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Oxygen transfer reaction from cyclic nitrones to triphenylphosphine 1962

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OXYGEN TRANSFER REACTION FROM CYCL IC NITRONES TO TRIPHENYLPHOSPHINE b y FRANCO AGOL IN I LAUREA IN CHEMISTRY UNIVERS ITY OF MODENA (1958) A THES IS SUBMITTED IN PART IAL FULF ILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SC I ENCE i n t h e D e p a r t m e n t o f CHEMISTRY 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 t h e r e q u i r e d s t a n d a r d THE UN IVERS ITY OF BR IT I SH COLUMBIA, J u l y , 1962. In presenting this thesis in p a r t i a l fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make i t 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 representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department of C / The University of British Columbia, Vancouver 8 , Canada. Date fj* • ( ( i i ) A B S T R A C T The compounds in the series from triphenylphosphine to triphenyTbismuthine were examined as acceptors in oxygen transfer reactions involving the l-pyrroline-l-oxides. Triphenylphosphine was found to offer a useful route from the l-pyrroline-l-oxides to the corresponding pyrrolines. The second part of this work is centred on the structural investigation of Sanno's "base (XV) ( l ) , obtained as a "by-product in the reductive cyclization of ethyl 2-acetyl-2-ethyl-U-methyl-3-nitromethyl valerate (ay -nitro- ketone) and, formulated "by the author as having the A* -pyrroline structure; this compound has since "been found to "be a cyclic nitrone (XVI). In the case of this complex nitrone, the oxygen transfer reaction to triphenylphosphine has "been successful, yielding two isomeric A' -pyrrolines. The isolation of a A -pyrroline structure is confirmation of the proposed cyclic nitrone (XVI) structure for Sanno's "base and •as this provides a practical application of this reaction in structural work as well as showing that triphenylphosphine w i l l reduce N-oxides in the presence of an ester group. ( i ) ACKNOWLEDGMENT I w o u l d l i k e t o e x p r e s s my deep a p p r e c i a t i o n t o D r s . R. Bo n n e t t and D. E. McGreer f o r t h e i r c o n s t a n t h e l p and encouragement d u r i n g t h i s work. ( i i i ) CONTENTS Page: Acknowledgment i A b s t r a c t i i Tab l e o f C o n t e n t s i i i T a b l e o f F i g u r e s v PART I : I n t r o d u c t i o n 1 R e s u l t s and D i s c u s s i o n 12 PART I I : I n t r o d u c t i o n 17 R e s u l t s and D i s c u s s i o n 22 EXPERIMENTAL: I . P r e p a r a t i o n of 2 , i 4 . , i 4 . - t r i m e t h y l - l - p y r r o l i n e from 2 , U , U - t r i m e t h y l - l - p y r r o l i n e - l - o x i d e 29 I I . P y r o l y s i s of 5 , 5 - d i m e t h y l - l - p y r r o l i n e - 1-oxide 30 I I I . P r e p a r a t i o n o f 5 , 5 - d i m e t h y l - l - p y r r o l i n e from the c o r r e s p o n d i n g n i t r o n e 31 IV. P r e p a r a t i o n o f 3 - m e t h y l - l - n i t r o - 2 - b u t a n o l 32 V. P r e p a r a t i o n of 2 - a c e t o x y - 3 - m e t h y l - l - n i t r o b u t e n e 32 V I . P r e p a r a t i o n o f 3 - r n e t h y l - l - n i t r o b u t e > n e - 2 33 V I I . P r e p a r a t i o n of E t h y l 2 - a c e t y l - 2 - e t h y l - U - m e t h y l - 3 - n i t r o m e t h y l v a l e r a t e 3*4- V I I I . P r e p a r a t i o n o f E t h y l U - e t h y l - 3 - i s o p r o p y l - 5 - m e t h y l - l - p y r r o l i n e - l - o x i d e - l ( - - c a r b o x y l a t e 3h ( i v ) Page: IX. P r e p a r a t i o n of E t h y l k-ethyl-3-isopropyl - 5 - m e t h y l - l - p y r r o l i n e - U - c a r b o x y l a t e 36 X. Oxygen t r a n s f e r r e a c t i o n to t r i p h e n y l - phosphine 38 X I . A n a l y s i s of the components 39 BIBLIOGRAPHY hi (v) TABLES AND FIGURES Page: TABLE I Oxygen transfer from 2,l+,U-trimethyl- 1-pyrroline-l-oxide 11+ FIGURE I Vapour phase chromatogram of the deoxygenation of Sanno's "base 28 1 I N T R ODD" C T I 0 N PART I The reduction of l - p y r r o l i n e - l - o x i d e s ( c y c l i c nitrone) to the corresponding pyrrolines has previously (2) "been car r i e d out i n two ways: 2,l+,I|.-trimethyl-l-pyrroline- 1-oxide, f o r example, on treatment with zinc and acetic acid gave a 6695 y i e l d of the corresponding pyrroline p i c r a t e , while a 15^ y i e l d was obtained when sulphur dioxide i n chloroform was the reducing agent. As the nitrones represent a reactive 1,3-system (3) and because of the necessity to stop the reduction at the pyrroline stage, investigations were carr i e d out to f i n d a suitable reducing agent, which would have to combine s e l e c t i v i t y , r a p i d i t y and effectiveness. This agent has been sought among the triphenyl derivatives of group V, p a r t i c u l a r l y since triphenylphosphine O' 2 has "been used successfully to remove oxygen from many substrates (k). Although phosphorus follows nitrogen i n Group V there i s very l i t t l e resemblance between the organic chemistry of these two elements. These d i s s i m i l a r i t i e s arise because of the lower electronegativity of phosphorus which permits stronger bond formation with oxygen and halogens and because of the greater r e a c t i v i t y of the unshared electrons on the tervalent phosphorus, which r e s u l t s i n a stronger tendency to the quinquavalency ( 5 ) . These are the main differences by which the organic chemistry of the phosphorus i s r i c h e r than that of the nitrogen. In a l l i t s reactions the dr i v i n g force i s the tendency to the quinqua- valency, tendency that can be i l l u s t r a t e d through numerous examples as i n the Arbusov reaction ( 6 ) , where t r i a l k y l phosphites react with halogen derivatives to give d i a l k y l - alkyl-phosphonates and halogen derivatives, according to the scheme: RO RO- 0 + R'X R RO This reaction provides a useful route to prepare some a l k y l halides which are not otherwise r e a d i l y accessible. Another example i s the Michealis reaction (7 ) where a l k a l i 3 metal derivatives of dialkylphosphites react with a l k y l halides to give d i a l k y l alkylphosphonates: That the "bond "between phosphorus and oxygen, which i s formally written as double "bond, does, i n f a c t , have a considerable amount o f double bond character i s shown by i t s dipole moment, by i t s short length and by i t s resemblance to the carbonyl group i n producing o< -methylene r e a c t i v i t y . For t h i s reason the bond is probably better represented as the hybrid: — P = 0 < * -p — o A l l the tervalent phosphorus compounds are susceptible to oxidation ( 8 ) . This is p a r t i c u l a r l y true of those i n which the phosphorus atom has attached to i t a l k y l groups which, since they are electron r e p e l l i n g , increase the already high electron density on the phosphorus atom. Triphenylphosphine i s outstanding among the triphenyl derivatives of Group V. A comparison of the dipole moments: D i p o l e moments o f the t r i p h e n y l d e r i v a t i v e s Group V Ph,N Ph,P Ph,As PkuSb P h , B i 3 3 3 3 3 0.22 D 1.U5 D 1.07 D 0.57 D 0.00 D shows t h a t as the s e r i e s i s descended the d i p o l e moments de c r e a s e s t e a d i l y and so the n u c l e o p h i l i c c h a r a c t e r (9) a l s o d e c r e a s e s . T h i s has been once e x p l a i n e d (10) on the grounds of an i n c r e a s e i n c o n j u g a t i o n t h a t i s e x p e c t e d p a s s i n g from a t r i a n g u l a r p y r a m i d arrangement as i t i s i n t r i p h e n y l p h o s p h i n e , where the phosphorus i s l o c a t e d a t the apex o f the p y r a m i d , t o the p l a n a r t r i a n g u l a r arrangement o f t r i p h e n y l b i s m u t h i n e . However, on the b a s i s o f a s t u d y o f the U.V. s pectrum o f t r i p h e n y l a r s i n e , C u l l e n (11) has r e c e n t l y s u g g e s t e d t h a t t h e r e i s l i t t l e o r no c o n j u g a t i o n o f the l o n e p a i r o f a r s e n i c w i t h the p h e n y l groups and t h a t the same i s t r u e f o r the compounds Ph }M (-here M = P , S b , B i ) , as t h e i r s p e c t r a resemble t h a t o f t r i p h e n y l a r s i n e . A c u r r e n t i n t e r p r e t a t i o n i s t h a t as the s e r i e s i s descended the l o n e p a i r o r b i t a l a c q u i r e s more " s " c h a r a c t e r w h i c h l e a d s t o a subsequent d e c r e a s e i n b o t h the d i p o l e moment and the n u c l e o p h i l i c c h a r a c t e r . A l t h o u g h t r i p h e n y l p h o s p h i n e r e a c t s v e r y s l o w l y a t o r d i n a r y c o n d i t i o n s w i t h a t m o s p h e r i c oxygen (12), i t s c a p a c i t y t o a b s t r a c t oxygen from th o s e s u b s t r a t e s where t h e r e i s a v a i l a b l e an oxygen atom weakly bonded i s v e r y w e l l known. The r e a c t i o n o f b e n z o y l p e r o x i d e w i t h t r i - 5 p h e n y l p h o s p h i n e t o g i v e "benzoic a n h y d r i d e and t r i p h e n y l - p h osphine o x i d e was f i r s t d i s c o v e r e d by C h a l l e n g e r and W i l s o n ( 1 3 ) : 0 O 0 0 C 6H , G 0 OCC.H, * C.H.C-O-CC.H, - F\PO L a t e r , Shonberg r e p o r t e d t h a t d i b e n z o y l d i s u l f i d e was re d u c e d i n s i m i l a r f a s h i o n t o d i b e n z o y l s u l f i d e ( l l + ) . R e c e n t l y , Horner and J u g e l e i t (15) have made a th o r o u g h s t u d y o f the r e a c t i o n o f s e v e r a l t y p e s o f p e r o x i d e s w i t h t r i - s u b s t i t u t e d p h o s p h i n e s . I n g e n e r a l , a l l the compounds i n v e s t i g a t e d r e a c t w i t h t r i p h e n y l p h o s p h i n e t o g i v e p r o d u c t s i n v e r y h i g h y i e l d and p u r i t y . Hydrogen p e r o x i d e i s reduced r a p i d l y i n e t h e r e a l s o l u t i o n t o g i v e w a t e r and t r i p h e n y l p h o s p h i n e o x i d e . n - B u t y l h y d r o p e r o x i d e r e a c t s w i t h s t r o n g e x o t h e r m i c r e a c t i o n t o g i v e the c o r r e s p o n d i n g a l c o h o l i n 9Cr% y i e l d and i n s i m i l a r f a s h i o n t e t r a l i n a l c o h o l has been o b t a i n e d i n 98% y i e l d f r om t e t r a l i n h y d r o p e r o x i d e . An o l e f i n i c h y d r o p e r o x i d e was a l s o r e d u c e d s e l e c t i v e l y w i t h no a f f e c t t o the double bond. On the o t h e r hand, d i a l k y l p e r o x i d e s are i n g e n e r a l v e r y r e s i s t a n t t o r e d u c t i o n and o n l y i n the case o f the q u a l i t a t i v e r e d u c t i o n o f d i e t h y l p e r o x i d e t o d i e t h y l e t h e r has i t been r e p o r t e d . Horner c l a i m e d t h a t d i - t - b u t y l p e r o x i d e a f t e r s e v e r a l hours o f h e a t i n g a t 111-120° w i t h t r i p h e n y l p h o s p h i n e 6 gave the corresponding ether: ( C H A ) 4 C O O C ( C H , \ PhiP However, this reaction has "been reinvestigated "by Walling (16) and i t has "been shown that the reaction goes "by a free radical mechanism and triphenylphosphine does not participate. Horner reported also the satisfactory reduction of ozonides; cyclo- hexane ozonide gave the corresponding dialdehyde in 70% yield: An endo peroxide (ascaridol) was reduced to the corresponding endo oxide: C H + CH CHj CH, C H , C H , The reduction of acyl peroxides, peracids, peresters, proceeds 7 smoothly. In general, a l l these reactions proceed rapidly at room temperature in solvents such as pentane or ether. A free radical mechanism for these reactions does not seem l i k e l y as (a) there is no attack on the solvent (b) the products of the reaction do not correspond to those of the known radical decomposition of peroxides (c) the reaction is not prevented by the addition of radical inhibitors. Horner has suggested that the reaction proceeds by the formation of an i n i t i a l adduct between triphenylphosphine and the peroxide and then subsequent attack by triphenyl- phosphine on one oxygen with the formation of a phosphonium ion, which can then combine to give the product and triphenylphosphine oxide according to the scheme: R O O R ' -. p h jp ROOR' •— ^ RC? 0—R 'PPh © e RO R' Ph3PO -* ROR + PhjPO Since these reactions proceed rapidly in non polar solvents conditions which are unfavourable for ionic reactions, Hoffmann (17 ) investigated the reaction to determine how free any formed ions were, i f indeed any ions were formed 8 a t a l l . He p o s t u l a t e d the f o r m a t i o n o f an i o n - p a i r whose r a t e of c o l l a p s e depends t o a l a r g e degree on the p o l a r i t y o f the s o l v e n t . I n n o n - p o l a r s o l v e n t s the c o l l a p s e i s q u i t e r a p i d as compared t o more p o l a r s o l v e n t s where t h i s i o n - p a i r i s " l o o s e " enough so t h a t a f o r e i g n i o n can i n t e r v e n e t o a l a r g e r degree and a l t e r the n a t u r e of the p r o d u c t s . The e f f e c t i v e n e s s of t r i p h e n y l p h o s p h i n e as a s e l e c t i v e r e d u c i n g agent has a l s o "been t e s t e d on those s u b s t r a t e s where t h e r e i s an oxygen atom weak l y bonded. T r i m e t h y l a m i n e o x i d e (h) r e a c t s i n h o t g l a c i a l a c e t i c a c i d t o g i v e q u a n t i t a t i v e l y t r i m e t h y l a m i n e and t r i p h e n y l p h o s p h i n e o x i d e : * \ e © p. p \ y / C H 3 C H » I t has been o b s e r v e d t h a t the ease of removal of the oxygen from the amine o x i d e s d e c r e a s e s w i t h the d i p o l e moment. P y r i d i n e - N - o x i d e and q u i n o l i n e - N - o x i d e are r e s i s t a n t , however, they have been r e d u c e d (18) by m i x i n g the r e a g e n t s t o g e t h e r i n absence o f s o l v e n t and u s i n g a Wood's m e t a l b a t h : Ph,P + PhjPO l\J 9 The q u a n t i t a t i v e r e d u c t i o n o f a z o x y b e n z e n e (19) t o a z o b e n z e n e was e f f e c t e d a t 1 5 0 ° : ® Ph P C 6 H , N = N C , H r • CtH,N=l\ICtHf * P K 5 P 0 0 ® I o d o s o b e n z e n e was r e d u c e d t o i o d o b e n z e n e ( 2 0 ) : C 6 H,I0 K > P > Q H , I + a4Po No r e a c t i o n was o b s e r v e d w i t h n i t r o c o m p o u n d s , a l t h o u g h a deep c o l o u r d e v e l o p e d on m i x i n g n i t r o b e n z e n e and t r i p h e n y l p h o s p h i n e . R e c e n t l y (21) i t h a s b e e n r e p o r t e d t h a t n i t r o a r o m a t i c compounds r e a c t w i t h p h o s p h i n e i n the p r e s e n c e o f b a s e t o g i v e a z o x y b e n z e n e i n 96% y i e l d : 0 ° *C6H,N0, — ^ * C tH fN = NC eH f 0 H © The p o s s i b i l i t y t h a t e v e n t r i p h e n y l p h o s p h i n e m i g h t b e u s e d w i t h s u c c e s s c a n n o t be d i s r e g a r d e d . The r e d u c t i o n o f a n a l d o n i t r o n e (h) a n d o x a z i r a n s (22) has b e e n n o t e d : 1 0 o 0 R-N = CH-R' P h* P > R-N = CH-R - P^PO ® E t h y l e n e o x i d e s a r e more r e s i s t a n t , however, t h e y have "been r e d u c e d a t 1 5 0 ° t o the c o r r e s p o n d i n g o l e f i n s (k): \ / Pv>, P \ / ; c — < — - — > > = < - P ^ P O T r i p h e n y l p h o s p h i n e r e a c t s a t 1 5 0 ° i n o-xylene w i t h N - s u b s t i t u t e d t r i c h l o r o a c e t a m i d e s t o g i v e the c o r r e s p o n d i n g v i n y l a m i n e i n good y i e l d ( 2 3 ) : CI o C l a CI C C N > C = C + Pu PO / \ / \ 1 E t h y l e n e and s u b s t i t u t e d e t h y l e n e c a r b o n a t e s r e a c t w i t h t r i p h e n y l p h o s p h i n e (21+) g i v i n g the o l e f i n c o r r e s p o n d i n g t o the c a r b o n a t e used. E t h y l e n e c a r b o n a t e and t r i p h e n y l - 11 phosphine heated over the temperature range 130-200° i n the absence of solvent gave triphenylphosphine oxide in 93$ yield and the olefin in 68$ yield: C H t 0 \ C=0 C H , / O Ph.P PhiP0 «• L0t • C H ^ C H , With higher molecular weight carbonates, phosphine oxidation and subsequent olefin synthesis occur only i f a catalyst is used. Large ring carbonates do not react. The use of triphenylarsine as an oxygen acceptor has not been so extensively investigated although the satis- factory reduction of acyl peroxides to the corresponding anhydrides has been reported (U). No information appears to be available concerning the applicability of triphenyl- stibine and triphenylbismuthine as oxygen acceptors. 12 RESULTS AND DISCUSSION PART I A c o n v e n i e n t method has been sought f o r the r e d u c t i o n of n i t r o n e s t o p y r r o l i n e s w h i c h would a v o i d aqueous o r a c i d i c c o n d i t i o n s and w h i c h , moreover, would g i v e the p r o d u c t d i r e c t l y under c o n d i t i o n s t h a t c o u l d y i e l d a minimum o f s t r u c t u r a l changes. Such a p r o c e s s i s r e q u i r e d f o r example i n ca s e s where the p r o d u c t o f a p r e p a r a t i v e sequence i s the 1 - p y r r o l i n e - l - o x i d e from w h i c h i t i s t h e n d e s i r e d t o make the p y r r o l i n e . Oxygen t r a n s f e r f r o m n i t r o g e n t o compounds o f o t h e r elements o f Group V s u g g e s t e d i t s e l f as a p o t e n t i a l method, e s p e c i a l l y s i n c e t r i p h e n y l p h o s p h i n e has been used s u c c e s s f u l l y t o 0 remove oxygen from many s u b s t r a t e s . The r e d u c t i o n o f an a l d o n i t r o n e has been noted b u t no i n f o r m a t i o n appears t o be a v a i l a b l e c o n c e r n i n g the a p p l i c a b i l i t y o f the r e a c t i o n t o p u r e l y a l i p h a t i c n i t r o n e s , i n c l u d i n g the 1 - p y r r o l i n e - 1 - o x i d e s . 2 , 4 , ^ - t r i m e t h y l - l - p y r r o l i n e - l - o x i d e ( I ) was chosen as a model compound and was f o u n d t o be reduced by t r i p h e n y l p h o s p h i n e . I n o r d e r to determine the b e s t c o n d i t i o n s f o r the r e d u c t i o n e x p e r i m e n t s were c a r r i e d out under a v a r i e t y o f c o n d i t i o n s . I t was found t h a t the r e a c t i o n d i d not p r o c e e d t o a u s e f u l degree i n r e f l u x i n g 13 benzene or toluene. The reaction occurred r a p i d l y , when the substances were heated together with a free flame, and the product, 2,U , U-trimethyl-l-pyrroline ( I I ) was d i s t i l l e d d i r e c t l y from the reaction mixture: CH.- — I A I. C H , I I -CH, PhlPO A s i m i l a r r e s u l t was obtained with triphenylarsine. With trip h e n y l s t i b i n e and triphenylbismuthine, however, extensive decomposition was evident, and i n the l a t t e r case the main product i n the d i s t i l l a t e was benzene. Triphenylphosphine oxide was i s o l a t e d from the residue thus confirming that the reaction involves oxygen transfer to phosphorus. The results are summarized and some comparisons drawn i n Table I. These res u l t s were not surprising, because i t was expected that as this series was descended the decreasing s t a b i l i t y of b6th the carbon-metal bond and metal-oxygen bond would intervene at some stage and give side reactions which would make the reaction useless as a preparative method. Ik TABLE I Oxygen T r a n s f e r From 2,U ,1+-Trimethyl- 1 - P y r r o l i n e - l - O x i d e . R e a c t i o n E f f e c t o f Weight of % Y i e l d Reagent W i t h H e a t i n g D i s t i l l a t e % Y i e l d o f CH,1 (25) A l o n e * (g) P i c r a t e / P h 3 P R a p i d R e f l u x e s 0.66 75 57 Ph 3As Slow R e f l u x e s S l i g h t Decorap. 0.61 70 U2 Ph,Sfe 5 N i l Decomp. 0.1k # 3k P h , B i N i l Decamp. 1.6 # Trace * Under the r e a c t i o n c o n d i t i o n s . One-G-ram p o r t i o n s o f n i t r o n e h e a t e d w i t h a n e q u i m o l a r amount o f the r e a g e n t . / P r e p a r e d i n m o i s t e t h e r . # D i s t i l l a t e e x t e n s i v e l y c o n t a m i n a t e d b y d e c o m p o s i t i o n p r o d u c t s o f the o r g a n o m e t a l l i c compounds. 15 I t was found that when the nitrone was heated alone with a free flame for 10 minutes there was a complete recovery of unchanged s t a r t i n g material. This would exclude at once the p o s s i b i l i t y of a p y r o l y t i c deoxy- genation, a process which has been observed with c e r t a i n amine oxides as for example K-methylpipefidine-N-oxide ( 2 6 ) : The reaction was also applied to 5 , 5-dimethyl-l- pyrroline-l-oxide ( i l l ) , a c y c l i c aldonitrone. In contrast to the c y c l i c ketonitrone, I, which i s f a i r l y stable to heat, 5 , 5-dimethyl-l-pyrroline-l-oxide i s thermolabile. The decomposition i s attended by the development i n the i n f r a r e d spectrum of a broad absorption band i n the 1660 cm-' region. This has l e d to the supposition that isomerization to the corresponding lactam may be one of the reactions involved: CH A 16 However, the oxygen transfer reaction evidently proceeds more rapidly than the isomerization, for the reaction gave a 65% yield of the crude 5 ,5-dimethyl-l-pyrroline (IV) (39% yield as the picrate) and triphenylphosphine oxide (57%) was isolated from the residue: I I I IV 17 I N T R O D U C T I O N PART I I Sanno ( l ) reported that i n the c y c l i z a t i o n of ethyl 2-acetyl - 2-ethyl-U-methyl - 3-nitromethyl valerate ( V ) , with zinc and acetic acid, there was i s o l a t e d as a "by- product a compound which he claimed to he the ethyl U-ethyl - 5-hydroxy - 3-isopropyl - 5-methyl-A - p y r r o l i n e - U-carboxylate ( V I ) : C ^ COOC»Hff N C H 3 CH,- 2n /CHjCOOH HO o / CH, CH NO, V V I T h i s f o r m u l a t i o n may he q u e s t i o n e d on the b a s i s o f the f o l l o w i n g more r e c e n t e x p e r i m e n t a l work. Of the f i v e p o s s i b l e s t r u c t u r e s ( V I I - X l ) w h i c h can be w r i t t e n f o r 2 - s u b s t i t u t e d p y r r o l i n e s o n l y A and A* have been shown c o n c l u s i v e l y t o e x i s t : 18 i H i H N' i H VII VUI IX There i s no c o n t r o v e r s y c o n c e r n i n g the e x i s t e n c e and the i d e n t i t y o f A * - p y r r o l i n e s ( 2 7 ) . Compounds of t h i s s t r u c - t u r e a re the u s u a l , h u t not the e x c l u s i v e ( 2 8 , 29) p r o d u c t s o b t a i n e d from the p a r t i a l r e d u c t i o n of s u b s t i t u t e d p y r r o l e s . However, c o n f u s i o n has c e n t r e d around the e x i s t e n c e o f A' - p y r r o l i n e s ( V I I and X I ) and A * - p y r r o l i n e s ( V I I I and X ) . S e v e r a l workers (30-36) have a r b i t r a r i l y a s s i g n e d a A - s t r u c t u r e t o t h e i r compounds, w h i l e C l o k e (37, 38) s u g g e s t e d e i t h e r the A o r A* form or a t a u t o - m e r i c m i x t u r e of the two. The q u e s t i o n has been r e c o n s i d e r e d r e c e n t l y (39 - U 3 ) , and i n g e n e r a l the c o n c l u s i o n has been drawn t h a t these s u b s t a n c e s e x i s t p r e d o m i n a n t l y i n the A' -form. B o t h c h e m i c a l and p h y s i c a l e v i d e n c e s have been adduced t o s u p p o r t t h i s f o r m u l a t i o n . The Z e r e w i t i n o f f d e t e r m i n a t i o n s (kht U3) have p r o b a b l y been the most s i g n i f i c a n t c h e m i c a l e v i d e n c e s i n c e they have shown t h a t i n the examples s t u d i e d , l i t t l e o r no a c t i v e hydrogen was i m m e d i a t e l y a v a i l a b l e . P h y s i c a l e v i d e n c e has been b a s e d on a number of s t u d i e s o f u l t r a v i o l e t s p e c t r a ( U 6 ) , 19 b u t t h e most s i g n i f i c a n t r e s u l t s have come from i n f r a r e d s t u d i e s (39, U l , 1+2, 1+1+). I n g e n e r a l , the p y r r o l i n e s have shown l i t t l e o r no a b s o r p t i o n i n the N-H s t r e t c h i n g r e g i o n , b u t a s t r o n g band, a t t r i b u t e d to C = N a b s o r p t i o n , i s p r e s e n t i n the 1620-1650 cm"' r e g i o n . The s t r e n g t h o f the C = N a b s o r p t i o n band, and e s p e c i a l l y the absence o f N-H a b s o r p t i o n a r e o f c o n s i d e r a b l e i m p o r t a n c e . I n the l a t t e r a r e a d i f f i c u l t i e s have a r i s e n i n c e r t a i n i n s t a n c e s . Thus, Evans (1+0) r e p o r t e d t h a t 2 - m e t h y l p y r r o l i n e showed a weak band a t 3.02yu , and B u r c k h a l t e r and S h o r t (1+1) c o n s i d e r e d a s i m i l a r band a t 3 . 0 5 - 3 .10 jx i n the spectrum o f 2 - b e n z y l p y r r o l i n e t o be anomalous s i n c e the compound d i d not c o n t a i n a c t i v e hydrogen. Other workers have c o n s i d e r e d t h a t " t h e N-H r e g i o n o f the i n f r a r e d a b s o r p t i o n s p e c t r a o f p y r r o l i d i n e s and p y r r o l i n e s i s d i f f i c u l t t o i n t e r p r e t " (1+1+, 1+7), and i t i s , of c o u r s e , t r u e t h a t a b s o r p t i o n i n t h i s r e g i o n c o u l d be caused by s p e c i e s , n o t a b l y t r a c e s o f m o i s t u r e o r o f dimer, o t h e r t h a n the 2 - p y r r o l i n e , w h i c h i s presumed t o be t a u t o m e r i c w i t h the A' -form. F o r t u n a t e l y , p r o t o n m a g n e t i c resonance p r o v e d a v e r y u s e f u l t o o l . B o n n e t t and M C G r e e r (1+8) showed f o r a number o f cases t h a t the p y r r o l i n e s i n q u e s t i o n d i d not g i v e a s i g n a l i n the o l e f i n i c p r o t o n r e g i o n ( 2 . 0 - 5 . 5 t ) e and t h i s was c o n s i s t e n t . w i t h o n l y t h a t s t r u c t u r e c o n t a i n i n g the double bond i n the d - p o s i t i o n s i n c e a l l p o s s i b l e tautoraers would have a t l e a s t one o l e f i n i c p r o t o n . The 20 p r o t o n m a g n e t i c resonance s p e c t r a have s t r o n g l y r e i n f o r c e d p r e v i o u s c o n c l u s i o n s r e g a r d i n g the A - s t r u c t u r e o f the p y r r o l i n e s i n v e s t i g a t e d . F u r t h e r m o r e , B o n n e t t and McGreer i n v e s t i g a t e d the p y r r o l i n e - l - o x i d e s , w h i c h a re the f i r s t monomeric non- a r o m a t i c n i t r o n e s p r e p a r e d by Todd (1+9) "by r e d u c t i o n of j»- n i t r o c a r b o n y l compounds w i t h z i n c and ammonium c h l o r i d e . Todd e t a l (2) a s s i g n e d them the A" - s t r u c t u r e . B o t h c h e m i c a l and p h y s i c a l e v i d e n c e s have been adduced t o s u p p o r t t h i s f o r m u l a t i o n . I n f a c t , the n i t r o n e s were r e a d i l y r e d u c e d to c y c l i c s e condary h y d r o x y l a m i n e by aqueous KBH^; by t r e a t m e n t w i t h z i n c and a c e t i c a c i d they gave t h e A' - p y r r o l i n e , w h i l e w i t h t i n and h y d r o c h l o r i c a c i d t h e y gave the c o r r e s p o n d i n g p y r r o l i d i n e . The s t r u c t u r e s were s u p p o r t e d by the p h y s i c a l p r o p e r t i e s t h a t t h e s e compounds showed a s i n g l e u l t r a v i o l e t a b s o r p t i o n maximum a t 229-235 (£ ~ 9 0 0 0 ) a t t r i b u t a b l e t o the yC = N - 0 chromophore and they e x h i b i t s t r o n g i n f r a r e d a b s o r p t i o n , the f r e q u e n c y r a n g i n g from 1600 t o 1620 cm"' f o r those b e a r i n g a 2 - a l k y l s u b s t i t u e n t and fr o m 1570 t o 1590 cm"' when no such s u b s t i t u e n t s were p r e s e n t . B o n n e t t and McGreer c o n f i r m e d the assignment u s i n g N.M.R. methods; the l a c k o f s i g n a l i n the o l e f i n i c p r o t o n r e g i o n i s c o n s i s t e n t o n l y w i t h s t r u c t u r e (XII) 1 c o n t a i n i n g the double bond i n the A - p o s i t i o n s i n c e i t s 21 isomer (XIII) would have an o l e f i n i c proton: N 0 N' O H XII XIII 22 RESULTS AND D ISCUSS ION PART I I S anno ( l ) r e p o r t e d the p r e p a r a t i o n o f a compound C ^ H ^ N O ^ , f o r m u l a t e d a s X V , b y t he f o l l o w i n g r o u t e : - CHj C H - I / \ CH, •CH, X I V cw / CH> p COOCiHs C H CH,- N C H , H O J I C H ^ h K XV 23 Much of the chemical evidence for this structure i s summarized in the scheme I below: CH,- HO y CH, l I H <** LOO*** ^ CH. CH, 0 I O = C I C H , COCH, SCHEME I Bonnett et al ( 5 0 ) have proved that compound XV is not a A' -pyrroline but is instead the corresponding 1-pyrroline- 1-oxide (XVI): C H t - C H j - ^CH» XVI 2h and have reinterpreted the reactions as indicated in Scheme II: N 0" © CHy CH, N A CH 3 C«i cooCi«* ^ CH, ^ C H , l " I O C O C H , O.c CHj, SCHEME II 25 The r e s u l t s o b t a i n e d below s t r o n g l y r e i n f o r c e the c o n c l u s i o n r e a c h e d b y B o n n e t t . The s u g g e s t i o n t h a t the Sanno p r o d u c t XV was a n i t r o n e p r o v i d e d an o p p o r t u n i t y f o r the a p p l i c a t i o n o f t h e oxygen t r a n s f e r r e a c t i o n w i t h t r i p h e n y l p h o s p h i n e . Of p a r t i c u l a r i n t e r e s t was the p o s s i b i l i t y t o i n v e s t i g a t e t h e r e a c t i o n on a compound c o n t a i n i n g the e s t e r group. F o r p urposes of c o mparison the p y r r o l i n e was p r e p a r e d by Sanno's p r o c e d u r e ( l ) : \ CH. CHj .CH NCH c H i COOCj^S  1 CH, CH. CH \ I CH,- r u 0 / C " 3 M O , CH, N S i n c e by o r d i n a r y d i s t i l l a t i o n i t was not p o s s i b l e t o e l i m i n a t e the n i t r o n e p r e s e n t as i m p u r i t y , the p y r r o l i n e was p u r i f i e d by v a p o r phase chromatography. The chromato- gram i n d i c a t e d the p r e s e n c e of two components i n r a t i o 55 t o h5%, the i n f r a r e d s p e c t r a of which showed s t r i k i n g s i m i l a r i t i e s e x c e p t i n the f i n g e r p r i n t r e g i o n , i n d i c a t i n g t h a t t h e s e were c i s and t r a n s i s o m e r s . The N.M.R. s p e c t r a o f b o t h were so s i m i l a r t h a t no f i r m c o n c l u s i o n c o u l d be e drawn as to the s t e r / o c h e m i s t r y o f each i s o m e r . The i m p o r t a n t r e s u l t was t h a t n e i t h e r o f the components p o s s e s s e d a b s o r p t i o n i n the o l e f i n i c p r o t o n r e g i o n of the 26 s p e c t r u m . S i n c e a n a l y s i s o f the p i c r a t e s i n d i c a t e d t h a t t h e "bases were i s o m e r i c , t h e y are e v i d e n t l y t h e c i s and t r a n s - 1 - p y r r o l i n e s , f o r w h i c h the a b s o l u t e s t e r e o c h e m i s t r y i s s t i l l unknown: (A CH, CH, X V I I c i s and t r a n s The n i t r o n e XVI ( e t h y l U - e t h y l - 3 - i s o p r o p y l - 5 - m e t h y l - 1 - p y r r o l i n e - l - o x i d e - U - c a r b o x y l a t e ) was s u b j e c t e d to the d e o x y g e n a t i o n r e a c t i o n w i t h t r i p h e n y l p h o s p h i n e , and the p r o d u c t of t h e d i s t i l l a t i o n was p u r i f i e d by v a p o r phase chromatography, T r i p h e n y l p h o s p h i n e o x i d e was i d e n t i f i e d i n the r e s i d u e . The chromatogram of the d i s t i l l a t e (see p.28) i n d i c a t e d the p r e s e n c e of s i x components; two o f them were the e x p e c t e d two i s o m e r i c p y r r o l i n e s ( X V I I ) ; a t h i r d component was i d e n t i f i e d by i t s i n f r a r e d and N.M.R. s p e c t r a and f rom the a n a l y s i s o f i t s p i c r a t e t o be a n o t h e r p y r r o l i n e ( X V I I I ) i n which the c a r b o e t h o x y group a t p o s i t i o n k was not p r e s e n t . The o t h e r t h r e e comppnents were d e c o m p o s i t i o n p r o d u c t s and were not i d e n t i f i e d . The o x y g e n - t r a n s f e r r e a c t i o n had e v i d e n t l y been accompanied, t o the e x t e n t o f about 20$, by a p y r o l y t i c e s t e r e l i m i - 27 nation, followed by decarboxylation, a sequence not surprising i n view of the high temperatures involved. The reaction can be summarized as follows: CH, CH, CH, N A c«4 CHj c o o c ^ I CH- CH. 'CH, CH2 CHS l .C* / V C H 4 afcpo c i s and trans XVII X V I I I In order to prevent the py r o l y s i s of the ester, the nitrone was treated with triphenylphosphine i n anhydrous benzene and the mixture was refluxed for 15 hours. The oxygen transfer to triphenylphosphine did not occur since triphenylphosphine was recovered and a complete recovery of nitrone was obtained. These r e s u l t s show that Sanno's base i s a mixture of c i s and trans forms (which have been i s o l a t e d and characterized at the pyrroline oxidation l e v e l ) , and strongly support the view that Sanno's base has the nitrone and not the A -pyrroline structure. They also constitute the f i r s t a pplication of the oxygen transfer reaction to s t r u c t u r a l work i n the pyrroline s e r i e s . r 28 29 EXPER IMENTAL . I. P r e p a r a t i o n o f 2 , l + . U - t r i m e t h y l - l - p y r r o l i n e f r o m 2 « U t U - t r i m e t h y l - l - p y r r o l i n e - l - o x i d e . T 2 . i + . i f - ^ r i m e t h y l - l - p y r r o l i n e - l - o x i d e ( i ) was p r e p a r e d b y t h e p r o c e d u r e o f T o d d e t a l ( 2 ) . ( a ) The n i t r o n e ( I ) ( l g ) (0.0078 m o l e ) a n d E a s t m a n Kodak t r i p h e n y l p h o s p h i n e ( m . p . 79°) ( l i t . m . p . 79°) (51) ( 2 . 5 g ) (0.0095 m o l e ) were h e a t e d ( f r e e f l a m e ) i n a d i s t i l l a t i o n a p p a r a t u s . The v o l a t i l e l i q u i d w h i c h f o r m e d a f t e r a s h o r t t i m e was r e f l u x e d g e n t l y f o r a b o u t 15 m i n u t e s a n d t h e n d i s t i l l e d a t a t m o s p h e r i c p r e s s u r e , b . p . 1 10-130° (0.66 g 75%). The i n f r a r e d s p e c t r u m ( f i l m ) o f t h e b a s i c l i q u i d showed a b a n d a t 3620 cm" ' a t t r i b u t e d t o m o i s t u r e p r e s e n t i n t h e h y g r o s c o p i c s t a r t i n g m a t e r i a l , t o g e t h e r w i t h a s t r o n g s h a r p b a n d a t 1650cm ( C = N ) . NO n i t r o n e b a n d was p r e s e n t s i n c e no a b s o r p t i o n b a n d was f o u n d a t 1621 c m " , = N - 0 ) . The p i c r a t e , m . p . 1 9 5 - 1 9 6 ° , was p r e p a r e d i n e t h e r , a n d r e c r y s t a l l i z e d f r o m e t h a n o l . No d e p r e s s i o n was o b t a i n e d i n the m i x e d m e l t i n g p o i n t w i t h a n a u t h e n t i c s a m p l e o f t he p y r r o l i n e p i c r a t e o b t a i n e d b y t he p r o c e d u r e o f T o d d ejt a l ( 2 ) . The i n f r a r e d s p e c t r u m o f t h e two p i c r a t e s ( N u j o l m u l l ) we re i d e n t i c a l . 30 The residue (2.6 g) from the d i s t i l l a t i o n was extracted with cyclohexane and the solution treated with Norite. On cooling, colorless needles were formed and after crystallization from cyclohexane (0.6 g 23$) triphenylphosphine oxide, m.p. 156-158° was obtained ( l i t . m.p. 156°) (51). (b) In three t r i a l experiments the reaction was repeated as above, except that the phosphine was replaced by equimolar quantities of triphenylarsine, triphenylstibine and triphenylbismuthine (Eastman Kodak). In the last two cases decomposition products from the organometallic compound were present in the d i s t i l l a t e s . The results of these experiments are indicated in Table I. II. Pyrolysis of 5.5-dimethyl-l-pyrroline-l-oxide. 5,5-^imethyl-l-pyrroline-l-oxide was prepared by the procedure of Todd et al (2). A sample of 5,5-dimethyl-l-pyrroline-l-oxide was heated in a closed flask in an o i l bath at 100° and the infrared spectrum of the mixture was taken at intervals. During the course of 3 hours a peak at about 1660 cm"', very weak i n i t i a l l y , increased slightly in intensity. After a further hour at 180° the sample became very dark. The peak at 1660 cm-1 had become very sharp and strong 31 w h i l s t the i n i t i a l peak o f the n i t r o n e a t 1575 cm <s> © ()C = N - 0) was now a b s e n t . Thermal p y r o l y s i s i s t h e r e f o r e s l o w a t 100° b u t measurable a t 180°. The p y r o l y s i s p r o d u c t was not i d e n t i f i e d . I I I . P r e p a r a t i o n of 5 , 5 - d i m e t h y l - l - p y r r o l i n e ( IV) from the c o r r e s p o n d i n g n i t r o n e I I I . 5 , 5 - ^ i m e t h y l - l - p y r r o l i n e - l - o x i d e ( I I I ) ( l g) (0.0088 mole) was t r e a t e d w i t h t r i p h e n y l p h o s p h i n e (2.62 g) (0.01 mole) as above, and the v o l a t i l e l i q u i d b o i l i n g up t o 10k° was c o l l e c t e d as crude 5 , 5 - d i m e t h y l - l - p y r r o l i n e (IV) (0.55 g 6 5 $ ) , the i n f r a r e d spectrum of w h i c h showed a sh a r p peak a t 1618 cm"' ( C = N ). That n i t r o n e band was p r e s e n t - 1 © © was shown by the l a c k o f a band a t 1575 cm (^C = N-0). The y i e l d was not improved by u s i n g a Wood's m e t a l b a t h a t 300° i n p l a c e o f a f r e e f l a m e . A f t e r p u r i f i c a t i o n by vapor phase chromatography the p r o d u c t had the same i n f r a r e d spectrum as a s i m i l a r l y p u r i f i e d sample o f the a u t h e n t i c base p r e p a r e d a c c o r d i n g t o the pr o c e d u r e of Todd e_t a l ( 2 ) . The p y r r o l i n e I V (0.37 g) was t r e a t e d w i t h a s a t u r a t e d s o l u t i o n of p i c r i c a c i d i n m o i s t e t h e r t o g i v e the p i c r a t e (1.13 g 37%) w h i c h was i d e n t i c a l w i t h an a u t h e n t i c sample. The r e s i d u e (2.5 g) was d i s s o l v e d i n a v e r y s m a l l q u a n t i t y o f methanol (5 ml) and t h i s s o l u t i o n was po u r e d onto a column o f d r y a l u m i n a . E l u t i o n w i t h p e t r o l - e t h e r (65-110°) gave c o l o r l e s s n e e d l e s , which were c r y s t a l l i z e d from c y c l o - • 32 hexane to give 1.52 g (57$) of triphenylphosphine oxide, m.p. 156-158°. IV. Preparation of 3-methyl-l-nitro - 2-butanol. To a mixture of 100 g (1.63 mole) of nitromethane, 11.h g (0.082 mole) of potassium carbonate and 70 ml of water, there was added dropwise, with s t i r r i n g at a temperature kept below 50° (the reaction i s s l i g h t l y exothermic - no heating i s needed) 76 g (1 .05 mole) of isobutyraldehyde. As the reaction proceeded the mixture became red-orange. After the addition the reaction mixture was s t i r r e d at room temperature f o r a further 2 hours. Then i t was cooled i n an ice bath and brought to a ptf of 3 hy adding d i l u t e hydrochloric acid. The r e s u l t i n g mixture was extracted with ether, washed with water, aqueous sodium bicarbonate and again with water. The ethereal extract was dried over magnesium su l f a t e , then concentrated and d i s t i l l e d under reduced pressure to give 105 g (80$) of the n i t r o alcohol (b.p.g 72-7U° , n^ 5 1.104-62) ( l i t . (52) b.p.g 7 2 - 7 U ° ) . The product showed inf r a r e d bands at 3U72 cm""' (OH), 1560 cm"' (asymmetric N0 2) and 1387 cm-' (symmetric N0 2). V. Preparation of 2-acetoxy-3-methyl-l-nitrobutane. To a solution of 100 g (0.75 mole) of the n i t r o - alcohol i n 65 ml of chloroform there was added dropwise 33 w i t h s t i r r i n g a t room t e m p e r a t u r e 59 g (0 . 7 5 m o l e ) o f a c e t y l c h l o r i d e d i s s o l v e d i n 60 m l o f c h l o r o f o r m . A f t e r t he a d d i t i o n was c o m p l e t e d , t h e r e a c t i o n m i x t u r e was r e f l u x e d f o r 2 h o u r s a n d t h e n a l l o w e d t o s t a n d o v e r n i g h t . The s o l v e n t was d i s t i l l e d o f f a n d the o i l t h u s o b t a i n e d was d i s t i l l e d u n d e r r e d u c e d p r e s s u r e to g i v e 120 g (91%) o f p r o d u c t ( b . p . 0 > 5 7 8 - 8 0 ° , n 2 5 1 . 4 3 4 5 ) ( l i t . (52) * . p . 2 . 5 8 2 - 8 5 ° , 1 . U 3 U 5 ) . The i n f r a r e d s p e c t r u m showed b a n d s a t 1754 c m " ' ( C = 0 ) , 1563 c m " ' ( a s y m m e t r i c N O g ) , 1381 cm"" 1 ( s y m m e t r i c N 0 2 ) a n d 1238 cm"" ( C - 0 a c e t a t e g r o u p ) . V I . P r e p a r a t i o n o f 3 - m e t h y l - l - n i t r o b u t e n e - 2 . The o l e f i n was p r e p a r e d b y a p r o c e d u r e s i m i l a r t o t h a t r e p o r t e d b y D r a k e and R o s s ( 5 3 ) . A m i x t u r e o f 110 g ( 0 . 628 m o l e ) o f the n i t r o a c e t a t e , 69 g ( 0 . 7 2 8 m o l e ) o f a n h y d r o u s s o d i u m c a r b o n a t e and 800 m l o f b e n z e n e were s t i r r e d v i g o r o u s l y u n d e r r e f l u x u n t i l no more w a t e r was c o l l e c t e d i n a w a t e r - t r a p c o n n e c t e d to t h e r e f l u x i n g f l a s k . A f t e r 6 h o u r s t h e r e a c t i o n was c o m p l e t e d . The e x c e s s o f s o d i u m c a r b o n a t e and t h e s o d i u m a c e t a t e were f i l t e r e d o f f and washed w i t h b e n z e n e . The s o l v e n t was d i s t i l l e d o f f and the o i l d i s t i l l e d u n d e r r e d u c e d p r e s s u r e t o g i v e 50 g (72 .3%) o f o l e f i n ( b . p . 1 3 6 6 - 6 7 ° ) ( l i t . (52) b . p . ^ 3 6 6 - 6 7 ° ) . The i n f r a r e d s p e c t r u m showed b a n d s a t 1 6 5 0 c m " ' ( C = C ) , 1538 c m " 1 ( N O g ) a n d 1357 c m " ' ( N O g ) . 3k V I I . P r e p a r a t i o n of E t h y l 2 - a c e t y l - 2 - e t h y l - U - m e t h y l - 3 - n i t r o m e t h y l v a l e r a t e ( V ) . 1 - E t h y l a c e t o a c e t i c a c i d e t h y l e s t e r was p r e p a r e d by a s i m i l a r p r o c e d u r e t o t h a t r e p o r t e d by R o b i n s o n (5U) . To a s o l u t i o n of 76 g (C-.I4.8l mole) o f 1 - e t h y l a c e t o - a c e t i c a c i d e t h y l e s t e r i n l i i O ml anhydrous e t h e r and kO ml 2% NaOEt-EtOH t h e r e was added 3 6 . 5 g (0.385 mole) of 3 - m e t h y l - l - n i t r o b u t e n e - 2 i n 1+0 ml anhydrous e t h e r dropwise w i t h s t i r r i n g a t room t e m p e r a t u r e . A f t e r the a d d i t i o n was completed 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 3 hours and t h e n a l l o w e d t o s t a n d a t room tem p e r a t u r e f o r 2k h o u r s . Then the s o l u t i o n was n e u t r a l i z e d w i t h a c e t i c a c i d , d i l u t e d w i t h w a t e r and e x t r a c t e d w i t h e t h e r . The e t h e r e x t r a c t was washed w i t h 8% sodium b i c a r b o n a t e , w i t h w a t e r and t h e n d r i e d o ver magnesium s u l f a t e . A f t e r e v a p o r a t i o n o f the s o l - v e n t , the o i l was d i s t i l l e d under r e d u c e d p r e s s u r e t o g i v e 36 g (kl.6%) o f p r o d u c t b . p ^ 135° ( l i t . (52) b . p ^ 1 3 5 ° ) . V I I I . P r e p a r a t i o n o f E t h y l k - e t h y l - 5 - i s o p r o p y l - 5 - m e t h y l - 1 - p y r r o l i n e - l - o x i d e - U - c a r b o x v l a t e . (XVI) To a m i x t u r e of 10 g (0.036 mole) o f e t h y l 2 - a c e t y l - 2 - e t h y l - U - m e t h y l - 3 - n i t r o m e t h y l v a l e r a t e , 2 g (0.373 mole) o f ammonium c h l o r i d e i n 60 ml t e t r a h y d r o f u r a n and 20 ml o f w a t e r , t h e r e was added p o r t i o n w i s e 13.1+ g o f z i n c d u s t w i t h v i g o r o u s s t i r r i n g w h i l e the temperature was k e p t between 25-30° . A f t e r t h e a d d i t i o n was completed the 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 3 h o u r s . The s o l i d was th e n f i l t e r e d o f f and washed w i t h 60 ml o f hot me t h a n o l . The f i l t r a t e was c o n c e n t r a t e d and then d i s t r i b u t e d between 50 ml o f 5N h y d r o c h l o r i c a c i d and 50 ml of e t h e r . The e t h e r l a y e r was d i s c a r d e d and the aqueous l a y e r was made a l k a l i n e by the a d d i t i o n o f p o t a s s i u m h y d r o x i d e . The b a s i c p r o d u c t was e x t r a c t e d s e v e r a l times from the aqueous s o l u t i o n w i t h d i c h l o r o m e t h a n e and the di c h l o r o r a e t h a n e s o l u t i o n was d r i e d over magnesium s u l p h a t e . The s o l v e n t was d i s t i l l e d o f f and the r e s i d u a l o i l was d i s t i l l e d a t re d u c e d p r e s s u r e t h r o u g h a V i g r e u x column t o g i v e 5.5 g (63.7%) o f a v e r y v i s c o u s y e l l o w - g r e e n l i q u i d b.p.^ 180-182°. The p r o d u c t showed u l t r a v i o l e t a b s o r p t i o n ( d e t e r m i n e d i n 95% e t h a n o l s o l u t i o n ) # © © a t A max 237.5 (£ = 7935) ()C = N—0 chromophore) and the i n f r a r e d spectrum o f the pure l i q u i d ( f i l m ) showed a band a t 1608 cm ()C = N — 0 ) . The N.M.R. spectrum d e t e r m i n e d i n C C l ^ showed a q u a r t e t c e n t r e d a t 5.86T (CHg i n COOCHgCH^) an u n r e s o l v e d b r o a d band i n the r e g i o n 8 t o 8.35 £(corres- p o n d i n g t o 5 H), a t r i p l e t c e n t r e d a t 8.75s (CH^ i n COOCHgCH^) and two s i n g l e t s a t 9.05 and 9.15?, and no peaks a t t r i b u t a b l e t o o l e f i n i c hydrogen atoms. The p i c r a t e was made fr o m a s a t u r a t e d s o l u t i o n o f p i c r i c a c i d i n e t h a n o l and a f t e r c r y s t a l l i z a t i o n f r o m e t h a n o l i t had m.p. 106-107° ( l i t . (52) m.p. 102°). 36 I X . P r e p a r a t i o n o f E t h y l U - e t h y l - ^ - i s o p r o p y l - S - m e t h y l - 1 - p y r r o l i n e - i j — c a r b o x y l a t e . (XIV) To a m i x t u r e o f 17 g (0.062 mole) of e t h y l 2 - a c e t y l - 2 - e t h y l - 4 - m e t h y l - 3 - n i t r o m e t h y l v a l e r a t e i n 90 ml of a c e t i c a c i d t h e r e was added p o r t i o n - w i s e 23.35 g z i n c d u s t w i t h v i g o r o u s s t i r r i n g w h i l e the temperate was k e p t a t 85-90°. A f t e r the a d d i t i o n was completed the 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 2 hours on a steam b a t h . Then i t was po u r e d i n t o h.00 ml of c o o l water and n e u t r a l i z e d w i t h sodium h y d r o x i d e and e x t r a c t e d s e v e r a l times w i t h e t h e r . The e t h e r e x t r a c t was c o n c e n t r a t e d and d i s t r i b u t e d between 50 ml 1 N h y d r o c h l o r i c a c i d and 50 ml of e t h e r . The e t h e r l a y e r was d i s c a r d e d w h i l e t h e aqueous l a y e r was made a l k a - l i n e and t h e n e x t r a c t e d w i t h e t h e r . The e t h e r e x t r a c t was d r i e d o ver magnesium s u l f a t e and t h e n c o n c e n t r a t e d t o a r e s i d u a l o i l w h i c h was d i s t i l l e d under r e d u c e d p r e s s u r e . Two f r a c t i o n s were c o l l e c t e d ; the f i r s t one (6 g) b o i l i n g a t 100-107°/3 mm and the second one (2 g) a t 178-183°/3 mm. The i n f r a r e d spectrum o f the f i r s t crude f r a c t i o n e x h i b i t s a s t r o n g band a t 16U7 cm"*' ( C = N) t o g e t h e r w i t h a s m a l l - I 0 ®v a l t h o u g h s h a r p band a t 1608 cm ( NC = N — 0 ) . The i n f r a r e d s p e c t r u m o f the second f r a c t i o n showed a s t r o n g band a t 1608 cm"'. Thus the f i r s t f r a c t i o n was m a i n l y p y r r o l i n e and t h e second f r a c t i o n was the 1-oxide p r e p a r e d above. The u l t r a v i o l e t spectrum of the second f r a c t i o n ( d e t e r m i n e d i n 95$ e t h a n o l s o l u t i o n ) showed a maxima a t 237.5 tyx. 37 U = 7935) (;c = N - 0 ) . The p i c r a t e , m.p. 106-107°, of t h i s l a s t f r a c t i o n was made as b e f o r e and t h e r e was no d e p r e s s i o n f o r a m i x t u r e m e l t i n g p o i n t w i t h the p i c r a t e o f e t h y l i + - e t h y l - 3 - i s o p r o p y l - 5 - m e t h y l - l - p y r r o l i n e - l - o x i d e - l + - c a r b o x y l a t e . The N.M.R. o f the 1-oxide f r a c t i o n ( d e t e r m i n e d i n C C l ^ ) showed no a b s o r p t i o n a t t r i b u t a b l e t o o l e f i n i c hydrogen. The f i r s t f r a c t i o n was r e d i s t i l l e d t h r e e t i m e s , b u t i t was not p o s s i b l e t o e l i m i n a t e the 1-oxide i m p u r i t y . A t t h i s s t a g e , a gas chromatogram t h r o u g h a 5 - f t Uconpolar column a t 175° w i t h a h e l i u m f l o w r a t e of 67 cc./min. gave two peaks a t 15, 16.3 min. i n r a t i o 55 t o hb%, d e t e r m i n e d by the we i g h t o f paper c u t s o f the peaks ( t h e 1-oxide was not e l u t e d a t t h i s t e m p e r a t u r e ) . S e p a r a t i o n gave each w i t h a p u r i t y of 95 and 91% r e s p e c t i v e l y . The i n f r a r e d s p e c t r a ( f i l m s ) of these two components showed a b s o r p t i o n bands a t 1733 can"' ( C = 0) and a t 1647 cm"' ( C = N) common t o b o t h o f them b u t i t r e v e a l e d a l s o s i g n i f i c a n t d i f f e r e n c e s i n t he f i n g e r p r i n t r e g i o n : t h u s , the f i r s t component had a b s o r p t i o n bands a t 1309. 111+2 and 971 cm"' w h i c h were not p r e s e n t i n the spectrum o f the second base. The 1-oxide band a t 1608 cm""' was now ab s e n t . I t i s thus apparant t h a t the two components are i s o m e r i c p y r r o l i n e s . The N.M.R. spectrum d e t e r m i n e d i n C C l ^ showed f o r t h e f i r s t component a q u a r t e t c e n t r e d a t 5.85 ? ( C H 2 i n -COOCHgCH^), an u n r e s o l v e d b r o a d band between 7.8 and 8.5^ ( c o r r e s p o n d i n g 38 t o 5 H ) , a t r i p l e t a t 8.75 ? (CH, i n COOCH_CEL) and two 3 c. 3 s i n g l e t s a t 9 . 0 5 ? and 9.15 2" . The N.M.R. f o r the second component showed a q u a r t e t c e n t r e d a t 5 . 8 5 t ( C H 2 in-COOCHgCH^) an u n r e s o l v e d "broad hand a t 7 .8 and 8 .5 ? ( c o r r e s p o n d i n g t o 5 H ) , a t r i p l e t a t 8.75 T (CH^ i n -COOCHgCH^) and two s i n g l e t s a t 9 .05 2" and 9.15? and no a b s o r p t i o n a t t r i b u t a b l e t o o l e f i n i c h ydrogen. I t was c o n c l u d e d t h a t these two components a r e -the Wa s c i s and t r a n s i s o m e r s b u t A a b s o l u t e geometry^not d e t e r m i n e d . The p i c r a t e of t h e f i r s t component was p r e p a r e d from a s a t u r a t e d s o l u t i o n o f p i c r i c a c i d i n e t h a n o l and was r e c r y s t a l l i z e d t h r e e t i m e s , m.p. 1 5 9 - 1 6 1 ° . The i n f r a r e d s p e ctrum o f the p i c r a t e ( N u j o l m u l l ) showed bands a t 1629 cm"' ( C = N ) , 1695 cm"' ()C = N - H) and a t 1745 cm"' 1 ( C = 0 ) . A n a l . - C a l c d . C ^ H g g N ^ : C, 5 0 . 2 1 ; H, 5 .77; N, 1 2 . 3 3 . Pound: C, 5 0 . 3 2 ; H, 5 . 8 4 ; N, 1 2 . 4 2 . The p i c r a t e o f the second f r a c t i o n was p r e p a r e d i n a s i m i l a r manner, m.p. 1 5 0 - 1 5 1 ° . The i n f r a r e d spectrum ( N u ^ o l m u l l ) was s i m i l a r w i t h t h a t o f the f i r s t component. O - f - t K e « s o r t e r \ C pierrs.-te5 The m i x e d m e l t i n g p o i n t ^ w a s 148-149° ( l i t . ( l ) m.p. 144 ) A n a l . - Pound: C, 5 0 . 2 0 ; H , 5 . 8 4 ; N, 1 2 . 4 0 . X. Oxygen t r a n s f e r r e a c t i o n t o t r i p h e n y l p h o s p h i n e . E t h y l - 3 - i s o p r o p y l - 4 - e t h y l - 5 - m e t h y l - l - p y r r o l i n e - l - o x i d e - 4 - c a r b o x y l a t e ( l g) (0.00415 mole) and t r i p h e n y l - p h o s p h i n e (1.3 g) (0.00475 mole) were h e a t e d ( f r e e f l a m e ) 39 i n a d i s t i l l a t i o n a p p a r a t u s . The m i x t u r e "became dark a f t e r 10 m i n u t e s . I t was r e f l u x e d f o r 15 minutes and then d i s t i l l e d , t o g i v e 0.1+66 g b.p. 81+-1800, o f p r o d u c t . S i x components were i d e n t i f i e d by vapor chromatography o f t h i s p r o d u c t u s i n g a 5-ft U c o n p o l a r column a t 170°. The p e r c e n t a g e o f the t o t a l p r o d u c t s was d e t e r m i n e d by the w e i g h t s o f paper c u t s of the peaks. The r e s i d u e (1.1+ g) from the t r i p h e n y l - phosphine r e a c t i o n was d i s s o l v e d i n c y c l o h e x a n e , h e a t e d w i t h N o r i t e and gave, on c o o l i n g , 0.58 g (1+2.31+$) o f t r i p h e n y l p h o s p h i n e o x i d e m.p. 156-158° ( l i t . (51) m.p. 156°). X I . A n a l y s i s o f the v o l a t i l e components. I s o l a t i o n of the f i r s t component (19.6$ of the t o t a l ) gave a compound w h i c h was shown by chromatography t o have a p u r i t y o f 97$.' The i n f r a r e d s p ectrum showed a s t r o n g peak a t 161+7 cm - 1 ( C = N) and no a b s o r p t i o n i n the c a r b o n y l r e g i o n . The N.M.R. spectrum ( d e t e r m i n e d i n C C l ^ ) d i d not have a s i g n a l i n the o l e f i n i c p r o t o n r e g i o n and the q u a r t e t and the t r i p l e t o f the CR"2 and CH^ o f the c a r b o e t h o x y group were not p r e s e n t . I t i s apparant t h a t e s t e r p y r o l y s i s and d e c a r b o x y l a t i o n has o c c u r r e d . The p i c r a t e was made i n the u s u a l manner, m.p. 128-129°. The i n f r a r e d spectrum o f the p i c r a t e ( N u j o l m u l l ) showed bands a t I63I+ cm"' ( C = N) and 1681+ cm"' ()C = I - H). A n a l . - C a l c d . C-^H^N^O-, : C,50.21+; H,5.80; N,ll+.65. Pound: C,50.2i+; H,5.75; N,ll+.60. ho The chromatogr .am gave t he s e c o n d , t h i r d a n d f o u r t h c o m p o n e n t s i n t h e f o l l o w i n g p e r c e n t a g e r a t i o : 1 0 . 5 - 1 0 . 5 - 1 7 . 9 . T h e s e t h r e e c o m p o n e n t s c o u l d n o t he i s o l a t e d i n s u f f i c i e n t p u r i t y f o r i d e n t i f i c a t i o n . The l a s t two c o m p o n e n t s o b t a i n e d i n the f o l l o w i n g p e r c e n t a g e r a t i o : 23.27 a n d 1 8 . 1 6 were i d e n t i f i e d b y means o f t h e i r i n f r a r e d s p e c t r a , N . M . R . s p e c t r a and p i c r a t e s , a n d f o u n d t o b e i d e n t i c a l w i t h t h e two i s o m e r i c p y r r o l i n e s i s o l a t e d f r o m t h e z i n c d u s t and a c e t i c a c i d r e d u c t i o n o f e t h y l 2 - a c e t y l - 2 - e t h y l - U - m e t h y l - 3 - n i t r o m e t h y l v a l e r a t e . The p i c r a t e s ( m . p . 1 5 9 - 1 6 1 ° a n d 1 5 0 - 1 5 1 ° r e s p e c t i v e l y ) showed no d e p r e s s i o n i n m . p . when m i x e d w i t h t h e two c o r r e s p o n d i n g p y r r o l i n e s p r e p a r e d b y s y n t h e s i s . hi BIBLIOGRAPHY 1. Y. 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