a p r o j e c t t o attempt t h e s y n t h e s i s of t h e p e n t a p y r r o l e a n a l o g of p o r p h y r i n . T h i s p r o j e c t was aimed a t t h e s y n t h e s e s of d e c a m e t h y l p e n t a -37 p y r r o l e and o t h e r p e n t a p y r r o l e m a c r o c y c l e s . Employing the "3 + 2" 15 c o u p l i n g analogous t o M a c D o n a l d ' s "2 + 2" c o u p l i n g (see Scheme 1 ) , t r i p y r r a n e d i a c i d and d i a l d e h y d e 27 (a & b) were used w i t h d i p y r r o m e t h a n e d i a l d e h y d e and t h e d i a c i d 28 (a & b) r e s p e c t i v e l y i n the presence o f c a t a l y t i c amounts o f p - t o l u e n e s u l f o n i c a c i d i n oxygenated e t h a n o l and methanol (see Scheme 3 ) . The c o u p l i n g r e a c t i o n s were f o l l o w e d and m o n i t o r e d u s i n g e l e c t r o n i c a b s o r p t i o n f o r s e v e r a l days and i n some c a s e s f o r weeks, y i e l d i n g p o r p h y r i n s i n s t e a d of the p e n t a p y r r o l e m a c r o c y c l e s . 38 Another attempt was made t o s y n t h e s i z e t h e s e p e n t a p y r r o l e m a c r o c y c l e s i n methylene c h l o r i d e w i t h anhydrous hydrogen c h l o r i d e g a s . The same 37 p o r p h y r i n p r o d u c t s as r e p o r t e d e a r l i e r were o b t a i n e d . Franck and 39 c o - w o r k e r s attempted t o s y n t h e s i z e p e n t a - and h e x a p y r r o l i c m a c r o c y c l e s d i r e c t l y by c o n d e n s a t i o n of the t r i - and t e t r a p y r r o l e s w i t h d i p y r r o m e t h a n e d i a l d e h y d e s i n oxygenated methanol i n the presence of hydrogen bromide ( i n a c e t i c a c i d ) . In s p i t e of t h e v e r y m i l d r e a c t i o n c o n d i t i o n s , p o r p h y r i n s were o b t a i n e d accompanied by e l i m i n a t i o n of p y r r o l e u n i t s . U s i n g t h e same 40 s t a r t i n g p y r r o l e s Franck attempted a g a i n the s y n t h e s e s of p e n t a - and h e x a p y r r o l e m a c r o c y c l e s i n g l a c i a l a c e t i c a c i d a t room t e m p e r a t u r e i n t h e presence of 0.25% h y d r i o d i c a c i d . The r e s u l t was not d i f f e r e n t from t h o s e 39 r e p o r t e d e a r l i e r . The f i r s t s u c c e s s f u l s y n t h e s i s of p e n t a p y r r o l i c m a c r o c y c l e a n a l o g o u s t o t h e p o r p h y r i n s , i e . h a v i n g f i v e p y r r o l e r i n g s w i t h f i v e 41 methine b r i d g e s , was r e p o r t e d by Gossauer and Rehausen . The f i v e membered m a c r o c y c l e f o r which t h e y suggested the t r i v i a l name p e n t a p h y r i n 2 9 , was o b t a i n e d by the c o n d e n s a t i o n of the d i p y r r o m e t h a n e 30 w i t h t h e t r i p y r r a n e d i a l d e h y d e 31_ u s i n g methylene c h l o r i d e as s o l v e n t and HBr i n 16 ) O 2 8 a: R=C02H, R^-CHO : R=CHO, Rlt=C02H S C H E M E 3 17 a c e t i c a c i d as c a t a l y s t w i t h o x i d a t i o n of the i n i t i a l c y c l i z a t i o n p r o d u c t w i t h c h l o r a n i l (Scheme 4 ) . 37 38 For a l o n g t i m e now work i n our group • i n a t t e m p t i n g t o shed l i g h t to v a r i o u s a s p e c t s of t h e p e n t a p h y r i n system was hampered by the f a i l u r e o f the p r e c u r s o r s or systems t o c y c l i z e . T h i s work was t h e r e f o r e undertaken i n o r d e r to s y n t h e s i z e s e v e r a l p e n t a p h y r i n s w i t h d i f f e r e n t p e r i p h e r a l s u b s t i t u e n t s and i n v e s t i g a t e t h e e f f e c t s of t h o s e groups on c y c l i z a t i o n y i e l d s , s p e c t r a l p r o p e r t i e s and m e t a l a t i o n and t h e r e b y complete t h e work a l r e a d y s t a r t e d i n t h i s g r o u p . S C H E M E 4 18 2. RESULTS AND DISCUSSIONS 19 2.1 SYNTHETIC STRATEGY In t h e s y n t h e s e s of p e n t a p y r r o l i c m a c r o c y c l e s from p y r r o l i c p r e c u r s o r s , the 3 + 2 c o n d e n s a t i o n analogous t o the M a c D o n a l d ' s 2 + 2 p o r p h y r i n s y n t h e s i s (Scheme 1) can be e m p l o y e d . T h i s c o n d e n s a t i o n method p l u s the 4 + 1 c o n d e n s a t i o n were used i n the s a p p h y r i n s y n t h e s e s . In as much as l i n e a r t e t r a p y r r o l e s ( t e t r a p y r r a n e s or b i l a n e s ) w i t h o u t e l e c t r o n -w i t h d r a w i n g s t a b i l i z a t i o n on each p y r r o l e r i n g are d i f f i c u l t t o h a n d l e , or even s y n t h e s i z e , most a t t e n t i o n was d i r e c t e d t o p o s s i b l e 3 + 2 s y n t h e s i s . The s y n t h e s e s of t h e s e m a c r o c y c l e s r e q u i r e " f o r m y l p y r r o l e s " as t h e e l e c t r o p h i l i c component. Hence t h e two r e l e v a n t 3 + 2 approaches i n v o l v e t h e c o u p l i n g of e i t h e r a t e r m i n a l l y u n s u b s t i t u t e d t r i p y r r a n e w i t h a d i p y r r o m e t h a n e d i a l d e h y d e (Case A) or t h e r e a c t i o n of 5 , 5 ' - u n s u b s t i t u t e d d i p y r r o m e t h a n e w i t h a t r i p y r r a n e d i a l d e h y d e (Case B) as i l l u s t r a t e d i n f i g u r e 2 . Figure 2. The 3 + 2 mode of approaches 1n Pentaphyrln Syntheses 20 In g e n e r a l d i - a - u n s u b s t i t u t e d t r i p y r r a n e s and dipyrromethanes w i t h o u t e l e c t r o n - w i t h d r a w i n g groups are very u n s t a b l e and r e q u i r e s p e c i a l h a n d l i n g p r o c e d u r e s . Moreover, they are o b t a i n e d by s u b l i m a t i o n from t h e i r d i a c i d s a t h i g h temperatures w i t h p o s s i b i l i t y o f f r a g m e n t a t i o n due t o t h e p r e s e n c e of c a t a l y s t used i n the s u b l i m a t i o n . Due t o t h e above r e a s o n s , i t was d e c i d e d t h a t the use of the d i c a r b o x y l i c a c i d i n s t e a d o f t h e d i - a -u n s u b s t i t u t e d dipynomethane would be more a p p r o p r i a t e . The t r i p y r r a n e o r dipyrromethane d i c a r b o x y l i c a c i d , a p a r t from i t s r e l a t i v e l y s t a b l e n a t u r e , r e a d i l y undergoes d e c a r b o x y l a t i o n under the a c i d c o n d i t i o n s used f o r c y c l i z a t i o n . Of the two r e l e v a n t 3 + 2 a p p r o a c h e s , ( f i g u r e 1 ) , c a s e B has been found t o be the o n l y r o u t e t o the s y n t h e s i s of the p e n t a p y r r o l i c 41 m a c r o c y c l e . Most o f the u n s u c c e s s f u l attempts i n the s y n t h e s i s o f t h e 0 7 OO Oft A 1 p e n t a p y r r o l e m a c r o c y c l e s » J B t j y » u t i l i z e d the c o u p l i n g of d i p y r r o m e t h a n e d i a l d e h y d e s and d i - a - u n s u b s t i t u t e d t r i p y r r a n e s ( f i g u r e 1 , case A) r e s u l t i n g i n o n l y p o r p h y r i n f o r m a t i o n w i t h o u t even t r a c e s o f t h e d e s i r e d p e n t a p y r r o l i c 41 p r o d u c t . In f a c t Gossauer et a l . i n i t i a l l y f a i l e d i n t h e i r attempt u s i n g t h e s e p r e c u r s o r s . Thus the " d i f o r m y l " must be on t h e t r i p y r r o l i c u n i t r a t h e r than the dipyrromethane component i n o r d e r t o cause c y c l i z a t i o n l e a d i n g t o the r e q u i r e d m a c r o c y c l e . G e n e r a l l y , the f r e e base dipyrromethenes and t r i p y r r e n e s d i a l d e h y d e s are v e ry u n s t a b l e and t h u s , t r i p y r r e n e s cannot be used as such f o r case B. However, t r i p y r r e n e s can be a c o n v e n i e n t s o u r c e o f t r i p y r r a n e s when p r o p e r l y r e d u c e d . One of the t a r g e t m o l e c u l e s i s the d e c a m e t h y l - d e r i v a t i v e o f our macrocycle and so i t was found c o n v e n i e n t t o use t h e t e t r a m e t h y l d i p y r r o m e t h a n e d i c a r b o x y l i c a c i d 32 and h e x a m e t h y l -t r i p y r r a n e d i a l d e h y d e 3 3 . The e f f e c t o f an e l e c t r o n - w i t h d r a w i n g group on 21 the m a c r o c y c l e was a l s o c o n s i d e r e d . T r i p y r r a n e s , v e r y v u l n e r a b l e t o random a c i d - c a t a l y s e d f r a g m e n t a t i o n i n the absence of e l e c t r o n - w i t h d r a w i n g g r o u p s , become t h e o b v i o u s c h o i c e f o r t h e i n t r o d u c t i o n of t h i s g r o u p . T h u s , a t r i p y r r a n e whose c e n t r a l p y r r o l i c n u c l e u s would be as d e a c t i v a t e d as p o s s i b l e t o i n t e r n a l f r a g m e n t a t i o n was c o n s i d e r e d . T h i s r e q u i r e d t h e presence of at l e a s t one e l e c t r o n - w i t h d r a w i n g group on the c e n t r a l p y r r o l i c u n i t , and f o r such a g r o u p , t h e e s t e r g r o u p , e t h o x y c a r b o n y l was c h o s e n . We d e c i d e d t o change the p - s u b s t i t u e n t s of our d i a c i d from the t e t r a m e t h y l t o the t e t r a e t h y l , c o u p l e i t w i t h t h e t r i p y r r a n e monoester d i a l d e h y d e 34 and f i n d out how i t would a f f e c t the m a c r o c y c l e . A p a r t from b e i n g u n s t a b l e i n comparison t o t h e t e t r a m e t h y l , the t e t r a e t h y l a n a l o g would be much s o l u b l e . The use of s e v e r a l d i f f e r e n t l y s u b s t i t u t e d p y r r o l e s f o r t h e c y c l i z a t i o n would a l s o p r o v i d e markers f o r some p o s s i b l e f r a g m e n t a t i o n modes s h o u l d t h e r e a c t i o n g i v e o n l y p o r p h y r i n s and p o l y m e r s . I t was d e c i d e d to s t a r t t h i s p r e s e n t work by f i r s t s y n t h e s i z i n g 41 t h e m a c r o c y c l e r e p o r t e d i n l i t e r a t u r e u s i n g improved methods. T h e r e f o r e , the t r i p y r r a n e d i a l d e h y d e s and d i p y r r o m e t h a n e d i c a r b o x y l i c a c i d s t o be s y n t h e s i z e d a r e shown i n f i g u r e 3 . Figure 3. Intermediates for the syntheses of macrocycles 23 2.2 SYNTHESIS OF INTERMEDIATES The e s s e n t i a l b a s i c p y r r o l e s used i n t h e p r e p a r a t i o n of t h e p r i m a r y p r e c u r s o r s , ( d i p y r r o m e t h a n e d i a c i d s and t r i p y r r a n e d i a l d e h y d e s ) , were a v a i l a b l e i n our l a b o r a t o r y . These had been p r e v i o u s l y s y n t h e s i z e d 37 from a c y c l i c p r e c u r s o r s u s i n g s t a n d a r d p r o c e d u r e s . T h e i r p u r i t y was checked by m e l t i n g p o i n t and s p e c t r o s c o p i c a n a l y s i s p r i o r t o u s e . The s y n t h e s i s o f t h e t r i p y r r a n e 43 i s o u t l i n e d i n Scheme 5 . The t r i m e t h y l p y r r o l e 36 was c o n v e r t e d t o i t s a - c a r b o x y p y r r o l e 37 d e r i v a t i v e by t r e a t i n g 36 i n d r y e t h e r w i t h s u r f u r y l c h l o r i d e and h y d r o l y s i n g t h e i n t e r m e d i a t e t r i c h l o r o p r o d u c t . To p r e p a r e compound 40 an i m p o r t a n t p r e c u r s o r f o r t h e s y n t h e s i s o f t r i p y r r a n e 43 t h e a - c a r b o x y p y r r o l e 37 was f i r s t t r a n s f o r m e d to the a - f r e e p y r r o l e by d e c a r b o x y l a t i o n . T h i s d e c a r b o x y l a t i o n was o b t a i n e d by an i n d i r e c t i o d i n a t i o n procedure ( v i a 38) which g i v e s h i g h y i e l d s and pure p r o d u c t s . In p r a c t i s e , the d e c a r b o x y l a t i v e i o d i n a t i o n of 3_7 was c a r r i e d out i n the two phase system of d i c h l o r o e t h a n e and w a t e r , u s i n g sodium b i c a r b o n a t e t o s o l u b i l i z e t h e s t a r t i n g m a t e r i a l as i t s a n i o n . The d i c h l o r o e t h a n e e x t r a c t s t h e i o d o p y r r o l e 38 as i t i s f o r m e d , p r e v e n t i n g t h e f o r m a t i o n of s o l i d 43 p y r r o l e - i o d i n e c h a r g e - t r a n s f e r complexes . S i n c e t h e m o l e c u l a r i o d i n e complexes cannot f o r m , the i o d i n e taken i n e x c e s s ( i n aqueous p o t a s s i u m i o d i d e ) was r a p i d l y a d d e d . The p r o d u c t was i s o l a t e d from the o r g a n i c phase a f t e r d e s t r o y i n g the e x c e s s i o d i n e w i t h b i s u l f i t e . The y i e l d of the r e c r y s t a l l i s e d p r o d u c t was 80%. The subsequent d e i o d i n a t i o n was c a r r i e d out by the use of h y d r i o d i c a c i d (a m i x t u r e of p o t a s s i u m i o d i d e and 24 0 , 35 1) 3 S0 2C1 2 2) H20 S C H E M E 5 2 5 c o n c e n t r a t e d h y d r o c h l o r i c a c i d ) . The o - f r e e p y r r o l e 3 9 _ was p u r i f i e d by chromatography and o b t a i n e d i n g r e a t e r than 8 5 % y i e l d . The 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e 3 9 _ was next s u b j e c t e d t o h y d r o g e n a t i o n i n o r d e r t o c l e a v e t h e b e n z y l e s t e r g r o u p . The d e b e n z y l a t i o n was c a r r i e d out i n t e t r a h y d r o f u r a n a t room t e m p e r a t u r e and a t m o s p h e r i c p r e s s u r e u s i n g 1 0 % p a l l a d i u m on c h a r c o a l as t h e c a t a l y s t t o o b t a i n t h e a - c a r b o x y - a - f r e e p y r r o l e 4 0 _ i n over 9 5 % y i e l d . I t was used as i t i s i n t h e next s t e p . The 2 - b e n z y l o x y c a r b o n y l - 4 - m e t h o x y c a r b o n y l e t h y l - 3 , 5 - d i m e t h y l p y r r o l e 4 J _ w a s a c e t y l a t e d u s i n g one e q u i v a l e n t of l e a d 4 4 t e t r a a c e t a t e i n a c e t i c a c i d . The r e s u l t i n g p r o d u c t 4 2 was r e c r y s t a l l i z e d f r o m methylene c h l o r i d e - h e x a n e t o g i v e a f l u f f y s o l i d i n a p p r o x i m a t e l y 6 0 % y i e l d . H a v i n g s y n t h e s i z e d p y r r o l e s 4 0 and 4 2 t h e next s t e p was t h e p r e p a r a t i o n of t h e s y m m e t r i c a l t r i p y r r a n e 4 3 . T h i s was e f f e c t e d v i a t h e 4 5 method used by C l e z y and L i e p a . The p y r r o l e s 4 0 and 4 2 i n p y r i d i n e s o l u t i o n were heated on a s t e a m - b a t h o v e r n i g h t . The p r e c i p i t a t e o b t a i n e d was c r y s t a l l i z e d f r o m e t h a n o l t o g i v e c o l o r l e s s p l a t e s i n a p p r o x i m a t e l y 3 1 % y i e l d . Scheme 6 o u t l i n e s t h e c o n v e r s i o n of t h e t r i p y r r a n e d i b e n z y l e s t e r 4 _ 3 t o t h e t r i p y r r a n e d i a l d e h y d e 3 5 _ r e q u i r e d f o r c o u p l i n g . T r i p y r r a n e 4 3 was hydrogenated as i n compound 3 9 and t h e r e s u l t i n g crude t r i p y r r a n e 4 6 d i c a r b o x y l i c a c i d 4 4 _ f o r m u l a t e d . Thus t h e d i a c i d 4 4 d i s s o l v e d i n t r i f l u o r o a c e t i c a c i d w i t h s t i r r i n g near 0 ° C under argon atmosphere, underwent r a p i d d e c a r b o x y l a t i o n . A f t e r 1 5 m i n u t e s , t r i e t h y l o r t h o f o r m a t e was a d d e d , r e a c t i n g w i t h t h e newly produced b i s a - f r e e t r i p y r r a n e 4 5 . The p r o d u c t was d i s s o l v e d i n methylene 26 S C H E M E 6 27 c h l o r i d e and r e c r y s t a l l i z e d from methanol t o g i v e t h e t r i p y r r a n e d i a l d e h y d e 31 i n about 43% y i e l d . The s y n t h e s i s o f t r i p y r r a n e 33 was a c c o m p l i s h e d v i a t h e t r i p y r r i n 51 whose s y n t h e s i s i s o u t l i n e d i n Scheme 7. E s t e r s r e q u i r i n g m i l d e r and d i f f e r e n t means of removal have become e s t a b l i s h e d as t h e f u n c t i o n a l i t i e s of c h o i c e f o r many a p p l i c a t i o n s . These i n c l u d e t h e ^ - b u t y l e s t e r s , r e a d i l y d e p r o t e c t e d i n s t r o n g a c i d and b e n z y l e s t e r s , w h i c h on c a t a l y t i c h y d r o g e n o l y s i s a f f o r d t h e c a r b o x y p y r r o l e s under m i l d , n e u t r a l c o n d i t i o n s . The key I n t e r m e d i a t e h e r e , t h e r e f o r e , i s the d i p y r r o m e t h a n e 48 w i t h t - b u t y l and b e n z y l e s t e r s a t 5 and 5* p o s i t i o n s a l l o w i n g m a n i p u l a t i o n of t h e two p o s i t i o n s i n d e p e n d e n t l y . P y r r o l e 47 was o b t a i n e d by t r e a t m e n t o f p y r r o l e 46 w i t h one e q u i v a l e n t of l e a d t e t r a a c e t a t e i n g l a c i a l a c e t i c a c i d and r e c r y s t a l l i z e d from hexane. 47 F o r t h e c o u p l i n g o f p y r r o l e m o n o e s t e r s , MacDonald e t a l . have d e v i s e d a procedure whereby a b r o m o m e t h y l p y r r o l e or an a c e t o x y m e t h y l -p y r r o l e i s r e f l u x e d w i t h an a - u n s u b s t i t u t e d p y r r o l e i n sodium a c e t a t e 44 b u f f e r e d a c e t i c a c i d . Smith and c o l l a b o r a t o r s have s y n t h e s i z e d d i p y r r o m e t h a n e s u s i n g a c e t o x y m e t h y l p y r r o l e and a - u n s u b s t i t u t e d component by b o i l i n g them i n g l a c i a l a c e t i c a c i d t o a t e m p e r a t u r e o f 1 2 0 - 1 3 0 ° C. The main draw-back 1n a s y n t h e s i s of t h i s type 1s t h e p o s s i b i l i t y of s e l f - c o n d e n s a t i o n o f t h e bromomethyl o r a c e t o x y m e t h y l component v i a a s o l v o l y t i c p r o c e s s t o g i v e t h e s y m m e t r i c a l d i p y r r o m e t h a n e . The m i l d e r 48 r e a c t i o n c o n d i t i o n s used by B a t t e r s b y e t a l . were employed here s i n c e l e s s d e c o m p o s i t i o n p r o d u c t s were o b t a i n e d . The p y r r o l e 47 1n methylene c h l o r i d e was added d r o p w i s e o v e r a twenty minute p e r i o d t o a s o l u t i o n of S C H E M E 7 29 t h e a - u n s u b s t i t u t e d p y r r o l e 39 i n methylene c h l o r i d e c o n t a i n i n g c a t a l y t i c q u a n t i t y of P - t o l u e n e s u l f o n i c a c i d , under a n i t r o g e n atmosphere. The r e s u l t i n g o i l o b t a i n e d d i s s o l v e d i n methylene c h l o r i d e and p e t r o l e u m e t h e r t o produce a w h i t e powder a p p r o x i m a t e l y 10% y i e l d which was shown by nmr t o be the s y m m e t r i c a l d l b e n z y l e s t e r 4 9 . A f t e r f i l t e r a t i o n , t h e f i l t r a t e and t h e washings were evaporated and r e c r y s t a l l i z e d from warm p e t r o l e u m e i t h e r t o produce the r e q u i r e d dipyrromethane mixed e s t e r s 48 i n a p p r o x i m a t e l y 84% y i e l d . The o x i d a t i o n o f a - m e t h y l p y r r o l e 36 t o the c o r r e s p o n d i n g f o r m y l p y r r o l e 50 can be a c h i e v e d i n d i f f e r e n t ways. The u s u a l o x i d a n t s are s u l f u r y l c h l o r i d e , t e r t i a r y b u t y l h y p o c h l o r i d e or l e a d t e t r a a c e t a t e * * * and the r e a c t i o n c o n d i t i o n s are s i m i l a r t o those used f o r m o n o o x i d a t i o n , except t h a t two e q u i v a l e n t s are u s e d . W i t h s u l f u r y l c h l o r i d e , a l a c k of s e l e c t i v i t y c o u p l e d w i t h a competing r e a c t i o n w i t h e t h e r s o l v e n t o f t e n l e a d s t o incomplete o x i d a t i o n and f o r m a t i o n o f s y m m e t r i c a l dipyrromethane from the i n t e r m e d i a r y c h l o r o m e t h y l p y r r o l e upon h y d r o l s y i s . T h i s can be avoided by the use o f methylene c h l o r i d e as t h e o n l y s o l v e n t and p e r f o r m i n g the o x i d a t i o n a t h i g h d i l u t i o n near 0 ° C . 49 Lead t e t r a a c e t a t e r e q u i r e s h e a t i n g t o induce the second e q u i v a l e n t t o r e a c t . I t may be t a k e n i n c o n s i d e r a b l e e x c e s s , as i t cannot o x i d i z e a - p y r r l m e t h y l s beyond the aldehyde stage (presumably due t o i n - s i t u 30 d e c o m p o s i t i o n o f t h e d i a c e t o x y m e t h y l p y r r o l e t o t h e f r e e aldehyde and a c e t i c a n h y d r i d e ) . T h u s , 2 - b e n z y l o x y c a r b o n y l - 3 , 4 , 5 - t n e t h y l p y r r o l e 36 was d i s s o l v e d i n g l a c i a l a c e t i c a c i d and one e q u i v a l e n t o f l e a d t e t r a a c e t a t e added f a i r l y r a p i d l y . T h i s a l l o w s the e x o t h e r m i c i t y of the r e a c t i o n t o heat up t h e s o l u t i o n which a l l o w s the second e q u i v a l e n t o f o x i d a n t t o r e a c t p r o m p t l y . A temperature of 7 0 - 8 0 ° C was m a i n t a i n e d on a steam-bath w i t h o c c a s i o n a l manual s w i r l i n g u n t i l a l l the s o l i d s were d i s s o l v e d . Water was added t o c r y s t a l l i z e out the p r o d u c t . The p r o d u c t was r e c r y s t a l l i z e d from methylene c h l o r i d e - h e x a n e t o g i v e s o l i d o f 73% y i e l d o f compound 5 0 . For c e r t a i n p u r p o s e s , t - b u t y l e s t e r s may be d e p r o t e c t e d and t h e r e s u l t i n g c a r b o x y l i c a c i d d e c a r b o x y l a t e d by d i s s o l u t i o n i n t r i f l o u r o a c e t i c 50 a c i d . C l e z y has e s t a b l i s h e d t h a t b i s - a - f r e e dipyrromethenes are s t a b l e i o n t h i s s o l v e n t f o r up t o a week a t room t e m p e r a t u r e . Kenner e t a l . ^ have r o u t i n e l y used t r i f u o r o a c e t i c a c i d t o c l e a v e t - b u t y l e s t e r s 4 8 . In t h e s y n t h e s i s o f t r i p y r r i n hydrobromide 51 t h e r e p o r t e d method of Smith 51 e t a l . was u s e d . Compound 48 was t r e a t e d w i t h neat t r i f l u o r o a c e t i c a c i d w i t h s t i r r i n g under a n i t r o g e n atmosphere at ambient temperature f o r about 5 m i n u t e s . The f o r m y l p y r r o l e 50 p r e v i o u s l y d i s s o l v e d i n methanol was added a l l a t o n c e . The r e d d i s h s o l u t i o n was s t i r r e d f o r an a d d i t i o n a l 90 5Q 4 8 31 minutes p e r i o d f o l l o w e d by the a d d i t i o n o f hydrogen bromide i n a c e t i c a c i d (30-32%) and e t h e r . The f l u f f y r e d d i s h s o l i d , s e p a r a t e d out a f t e r 15 minutes s t i r r i n g , was f i l t e r e d , washed w i t h e t h e r and a i r d r i e d t o g i v e 76% y i e l d o f t r i p y r r i n hydrobromide 5 1 . To o b t a i n t r i p y r r a n e d i a l d e h y d e 33 (Scheme 8) t h e t r i p y r r i n hydrobromide 51 was c a t a l y t i c a l l y hydrogenated i n o r d e r t o c l e a v e t h e b e n z y l e s t e r groups and t o hydrogenate the double bond. The r e a c t i o n was c a r r i e d out i n t e t r a h y d r o f u r a n w i t h few drops o f t r i e t h y l a m i n e and sodium a c e t a t e , a t room temperature and atmospheric p r e s s u r e u s i n g 10% p a l l a d i u m on c h a r c o a l as the c a t a l y s t . The t r i p y r r a n e d i a c i d 24 was o b t a i n e d as a r e d powder. The crude t r i p y r r a n e d i a c i d 24 was s u b j e c t e d to thermal d e c a r b o x y l a t i o n w i t h o u t f u r t h e r p u r i f i c a t i o n . S e v e r a l h i g h b o i l i n g s o l v e n t s are g e n e r a l l y used f o r t h i s purpose o f which dimethylformamide has a d i s t i n c t advantage over the o t h e r s f o r t h i s work. I t ' s r e f l u x temperature of 153° C i s s u f f i c i e n t not o n l y t o d e c a r b o x y l a t e the t r i p y r r a n e but a l s o t o remove any r e m a i n i n g t o l u e n e ( t h e byproduct o f h y d r o g e n o l y s i s o f the benzyl e s t e r s ) , from t h e crude s t a r t i n g m a t e r i a l . Furthermore dimethylformamide i s one o f the r e a g e n t s used i n t h e n e x t r e a c t i o n , i . e . the V i l s m e i e r f o r m y l a t i o n and t h e r e f o r e i t i s not n e c e s s a r y t o i s o l a t e the d e c a r b o x y l a t e d p r o d u c t . The d e c a r b o x y l a t i o n o f 24 i n dimethylformamide was f o l l o w e d by uv s p e c t r o s c o p y . The s t a r t i n g m a t e r i a l e x h i b i t e d a s i n g l e a b s o r p t i o n band at a p p r o x i m a t e l y 285 nm. A f t e r one hour o f r e f l u x , t h i s band was observed t o be removed c o m p l e t e l y i n d i c a t i n g the c o m p l e t i o n of the d e c a r b o x y l a t i o n . The r e a c t i o n m i x t u r e was c o o l e d and t h e produce 52 used i n t h e dimethylformamide s o l u t i o n f o r the f o r m y l a t i o n r e a c t i o n . 32 33 The i n t r o d u c t i o n o f t h e f o r m y l group was e f f e c t e d by t h e V i l s m e i e r 52 r e a c t i o n whereby the b i s-a - u n s u b s t i t u t e d t r i p y r r a n e 52 i n d i m e t h y l f o r m a m i d e s o l u t i o n i s t r e a t e d w i t h phosphorous o x y c h l o r i d e o r 53 b e n z o y l c h l o r i d e . T h i s i s known t o proceed v i a an iminium s a l t of the t y p e 5 3 . The i m i n i u m s a l t c o u l d be i s o l a t e d i n c r y s t a l l i n e form i f b e n z o y l c h l o r i d e i s used and t h i s can s u b s e q u e n t l y be h y d r o l y s e d i n aqueous base t o g i v e t h e t r i p y r r a n e d i a l d e h y d e 3 3 . A w e a k l y b a s i c medium i s u s u a l l y p r o v i d e d f o r the h y d r o l y s i s by u s i n g sodium b i c a r b o n a t e o r 52 53 sodium a c e t a t e * . The f o r m y l a t i o n o f t r i p y r r a n e 52 was e f f e c t e d u s i n g b e n z o y l c h l o r i d e , t h e Iminium s a l t was not I s o l a t e d but h y d r o l y s e d d i r e c t l y i n aqueous sodium b i c a r b o n a t e (pH 8 - 9 ) . The p r e c i p i t a t e was d i s s o l v e d i n methylene c h l o r i d e and r e c r y s t a l l i z e d from methanol t o g i v e 33 as an orange s o l i d . The s y n t h e s i s o f t r i p y r r a n e 59 1s o u t l i n e d i n Scheme 9 . The p y r r o l e 54 used as t h e p r e c u r s o r t o t h e c e n t r a l u n i t o f compound 59 was s a p o n i f i e d r e a d i l y t o t h e d i s o d i u m s a l t 55_ by h e a t i n g w i t h two e q u i v a l e n t s o f sodium h y d r o x i d e . To maximize t h e y i e l d , t h e r e s u l t i n g s o l u t i o n o f t h e d i s o d i u m s a l t was i o d i n a t e d d i r e c t l y as b e f o r e t o g i v e t h e d i i o d o p y r r o l e 56 as a dense g r a n u l a r c r y s t a l l i n e s o l i d . T h i s was d e l o d i n a t e d , w i t h o u t f u r t h e r p u r i f i c a t i o n , d i r e c t l y t o t h e d i a - f r e e p y r r o l e 57 as d e s c r i b e d f o r p y r r o l e 38 (Scheme 5 ) . T h e d i-a - f r e e p y r r o l e 57 r e a c t e d s p o n t a n e o u s l y i n methylene c h l o r i d e a t room t e m p e r a t u r e w i t h two e q u i v a l e n t s of the a - c h l o r o m e t h y l p y r r o l e 58 t o g i v e t h e t r i p y r r a n e 5 9 . The a - c h l o r o m e t h y l p y r r o l e 58 i n t u r n was p r e p a r e d by s u l f u r y l c h l o r i d e o x i d a t i o n o f 2 - b e n z y l o x y c a r b o n y l - 3 , 4 , 5 - t r i m e t h y l - p y r r o l e 36 i n c a r b o n 34 SCHEME 9 35 t e t r a c h l o r i d e . The t r i p y r r a n e 59 was o b t a i n e d from the r e a c t i o n m i x t u r e , t o g e t h e r w i t h the s y m m e t r i c a l d i p y r r o m e t h a n e 49 and was i s o l a t e d i n pure form by p r e f e r e n t i a l c r y s t a l l i z a t i o n u s i n g t e t r a h y d r o f u r a n - m e t h a n o l . The y i e l d was o n l y 39%. The t r i p y r r a n e 59 was c a t a l y t i c a l l y hydrogenated t o g i v e the d i a c i d 60 (Scheme 1 0 ) . The same p r o c e s s used t o o b t a i n compound 33 was used i n o b t a i n i n g compound 34 e x c e p t t h a t , the d e c a r b o x y l a t i o n of 60 took about 2 hours and the f o r m y l a t i o n was a c h i e v e d by u s i n g phosphorous o x y c h l o r i d e . With the t r i p y r r a n e d i a l d e h y d e s r e a d y , the next s t e p was t h e s y n t h e s e s o f d i p y r r o m e t h a n e d i a c i d s f o r t h e c o u p l i n g r e a c t i o n s . With t h e p y r r o l e 63 i n h a n d , t r a n s b e n z y l a t i o n was c o n s i d e r e d . T r a n s b e n z y l a t i o n i s a u s e f u l r e a c t i o n i n p y r r o l e c h e m i s t r y due t o i t s h i g h y i e l d s and t h e ease o f removal of the b e n z y l e s t e r s when r e q u i r e d . Thus the s y n t h e s e s of d i p y r r o m e t h a n e d i a c i d s 32 and 35 a r e i l l u s t r a t e d i n Scheme 11. The p y r r o l e 64 was o b t a i n e d i n g r e a t e r than 90% y i e l d from i t s e t h y l e s t e r a n a l o g 63_ by t r a n s e s t e r i f i c a t i o n i n r e d i s t i l l e d b e n z y l a l c o h o l a t 54 55 r e f l u x m g t e m p e r a t u r e u s i n g sodium b e n z y l o x i d e as a c a t a l y s t ' . A 45 s l i g h t m o d i f i c a t i o n o f C l e z y and L i e p a p r o c e d u r e was used i n t h e p r e p a r a t i o n of the d i p y r r o m e t h a n e . 2 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i e t h y l - 5 -methyl p y r r o l e 63 was a c e t y l a t e d i n t h e u s u a l manner i n g l a c i a l a c e t i c a c i d w i t h l e a d t e t r a a c e t a t e . A f t e r p r e c i p i t a t i n g the p r o d u c t 65_ w i t h w a t e r , i t was f i l t e r e d , and d i s s o l v e d i n 80% g l a c i a l a c e t i c a c i d and heated to r e f l u x . The r e a c t i o n was f o l l o w e d w i t h t i c , and when a l l t h e s t a r t i n g m a t e r i a l s had r e a c t e d t o g i v e a s i n g l e p r o d u c t on t i c , t h e r e a c t i o n m i x t u r e was c o o l e d and water added to p r e c i p i t a t e the p r o d u c t . The p r o d u c t was c o l l e c t e d and r e c r y s t a l l i z e d from e t h a n o l t o g i v e s o l i d s SCHEME "10 37 i n 76% y i e l d o f 6 6 . In a s i m i l a r way t h e d i b e n z y l e s t e r 49 was p r e p a r e d from p y r r o l e 36_ t h r o u g h 6 7 . The d i b e n z y l e s t e r 66 was c o n v e r t e d t o the d i a c i d 35 by c a t a l y t i c h y d r o g e n a t i o n i n t e t r a h y d r o f u r a n a t room t e m p e r a t u r e and a t m o s p h e r i c p r e s s u r e . When the uptake of hydrogen c e a s e d , the c a t a l y s t was f i l t e r e d o f f and t h e f i l t r a t e made up t o known volume and s t o r e d i n t h e f r i d g e i n the dark due t o the u n s t a b l e n a t u r e of d i a c i d 3 4 . The d i a c i d 32 was p r e p a r e d by h y d r o g e n o l s i s o f t h e d i b e n z y l e s t e r 49 i n t h e same way as 6 6 . With the d i a c i d 32 a f t e r f i l t r a t i o n , the s o l v e n t was e v a p o r a t e d on t h e r o t a r y e v a p o r a t o r a t room t e m p e r a t u r e . The l i g h t - y e l l o w i s h s o l i d was s t o r e d i n the f r i d g e i n the dark and used as i t was f o r the c y c l i z a t i o n r e a c t i o n w i t h o u t p u r i f i c a t i o n . 38 35 SCHEME 11 39 2.3 SYNTHESIS OF THE MACROCYCLES The e x c l u s i v e f o r m a t i o n o f p o r p h y r i n s and non c y c l i c p o l y m e r i c p r o d u c t s i n a t t e m p t s t o s y n t h e s i z e t h e p e n t a p y r r o l i c m a c r o c y c l e from d i p y r r o m e t h a n e d i a l d e h y d e and t h e d i - a - u n s u b s t i t u t e d t r i p y r r a n e p r e c u r s o r s has a l r e a d y been m e n t i o n e d . I t must be added t h a t t h e f o r m a t i o n of p o r p h y r i n s i s not l i m i t e d t o t h e a f o r e m e n t i o n e d p y r r o l e s but was a l s o o b s e r v e d d u r i n g t h i s work. T h i s was e a s i l y d e t e c t e d by u v - v i s i b l e s p e c t r o s c o p y 1n m o n i t o r i n g t h e r e a c t i o n and by t h e c h a r a c t e r i s t i c f l u o r e s c e n c e o f p o r p h y r i n s on t h e p l a t e s under l o n g wavelength uv l i g h t . 39 Franck e t a l . a t t r i b u t e d t h i s b e h a v i o u r t o t h e s t r o n g p r e f e r e n c e f o r p o r p h y r i n f o r m a t i o n compared t o t h e p e n t a p h y r i n m a c r o c y c l e . T h i s p r e f e r e n c e i s e x p l a i n e d by t h e s t r o n g d e s t a b i l i z i n g s t e r i c i n t e r a c t i o n of t h e s i d e c h a i n i n t h e fi-position i n t h e l i n e a r c o n f o r m a t i o n 68 of t h e o p e n - c h a i n t e t r a p y r r o l e p o r p h y r i n p r e c u r s o r s . The h e l i c a l c o n f o r m a t i o n 69_ i s thought t o p r o v i d e t h e p r e r e q u i s i t e s f o r r i n g c l o s u r e t o a f f o r d p o r p h y r i n s due t o r e d u c t i o n i n such i n t e r a c t i o n s . 40 T h u s , a p o s s i b l e mechanism f o r t h e p e n t a p h y r i n and t h e p r e f e r r e d p o r p h y r i n f o r m a t i o n can be d e r i v e d as i l l u s t r a t e d i n Scheme 12. If t r i p y r r a n e d i a l d e h y d e 33 c o u p l e s w i t h d i p y r r o m e t h a n e d i a c i d 32 i n a c i d i c medium, a h e l i c a l c o n f o r m a t i o n o f p e n t a p y r r o l e 70 r e s u l t s w i t h two p o s s i b l e modes f o r c y c l i z a t i o n . F i r s t , t h e r e i s a h i g h p r o b a b i l i t y of p r o t o n a t i o n a t t h e e l e c t r o n - r i c h a - p o s i t i o n o f t h e p y r r o l e r i n g E w i t h t h e r e s u l t a n t e l i m i n a t i o n o f f o r m y l p y r r o l e and subsequent c y c l i z a t i o n and o x i d a t i o n t o g i v e t h e p o r p h y r i n ( r o u t e B ) . The second ( r o u t e A) i s t h e p r o t o n a t i o n of t h e a l d e h y d e on t h e r i n g E f o l l o w e d by c y c l i z a t i o n , d e h y d r a t i o n and o x i d a t i o n t o g i v e t h e r e q u i r e d p e n t a p h y r i n . Thus, t h e p o r p h y r i n s which appear as a n a t u r a l p r o d u c t i s e x t r e m e l y f a v o r e d i n i t s f o r m a t i o n . In many of t h e a t t e m p t e d s y n t h e s e s of t h e p e n t a p h y r r i n m a c r o c y c l e , a s t r e a m of a i r was bubbled or a l l o w e d t o d i f f u s e t h r o u g h t h e r e a c t i o n m i x t u r e and t h e end p r o d u c t r e s u l t i n g i n p o r p h y r i n w i t h o u t any t r a c e s o f p e n t a p h y r i n . T h i s was noted t o be t h e case i n t h i s work when a i r a c c i d e n t a l l y d i f f u s e d t h r o u g h t h e r e a c t i o n m i x t u r e . Thus o x y g e n , t h e main o x i d i z i n g agent 1n t h e s y n t h e s e s of p o r p h y r i n s i n t h e l a b o r a t o r y p o s s i b l y f a v o r s e x c l u s i v e p r o d u c t i o n o f p o r p h y r i n p r o b a b l y t h r o u g h r o u t e B (scheme 1 2 ) . In t h e p e n t a p h y r i n s y n t h e s i s , t h e b r i d g i n g c a r b o n s of t h e t r i p y r r o l i c u n i t must be a t t h e methane o x i d a t i o n l e v e l s i n c e methenes would be promoted under a c i d i c c o u p l i n g c o n d i t i o n s and t h u s be e f f e c t i v e l y n o n - n u c l e o p h i l i c . T h i s has a l s o been o b s e r v e d i n t h e s a p p h y r r i n s y n t h e s e s . 41 SCHEME 12 42 To e f f e c t the c o u p l i n g , the r e a c t i o n was c a r r i e d out at h i g h d i l u t i o n t o m i n i m i z e l i n e a r p o l y m e r i z a t i o n . The r e a c t i o n was a l s o c a r r i e d out a room temperature t o m i n i m i z e random f r a g m e n t a t i o n . S i n c e l i t t l e i s known about the s e n s i t i v i t y of these m a c r o c y c l e s t o l i g h t , they were p r o t e c t e d from l i g h t from the c o u p l i n g r e a c t i o n through work up t o t h e f i n a l p r o d u c t ( c f w i t h i n t e r m e d i a t e s i n p o r p h y r i n s y n t h e s i s ) . In a t y p i c a l r e a c t i o n , dipyrromethane d i a c i d 32 (Scheme 13) was suspended i n methylene c h l o r i d e (which has been "degased" by b u b b l i n g argon through f o r 2 hours) and s t i r r e d f o r 20 minutes under a r g o n . T r i p y r r a n e d i a l d e h y d e 33 was added and the r e a c t i o n m i x t u r e s t i r r e d f o r an a d d i t i o n a l 15 minutes a f t e r which HBr i n a c e t i c a c i d (30-32%) ( c a t a l y t i c q u a n t i t y ) was added t o e f f e c t the c o n d e n s a t i o n . The c o l o r of t h e r e a c t i o n m i x t u r e passed through a s e r i e s of changes, the o r i g i n a l y e l l o w i s h s o l u t i o n q u i c k l y t u r n i n g orange and s u b s e q u e n t l y t o r e d ( a l s o o b s e r v e d i n dipyrromethene c o u p l i n g p a s s i n g through the p o r p h o d i m e t h e n e s ) . The r e a c t i o n m i x t u r e was a l l o w e d t o s t i r f o r 2 h o u r s , the o x i d i z i n g a g e n t , c h l o r a n i l added and the r e a c t i o n - s o l u t i o n was s t i r r e d f u r t h e r f o r 36 h o u r s . The r e a c t i o n was monitored u s i n g e l e c t r o n i c a b s o r p t i o n ; the v i s i b l e and t h e n e a r - u l t r a v i o l e t r e g i o n s of the spectrum were found most u s e f u l . From t h e u v - v i s i b l e s p e c t r a o f the r e a c t i o n m i x t u r e , a s u c c e s s f u l r e a c t i o n becomes e v i d e n t 30 minutes a f t e r the a d d i t i o n of the a c i d c a t a l y s t , HBr ( i n a c e t i c a c i d ) . A c h a r a c t e r i s t i c band around 450-460 nm, t h e S o r e t i s a d e f i n i t e s i g n of the f o r m a t i o n of t h e p e n t a p h y r i n . A l s o p r e s e n t i n almost equal i n t e n s i t y , at t i m e s , t o the above mentioned band i s another band around 480-490 nm. On the a d d i t i o n o f the o x i d i z i n g 43 a g e n t , t e t r a c h l o r o b e n z o q u i n o n e , t h e r e i s a s h i f t of the 480-490 nm band t o 500 nm w h i c h , a t t i m e s , competes w i t h the S o r e t band i n i n t e n s i t y . In most c a s e s t h e i n t e n s i t y o f the S o r e t i n c r e a s e d a p p r e c i a b l y compared t o t h e o t h e r band which was found t o be due t o p o l y m e r i c p y r r o l e s . The s o l v e n t was evaporated t o dryness i n vacuo t o g i v e a dark brown r e s i d u a l p r o d u c t . T i c s t u d i e s showed t h a t e t h y l a c e t a t e was a good e l u t i n g s o l v e n t i n t h a t most of the p o r p h y r i n i c and o t h e r b y p r o d u c t s are "washed o f f " l e a v i n g the d e s i r e d product and o t h e r i m p u r i t i e s as a S C H E M E 13 44 d a r k - g r e e n band at the o r i g i n . Thus p r e p a r a t i v e chromatography u s i n g s i l i c a g e l w i t h f l u o r e s c e n t i n d i c a t o r and e t h y l a c e t a t e as t h e e l u e n t was u s e d . A f t e r p r o p e r l y d r y i n g the p l a t e s , the d a r k - g r e e n i s h f r a c t i o n which s t a y e d a t t h e o r i g i n was s c r a p e d and e l u t e d w i t h methylene c h l o r i d e - m e t h a n o l ( 1 0 : 1 ) . (The s o l u b i l i t y of the d e c a m e t h y l p e n t a p h y r i n was found t o be q u i t e d i f f e r e n t from the o t h e r s i n b e i n g l e s s s o l u b l e , and t h u s , t h e p o l a r i t y of the s o l v e n t had t o be i n c r e a s e d t o methylene c h l o r i d e - m e t h a n o l ( 5 : 1 ) 1 . The s o l v e n t was e v a p o r a t e d o f f and the r e s i d u a l p r o d u c t was t w i c e chromatographed on a column u s i n g s i l i c a g e l and e l u t e d w i t h 5% methanol i n methylene c h l o r i d e . The green f r a c t i o n was c o l l e c t e d and the s o l v e n t e v a p o r a t e d t o g i v e an orange d e c a m e t h y l p e n t a p h y r i n 7_1_ of about 21% y i e l d . A l l t h e p e n t a p h y r i n s s y n t h e s i z e d d u r i n g the c o u r s e of t h i s work c o u l d not be s u b j e c t e d t o combustion a n a l y s i s due t o the i n a b i l i t y o f o b t a i n i n g s o l i d s a m p l e s . The z i n c complexes of p e n t a p h y r i n s 7J_ and 74 were a l s o p r e p a r e d . The " a c e t a t e m e t h o d " ^ a > t 0 u s ^ n g anhydrous z i n c a c e t a t e was employed i n t h i s s y n t h e s e s . The c h o i c e o f s o l v e n t was methanol i n which both t h e p e n t a p h y r i n s and z i n c a c e t a t e are r e a d i l y s o l u b l e . A m e t h a n o l i c s o l u t i o n of p e n t a p h y r i n w i t h anhydrous z i n c a c e t a t e and sodium a c e t a t e was s t i r r e d f o r 5 hours and a l l o w e d t o s t a n d at room t e m p e r a t u r e f o r t h r e e d a y s . The r e a c t i o n was m o n i t o r e d by u v - v i s i b l e s p e c t r o s c o p y . S p e c t r a l changes 45 i n d i c a t e d t h a t p e n t a p h y r i n s , l i k e p o r p h y r i n s and s a p p h y r i n , form metal c o m p l e x e s . A y i e l d o f 6 6 . 8 % and 54% was o b t a i n e d f o r compounds 72 and 73 r e s p e c t i v e l y . 46 3. EXPERIMENTAL 47 3 . 1 GENERAL METHODS M e l t i n g p o i n t d e t e r m i n a t i o n were o b t a i n e d u s i n g a 6548-J17 m i c r o s c o p e equipped w i t h a Thomas Model 40 m i c r o hot stage E l e m e n t a l a n a l y s i s was performed by Mr. P. Borda of the M i c r o A n a l y t i c a l L a b o r a t o r y , UBC E l e c t r o n i c a b s o r p t i o n s p e c t r a i n the uv and v i s i b l e r e g i o n were r e c o r d e d u s i n g a Cary 17 s p e c t r o m e t e r *H nmr s p e c t r a of the p e n t a p h y r r i n s were r e c o r d e d at 400 MHz u s i n g a B r u k e r WH-400 s p e c t r o m e t e r . A l l t h e i n t e r m e d i a t e s were g e n e r a l l y r e c o r d e d at 100 MHz w i t h a V a r i a n XL-100 F o u r i e r - t r a n s f o r m s p e c t r o m e t e r 1 3 C nmr s p e c t r a were r e c o r d e d a t 75 MHz on t h e V a r i a n XL-300 Mass s p e c t r a were r e c o r d e d on a V a r i a n MAT CH4-B s p e c t r o m e t e r or a K r a t o s / A E I MS-902 T h i n l a y e r chromatography was c a r r i e d out u s i n g p r e c o a t e d s i l i c a g e l GF p l a t e s ( A n a l t e c h , 250 u) P r e p a r a t i v e chromatography was c a r r i e d out u s i n g s i l i c a g e l GF ( A n a l t e c h , 20 x 20 cm, 2000 u) Column chromatography was c a r r i e d out u s i n g s i l i c a g e l GF60 ( 2 3 0 - 4 0 0 , Merck) 48 3 . 2 STARTING MATERIALS OH M o l . Formula C ^ H ^ N O ^ M o l . Wt. 2 7 3 . 3 M . P . 2 1 1 - 2 1 3 ° C L i t 5 6 : 2 1 2 - 2 1 4 ° C Ph Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 2 7 3 ( 1 7 ) , 91(100) lH nmr: (S.DMSO^-dg) 2 . 3 0 ( 6 H , S ) , 5 . 3 7 ( 2 H , S ) , 7 . 4 3 ( 5 H , S ) , 9 . 4 2 ( 1 H , N H ) , 11 .52(1H,S,C00H) II ^ Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 3 1 5 ( 1 9 ) , 0 2 4 2 ( 2 9 ) , 91(100) X H nmr: ( 6 , C D Q 3 ) 2 . 2 2 ( 3 H , S ) , 2 . 3 K 3 H . S ) , 2 . 3 8 ( 2 H , q , J = 7 . 5 H z ) , 2 . 6 7 ( 2 H , q , J = 7 . 5 H z ) , 3 . 6 8 ( 3 H , S ) , 5 . 3 0 ( 2 H , S ) , 7 . 3 9 ( 5 H , S ) , 8 . 5 0 ( l H , b r , N H ) PMe M o l . Formula C ^ H ^ N O ^ M o l . Wt. 3 1 5 . 3 "A M . P . 9 8 - 9 9 ° C L i t 5 7 : 9 9 - 1 0 1 ° C 49 M o l . Formula C 1 2 H 1 5 N 0 6 M o l . Wt. 2 6 9 . 2 M . P . 1 4 9 - 1 5 1 ° C L i t 5 8 : 1 5 0 ° C lH nmr: ( 6 t C D C A 3 ) 1 . 4 0 ( 3 H , t , J = 7 H z ) , 1 . 4 8 ( 3 H , t , J = 7 H z ) , 2 . 6 2 ( 3 H , S ) , 4 . 4 1 ( 2 H , q , J = 7 . 5 H z ) , 4 . 5 2 ( 2 H , q , J = 7 . 5 H z ) , 1 0 . 2 5 { l H , b r , N H ) , 1 4 . 8 0 ( 1 H , S , C 0 0 H ) M o l . Formula C 1 5 H 1 7 N 0 2 M o l . Wt. 2 4 3 . 3 M . P . 1 1 7 - 1 1 8 ° C L i t 2 6 : 1 1 9 - 1 2 0 ° C Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 2 4 3 ( 3 1 ) , 1 0 9 ( 1 3 ) , 91(100) lH nmr: 6(CDCA 3 ) 1 . 9 1 ( 3 H , S ) , 2 . 1 8 ( 3 H , S ) , 2 . 2 8 ( 3 H , S ) , 5 . 9 9 ( 2 H , S ) , 7 . 3 6 ( 5 H , m ) , 8 . 6 1 { l H , b s , N H ) 50 / \ M o l . Formula C 1 2 H 1 9 N 0 2 M o l . Wt. 2 0 9 . 3 /F~\ M . P . 7 6 - 7 7 ° C L i t 3 7 : 7 5 ° C V\ \] Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 2 0 9 ( 4 6 ) , 0 1 9 4 ( 4 5 ) , 148(100) lH nmr: (6 ,CDCA 3 ) 1 . 0 3 ( 3 H , t , J = 7 H z ) , 1 . 3 8 ( 3 H , t , J = 7 H z ) , 2 . 2 5 ( 3 H , S ) , 2 . 4 0 ( 2 H , q , J = 7 . 5 H z ) , 2 . 7 0 ( 2 H , q , J = 7 . 5 H z ) , 8 . 7 2 ( l H . b s . N H ) M o l . Formula C 1 2 H 1 9 N 0 2 M o l . Wt. 2 0 9 . 3 M . P . 1 3 6 - 1 3 8 ° C L i t 5 9 : 1 3 7 - 1 3 8 ° C Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) , 2 0 9 ( 1 7 ) , 1 5 3 ( 5 4 ) , 135(100) lH nmr: (6 ,CDCA 3 ) 1 . 1 0 ( 9 H , S ) , 1 . 9 3 ( 3 H , S ) , 2 . 2 0 ( 3 H , S ) , 2 . 2 5 ( 3 H , S ) , 8 . 8 3 ( l H , b s , N H ) 51 .. 3.3 SYNTHESES OF INTERMEDIATES 0 2 - B e n z y l o x y c a r b o n . y l - 5 - i o d o - 3 , 4 - d i m e t h y 1 p y r r o l e (38) 5 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l - 2 - c a r b o x y l i c a c i d ( 8 . 2 g , 0 . 0 3 moles) 3 7 , sodium b i c a r b o n a t e ( 1 0 . 1 g , 0 .12 m o l e s ) , water (60 mL) and d i c h l o r o e t h a n e (60 mL) were p l a c e d i n an e r l e n m e y e r f l a s k and heated on a hot p l a t e w h i l e s t i r r i n g . The s t a r t i n g m a t e r i a l d i s s o l v e d w i t h e f f e r v e s c e n c e . When t h e t e m p e r a t u r e of t h e s o l u t i o n r e a c h e d 7 1 ° C, a s o l u t i o n of i o d i n e ( 8 . 9 g , 0 . 0 3 5 m o l e s ) , sodium i o d i d e ( 9 . 0 g , 0 . 0 6 moles) and water (60 mL) was added w i t h i n 10 m i n u t e s by t h e a i d o f a d r o p p i n g f u n n e l . The s o l u t i o n was r e f l u x e d f o r one hour and t h e e x c e s s i o d i n e was d e s t r o y e d w i t h sodium b i s u l f i t e (a p a l e y e l l o w c o l o r remained i n t h e o r g a n i c l a y e r w h i l e the aqueous l a y e r t u r n e d c o l o r l e s s ) . The o r g a n i c phase was s e p a r a t e d , f i l t e r e d and e v a p o r a t e d t o d r y n e s s . The crude p r o d u c t was r e d i s s o l v e d i n e t h a n o l (100 mL) and the s o l i d was r e p r e c i p i t a t e d by a d d i n g w a t e r , c o l l e c t e d by f i l t r a t i o n and washed w i t h 50% e t h a n o l - w a t e r f o l l o w e d by water t o g i v e 5 . 7 g ( 5 3 . 5 % ) . The mother l i q u o r s were c o n c e n t r a t e d f o r a second c r o p of 2 . 8 g ( 2 6 . 5 % ) . M . P . : 1 2 5 - 1 2 6 ° C L i t 1 * 2 : 1 2 6 - 1 2 8 ° C M o l . W t . : 3 5 5 . 2 lH nmr: (6 , C D a 3 ) 1 . 9 8 ( 3 H , S ) , 2 . 3 3 ( 3 H , S ) , 5 . 3 3 ( 2 H , S ) , 7 . 3 9 ( 5 H , S ) , 8 . 8 8 ( l H , b r ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 3 5 5 ( m + , 1 9 ) , 2 2 8 ( 6 ) , 9 1 ( 1 0 0 ) , 65(15) 52 2 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e (39) 2 - B e n z y l o x y c a r b o n y l - 5 - i o d o - 3 , 4 - d i m e t h y l p y r r o l e ( 2 1 . 3 g , 0 . 0 6 moles) 38 was d i s s o l v e d i n 95% e t h a n o l (150 mL) by warming on a steam b a t h . A s o l u t i o n of p o t a s s i u m i o d i d e (11 .6 g , 0 . 0 7 moles) i n water (20 mL) and c o n c e n t r a t e d h y d r o c h l o r i c a c i d (25 mL) was added l i b e r a t i n g i o d i n e . 50% aqueous hypophosphorous a c i d (40 mL) was added t o d i s c h a r g e the i o d i n e c o l o r and the r e a c t i o n m i x t u r e heated on the steam b a t h f o r 20 m i n u t e s . The s o l u t i o n was c o o l e d , methylene c h l o r i d e (150 mL) and w a t e r (100 mL) a d d e d , the o r g a n i c phase i s o l a t e d and d r i e d (NajSO^). The s o l v e n t was e v a p o r a t e d under reduced p r e s s u r e and t h e r e s i d u a l p r o d u c t d i s s o l v e d i n methylene c h l o r i d e (15 mL) and chromatographed on s i l i c a g e l u s i n g methylene c h l o r i d e as t h e e l u t i n g s o l v e n t . A l l o f the c o l o r e d i m p u r i t i e s remained at the o r i g i n and the a - f r e e p y r r o l e e l u t e d out c l e a n as a p a l e y e l l o w l i q u i d . The s o l v e n t was e v a p o r a t e d and t h e p r o d u c t c r y s t a l l i z e d out from Hexane. The y i e l d of the a - f r e e p y r r o l e was 11.7 g ( 8 5 . 2 % ) . M . P . : 7 4 - 7 5 ° C L i t . 5 8 : 6 4 - 6 6 ° C M o l . W t . : 2 2 9 . 3 lH nmr: ( 6 , C D C A 3 ) 2 . 0 3 ( 3 H , S ) , 2 . 3 0 ( 3 H , S ) , 5 . 3 1 ( 2 H , S ) , 6 . 6 6 ( l H , d ) 7 . 4 0 ( 5 H , S ) , 8 . 7 0 ( l H , b r ) Mass Spectrum: m/e ( r e l a t i v e i n t e n s i t y ) 2 2 9 ( m + , 3 2 ) , 1 3 8 ( 2 4 ) , 9 1 ( 1 0 0 ) , 65(24) 53 2 - c a r b o x y - 3 , 4 - d i m e t h y l p y r r o l e (40) 2 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e ( 4 . 6 g , 0 . 0 2 moles) 39 i n THF (100 mL) was s t i r r e d o v e r n i g h t under hydrogen i n the p r e s e n c e o f 10% p a l l a d i u m on c h a r c o a l (400 mg). When t h e uptake o f hydrogen c e a s e d , t h e c a t a l y s t was f i l t e r e d and the s o l u t i o n checked by TLC f o r any u n c o n v e r t e d s t a r t i n g m a t e r i a l . The s o l v e n t was e v a p o r a t e d o f f , i n v a c u o , l e a v i n g pure w h i t e p r o d u c t . Y i e l d 2 . 6 5 g ( 9 5 . 3 % ) . M . P . : decompose around 1 7 8 - 1 7 9 ° C L i t 6 1 : 1 8 0 ° C ( s u b l i m e ) M o l . Wt. 139.1 lH nmr: ( 6 , D M S 0 - d 6 ) : 1 . 9 0 ( 3 H , S ) , 2 . 1 5 ( 3 H , S ) , 6 . 6 5 ( l H , d ) , 1 1 . 0 ( 1 H , S ) , 9 . 5 0 ( l H , b s ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 1 3 9 ( m + , 7 4 ) , 1 2 1 ( 5 9 ) , 94(71) 54 Y 0 Ph 0 u 2 - A c e t o x y m e t h y l - 5 - B e n z y l o x y c a r b o n y l - 3 ( 2 - m e t h o x y c a r b o n y l e t h y l ) -4 - m e t h y l p y r r o l e (42) 2 - B e n z y l o x y c a r b o n y l - 3 ( 2 - m e t h o x y c a r b o n y l e t h y l ) - 3 , 5 - d i m e t h y l - p y r r o l e ( 1 3 . 8 g , 44 rnnoles) 4T_ was d i s s o l v e d i n g l a c i a l a c e t i c a c i d (150 mL) and l e a d t e t r a a c e t a t e ( 2 1 . 0 g , 47 mrnoles) was added a l l a t o n c e . The m i x t u r e was s w i r l e d m a n u a l l y and warmed on a steam bath to 6 0 ° C to complete the r e a c t i o n . E t h y l e n e g l y c o l (5 mL) was a d d e d . The r e a c t i o n m i x t u r e was c o o l e d and d i l u t e d w i t h water (500 mL) to p r e c i p i t a t e the p r o d u c t w h i c h was f i l t e r e d and d i s s o l v e d i n methylene c h l o r i d e (150 mL) . The o r g a n i c phase was s e p a r a t e d , f i l t e r e d , d r i e d (MgSO^) and c o n c e n t r a t e d . The p r o d u c t was r e c r y s t a l l i z e d from hexane. Y i e l d 10.5 g (64%). M . P . : 1 0 9 - 1 1 0 ° C L i t . 5 7 : 1 1 1 - 1 1 2 ° C M o l . W t . : 3 7 3 . 4 lH nmr: ( 6 , C D Q 3 ) , 2 . 0 7 ( 3 H , S ) , 2 . 3 0 ( 3 H , S ) , 2 . 5 0 ( 2 H , q , J = 7 . 5 H z ) , 2 . 7 5 ( 2 H , q , J = 7 . 5 H z ) , 3 . 6 8 ( 3 H , S ) , 5 . 0 5 ( 2 H , S ) , 5 . 3 0 ( 2 H , S ) , 7 . 4 0 ( 5 H , S ) , 9 . 1 0 ( 1 H , S ) . Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 3 7 3 ( m + , 8 ) , 3 1 3 ( 1 5 ) , 1 7 9 ( 1 5 ) , 9 1 ( 1 0 0 ) , 65(19) 55 2 , 5 - B i s [ ( 5 - b e n z y l o x y c a r b o n y l - 3 - ( 2 - m e t h o x y c a r b o n y l e t h y l ) - 4 - m e t h y l p y r r o l - 2 - y l ) - m e t h y l ] - 3 , 4 - d i m e t h y l p y r r o l e (43) 2 - A c e t o x y m e t h y l - 5 - b e n z y l o x y c a r b o n y l - 3 - ( 2 - m e t h o x y c a r b o n y l e t h y l ) -4 - m e t h y l p y r r o l e ( 6 . 0 g , 0.016 moles) 42 and 2 - c a r b o x y - 3 , 4 - d i m e t h y l p y r r o l e ( 1 . 5 g , 0.011 moles) 40 were d i s s o l v e d i n p y r i d i n e (10 mL) and heated o v e r n i g h t on the steam b a t h . Ice c o l d water (50 mL) was added and the t a r r y p r e c i p i t a t e t r i t u r a t e d w i t h a s m a l l q u a n t i t y of warm e t h a n o l . The p r o d u c t was f i l t e r e d a f t e r 6 hours and t w i c e r e c r y s t a l l i z e d from e t h a n o l . Y i e l d 2 . 4 g ( 3 0 . 8 % ) . M . P . : 1 4 0 - 1 4 1 ° C L i t 4 5 : 1 3 9 - 1 4 1 ° C M o l . W t . : 721.8 XH nmr: (6 ,CDCA 3 ) 1 . 9 8 ( 6 H , S ) , 2 . 2 3 ( 6 H , S ) , 2 . 3 5 ( 4 H , q , J = 7 . 5 H z ) , 2 . 6 0 ( 4 H , q , J = 7 . 5 H z ) , 3 . 5 8 ( 6 H , S ) , 3 . 6 3 ( 4 H , S ) , 4 . 7 4 ( 4 H , S ) , 7 . 2 8 ( 1 0 H , S ) , 8 . 2 5 ( 1 H , S ) , 9 . 2 5 ( 2 H , S ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 7 2 1 ( m + , 1 0 ) , 3 1 3 ( 1 6 ) , 1 9 8 ( 1 2 ) , 1 8 4 ( 1 2 ) , 9 1 ( 1 0 0 ) , 65(28) 56 Z . S - B i s L t S - f o r m y l - S t Z - m e t h o x y c a r b o n y l e t h y D - A - m e t h y l p y r r o l - Z - y l ) - m e t h y 1 ] - 3 , 4 - d i m e t h y 1 p y r r o l e (31_) 2 , 5 - B i s [ ( 5 - b e n z y l o x y c a r b o n y 1 - 3 - ( 2 - m e t h o x y c a r b o n y l e t h y 1 ) - 4 - m e t h y l p y r r o l - 2 - y l ) - m e t h y l ] - 3 , 4 - d i m e t h y l p y r r o l e ( 0 . 6 5 g , 0 . 9 mmole) i n THF (80 mL) was s t i r r e d o v e r n i g h t under hydrogen (1 atmosphere) 43 i n the p r e s e n c e of 10% p a l l a d i u m on c h a r c o a l (200 mg). When the uptake o f hydrogen c e a s e d , t h e c a t a l y s t was f i l t e r e d t h r o u g h a c e l i t e p l u g and t h e s o l u t i o n checked by t h e TLC f o r any unconverted s t a r t i n g m a t e r i a l . The s o l v e n t was e v a p o r a t e d o f f , i n v a c u o , l e a v i n g a red powder 4 4 , and was used as i s , i n the next r e a c t i o n . Compound 44 was d i s s o l v e d i n t r i f l u o r o a c e t i c a c i d (5 mL) at 0 ° C under a r g o n . A f t e r 15 m i n u t e s of s t i r r i n g , t r i e t h y l o r t h o f o r m a t e (3 mL) was added i n 3 p o r t i o n s . The h o n e y - y e l l o w c o l o r of the s o l u t i o n t u r n e d b l a c k i n s t a n t a n e o u s l y . A f t e r a n o t h e r 5 minutes a t 0 ° C and 20 minutes a t room t e m p e r a t u r e , t r i f l u o r o a c e t i c a c i d was e v a p o r a t e d i n v a c u o . The r e s i d u a l p r o d u c t was n e u t r a l i z e d w i t h i c e c o l d sodium b i c a r b o n a t e s o l u t i o n and the water phase was t w i c e e x t r a c t e d w i t h methylene c h l o r i d e (50 mL). The s o l u t i o n was d r i e d (MgS04) and' e v a p o r a t e d a t room t e m p e r a t u r e and the 57 p r o d u c t r e e r y s t a l l i z e d from methylene c h l o r i d e - m e t h a n o l m i x t u r e . The y i e l d of the d i a l d e h y d e was 200 mg ( 4 2 . 6 % ) . M . P . : 1 8 6 - 1 8 8 ° C M o l . W t . : 509 lH nmr: (6,CDCJt3) 2 . 0 0 ( 6 H , S ) , 2 . 2 5 ( 6 H , S ) , 2 . 4 3 ( 2 H , q , J = 7 . 5 H z ) , 2 . 6 8 ( 2 H , q , J = 7 . 5 H z ) , 3 . 6 8 ( 6 H , S ) , 3 . 8 7 ( 4 H , S ) , 9 . 0 0 ( l H , b s ) , 9 . 2 5 ( 2 H , b s ) , 9 . 9 1 ( 2 H , b s ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 509(m+,100), 4 2 2 ( 3 0 ) , 3 0 1 ( 9 8 ) , 2 2 7 ( 3 8 ) , 2 0 7 ( 4 4 ) , 199(20) 58 X o o Y 0 5 - A c e t o x y m e t h y 1 - 2 - t - b u t o x y c a r b o n y 1 - 3 , 4 - d i m e t h y l p y r r o l e (47) 2 - C a r b o - t - b u t o x y - 3 , 4 , 5 - t r i m e t h y l p y r r o l e (11.1 g , 0 . 0 5 3 moles) 46 i n g l a c i a l a c e t i c a c i d (50 mL) was t r e a t e d w i t h l e a d t e t r a a c e t a t e ( 2 . 4 7 g , 0 . 0 5 6 moles) i n s e v e r a l p o r t i o n s . The r e a c t i o n m i x t u r e was s w i r l e d m a n u a l l y and t h e r e a c t i o n was complete w i t h i n 15 minutes (checked by TLC) w i t h e v o l u t i o n of c o n s i d e r a b l e h e a t . E h t y l e n e g l y c o l (5 mL) was added and t h e m i x t u r e d i l u t e d s l o w l y w i t h water (100 mL) t o p r e c i p i t a t e t h e p r o d u c t , which was f i l t e r e d and t h o r o u g h l y washed w i t h w a t e r . The wet p r o d u c t was d i s s o l v e d i n methylene c h l o r i d e (100 mL) . The o r g a n i c l a y e r was f i l t e r e d , d r i e d (MgSO^) and e v a p o r a t e d t o d r y n e s s . The r e s i d u e was r e c r y s t a l l i z e d f r o m methylene c h l o r i d e - h e x a n e . Y i e l d 11.88 g (84%) M . P . : 1 2 6 - 1 2 8 ° C L i t 5 6 : 126-127 M o l . Wt. 2 6 7 . 3 lH nmr: ( 6 , C D C * 3 ) 1.58(9H,S,C(OJ3 ) 3 ) • 2 . 0 0 ( 3 H , S ) , 2 . 0 6 ( 3 H , S ) , 2 . 2 3 ( 6 H , S ) , 5 . 0 2 ( 2 H , S ) , 9 . 8 9 ( l H , b r , N H ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 267(m+,36), 2 1 1 ( 4 6 ) , 1 6 8 ( 1 6 ) , 1 5 2 ( 9 9 . 7 ) , 151(100), 133(48) 59 o P h 0 5 - B e n z y l o x y c a r b o n y l - 5 ' - t - b u t o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a m e t h y l -2 , 2 ' - d i p y r r o m e t h a n e (48) 5 - A c e t o x y m e t h y l - 2 - c a r b o - t - b u t o x y - 3 , 4 - d i m e t h y l p y r r o l e ( 5 . 3 g , 0 . 0 2 moles) 47 i n methylene c h l o r i d e (80 mL) was added d r o p w i s e o v e r a 20 minutes p e r i o d , t o a s o l u t i o n of 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e ( 4 . 6 , 0 . 0 2 moles) 39 c o n t a i n i n g t o l u e n e - p - s u l f o n i c a c i d (10 mg). A f t e r b e i n g s t i r r e d a t room t e m p e r a t u r e under argon f o r 90 m i n u t e s , t h e s o l u t i o n was washed w i t h s a t u r a t e d b i c a r b o n a t e and w a t e r , d r i e d (MgSO^) and e v a p o r a t e d o f f . The r e s u l t i n g o i l was c r y s t a l l i z e d f r o m m e t h y l e n e c h l o r i d e - p e t r o l e u m e t h e r ( 3 5 - 6 0 ° C ) . The powder so o b t a i n e d was found t o be more o f t h e s y m m e t r i c a l d i p y r r o m e t h a n e by nmr. The f i l t r a t e was e v a p o r a t e d , and t h e r e s i d u e t a k e n i n t o warm p e t r o l e u m e t h e r and kept i n t h e f r i d g e o v e r n i g h t . The c r y s t a l s were f i l t e r e d and a i r d r i e d . Y i e l d 7 . 3 2 g (84%) M . P . : 1 3 3 - 1 3 4 ° C L i t 2 6 : 1 3 2 - 1 3 4 ° C M o l . W t . : 4 3 6 . 5 1H nmr: 6 ( C D C * 3 ) 1 . 5 2 ( 9 H , S ) , 1 . 9 2 ( 6 H , S ) , 2 . 2 3 ( 3 H , S ) , 2 . 2 8 ( 3 H , S ) , 3 . 8 K 2 H . S ) , 5 . 2 7 ( 2 H , S ) , 7 . 3 7 ( 5 H , S ) , 8 . 5 4 ( 1 H , S ) , 8 . 7 5 ( 1 H , S ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 436 (m+,22), 3 8 0 ( 3 2 ) , 2 2 7 ( 2 0 ) , 1 8 5 ( 2 0 ) , 1 5 1 ( 5 6 ) , 91(100) 60 0 o 5 - B e n z y l o x y c a r b o n y l - 5 - f o r m y 1 - 3 , 4 - d i m e t h y 1 p y r r o l e (50) 2 - B e n z y l o x y c a r b o n y l - 3 , 4 , 5 - t r i m e t h y l p y r r o l e ( 1 0 . 9 g , 0 . 0 4 5 moles) 36 was d i s s o l v e d i n g l a c i a l a c e t i c a c i d (200 mL) and l e a d t e t r a a c e t a t e (41 g , 0 . 0 9 2 moles) was added i n p o r t i o n s o v e r a 30 m i n u t e p e r i o d . The m i x t u r e was then heated on a steam bath f o r 45 minutes and e t h y l e n e g l y c o l (5 mL) a d d e d . Water (200 mL) was added s l o w l y t o the hot s o l u t i o n t o h y d r o l y z e t h e d i a c e t a t e . When c r y s t a l l i z a t i o n s e t i n , t h e s u s p e n s i o n was f u r t h e r d i l u t e d w i t h water (200 mL). The p r e c i p i t a t e was f i l t e r e d , washed w i t h water and d i s s o l v e d i n methylene c h l o r i d e (100 mL). The s o l u t i o n was a g a i n w a t e r - w a s h e d , d r i e d (MgS0 4 ) and f i l t e r e d and e v a p o r a t e d . The r e s i d u a l p r o d u c t was t w i c e r e c r y s t a l l i z e d from methylene c h l o r i d e - h e x a n e . Y i e l d 8 . 4 g (73%) M . P . : 1 2 0 - 1 2 1 ° C L i t 5 8 : 1 1 9 - 1 2 0 ° C M o l . W t . : 2 5 7 . 3 *H nmr: 6(CDCA3) 2 . 3 0 ( 6 H , S ) , 5 . 3 5 ( 2 H , S ) , 9 . 8 0 ( 1 H , S , C H 0 ) , 9 . 3 7 ( 1 H , S , N H ) Mass Spectrum: m/e ( r e l a t i v e i n t e n s i t y ) 2 5 7 ( m + , 1 9 ) , 1 6 6 ( 1 2 ) , 9 1 ( 1 0 0 ) , 67(14) 61 5 - ( 5 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l - 2 y l - m e t h y l ) - 5 ' - b e n z y 1 - c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a m e t h y l - 2 , 2 ' - d i p y r r o m e t h e n e Hydrobromide (51) 5 - B e n z y l o x y c a r b o n y 1 - 5 ' t - b u t o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a m e t h y l - 2 , 2 1 -d i p y r r o m e t h a n e ( 1 . 3 g , 3 nmoles) 48 i n a 100 mL round bottom f l a s k was t r e a t e d w i t h t r i f l u o r o a c e t i c a c i d (5 mL) w i t h s t i r r i n g under a n i t r o g e n atmosphere at room t e m p e r a t u r e f o r 5 m i n u t e s . The f o r m y l p y r r o l e ( 0 . 7 7 g , 3 mrnoles) 50 p r e v i o u s l y d i s s o l v e d i n methanol (60 mL) was added a t o n c e . The red s o l u t i o n was s t i r r e d an a d d i t i o n a l 90 minutes f o l l o w e d by the a d d i t i o n o f 30-32% hydrogen bromide i n a c e t i c a c i d (1 m L ) , and e t h e r (25 mL). C o n t i n u a l s t i r r i n g f o r 15 minutes r e s u l t e d i n the f o r m a t i o n of r e d d i s h - o r a n g e c r y s t a l s . The p r e c i p i t a t e was f i l t e r e d , washed w i t h e t h e r and a i r d r i e d , t o g i v e a y i e l d of 1 .59 g (76%). M . P . : 1 9 7 - 1 9 9 ° C M o l . W t . : 6 5 6 . 6 X H nmr: (6,CDCJt3) 2 . 0 3 ( 3 H , S ) , 2 . 0 6 ( 3 H , S ) , 2 . 2 5 ( 6 H , S ) , 2 . 8 6 ( 6 H , S ) , ' 4 . 5 0 ( 2 H , S ) , 5 . 2 9 ( 2 H , S , C 6 H 5 C H 2 ) , 5 . 5 0 ( 2 H , S , C 6 H 5 C H 2 ) , 7 . 3 0 ( 1 0 H , S , C 6 H 5 C H 2 ) , 7 . 5 0 ( l H , d=CH) , 1 0 . 6 7 ( IH . S . N H ) , 1 2 . 4 5 ( 1 H , S , N H ) , 14.86(1H,S,NH) 62 Mass Spectrum: m/e ( r e l a t i v e i n t e n s i t y ) 5 7 7 ( 8 ) , 3 3 6 ( 2 4 ) , 2 4 1 ( 2 6 ) , 1 0 8 ( 4 3 ) , 9 1 ( 1 0 0 ) , 65(31) A n a l . C a l d . f o r C 3 6 H 3 8 N 3 B r 0 l t : C . 6 5 . 8 6 ; H . 5 . 8 3 ; N . 6 . 4 0 ; B r , 1 2 . 1 7 . Found: C . 6 6 . 2 1 ; H . 5 . 9 5 ; N , 6 . 4 3 ; B r , 1 2 . 0 0 63 2 , 5 - B i s ( 5 - f o r m y l - 3 , 4 - d i m e t h y 1 p y r r o l - 2 - y l - m e t h y l ) - 3 , 4 -d i m e t h y l p y r r o l e (33) T r i p y r r i n hydrobromide (1.4 g , 2 . 2 mmoles) 51_ was d i s s o l v e d i n THF (600 mL) and hydrogenated a t a t m o s p h e r i c p r e s s u r e and room t e m p e r a t u r e i n t h e p r e s e n c e of t r i e t h y l a m i n e (5 d r o p s ) , sodium a c e t a t e (3 g) and 10% p a l l a d i u m on c h a r c o a l (200 mg). Hydrogen uptake was complete i n one hour but was a l l o w e d t o s t i r o v e r n i g h t . The c a t a l y s t was f i l t e r e d t h r o u g h a c e l i t e p l u g and t h e f i l t r a t e was e v a p o r a t e d t o d r y n e s s a t reduced p r e s s u r e . The c r u d e p r o d u c t 24_ was u s e d , as i s , i n t h e next r e a c t i o n . In an a p p a r a t u s c o n s i s t i n g of a 150 mL e r l e n m e y e r f l a s k f i t t e d w i t h a c l a i s e n a d a p t e r and an argon i n l e t , DMF (5 mL) was heated t o r e f l u x . To t h e b o i l i n g DMF, under a r g o n , were added f o u r s u c c e s s i v e 5 mL DMF p o r t i o n s of t h e b i s - a - c a r b o x y p y r r o l e . A drop of t h e s o l u t i o n b e f o r e h e a t i n g was d i l u t e d w i t h methylene c h l o r i d e and a uv a b s o r p t i o n spectrum was r e c o r d e d , showing a s i n g l e a b s o r p t i o n band a t X 286 nm. The m i x t u r e was r e f l u x e d under a r g o n , t h e o r i g i n a l r e d d i s h s o l u t i o n t u r n e d dark brown. The d e c a r b o x y l a t i o n was o v e r i n 30 minutes as t h e a b s o r p t i o n 64 band a t 286 nm had d i s a p p e a r e d . The s o l u t i o n s t i l l under argon was c h i l l e d i n i c e and used i n the next r e a c t i o n . B e n z o y l c h l o r i d e ( 2 . 0 g , 14.2 mmole) was added r a p i d l y d r o p w i s e t o t h e above r e a c t i o n m i x t u r e and was s t i r r e d f o r 30 minutes t o e n s u r e complete r e a c t i o n and l e f t t o s t a n d a t room t e m p e r a t u r e f o r two h o u r s . Water (60 mL) and sodium b i c a r b o n a t e ( 2 . 0 g , much e x c e s s ) were added to t h e r e a c t i o n m i x t u r e and was heated on steam b a t h f o r one h o u r , d u r i n g which time the p r o d u c t c o a g u l a t e d i n t o c r y s t a l l i n e lumps. The m i x t u r e was c o o l e d , t h e s o l i d f i l t e r e d , washed w i t h water and r e c r y s t a l l i z e d from methylene c h l o r i d e - m e t h a n o l go t i v e a y i e l d of 0.61 g ( 7 5 . 9 % ) . M . P . : >240° C M o l . Wt. 3 6 5 . 5 1H nmr: ( 6 , C D C * 3 ) 1 . 9 8 ( 6 H , S ) , 2 . 2 8 ( 6 H , S ) , 2 . 4 8 ( 6 H , S ) , 3 . 9 3 ( 4 H , S ) , 8 . 0 2 ( 1 H , S ) , 9 . 2 9 ( 1 H , S ) , 9 . 4 3 ( 1 H , S ) , 1 0 . 0 5 ( 1 H , S ) , 1 0 . 1 8 ( 1 H , S ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 3 6 5 ( m + , 2 ) , 2 5 8 ( 7 7 ) , 2 2 9 ( 2 4 , 2 0 1 ( 3 6 ) , 1 3 6 ( 1 0 0 ) , 1 2 3 ( 3 0 ) , 1 0 8 ( 4 0 ) , 94(36) A n a l . C a l c d . f o r C 2 2 H 2 7 N 3 0 2 : C , 7 2 . 3 1 ; H . 7 . 4 4 ; N.11 .50 Found: C . 7 1 . 9 7 ; H . 7 . 3 2 ; N .11 .48 65 r l 3 - E t h o x y c a r b o n y l - 4 - m e t h y l p y r r o l e (57) 2 - 4 - B i s - e t h o x y c a r b o n y l - 5 - c a r b o x y - 3 - m e t h y l p y r r o l e ( 1 2 . 0 g , 0 . 0 4 5 moles) 54 and sodium h y d r o x i d e ( 3 . 6 g , 0 . 0 9 moles) i n water (90 mL) were heated on t h e steam b a t h f o r 2 h o u r s , a f t e r which t i m e t h e pH had f a l l e n t o 8 - 9 . The s o l u t i o n was d i l u t e d w i t h water (180 mL) , sodium b i c a r b o n a t e ( 4 . 5 g , 0 . 5 4 moles) was added and the s o l u t i o n warmed t o a p p r o x i m a t e l y 60° C. A s o l u t i o n of i o d i n e ( 2 2 . 9 g ( 0 . 0 9 m o l e s ) ) i n sodium i o d i n e (25 g) and water (125 mL) was added f a i r l y r a p i d l y c a u s i n g m i l d e f f e r v e s c e n c e and the d e p o s i t i o n of dense g r a n u l a r l i g h t t a n s o l i d s . The m i x t u r e was k e p t warm f o r 2 hours t o e n s u r e complete i o d i n a t i o n . The s o l i d s were f i l t e r e d o f f , washed w i t h water and the w e t - c r u d e f i l t e r - c a k e was warmed w i t h 95% e t h a n o l (110 mL) on t h e steam b a t h , d i s s o l v i n g t o g i v e f a i r l y l i g h t brown s o l u t i o n . To t h i s s o l u t i o n was a d d e d , p o t a s s i u m i o d i d e (6 g ) , c o n c e n t r a t e d h y d r o c h l o r i c a c i d ( 5 . 4 mL) and 50% hypophosphorous a c i d (50 mL) i n t h a t o r d e r . The m i x t u r e was heated f o r 20 minutes t o e n s u r e complete r e d u c t i o n . The e n t h a n o l was e v a p o r a t e d o f f , the r e s i d u e d i s s o l v e d i n methylene c h l o r i d e (100 mL) and r i n s e d w i t h aqueous sodium b i c a r b o n a t e and w a t e r . The o r g a n i c phase was f i l t e r e d , d r i e d (MgSOJ and e v a p o r a t e d to d r y n e s s . The r e s i d u a l b l a c k o i l was d i s s o l v e d i n methylene c h l o r i d e (20 mL) and chromatographed on s i l i c a g e l u s i n g methylene c h l o r i d e as the e l u t i n g s o l v e n t . A l l the c o l o r e d i m p u r i t i e s remained at 66 t h e o r i g i n and the d i - a - f r e e p y r r o l e was e l u t e d as a p a l e y e l l o w l i q u i d . The s o l v e n t was e v a p o r a t e d to g i v e s o l i d of y i e l d 6 . 2 g ( 8 9 . 9 % ) . M . P . : 7 2 - 7 4 ° C L i t 6 0 : 7 3 ° C M o l . W t . : 153.2 lH nmr: 6(CDCA3) 1 . 3 5 ( 3 H , t , J = 7 . 0 H z ) , 2 . 3 ( 3 H , S ) , 4 . 3 ( 2 H , q , J = 7 . 5 H z ) , 6 . 5 ( l H , m ) Mass Spectrum: m/e ( r e l a t i v e i n t e n s i t y ) , 153(m+,43), 1 4 9 ( 2 0 ) , 1 2 4 ( 3 4 ) , 108(100) 67 2 - B e n z y 1 o x y c a r b o n y l - 5 - c h 1 o r o m e t h y 1 - 3 , 4 - d i m e t h y l p y r r o l e (58) 2 - B e n z y l o x y c a r b o n y l - 3 , 4 , 5 - t r i m e t h y l p y r r o l e ( 2 4 . 3 g , 0 . 1 moles) 35 was suspended i n anhydrous d i e t h y l e i t h e r (250 mL) and s t i r r e d a t room t e m p e r a t u r e , a s o l u t i o n of s u l f u r y l c h l o r i d e ( 1 3 . 8 g , 8 . 3 mL, 0 . 1 moles=13.5 g) i n carbon t e t r a c h l o r i d e (20 mL) was added d r o p w i s e over a 15 minute p e r i o d . The a d d i t i o n o f r e a g e n t caused a y e l l o w c o l o r t o form and a l l the s t a r t i n g m a t e r i a l d i s s o l v e d . When the r e a g e n t was about h a l f a d d e d , a f l u f f y w h i t e p r o d u c t began t o c r y s t a l l i z e out and t h e m i x t u r e became t h i c k . A f t e r s t a n d i n g f o r 45 m i n u t e s , the s o l i d s were f i l t e r e d o f f and r i n s e d w i t h e t h e r , then hexane. The p r o d u c t 13.1 g (47.2%) was s t o r e d i n t h e d a r k . M . P . : 1 4 3 - 1 4 4 ° C (decomposed) L i t 3 7 : 1 4 4 - 1 4 5 ° C (decomposed) M o l . W t . : 3 3 5 . 8 J H nmr: (6,CDCJc3) 2 . 0 1 ( 3 H , S ) , 2 . 2 6 ( H , S ) , 4 . 5 5 ( 2 H , S ) , 5 . 3 3 ( 2 H , S ) , 7 . 3 6 ( 5 H , S ) , 9 . 2 0 ( l H , b s ) 68 > 2,5-B i s - ( 5 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l - 2 - y l - m e t h y l ) -3 - e t h o x y c a r b o n y 1 - 4 - m e t h y 1 p y r r o 1 e (59) 2 - B e n z y l o x y c a r b o n y l - 5 - c h l o r o m e t h y l - 3 , 4 - d i m e t h y l p y r r o l e (12.0 g , 43 mmoles) 58 and 3 - e t h o x y c a r b o n y l - 4 - m e t h y l p y r r o l e ( 3 . 3 g , 22 nmoles) 57 were d i s s o l v e d i n methylene c h l o r i d e (60 mL) and s t i r r e d f o r 15 minutes a t room t e m p e r a t u r e . The s o l v e n t was b o i l e d down t o a s m a l l volume on a steam bath w i t h t h e s o l u t i o n t u r n i n g r e d . Methanol (50 mL) was added and t h e b o i l i n g c o n t i n u e d u n t i l amost a l l t h e methylene c h l o r i d e was b o i l e d o f f . The r e a c t i o n m i x t u r e was c o o l e d , t h e p r e c i p i t a t e f i l t e r e d and washed w i t h m e t h a n o l . The p r o d u c t was found t o be a m i x t u r e o f t h e d e s i r e d p r o d u c t and 5 , 5 ' - b e n z y l o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a m e t h y l - 2 , 2 ' -d i p y r r o m e t h a n e 6 8 , a b y p r o d u c t . The m i x t u r e was d i s s o l v e d i n methylene c h l o r i d e (50 mL) and d i l u t e d w i t h hot p e t r o l e u m e t h e r ( 3 5 ° - 6 0 ° C) (100 mL) , c a u s i n g t h e d i p y r r o m e t h a n e t o c r y s t a l l i z e . The s o l u t i o n was c o o l e d i n t h e r e f r i g e r a t o r t o complete t h e c r y s t a l l i z a t i o n , f i l t e r e d and t h e b y p r o d u c t r i n s e d w i t h more p e t r o l e u m e t h e r . The y i e l d of b y p r o d u c t was 0 . 8 g . The 69 f i l t r a t e and w a s h i n g s , were e v a p o r a t e d to d r y n e s s and t h e r e s u l t i n g s o l i d s r e d i s s o l v e d i n t e t r a h y d r o f u r a n (25 mL). Methanol was added to the b o i l i n g s o l u t i o n t o d i s p l a c e t h e t e t r a h y d r o f u r a n . The s o l u t i o n was c o o l e d , t h e c r y s t a l s were f i l t e r e d , washed w i t h methanol and a i r d r i e d . Y i e l d 5 . 5 g ( 3 9 . 3 % ) . M . P . : 1 8 1 - 1 8 2 ° C L i t 3 7 : 1 8 4 - 1 8 7 . 5 ° C M o l . W t . : 6 3 5 . 7 J H nmr: (6,CDCJc3) 1 . 3 8 ( 3 H , t , J = 7 . 0 ) , 1 . 7 5 ( 3 H , S ) , 1 . 8 3 ( 3 H , S ) , 2 . 4 0 ( 3 H , S ) , 2 . 4 6 ( 6 H , S ) , 3 . 3 8 ( 2 H , b S ) , 4 . l - 4 . 5 ( 8 H , m ) , 7 . 2 5 ( l O H , m ) , 9 . 5 8 ( 1 H , S , N H ) , 1 0 . 9 3 ( 1 H , S , N H ) , 11 .52(1H,S,NH) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 6 3 5 ( m + , 3 ) , 5 9 4 ( 6 0 ) , 4 3 6 ( 1 0 0 ) , 3 1 5 ( 4 1 ) , 91(90) 70 ) 2 - 5 - B i s - ( - 5 - f o r m y l - 3 , 4 - d i m e t h y l p y r r o l - 2 - y l - m e t h y l ) - 3 - e t h o x y - c a r b o n y l - 4 - m e t h y l p y r r o l e (34) 2 , 5 - B i s - ( 5 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l - 2 - y l - m e t h y l ) -3 - e t h o x y c a r b o n y l - 4 - m e t h y l p y r r o l e 59 ( 1 . 3 g , 2 mmoles) and 10% p a l l a d i u m on c h a r c o a l (200 mg) were s t i r r e d o v e r n i g h t under hydrogen (1 atmosphere a t room t e m p e r a t u r e ) i n t e t r a h y d r o f u r a n (150 mL). When the uptake o f hydrogen c e a s e d , t h e c a t a l y s t was f i l t e r e d o f f t h r o u g h a c e l i t e p l u g , r i n s e d w i t h t e t r a h y d r o f u r a n and the f i l t r a t e s were e v a p o r a t e d t o d r y n e s s i n vacuo a t 30° C l e a v i n g t h e b i s - c a r b o x y p y r r o l e as a p a l e y e l l o w s o l i d , t h e crude p r o d u c t was u s e d , as i s , i n the next r e a c t i o n . In an a p p a r a t u s c o n s i s t i n g of a 50 mL e r l e n m e y e r f l a s k f i t t e d w i t h a c l a i s e n a d a p t e r and an argon i n l e t , DMF (5 mL) was heated t o r e f l u x . To t h e b o i l i n g DMF under a r g o n , were added t h r e e s u c c e s s i v e 5 mL p o r t i o n s o f the b i s - c a r b o x y p y r r o l e i n DMF. A drop of t h i s s o l u t i o n was d i l u t e d w i t h methylene c h l o r i d e and a uv a b s o r p t i o n spectrum was r e c o r d e d , showing a s i n g l e a b s o r p t i o n band a t X 286 nm. The m i x t u r e was r e f l u x e d under a r g o n , t h e o r i g i n a l l y c o l o r l e s s s o l u t i o n t u r n e d dark brown and a t e v e r y 30 m i n u t e s , a drop was removed i n t o methylene c h l o r i d e and the uv spectrum 71 r e c o r d e d . The a b s o r p t i o n band a t 286 nm was reduced t o j u s t a s h o u l d e r i n one hour but a f u r t h e r h a l f - h o u r of h e a t i n g d i d not remove t h i s c o m p l e t e l y . The s o l u t i o n was c o o l e d i n i c e and used i n t h e next r e a c t i o n . To an i c e - c o o l e d s o l u t i o n of DMF (5 mL), phosphorous o x y c h l o r i d e ( 0 . 4 6 mL) was added and m a g n e t i c a l l y s t i r r e d . The V i l s m e i e r r e a g e n t thus p r e p a r e d , was t r e a t e d , r a p i d l y and d r o p w i s e , w i t h the c h i l l e d DMF s o l u t i o n o f the b i s - a - f r e e p y r r o l e p r e p a r e d a b o v e . Once t h e a d d i t i o n was c o m p l e t e , the s o l u t i o n was s t i r r e d f o r a f u r t h e r h a l f - h o u r t o ensure the c o m p l e t i o n o f t h e r e a c t i o n . The s o l u t i o n was poured i n t o c r u s h e d i c e . S o l i d sodium b i c a r b o n a t e was a d d e d , c a r e f u l l y w i t h s t i r r i n g , u n t i l the s o l u t i o n was w e a k l y b a s i c t o pH paper and then heated on t h e steam bath ( t h e s o l u t i o n became a c i d i c a g a i n and more b i c a r b o n a t e had t o be a d d e d ) . The hot s o l u t i o n was f i l t e r e d t o remove a few brown p a r t i c l e s and heated u n t i l t h e s o l u t i o n t u r n e d t u r b i d and a g r e y c o l o r e d s o l i d s e p a r a t e d o u t . The h e a t i n g was c o n t i n u e d f o r a f u r t h e r h a l f - h o u r , the m i x t u r e c o o l e d and t h e s o l i d f i l t e r e d and washed w i t h w a t e r . The p r o d u c t was r e c r y s a l l i z e d i n methylene c h l o r i d e - m e t h a n o l . The y i e l d was 0.78 g (92%). M . P . : 2 2 0 - 2 2 1 ° C L i t 3 7 : 2 2 1 - 2 2 1 . 5 ° C M o l . W t . : 4 2 3 . 5 1H nmr: (6,CDCJt3) 1 . 3 6 ( 3 H , t , J = 7 . 0 H z,CH3CH 2), 1 . 9 5 ( 3 H , S ) , 1 . 9 7 ( 3 H , S ) , 2 . 2 0 ( 3 H , S ) , 2 . 2 1 { 3 H , S ) , 2 . 2 9 ( 3 H , S ) , 3 . 7 9 ( 2 H , S ) , 4 . 3 0 ( 2 H , q , J = 7 . 0 H z , C H 3 C H 2 ) , 4 . 3 1 ( 2 H , S ) , 8 . 9 7 ( 1 H , S , CHO), 9 . 0 1 ( 1 H , S , C H 0 ) , 1 0 . 0 6 ( 1 H , S , N H ) , 1 0 . 9 7 ( 1 H , S , N H ) , 11 .03(1H,S,NH) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 4 2 3 ( m + , 1 0 0 ) , 3 0 0 ( 5 9 ) , 2 8 7 ( 4 5 ) , 2 5 4 ( 5 3 ) , 2 1 3 ( 3 8 ) , 136(57) 72 r o o Ph 5 - A c e t o x , y m e t h y l - 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e (6_7_) 2 - B e n z y l o x y c a r b o n y l - 3 , 4 , 5 - m e t h y l p y r r o l e (12.5 g; 51 mmole) 36 was d i s s o l v e d i n g l a c i a l a c e t i c a c i d (100 mL) and l e a d t e t r a a c e t a t e ( 2 3 . 7 g , 5 3 . 5 mmole) was added a l l a t o n c e . The m i x t u r e was s w i r l e d m a n u a l l y and warmed on a steam bath t o about 6 0 ° C t o complete t h e r e a c t i o n . The r e a c t i o n m i x t u r e was a l l o w e d t o c o o l and w a t e r added u n t i l t h e r e was no m i l k i n e s s . The p r e c i p i t a t e was f i l t e r e d and washed w i t h w a t e r . About 0 . 5 g of t h e wet p r o d u c t was d i s s o l v e d i n methylene c h l o r i d e , f i l t e r e d , d r i e d (MgSQi,), c o n c e n t r a t e d and r e c r y s t a l l i z e d from hexane. M . P . : 1 1 5 - 1 1 6 ° C M o l . W t . : 3 0 1 . 3 1H nmr: (6 ,CDCA3 ) 2 . 0 1 ( 3 H . S ) , 2 . 0 8 ( 3 H , S ) , 2 . 2 6 ( 3 H , S ) , 5 . 0 1 ( 2 H , S ) , 5 . 3 1 ( 2 H , S ) , 7 . 3 8 ( 5 H , S ) , 8 . 9 4 ( l H , b r ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 301(m+,3), 1 6 8 ( 1 5 ) , 9 1 ( 1 0 0 ) , 65(12) 73 Ph Ph 0 0 5 - 5 ' B i s b e n z y l o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a m e t h y l - 2 , 2 ' - d i p y r o m e t h a n e (49) The 5 - a c e t o x y m e t h y l - 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i m e t h y l p y r r o l e 67 was d i s s o l v e d i n a c e t i c a c i d - w a t e r ( 8 0 - 2 0 , 1 L) and heated to r e f l u x f o r 2 hours . A f t e r c h e c k i n g t h e r e a c t i o n m i x t u r e by TLC f o r complete c o n v e r s i o n of s t a r t i n g m a t e r i a l , the r e a c t i o n m i x t u r e was a l l o w e d to c o o l , and d i l u t e d w i t h water u n t i l t h e r e was no appearance o f m i l k i n e s s . The p r e c i p i t a t e was f i l t e r e d , washed w i t h water and r e c r y s t a l l i z e d from e t h a n o l . The y i e l d was 9 . 0 g (75%). M . P . : 1 7 7 - 1 7 9 ° C M o l . W t . : 4 7 0 . 5 1H nmr: (6,CDCA 3 ) 2 . 0 0 ( 6 H , S ) , 2 . 3 0 ( 6 H , S ) , 3 ( 2 H , S ) , 5 . 2 3 ( 4 H , S , C 6 H 5 C H 2 ) , 7 . 3 7 ( 1 0 H , S , C 6 H 5 C H 2 ) , 9 . 0 8 ( 2 H , S , N H ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 4 7 0 ( m + , 2 0 ) , 1 4 9 ( 1 9 ) , 9 1 ( 1 0 0 ) , 65(16) 74 5 , 5 ' - B i s c a r b o x y - 3 , 3 ' , 4 , 4 1 - t e t r a m e t h y 1 - 2 , 2 1 - d i p y r r o m e t h a n e (32_) 5 , 5 ' -B1sbenzy l o x y c a r b o n y 1 - 3 , 3 • , 4 , 4 ' - t e t r a m e t h y 1 - 2 , 2 • -d i p y r r o m e t h a n e 49 ( 2 . 3 g , 4 . 9 mmoles) i n THF (100 mL) was s t i r r e d o v e r n i g h t under hydrogen (1 atmosphere) i n t h e p r e s e n c e of 10% p a l l a d i u m on c h a r a c o a l (200 mg). When t h e uptake of hydrogen c e a s e d , t h e c a t a l y s t was f i l t e r e d through a c e l i t e p l u g and the s o l u t i o n checked by TLC f o r any u n c o n v e r t e d s t a r t i n g m a t e r i a l . The s o l v e n t was e v a p o r a t e d o f f , i n v a c u o , l e a v i n g t h e b i s c a r b o x y p y r r o l e as a p a l e y e l l o w i s h s o l i d . Because o f t h e u n s t a b l e n a t u r e of t h i s compound, 1t was not a n a l y s e d . The f l a s k was wrapped w i t h f o i l and k e p t i n t h e f r i d g e . 75 2 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i e t h y 1 - 5 - m e t h y l p y r r o l e (64) 2 - C a r b o e t h o x y - 3 , 4 - d i e t h y l - 5 - m e t h y l p y r r o l e (50 g , 0 . 2 4 moles) 63 was d i s s o l v e d i n r e d i s t i l l e d b e n z y l a l c o h o l (100 mL) and heated t o r e f l u x under n i t r o g e n i n an e r l e n m e y e r f l a s k equipped w i t h a c l a i s e n a d a p t e r and a n i t r o g e n i n l e t on the s i d e arm and a thermometer suspended i n t h e f l a s k . To p r e v e n t heat l o s s e s , t h e whole a p p a r a t u s was wrapped w i t h aluminum f o i l . A few drops of sodium b e n z y l o x i d e c a t a l y s t ( p r e p a r e d by d i s s o l v i n g sodium metal i n r e d i s t i l l e d b e n z y l a l c o h o l ) were added t o t h e r e f l u x i n g s o l u t i o n when the t e m p e r a t u r e reached 209° C c a u s i n g a t e m p e r a t u r e drop and e v o l u t i o n o f e t h a n o l v a p o u r s . When t h e r e a c t i o n s u b s i d e d more c a t a l y s t was a d d e d . The p r o c e d u r e was r e p e a t e d u n t i l no f u r t h e r r e a c t i o n was observed and the t e m p e r a t u r e of t h e r e f l u x i n g s o l u t i o n was a g a i n t h a t o f b e n z y l a l c o h o l ( 2 0 9 ° C ) . The hot s o l u t i o n was then poured i n t o a quenching m i x t u r e o f methanol (400 mL) and g l a c i a l a c e t i c a c i d (10 mL). Water (400 mL) was g r a d u a l l y added w h i l e s t i r r i n g . The c l e a r p a l e y e l l o w s o l u t i o n t u r n e d p i n k , and w h i t e g r a n u l a r m a t e r i a l p r e c i p i t a t e d from the s o l u t i o n and the s u s p e n s i o n was a l l o w e d t o s i t o v e r n i g h t . The p r o d u c t was f i l t e r e d , washed w i t h 40% m e t h a n o l - w a t e r and then w i t h w a t e r . The crude s o l i d was r e c r y s t a l l i z e d from methanol t o g i v e 5 5 . 4 g (83.5%) y i e l d . 76 M . P . : 7 2 - 7 3 ° C L i t 3 7 : 7 2 - 7 3 ° C M o l . W t . : 271 J H nmr: (6,CDCA 3 ) 1 . 0 3 ( 3 H , t , J = 7 . 0 H z ) , 1 . 1 0 ( 3 H , t , 7 . 0 H z ) , 2 . 1 4 ( 3 H , S ) , 2 . 3 8 ( 2 H , q , J = 7 . 5 H z ) , 2 . 7 0 ( 2 H , q , J = 7 . 5 H z ) , 2 . 7 2 ( 2 H , q , J = 7 . 5 H z ) , 7 . 3 6 ( 5 H , S ) , 8 . 7 2 ( l H , b s ) Mass Spectrum: m/e ( r e l a t i v e i n t e n s i t y ) 2 7 1 ( m + , 2 8 ) , 1 8 0 ( 3 6 . 5 ) , 1 6 2 ( 3 9 ) , 91(100) 77 Y 0 0 Ph 5 - A c e t o x y m e t h y l - 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i e t h y l p y r r o l e (65) 2 - B e n z y l o x y c a r b o n y l - 3 , 4 - d i e t h y l - 5 - m e t h y l p y r r o l e (27.1 g , 0 . 1 moles) 64 was d i s s o l v e d i n g l a c i a l a c e t i c a c i d (200 mL) and l e a d t e t r a a c e t a t e (48 g , 0 . 1 mole = 4 4 . 3 g) was added a l l a t o n c e . From t h i s p o i n t , the r e a c t i o n was c a r r i e d out as d e s c r i b e d f o r compound 6 7 . M . P . : 1 1 3 - 1 1 5 ° C L i t 5 9 : 1 1 3 . 5 - 1 1 5 ° C M o l . W t . : 3 2 9 . 4 i H - n m r : (6,CDCJc3) 1 . 1 0 ( 6 H , t , J = 7 . 0 H z ,CjH^ C H 2 ) , 2 . 0 8 ( 3 H , S ) , 2 . 4 4 ( 2 H , q , J = 7 . 5 H z , C H 3 C H 2 ) , 2 . 9 1 ( 2 H , q , J = 7 . 5 H z , C H 3 C H 2 ) , 5 . 0 0 ( 2 H , S , C H 3 C 0 2 C H 2 ) , 5 . 3 0 ( 2 H , S , C 6 H 5 C H 2 ) , 7 . 3 8 ( 5 H , S ) , 7 . 9 9 ( l H , b s ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 3 2 9 ( m + , 1 6 ) , 1 7 7 ( 3 9 ) , 1 6 3 ( 3 0 ) , 1 2 0 ( 4 8 ) , 91(100) 78 5 , 5 ' - B i s b e n z y l o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a e t h y l - 2 , 2 ' - d i p y r r o m e t h a n e (66) The 5 - a c e t o x y m e t h y l - 2 - b e n z y l o x y c a r b o n y l - 3 , 4 - d i e t h y l p y r r o l e 65 was d i s s o l v e d i n a c e t i c a c i d - w a t e r ( 8 0 - 2 0 , 200 mL) and heated t o r e f l u x f o r 2 h o u r s . From t h i s p o i n t , the r e a c t i o n and p u r i f i c a t i o n was c a r r i e d out as d e s c r i b e d f o r compound 4 9 . The y i e l d was 2 0 . 3 g {77.2%). M . P . : 1 1 9 - 1 2 0 ° C L i t 5 9 : 1 1 9 . 5 - 1 2 0 . 5 ° C M o l . W t . : 5 2 6 . 6 1H nmr: ( 6 , C D C * 3 ) 1 . 0 3 ( 6 H , t , J = 7 . 5 H z ) , 1 . 2 0 ( 6 H , t , J = 7 . 5 H z ) , 2 . 4 1 ( 4 H , q , J = 7 . 5 H z ,CH 2 CH 3 ) , 2 . 7 3 ( 4 4 , q , J = 7 . 5 H z , C H 2 C H 3 ) , 3 . 8 3 ( 2 H , S ) , 5 . 2 8 ( 4 H , S , C 6 H 5 C H 2 ) , 7 . 3 6 ( 1 0 H , S . C ^ C h y ) , 8 . 7 2 ( 2 H , b s , N H ) Mass S p e c t r u m : m/e ( r e l a t i v e i n t e n s i t y ) 5 2 6 ( m + , 1 7 ) , 2 6 9 ( 5 4 ) , 1 7 8 ( 2 3 ) , 91(100) 79 5 , 5 ' - B i s c a r b o x y - 3 , 3 ' , 4 , 4 ' - t e t r a e t h y l - 2 , 2 ' - d i p y r r o m e t h a n e (35) 5 , 5 ' - B i s b e n z y l o x y c a r b o n y l - 3 , 3 ' , 4 , 4 ' - t e t r a e t h y l - 2 , 2 ' - d i p y r r o m e t h a n e ( 1 . 1 g , 2 mmoles) 66 i n THF (100 mL) was hydrogenated as f o r compound 4 9 . As t h e p r o d u c t , d i c a r b o x y l i c a c i d i s v e r y u n s t a b l e , t h e f i l t r a t e was made up t o 250 mL o f THF, wrapped i n f o i l and s t o r e d i n the f r i d g e , w i t h o u t a n a l y s i n g i t . 80 3.4 SYNTHESES OF PENTAPHYRIN 2 - E t h o x y c a r b o n y 1 - 3 , 7 , 8 , 1 2 , 1 3 , 1 7 , 1 8 , 2 2 , 2 3 - n o n a m e t h y l p e n t a p h y r i n (74) Dipyrromethane d i a c i d ( 3 4 . 3 mg, 0.12 mmole) 32_was d i s s o l v e d i n methylene c h l o r i d e (300 mL) under argon ( i n a 1 L round bottomed s c h l e n k f l a s k ) which has been "degased" by b u b b l i n g argon t h r o u g h f o r 2 h o u r s . A f t e r s t i r r i n g t h e m i x t u r e f o r 30 m i n u t e s , t h e t r i p y r r a n e d i a l d e h y d e (50 mg, 0.12 mmole) 34_was a d d e d . The s o l u t i o n was s t i r r e d f o r 10 m i n u t e s and a c i d i f i e d w i t h HBr i n a c e t i c a c i d ( 0 . 9 mL) ( 3 0 - 3 2 % ) . The c o l o r of t h e r e a c t i o n m i x t u r e changed from y e l l o w t o p i n k i s h - r e d and then t o r e d which d i d not change w i t h s t i r r i n g f o r 2 h o u r s . C h l o r a n i l (280 mg) was added t o e f f e c t o x i d a t i o n and t h e r e a c t i o n m i x t u r e was s t i r r e d f o r a f u r t h e r 36 h o u r s . The development of t h e r e a c t i o n was f o l l o w e d by u v - v i s i b l e s p e c t r o s c o p y . The s o l v e n t was e v a p o r a t e d o f f on a r o t a r y e v a p o r a t o r and t h e r e s i d u a l p r o d u c t chromatographed ( p r e p a r a t i v e TLC) u s i n g s i l i c a g e l GF p l a t e s ( A n a l t e c h ) w i t h f l u o r e s c e n t i n d i c a t o r and e t h y l a c e t a t e as e l u e n t . A f t e r p r o p e r l y d r y i n g t h e p l a t e s , t h e dark green f r a c t i o n a t t h e o r i g i n was s c r a p e d and e l u t e d w i t h methylene c h l o r i d e - m e t h a n o l ( 1 0 : 1 ) . The s o l v e n t was e v a p o r a t e d o f f , and t h e r e s i d u a l p r o d u c t , t w i c e 81 chromatographecTusing 5% methanol i n methylene c h l o r i d e . The green f r a c t i o n was c o l l e c t e d and t h e s o l v e n t evaporated t o g i v e a y i e l d of 1 8 . 0 mg ( 2 6 . 1 % ) . A p r e p a r a t i o n on a 5 . 9 x l 0 " 2 mmole s c a l e gave 31.9% y i e l d . ! H nmr: (6,TFA/CDC13) 1 . 9 5 ( 3 H , t , J = 7 H z , C H 3 C H 2 ) , 4 . 1 3 ( 6 H , S , C H 3 ) , 4 . 1 5 ( 1 2 H , S , C H 3 ) , 4 . 1 9 ( 6 H , S , C H 3 ) , 4 . 5 1 ( 3 H , S ,CH3) , 5 . 1 8 ( 2 H , q , J = 7 . 5 H z , C H 3 C H 2 ) , 1 1 . 9 1 ( 2 H , b s , m e s o - H ) , 1 2 . 0 0 ( l H , b s , m e s o - H ) , 1 2 . 1 2 ( l H , b s , m e s o - H ) , 1 3 . 2 9 ( l H , b s , m e s o - H ) , - 4 . 3 3 ( 1 H , S , N H ) , - 4 . 6 3 ( 1 H , S , N H ) , - 4 . 7 0 ( 1 H , S , N H ) , - 4 . 7 6 ( 1 H , S , N H ) , - 4 . 8 0 ( 1 H , S , N H ) . 1 3 C nmr: (6,30%TFA/CDC13) 12.751. 1 2 . 8 8 1 ( 9 C , C H 3 ) , 2 9 . 8 0 8 ( 1 C , C H 2 C H 3 ) , 6 4 . 5 7 9 ( 1 C , 0 C H 2 C H 3 ) , 9 7 . 5 8 4 , 9 7 . 6 4 4 , 9 9 . 4 6 4 , 1 0 1 . 2 2 6 , 101,623(50 meso c a r b o n s ) , 131.511 , 136.547, 1 3 7 . 9 8 9 , 1 3 8 . 4 4 3 , 1 4 0 . 2 8 6 , 1 4 0 . 3 3 6 , 1 4 0 . 6 0 9 , 1 4 1 . 6 9 5 , 1 4 1 . 9 2 1 , 1 4 2 . 0 5 6 , 1 4 2 . 3 8 1 , 143.802 ( 2 0 C , a - B - c a r b o n s ) , 165.489(10,C=0) Mass Spectrum: EI m/e ( r e l a t i v e i n t e n s i t y ) 587(m++2, 4 . 7 ) , 588(m++3, 2 . 6 ) 4 8 0 ( 4 1 ) , 452(11) , 4 2 2 ( 2 3 ) , 108(100) FAB m/e m+l=586, m+2=587 m^ax(nm) 365 458 595 645 715 1 o 9 Sax 3 . 9 9 5 . 6 8 3 . 6 6 4 . 2 7 4 . 0 1 m^ax(nm) 345 450 642 l 0 9 emax 4 . 5 3 4 . 7 3 4 . 0 1 82 The synthesis and purification was carried out on 71 as described for compound 74. Tripyrrane dialdehyde 33 (50 mg, 1.3xl0"4 moles) and dipyrromethane diadd 32 (40 mg, 1.3xl0"4 moles) were used, to give a yield of 12 mg (21*). *H nmr: (6,TFA/CDCL3) 4.41(30H.S,CH3), 12.49(5H,S,meso-H), -5.52(5H,S,NH) 13Cnmr: (6.TFA): 14.478(10C,CH3), 102.009(5C,meso-C), 142.740(10C,BC), 147.328(10C,aC) Mass Spectrum: EI m/e (relative Intensity) 484(3), 476(3) FAB m/e m+l=528, m+2=529 UV-V1s1ble Spectrum: \nax(nm) 380 455 595 645 l 09 Emax 3.77 4.77 2.95 3.89 m^ax(nm) 395 425 474 670 1 o9 Sax 4.09 4.09 4.05 3.31 E t 2 - E t h o x y c a r b o n y l - 3 , 7 , 8 , 2 2 , 2 3 - p e n t a m e t h y 1 - 1 2 , 1 3 , 1 7 , 1 8 - t e t r a e t h y l p e n t a p h y r i n (75) The d i p y r r o m e t h a n e d i a c i d 35_ (0.12 mmole, 15.2 mL of the s t o c k s o l u t i o n i n THF) was t a k e n i n t o 1 L round-bottomed s c h l e n k f l a s k and t h e s o l v e n t e v a p o r a t e d o f f on a r o t a r y e v a p o r a t o r a t room t e m p e r a t u r e , and a l l o w i n g argon i n t o t h e f l a s k a t t h e e n d . M e t h y l e n e c h l o r i d e (300 ml) was added t o t h e d i a c i d and t h e s o l u t i o n " d e g a s s e d " by b u b b l i n g argon t h r o u g h f o r 2 h o u r s . The t r i p y r r a n e d i a l d e h y d e (50 mg, 0.12 mmole) 34 was added and t h e m i x t u r e s t i r r e d f o r 10 m i n u t e s . From t h i s p o i n t , t h e s y n t h e s i s and p u r i f i c a t i o n was c a r r i e d out as d e s c r i b e d f o r 7 4 . The y i e l d was 2 1 . 0 mg (28%). lHnmr: (6 ,TFA/CDC* 3 ) 2 . 0 5 ( 3 H , t , J = 7 H z , C 0 2 C H 2 CH3 ) , 2.17 (12H,m,CH2CH3 ), 4 . 2 6 ( 3 H , S , C H 3 ) , 4 . 2 7 ( 3 H , S , C H 3 ) , 4 . 3 3 ( 6 H , S , C H 3 ) , 4 . 6 5 ( 3 H , S , C H 3 ) , 4 . 7 5 ( 8 H , m , C H 2 C H 3 ) , 5 . 3 0 ( 2 H , q , J = 7 . 5 H z , JOCH^CHg), 1 2 . 1 6 ( 2 H , S , m e s o - H ) , 1 2 . 2 3 ( l H , S , m e s o - H ) , 1 2 . 4 0 ( l H , S , m e s o - H ) , 13.43(lH ,S,meso-H), -4.23(lH,bs,NH), - 4 . 4 8 ( 1 H , S ) , - 4 . 5 5(lH , b s , N H ) , - 4 . 5 8( lH , b s , N H ) , -4.61(lH,bs,NH) 1 3 C - n m r : (6,30%TFA/CDC1 3) : 1 3 . 0 3 7 , 1 4 . 4 9 8 , 1 7 . 5 9 8 , 1 7 . 6 9 5 , 1 7 . 8 7 5 , 2 0 . 7 4 7 , 2 0 . 8 0 0 , 2 7 . 2 8 5 , 2 9 . 7 1 0 ( 1 4 C ) , 6 3 . 7 9 2 ( 1 C , 0 C H 2 C H 3 ) , 9 6 . 1 6 7 , 9 6 . 5 2 9 , 9 8 . 4 5 2 , 101.170, 1 0 1 . 6 8 3 , (5C, meso C ) , 1 3 1 . 5 0 9 , 1 3 6 . 2 2 0 , 137.713, 1 3 8 . 2 4 7 , 1 3 9 . 6 8 9 , 1 4 0 . 1 0 5 , 1 4 0 . 5 2 9 , 1 4 1 . 0 9 3 , 141 ,431, 141 .613, 1 4 2 . 2 8 9 , 1 4 2 . 5 2 3 , 1 4 3 . 0 8 3 , 1 4 4 . 0 8 6 , 1 4 7 . 8 4 6 , 1 5 8 . 0 6 0 , 148,649 (20C, a - and B - c a r b o n s ) , 1 6 4 . 7 8 2 . Mass Spectrum: EI m/e ( r e l a t i v e i n t e n s i t y ) 6 4 1 ( m + , 1 . 8 ) , 642(m++2, 1 2 . 7 ) , 645(m + +4.12), 5 3 6 ( 1 0 0 ) , 5 0 8 ( 5 2 ) , 4 7 8 ( 6 3 ) , 1 2 2 ( 8 7 ) , 108(91) FAB m/e m+1+642, m+2=643 U V - V i s i b l e Spectrum: ( 0 . 2 mL TFA/CH2C12) X m a x ( n m ) 370 463 603 652 721 l o g e m a v 5 . 1 0 6.18 4 . 6 7 4 . 9 6 4 . 7 9 ( 0 . 1 mL Et 3 N/CH 2 Cl 2 ) X m a x ( n m ) 350 450 645 l o g e „ ¥ 5 .21 5 . 4 4 4 . 7 4 85 3,12-0imethoxycarbonylethyl-2,7,8,13,17,18,22,23- octamethylpentaphyrin (29) The synthesis and purification was carried out as described for compound 74. Tripyrrane dialdehyde 31 (50 mg, 0.1 mmoles) and dipyrromethane diacid (34mg, 0.11 mmoles) 32 were used. Yield 18 mg (27%). lH nmr: (6,30%TFA/CDC13) 3.68(4H,b,O12CH2C02CH3), 3.79(6H,S,C02CH3), 4.38(6H,S,CH3), 4.41(12H,S,CH3), 4.42(6H,S,CH3), 5.26(4H,b,gj2CH2C02CH3), 12.47(lH,S,meso-H), 12.48(2H,S, meso-H), 12.55(2H,S,meso-H), -5.10(2H,bs,NH), -5.17(1H,S,NH), 5.29(1H,S,NH), -5.22(H,bs.NH) 1 3C nmr: (6,TFA) 11.742, 11.870(bC,CH3), 21.912(40,0120^002013), 53.557(2C,0CH3), 99.4888. 99.111, 98.850(5C,meso-C), 139.458 139.889, 140.258, 140.317, 140.647, 144,700, 144.899, 144.929, 145.090, 145.194(lOC.a,0,BC), 179.989(1C,C0) Mass Spectrum: EI m/e (relative intensity) 674(m++2,36), 566.6(100), 494.5(89), 421.5(44), 108(78) FAB m/e,m+l=672, m+2=673 UV-Visible Spectrum: 645 706 3.94 3.66 ^max(nm) 375 458 590 l 09 emax 4.06 5.95 3.63 ^max(nm) 345 462 635 l 09 emax 4.56 4.78 3.76 86 Z i n c d e c a m e t h y l p e n t a p h y r r i n (72) Decamethylpentaphyrin 71 (20 mg. 3 . 8 x l 0 " 5 moles) was d i s s o l v e d i n s p e c t r a grade methanol (20 mL) and s t i r r e d i n the dark f o r 5 m i n u t e s . A s a t u r a t e d s o l u t i o n of z i n c a c e t a t e i n methanol (1 mL) and anhydrous sodium a c e t a t e (100 mg) were added and the r e s u l t i n g r e a c t i o n m i x t u r e was s t i r r e d a t room temperature f o r 5 hours and a l l o w e d t o stand at room temperature f o r 3 d a y s . U v - v i s i b l e s p e c t r o s c o p y was used t o f o l l o w the r e a c t i o n . Methylene c h l o r i d e (50 mL) was added, t h e s o l u t i o n washed t w i c e w i t h w a t e r (15 mL) d r i e d o v e r anhydrous magnesium s u l f a t e and evaporated a t room t e m p e r a t u r e i n vacuo t o g i v e a y i e l d o f 15 mg (67%). Mass Spectrum: EI m/e ( r e l a t i v e i n t e n s i t y ) 5 9 1 ( 3 ) , 484(100, 108(32) FAB m/e 591, 592 U V - V i s i b l e Spectrum: X m a v / n m v 388 395 468 495 600 628 655 87 Z i n c 2 - E t h o x y c a r b o n y l - 3 1 7 , 8 , 1 2 , 1 3 , 1 7 , 1 8 , 2 2 , 2 3 - n o n a m e t h y l p e n t a p h y r i n (73) 2 - E t h o x y c a r b o n y 1 , 3 , 7 , 8 , 1 2 , 1 3 , 1 7 , 1 8 , 2 2 , 2 3 - n o n a m e t h y 1 p e n t a p h y r i n 74 (15 mg, 2 . 6 x l 0 " 5 moles) i s d i s s o l v e d i n m e t h a n o l . S a t u r a t e d s o l u t i o n o f z i n c a c e t a t e (1 mL) and anhydrous sodium a c e t a t e (100 mg) was added and t h e r e a c t i o n c a r r i e d out as i n compound 72. Mass Spectrum: EI m/e ( r e l a t i v e i n t e n s i t y ) 5 4 2 ( 1 2 ) , 5 1 4 ( 3 ) , 484(5) FAB m/e 6 4 9 , 650 U V - V i s i b l e Spectrum: X m , n n v 362 398 474 485 485 465 590 88 4 . SPECTRAL ASSIGNMENTS 89 "4.1 ltt NMR DATA OF THE PENTAPHYRINS The p r o t o n nmr s p e c t r a o f t h e f o u r p e n t a p h y r i n s s y n t h e s i z e d d u r i n g t h e c o u r s e of t h i s work are i l l u s t r a t e d i n f i g u r e s 4 - 7 . The nmr spectrum o f each p e n t a p h y r i n was r e c o r d e d i n d e u t e r o c h l o r o f o r m - t r i f l u o r o a c e t i c a c i d (1 :1 v/v) u s i n g d e u t e r o c h l o r o f o r m as the i n t e r n a l s t a n d a r d r e f e r e n c e . The c h e m i c a l s h i f t s o f d e c a m e t h y l p e n t a p h y r i n 7J_, e x h i b i t e d a s i n g l e t resonance a t 6 12.49 c o r r e s p o n d i n g t o a s e t of f i v e methine (meso) p r o t o n s . The t e n p e r i p h e r a l methyl groups were o b s e r v e d as a s i n g l e t a t 6 4 . 4 1 w h i l e t h e i n n e r N-H p r o t o n s were s h i f t e d u p f i e l d as a s i n g l e t at 6 - 5 . 5 2 . These c h e m i c a l s h i f t s o f d e c a m e t h y l p e n t a p h y r i n compare w e l l w i t h t h e c h a r a c t e r i s t i c s e x h i b i t e d i n the nmr spectrum of o c t a m e t h y l p o r p h y r i n ( i n TFA) (6 1 0 . 9 8 , 3 . 7 8 , - 4 . 8 2 ) 6 3 f o r m e t h i n e , methyl and N-H p r o t o n s r e s p e c t i v e l y . With p e n t a p h y r i n 7 4 , the f i v e methine p r o t o n s gave s i g n a l s i n the r a t i o o f 2 : 1 : 1 : 1 a t 6 1 1 . 9 1 , 1 2 . 0 0 , 12.17 and 13.29 r e s p e c t i v e l y w h i l e compound 75 were at 6 1 2 . 1 6 , 1 2 . 2 3 , 12.40 and 13.43 w i t h the same r a t i o as o f compound 7_L The e f f e c t o f t h e e s t e r s i d e c h a i n on compounds 74 and 75 i s e v i d e n t i n the way i t a f f e c t s the resonance of the NH p r o t o n s i n comparison t o compound 71_. Whereas t h e NH p r o t o n s o f compounds 74 and 75 e x h i b i t e d resonance between 6 — 4 . 2 t o - 4 . 8 , t h a t of compound 7J_ i s a t 6 - 5 . 5 , showing t h e d e s h i e l d i n g a b i l i t y o f t h e e s t e r s i d e c h a i n . The m e t h y l and methylene p r o t o n s of e t h o x y c a r b o n y l , t h e e s t e r s i d e c h a i n o f compound 7 4 , gave a t r i p l e t o f 6 1 .95 and q u a r t e t a t 5.18 r e s p e c t i v e l y . The same p r o t o n s o f the e s t e r s i d e c h a i n of compound 75 gave a t r i p l e t a t 6 2 . 0 5 and a q u a r t e t a t 6 5 . 3 0 r e s p e c t i v e l y . The 90 . p r o t o n s o f t h e n i n e methyl groups o f compound 74_ e x h i b i t e d a r a t i o o f 2 :4 :2 :1 a t 6 4 . 1 3 , 4 . 1 5 , 4.19 and 4 . 5 1 . For compound 75 , t h e methylene p r o t o n s o f t h e e t h y l groups e x h i b i t e d a broad m u l t i p l e t a t 6 4 .75 and a n o t h e r m u l t i p l e t at 6 2.12 t o 2.21 w i t h the h i g h e s t peak a t 6 2.17 f o r t h e methyl p r o t o n s . The f i v e p e r i p h e r a l methyl groups showed resonance a t 6 4 , 2 6 , 4 . 2 7 , 4 . 3 3 , 4.65 o f r a t i o 1 : 1 : 2 : 1 . The c h e m i c a l s h i f t s o f compound 29 compared w e l l w i t h t h a t of d a t a 41 p u b l i s h e d i n l i t e r a t u r e . D e s p i t e the presence of the two p r o p i o n i c e s t e r s i d e c h a i n , t h e NH p r o t o n s r e s o n a n c e o c c u r between 6 — 5 . 1 t o - 5 . 2 w i t h a r a t i o of 2 :1 :1 :1 v e r y c l o s e to t h a t of compound 7J_. Thus the e s t e r s i d e c h a i n s have s m a l l d e s h i e l d i n g e f f e c t on the NH p r o t o n s . The f i v e meso p r o t o n s were observed as s i n g l e t s w i t h a r a t i o of i n t e n s i t i e s 1:2:2 a t 6 12 .47, 12.48, 12 .55. The e i g h t p e r i p h e r a l methyl groups gave s i n g l e t s of r a t i o 1:2:1 a t 6 4 . 3 8 , 4.41 and 4 . 4 2 . 91 92 93 94 95 "4.2 13C-NMR DATA OF THE PENTAPHYRINS 1 3 C nmr s p e c t r o s c o p y was used i n t h i s work p r i m a r i l y f o r t h e purpose of s u p p l e m e n t i n g p r o t o n nmr d a t a i n the c h a r a c t e r i z a t i o n o f the p e n t a p h y r i n s s y n t h e s i z e d . These a r e i l l u s t r a t e d i n f i g u r e s 8 - 1 1 . The s o l v e n t used was t r i f l u o r o a c e t i c a c i d e x c e p t f o r compounds 74 and 7_5 where 30% t r i f l u o r o a c e t i c a c i d i n d e u t e r o c h l o r o f o r m was used ( v / v ) . A l l t h e compounds were found to be u n s t a b l e i n a c i d . The 1 3 C r e s o n a n c e s o f t h e p e n t a p h y r i n , l i k e p o r p h y r i n s c o u l d be d i v i d e d i n t o t h r e e major g r o u p s ; (1) the a - and 3 - p y r r o l i c c a r b o n s , (2) t h e meso o r methine c a r b o n s and (3) t h e a l i p h a t i c carbons o f t h e s u b s t i t u e n t s . The s i m p l e s t of t h e s e p e n t a p h y r i n , d e c a m e t h y l p e n t a p h y r i n 7J_ e x h i b i t e d o n l y two r e s o n a n c e s i n t h e a r o m a t i c r e g i o n a t 6 ~142.7 and 6 ~147.3 ppm p r o b a b l y due to 0- and a - c a r b o n s r e s p e c t i v e l y . The f i v e meso c a r b o n s as e x p e c t e d gave o n l y one peak a t 6 ~102 ppm w h i l e t h e t e n p e r i p h e r a l methyl c a r b o n s gave a resonance at 6 ~14.5 ppm. The f i v e meso c a r b o n s o f p e n t a p h y r i n 29 gave t h r e e r e s o n a n c e s a t 6 ~ 9 8 . 9 , ~ 9 9 . 1 , ~ 9 9 . 5 ppm. The methoxy c a r b o n was o b s e r v e d a t 6 ~ 5 3 . 6 ppm w i t h the c a r b o n y l e x h i b i t i n g resonance at 6 ~180 ppm. P e n t a p h y r i n 74 meso c a r b o n s gave f i v e peaks a t 6 ~ 9 7 . 5 , ~ 9 7 . 6 , - 9 9 . 5 , ~101.2 and ~101.6 ppm w i t h the methylene carbon of the e t h o x y a p p e a r i n g at 6 ~ 6 4 . 6 ppm and the c a r b o n y l o f t h e same s i d e c h a i n e x h i b i t i n g resonance a t 6 ~ 1 6 5 . 5 ppm. L i k e p e n t a p h y r i n 74_, p e n t a p h y r i n 75_ methine c a r b o n s a l s o gave f i v e peaks a t 6 - 9 6 . 2 , 9 6 . 5 , 9 8 . 5 , - 1 0 1 . 2 and - 1 0 1 . 7 ppm. The c a r b o n y l and methylene carbons o f the e t h y l o x y c a r b o n y l s i d e c h a i n gave r e s o n a n c e s at 6 - 1 6 4 . 8 and - 6 3 . 8 ppm r e s p e c t i v e l y . 97 98 99 100 4.3 MASS SPECTRA OF PENTAPHYRINS AND DERIVATIVES A l l t h e p e n t a p h y r i n s and t h e metal d e r i v a t i v e s o f two o f them s y n t h e s i z e d d u r i n g the c o u r s e of t h i s work were s u b j e c t e d t o the f a s t atom bombardment and e l e c t r o n impact i o n i z a t i o n i n t h e mass s p e c t r o m e t e r and the s p e c t r a l are i l l u s t r a t e d i n f i g u r e s 12-17. The f a s t atom bombardment o f the p e n t a p h y r i n 75 e x h i b i t e d a peak a t 642 c o r r e s p o n d i n g to the m+1 p e a k , and m+2 peak a t 6 4 3 . E l e c t r o n impact i o n i z a t i o n o f t h i s compound showed an i n t e r e s t i n g p a t t e r n . The p a r e n t peak was e x h i b i t e d a t 641(m+ ) p l u s m+1, m+2, m+3, and m+4 peaks w i t h t h e h i g h e s t b e i n g m+2 and m+4 (12.66% and 12.16% o f base peak r e s p e c t i v e l y ) . T h i s h i g h m/e, up t o m+3 was not s u r p r i s i n g , r e f l e c t i n g t h e b a s i c i t y o f t h e p e n t a p h y r i n chromophore and p r o b a b l y p r o t o n a t i o n w i t h i n the mass s p e c t r o m e t e r 6 ^ . The same b e h a v i o u r was a l s o found when pc s a p p h y r i n was s u b j e c t e d t o mass s p e c t r o m e t r i c i n v e s t i g a t i o n . Three d i f f e r e n t Intense peaks were s u r p r i s i n g l y e x h i b i t e d at m/e 536 (base p e a k ) , 508 (51.33% o f base peak) and 478 (62.52% o f base p e a k ) . These t h r e e peaks were c a l c u l a t e d to be the parent peaks (m+) of p o r p h y r i n s 76_, 77 and 78 r e s p e c t i v e l y . 101 S i n c e th-is p e n t a p h y r i n c o n t a i n s t h r e e d i f f e r e n t p y r r o l e s , the n u c l e u s a p p a r e n t l y r e a r r a n g e s t o p o r p h y r i n n u c l e u s w i t h a l o s s o f a m o n o p y r r o l i c fragment f o r the t h r e e d i f f e r e n t m a s s e s . Peaks at m/e 704 and 697 c o r r e s p o n d i n g t o m+1 peaks o f copper and i r o n complexes of t h e p e n t a p h y r i n were a l s o e x h i b i t e d . A l s o e x h i b i t e d were copper and i r o n complexes o f t h e p o r p h y r i n s . A l l the o t h e r p e n t a p h y r i n s e x h i b i t e d the same f r a g m e n t a t i o n p a t t e r n as d e s c r i b e d a b o v e . With p e n t a p h y r i n 74 t h e m+1 and m+2 peaks were o b s e r v e d at 586 and 587 r e s p e c t i v e l y 1n the f a s t atom bombardment. I n s t e a d o f the p a r e n t peak a t 585 ( m + ) , a 4.7% o f base peak a t 587 c o r r e s p o n d i n g to m+2 was e x h i b i t e d w i t h m+3 and m+4 ( w i t h 2.6% and 2.8% of base peak r e s p e c t i v e l y ) . Another f e a t u r e i s t h e peaks a t 480 and 422 (41.45% and 22.70% of base peak) c o r r e s p o n d i n g to the m+ peaks of m o n o e t h o x y c a r b o n y l h e p t a m e t h y l p o r p h y r i n 7j3 and o c t a m e t h y l p o r p h y r i n 8 0 . Peaks were a l s o e x h i b i t e d f o r i r o n and copper complexes of the p e n t a p h y r i n 74 and t h e p o r p h y r i n s . 79 80 102 The f a s t atom bombardment of compound 29 e x h i b i t e d the m+1 and m+2 peaks a t 672 and 673 r e s p e c t i v e l y . The e l e c t r o n impact i o n i z a t i o n e x h i b i t e d the m+1, m+2 and m+3 peaks w i t h the m+2 and m+3 peaks b e i n g 35.69% and 19.22% o f base peaks r e s p e c t i v e l y . The m+1 peaks w i t h copper and i r o n were e x h i b i t e d . As u s u a l , w i t h two d i f f e r e n t p y r r o l e s making up t h e p e n t a p h y r i n n u c l e u s , two d i f f e r e n t t y p e s of p o r p h y r i n peaks were e x h i b i t e d . The base peak of m/e 5 6 6 . 5 c o r r e s p o n d t o p o r p h y r i n 81_ w h i l e t h e p o r p h y r i n 82 w i t h m+ a t m/e 4 9 4 . 5 had 89% i n t e n s i t y o f t h e base peak. The copper and i r o n complexes of t h e s e p o r p h y r i n s had 19.1% and 11.8% ( r e l a t i v e t o t h e base peaks) i n t e n s i t i e s . With d e c a m e t h y l p e n t a p h y r i n 7J_, t h e m+1 and m+2 peaks at m/e 528 and 529 r e s p e c t i v e l y were e x h i b i t e d w i t h f a s t atom bombardment. E l e c t r o n impact i o n i z a t i o n e x h i b i t e d peaks a t m/e 476 and 484 w i t h no m+ or m+1 peak of the p e n t a p h y r i n . The observed p e a k s , m/e 476 and 4 8 4 , c o r r e s p o n d t o t h e m+ and m+1 peaks of i r o n and copper complexes o f o c t a m e t h y l p o r p h y r i n 8 0 . 103 I t must be noted t h a t t h e p r e s e n c e of both copper and i r o n i n t h e s p e c t r a i s more p r o b a b l y due t o t h e s c a v e n g i n g of metal i o n s by the p e n t a p h y r i n s f r o m t h e i o n s o u r c e i n t h e s p e c t r o m e t e r . The same b e h a v i o u r has been o b s e r v e d i n our l a b o r a t o r y w i t h m e t a l - f r e e p o r p h y r i n mass s p e c t r a . In t h e f a s t bombardment, z i n c d e c a m e t h y l - p e n t a p h y r i n 72 e x h i b i t e d peaks a t m/e 591 and 592. One i n t e r e s t i n g f e a t u r e w i t h t h e e l e c t r o n impact i o n i z a t i o n i s t h a t i t e x h i b i t e d a peak a t m/e 591 of about 2.7 % i n t e n s i t y of t h e base p e a k . The base peak happened t o be a t m/e 4 8 4 , t h e mass of z i n c o c t a m e t h y l p o r p h y r i n 8 3 . The p a t t e r n a t m/e 484 was t h e same f o r 5 9 1 . Thus, t h e c o m p l e x , l i k e t h e m e t a l f r e e p e n t a p h y r i n n u c l e u s , r e a r r a n g e s g i v i n g a z i n c complex o f t h e p o r p h y r i n w i t h a l o s s of m o n o p y r r o l i c f r a g m e n t . The z i n c complex of d e c a m e t h y l s a p p h y r i n was pc o b s e r v e d t o behave i n t h e same way . F o r compound 73_, peaks a t m/e 649 and 650 were e x h i b i t e d w i t h t h e f a s t atom bombardment. With e l e c t r o n impact i o n i z a t i o n , peaks a t m/e 649 and 651 were e x h i b i t e d . L i k e compound 7 2 , t h i s complex n u c l e u s r e a r r a n g e s t o g i v e t h e complex o f p o r p h y r i n s 79_ and 80_ a t m/e 542 and 484 r e s p e c t i v e l y . 83 L26264 Iff 8f 6f 4f 2f f i n at tt 4f 2f f Iff e« tf 4f 20 f L26264.39 tTIC-3693248. lffW692S61 Et 476 I I I I I |'II I I I 44f 4S6 'i'l'l'l' Plvi'l r r f 411 460 4 If I I I I | I I I I I I 6ff I I | I I I I I I I I I | I I I I I I I I I | II I I I I I I I | I I I 62* B4f S60 58f I I I | I I I I I I I I I | 6Bi 62f 372 311 33f 357 ['I'l'l'l I I'l I I | II I'l I I I I I |'l I I I I I | | | | | I i i ri') I i'l'l'l I I I I | I'l 1 I I I ITI'I'I I I I 3ff 320 340 36f 24f Wr\A\ 2Sf 69 28f 387 I I I I t l I I I I I I I I I I I I I I I I I I I II 38f 4ff 42f fif Ih'l'l^ l'Pl'i i'i'Wl'|'i I'l'Plll'I'ii'l'Pl'lTi 8f Iff 120 t7 U l |ilZ2 I |l Hi 11 H I 1111  • • 1 136 I'i'i'ri'l1 2fS 'I'h'i'ri'i'i'iTi'i'i'i'ri'i I'l'i'i'i'i'i'ii'i i rrl'i i I'I n'i'n I'p'i'i'I'i i ITI'I 14' 16f 18f 20f 220 240 Figure 12: Mass Spectra of 71 26400A.99 tTIC>1688600. 1>0X«3BB26] EI C0 2 E I i n 80 6* 40 20 0 100 8* (0 40 20 111 80 80 4* 20 0 S34 . 843 800 628 580 ,872 .887 ,641 i'"I i—i "I" i—p**!—i—i—i—|—i—i—i" i "['" i—i—i—i—|—i—i—i—i—|—i—r 878 800 825 880 876 700 480 422 278 408 276 67 68 300 .83 3 2 6 i r 376 -j—r 400 462 i'-|-1 [••••i r^'"| i 1 l'a^a i ' | ' i I - I " ? 1 ! " - ! ' i ' r- 'r ' i r"'i • • i I IL|•• i I '" I1 | 360 ill in I,in...i.11 i L u 426 460 476 94 108 123 !i i,|illl|lil.[iiii| I l|liiilii,i|llll|iiiv,.l|,i,l|li,l|,,l |n 128 160 176 200 226 260 60 76 100 11" ' r ' " i ' Figure 13: Mass Spectra of 74 12640C 100 9* «» 40 20 100 80 60 40 20 28406A.8I tTIC-2701440, I00W29181 Cl 3 0 0 c • 20 i i i , . i i r /PO T T - r r t r r 1 1 1 | - I ' H ' I 1 1 1 1 i » p r i 1 1 1 1 1 1 1 | 1 1 1 1 1 1 1 I ' l j - r r T r r 1 1 1 1 | 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 11 1 1 | r 1 1 1 1 1 1 1 1 | 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 620 «4t 880 III 720 741 780 780 Iff 43 . H M B 171 441 I 483 T-t'f'?-? 11 n'Pr-i 1 111'l'l'l-i 1 i-i-l' I'IVI'I 1 1 1 ' tn .821 44f 460 481 SH I'l 1 I - I ' I ' I - I - I - I rl'l' 8 3 8 •90, 820 I'l'fl I I I I I I I I - I ' I ' I 1 I I | I I ' l I'I'l 1 iVfn 1 1 1 1 I I 1 I 540 880 • 80 800 • «• Figure 14: Mass Spectra of 75 I f f I f I f 41 2f I f f M I f 4f 2 f LZI3II.44 m c-MM72. l f f t ' t f > 2 4 ) II 11 iii11111111111111 [ 1111) i I 4 f «(> I' -I'K 111111111111111 j 11 i ' i 11 I I f 7f» 7 I f 300'C PMe I 1 1 1 11 1 1 11 111 11 11 11111 11 11 1111111 1 1 1 74J 7 l f 74* f M S i t 1 111111111 i-i 111 I'I'I I'I'1!1!1! 1 \i\ 44f 44* fl' I I I I | I I I I I I I 'I I | I I I'Y'I I A'V |' I I I I | I 11 I I I I I I I I 1 11 1 1 I I l'| I f f B2f I 4 f t t f III M f 121 l»f I f I f 4f 2f I f f M I f 4f 2f f 421 I I I I I I I I'l I I'l I I I'I'I I 24f 2 l f • I I I i ' l ' l ' l I I I I'l 1 2 I f M i l I I I I I I 1 I I I f f J 2 f I I I I I'l 'I I I I I 141 I I I I I I I I I l l f n-r+f! rm 911 I ' lWui 'M ' i I t " I f 13 'i'i I'l'ifl'iVi'irlVi'i'i in1! 11 I'I 1 I'I i'l'l'l 11 • I'l'iVi 1 •'I'l l'i l'i n'Pl'i l'i ['i'l'l'l 1 •i'l i n 2 " 2 f f Figure 15: Mass Spectra of 29 Figure 16: Mass Spectra of 72 L26368.S6 (TIOI063744. 10f(.41087] £1 100 80 6f 4* 20 0 100 80 60 40 20 0 100 •0 60 40 20 0 614 500 828 642 649 680 1 1 1 i 1 1 1 1 i 1 1 1 1 V 1 1 1 1 i 1 1 ' i I i i 6 7 6 " « ' » 650 .76 ' 7 „ 6 8278 484 275 2)6 i. 308 "I I " l I T -300 326 3tB " i — | — i — i — i — r 376 «B8 ,,469 400 "I—i—i—|—I—r-425 1 I ' ' 460 r _ r -478 69 .83 97 Ml O J i 60 75 100 129 •i.MiiilifiLhl.u,!.!,,i.t|„.^i..,..ph ...j, i | M [ ( >" ',7B 226 "I—I" 1*1*1 260 Figure 17: Mass Spectra of 73 110 4.4 ELECTRONIC ABSORPTION SPECTRA OF THE PENTAPHYRINS AND DERIVATIVES The v i s i b l e s p e c t r a o f p o r p h y r i n s , m e t a l l o p o r p h y r i n and t h e i r d e r i v a t i v e s i s a u s e f u l and c h a r a c t e r i s t i c p r o p e r t y . P o r p h y r i n s e x h i b i t a c h a r a c t e r i s t i c e l e c t r o n i c a b s o r p t i o n spectrum c o n s i s t i n g of one v e r y i n t e n s e band (e -lO^M^cm" 1 ) around 400 nm, known as t h e " S o r e t " band and f o u r l e s s i n t e n s e bands i n the r e g i o n from 500 - 700 nm. The S o r e t band i s observed i n a l l t e t r a p y r r o l e s i n which the n u c l e u s i s f u l l y c o n j u g a t e d and i s g e n e r a l l y regarded as a c h a r a c t e r i s t i c o f the m a c r o c y c l i c c o n j u g a t i o n . The r e l a t i v e i n t e n s i t i e s of the f o u r v i s i b l e bands are s e n s i t i v e t o t h e nature o f the p e r i p h e r a l s u b s t i t u e n t s . F a c t o r s which encourage i n c r e a s e i n n - e l e c t r o n d e n s i t y of the p e r i p h e r y of t h e p o r p h y r i n n u c l e u s cause s h i f t s t o l o n g e r wavelength i n the a b s o r p t i o n b o n d s ^ . Thus s h i f t s t o l o n g e r wavelength w i t h i n c r e a s e i n t e n s i t i e s are found as t h e e l e c t r o n - a t t r a c t i n g power ( f o r m y l , c a r b o x y l i c a c i d , e s t e r e t c . ) o f t h e s i d e c h a i n i n c r e a s e s . The p e n t a p h y r i n s s y n t h e s i z e d d u r i n g the c o u r s e of t h i s work e x h i b i t e d v ery i n t e r e s t i n g e l e c t r o n i c s p e c t r a as i l l u s t r a t e d i o n f i g u r e s 1 8 - 2 3 . The f r e e base p e n t a p h y r i n i s orange i n c o l o r but t u r n s green and y e l l o w i s h - g r e e n i n methanol and methylene c h l o r i d e r e s p e c t i v e l y . A drop o f TFA i n t o the methylene c h l o r i d e s o l u t i o n of the p e n t a p h y r i n t u r n s i t deep green and t h e y e l l o w i s h - g r e e n c o l o r can be o b t a i n e d a g a i n when a drop of t r i e t h y l a m i n e i s added. The pronated p e n t a p h y r i n g i v e s a deep b l u e c o l o r . The most s t r i k i n g f e a t u r e of the f r e e base ( i n the presence o f t r i e t h y l a m i n e ) and the t r i c a t i o n ( i n the presence o f t r i f l u o r o a c e t i c a c i d ) I l l s p e c t r a o f a l l the p e n t a p h y r i n s i s t h e i r d i s p l a y o f e x c e p t i o n a l l y s t r o n g u v - v i s i b l e a b s o r p t i o n . The f r e e base e x h i b i t t h r e e bands i n the r e g i o n from 330 t o 750 nm w i t h t h e e x c e p t i o n o f compound 7j_ which g i v e s f o u r b a n d s . The t r i c a t i o n s on the o t h e r hand e x h i b i t f i v e bands w i t h i n the same w a v e l e n g t h . In a l l c a s e s t h e S o r e t band i s observed between 450 t o 462 nm. The i n t e n s i t i e s of the a b s o r p t i o n bands of compound 75 are n o t i c e a b l y g r e a t e r than t h e o t h e r p e n t a p h y r i n s , w i t h t h e S o r e t i n p a r t i c u l a r b e i n g t e n t i m e s more i n t e n s e than the o t h e r s . Another i n t e r e s t i n g f e a t u r e o f 75 i s t h e s h i f t t o l o n g e r w a v e l e n g t h o f a l l t h e a b s o r p t i o n bands compared to the o t h e r s . The i n t e n s i t i e s and wavelengths o f t h e a b s o r p t i o n bands o b t a i n e d f o r p e n t a p h y r i n 29 are r e m a r k a b l y 41 d i f f e r e n t from the r e p o r t e d f i g u r e s . As what might be c a u s i n g t h e s e d i f f e r e n c e s i n wavelengths and i n t e n s i t i e s of the a b s o r p t i o n bands are not e a s y t o p r e d i c t , more a n a l y s e s ( e g . x - r a y s t u d i e s ) are needed b e f o r e a r e a s o n a b l e c o n c l u s i o n can be d r a w n . 1 Free-base Trication W A V E L E N G T H Figure 18: Electronic Absorption Spectra of 71 WAVELENGTH Figure 19; Electronic Absorption Spectra of 74 WAVELENGTH Figure 20: Electronic Absorption Spectra of 75 1 LU O Z -6 cn -4 < WAVELENGTH Figure 22; Electronic Absorption Spectra of 72 WAVELENGTH Electronic Absorption Spectra of 73 118 The s p e c t r a of the p e n t a p h y r i n s d i s c u s s e d so f a r p r o v i d e c o n f i r m a t i o n of t h e i r s t r u c t u r e s and a t t e s t t o t h e i r a r o m a t i c i t y . A l l t h e l H nmr s p e c t r a showed s t r o n g l y s h i e l d e d i n n e r N-H p r o t o n s and the p r o t o n s a t the p e r i p h e r y , meso-protons and 8-protons a r e s t r o n g l y d e s h i e l d e d . The a b i l i t y of t h e s e m a c r o c y c l e s t o s u s t a i n a l a r g e induce d i a m a g n e t i c r i n g c u r r e n t demonstrates the p r e s e n c e of a d e l o c a l i z e d a r o m a t i c u - s y s t e m . The p e n t a p h y r i n s k e l e t o n 84_ c o n t a i n s a t o t a l of 28 u - e l e c t r o n , so i f a l l t h e i t - e l e c t r o n s a r e d e l o c a l i z e d , t h e system would be a n t i - a r o m a t i c (4n + 2 = 2 8 , i . e . n = 6 . 5 ) which 1s not a whole number. A d e r e a l i z a t i o n scheme can be e n v i s a g e d however, where o n l y 22 * - e l e c t r o n s a r e d e l o c a l i z e d , t h u s 1n H u c k e l ' s (4n + 2) r u l e , n = 5. 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