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UBC Theses and Dissertations

A C14 tracer study of the Friedel-Crafts alkylation. 1956

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A C l l f TRACER STUDY OF THE FRIE DEL-CRAFTS ALKYLATION by ALLAN GUY FORMAN A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE I n the Department of CHEMISTRY We accept t h i s t h e s i s as conforming t o the standards r e q u i r e d from candidates f o r the degree of MASTER OF SCIENCE Members of the department of Chemistry THE UNIVERSITY OF BRITISH COLUMBIA August, 1956 i i ABSTRACT A n i s o l e was a l k y l a t e d w i t h 2-phenylethanol-l- and 2 - p h e n y l e t h y l - l - C l ^ c h l o r i d e r e s p e c t i v e l y , using aluminum c h l o r i d e as c a t a l y s t , to give p-methoxydibenzyl. R a d i o a c t i v i t y assay of the p-methoxydibenzyl and of the a n i s i c a c i d obtained by o x i d a t i v e degradation w i t h a l k a l i n e permanganate showed th a t a 50$ rearrangement of C1** from the C-1 t o C-2 p o s i t i o n s occurred w i t h both a l k y l a t i n g agents. The r e a c t i o n may proceed by means of e l e c t r o p h l l i c a t t a c k o f a f r e e carbonium i o n , or by a n u c l e o p h i l i c a t t a c k of a n i s o l e on a p o l a r i z e d complex between the a l k y l a t i n g agent and c a t a l y s t , I f i t may be assumed that the observed rearrangement has taken place during the formation of the p o l a r i z e d complex. The p o s s i b i l i t y e x i s t s that the rearrangement may a r i s e from a process separate from the a l k y l a t l o n r e a c t i o n i t s e l f * ACKNOWLEDGEMENTS The author wishes t o express h i s a p p r e c i a t i o n of the as s i s t a n c e and advice given by Dr. C. C. Lee during the course of t h i s research and i n the pre p a r a t i o n of the man- u s c r i p t . Determination of the r a d i o a c t i v i t y counts by Mary A. S t r e l i o f f i s g r a t e f u l l y acknowledged. TABLE OF CONTENTS Page ACKNOWLEDGEMENTS i ABSTRACT . i i HISTORICAL INTRODUCTION 1 THE PROPOSED WORK 19 RESULTS AND DISCUSSION 21 EXPERIMENTAL . i i .. 29 BIBLIOGRAPHY 35 1. HISTORICAL INTRODUCTION The new i n t e r e s t i n j e c t e d i n t o organic chemistry by Fran- kland's d i s c o v e r y of organozinc compounds st i m u l a t e d a s e r i e s of s t u d i e s on the a c t i o n of v a r i o u s metals on a l k y l h a l i d e s , one of which r e s u l t e d i n the d i s c o v e r y of the F r i e d e l - C r a f t s r e a c t i o n (20). P r i o r to the observations of these i n v e s t i g - a t o r s , s e v e r a l cases of a l k y l a t i o n by means of metals and m e t a l l i c compounds had been reported. I n I 8 6 9 , Zincke (90) reported the s y n t h e s i s of d i p h e n y l - methane from benzyl c h l o r i d e and z i n c i n benzene s o l u t i o n . I n subsequent p u b l i c a t i o n s , (91,92,93) Zincke reported s i m i l a r syntheses. Doebner and Stackmann (16) found that z i n c oxide would introduce chloroform or phenyltrichloromethane i n t o phenol t o y i e l d s a l i c y l a l d e h y d e or o-benzoyl phenol. I t was pointed out that z i n c c h l o r i d e was formed during the r e a c t i o n . As F r i e d e l and C r a f t s l a t e r showed, (19) z i n c c h l o r i d e was the a c t i v e condensing agent i n a l l of these syntheses. I n benzene, the r e a c t i o n was observed to y i e l d w e l l - d e f i n e d substances w i t h a l k y l h a l i d e s . Short or long-chained alkylbenzenes were obtained using aluminum c h l o r i d e together w i t h v a r i o u s a l k y l h a l i d e s . I n every case, hydrogen h a l i d e was e l i m i n a t e d . In these e a r l y papers, i t was pointed out that halogenbenzenes would not r e a c t i n the manner of a l k y l h a l i d e s ( 2 1 ) , and that a l k y l i o d i d e s were too unstable to be g e n e r a l l y u s e f u l i n the r e a c t i o n (20). Aluminum c h l o r i d e and z i n c c h l o r i d e were not the o n l y e f f i c i e n t 2. condensing agents. Ferrous c h l o r i d e , f e r r i c c h l o r i d e , and sodium aluminum c h l o r i d e were found t o be of value. I t was f u r t h e r pointed out that o n l y the anhydrous salt's were s u i t a b l e as con- densing agents (20). The mechanism of r e a c t i o n s e f f e c t e d i n the presence of ^ aluminum c h l o r i d e was assumed by F r i e d e l and C r a f t s t o take place through a primary exchange of hydrogen i n the hydrocarbon f o r an A12C1^ r e s i d u e : C 6 H 6 + • A 1 2 C 1 6 > C 6 H 5 A 1 2 C 1 5 + H C 1 The postul a t e d hydrocarbon-aluminum c h l o r i d e complex combined w i t h an a l i p h a t i c c h l o r i d e , thus: RC1 + C 6H 5A1 2C1 5 >A12C16 4- CgH^R They were unable to I s o l a t e the compound C ^ H j j A l ^ l j , although, a t about the same time, Gustavson (26) reported the formation of compounds of the type A l ^ r g ^ C g H ^ and Al^Br ^ . 6 c^Sg i n F r i e d e l - C r a f t s r e a c t i o n s of benzene or toluene i n the presence o f aluminum bromide. Walker (85) noted the v a r i a t i o n i n c o n d u c t i v i t y on the a d d i t i o n of small p o r t i o n s of aluminum c h l o r i d e t o mixtures of e t h y l bromide and benzene or naphthalene. Breaks i n the curves i n d i c a t e d the formation of compounds 3 X . A I C I 3 , 2X.A1C1<3, and X . A l C l ^ where X stands f o r a molecule of hydrocarbon. Since readings were taken before e v o l u t i o n of hydrogen bromide was noted, the brdaks were not due to a l k y l a t i o n of the hydrocarbon. Varying the p r o p o r t i o n of hydrocarbon used gave a corresponding v a r i a t i o n i n c o n d u c t i v i t y curves. Working on intermediate complexes i n the r e a c t i o n , N o r r i s 3. and Wood (55) prepared a t e r n a r y complex, A l ^ r ^ . a C s ^ C H ^ . C g H ^ B r by shaking together a mixture of mesitylene, e t h y l bromide, and aluminum bromide a t 0 ° . Attempts to prepare complexes of def- i n i t e composition, c o n t a i n i n g o n l y hydrocarbon and aluminum h a l i d e were u n s u c c e s s f u l , and i t was concluded that the presence of a t h i r d component seems to be necessary f o r the formation of an i s o l a b l e complex. Evidence f o r existence o f a complex between aluminum c h l o r i d e and a l k y l h a l i d e i s based on conductance s t u d i e s . Walker (85) noted considerable c o n d u c t i v i t y w i t h methyl-, e t h y l - , and n- p r o p y l iodifes as w e l l as w i t h e t h y l bromide and chloroform s o l u t i o n s of aluminum c h l o r i d e and assumed the formation of a compound between the c a t a l y s t and a l k y l h a l i d e . S h o r t l y a f t e r the d i s c o v e r y o f the F r i e d e l - C r a f t s r e a c t i o n , Gustavson (25) found that e i t h e r i s o p r o p y l bromide or' n-propyl bromide w i t h benzene and aluminum c h l o r i d e gave lsopropylbenzene. S i l v a (73) confirmed t h i s , using the two propyl c h l o r i d e s . Heise (32) was the f i r s t t o o f f e r a d e r i v a t i v e as proof of the s t r u c t u r e of the propylbenzene obtained. He observed that a t - 2 ° , n-propyl bromide w i t h benzene and aluminum c h l o r i d e gave n-propylbenzene, i d e n t i f i e d as i t s sulfonamide. Genvresse (22) obtained both n-propylbenzene and lsopropylbenzene by conducting the r e a c t i o n a t r e f l u x temperature. Konovalof (*f2) found that below 0 ° n-propyl c h l o r i d e gave n-propylbenzene, w h i l e from 0 ° t o r e f l u x temperatures i t gave mixtures of n-propylbenzene and lsopropylbenzene, the degree of i s o m e r i z a t i o n depending on the temperature. A recent study of i s o m e r i z a t i o n (36) has shown i t t o be dependent on the water content of the c a t a l y s t . For p r o p y l c h l o r i d e , the e f f e c t of aluminum c h l o r i d e i s strongest at - 5 0 ° t o 0 ° when the water content i s minimum. Higher a l k y l h a l i d e s r e act s i m i l a r l y to the simple h a l i d e s . Thus, b u t y l (27) and amyl ( 2 0 , 2 3 ) h a l i d e s were observed t o y i e l d l a r g e l y branched a l k y l substances. The r e s u l t i n g a l k y l groups above e t h y l are r a r e l y primary except from c y c l o p a r a f f i n s (2*+,38,75) and primary a l c o h o l s ( 3 8 ) and under m i l d c o n d i t i o n s from primary e s t e r s or h a l i d e s ( 5 > 3 8 ) . They are u s u a l l y secon- dary from a s t r a i g h t c h a in o l e f i n and other reagents, and t e r t i a r y from r e a c t a n t s having a branch adjacent to the f u n c t i o n a l group. The g e n e r a l i z a t i o n has been made that a l k y l a t i o n w i t h a primary a l k y l h a l i d e w i l l y i e l d a secondary alkylbenzene i f the a l k y l h a l i d e contains o n l y primary and secondary carbon atoms, and a t e r t i a r y alkylbenzene i f i t contains a t e r t i a r y carbon atom. The e x t r a p o l a t i o n was even so made ( 15) as to give the erroneous c o n c l u s i o n that a l k y l a t i o n of benzene w i t h n - b u t y l c h l o r i d e y i e l d s t-alkylbenzenes. A c t u a l l y a mixture of n- and sec-butylbenzene i s produced. The carbon s k e l e t o n i s r a r e l y Isomerized i n a l k y l a t i o n of aromatic hydrocarbons except w i t h neopentyl d e r i v a t i v e s . Even w i t h t h i s a l k y l a t i n g agent the product i s p r i m a r i l y 2-methyl - 3-phenylbutane r a t h e r than 2-methyl - 2-phenylbutane ( 5 9 ) . I s o b u t y l h a l i d e s and t - b u t y l h a l i d e s seem t o be the o n l y a l k y l h a l i d e s which y i e l d t - alkylbenzenes as the major r e a c t i o n product when aluminum c h l o r i d e i s used as c a t a l y s t . However, under vigorous con- d i t i o n s a s e c - b u t y l group has been rearranged to a t e r t i a r y s t r u c t u r e ( 5 2 ) . Balsohn's ( 2 ) d i s c o v e r y of the f a c i l e a l k y l a t i o n of benzene 5 . w i t h o l e f i n s and Schramm's (70) o b s e r v a t i o n of the formation of o l e f i n s during the course of a l k y l a t i o n w i t h a l k y l h a l i d e s l e d the l a t t e r author t o propose that a l k y l a t i o n w i t h a l k y l h a l i d e s proceeds through the intermediate formation of an o l e f i n . Thus, the production of t-butylbenzene from i s o b u t y l h a l i d e , benzene, and aluminum c h l o r i d e was assumed t o be due to dehydro- halogenation, f o l l o w e d by a d d i t i o n of benzene t o the double bond of the r e s u l t i n g o l e f i n . I s o b u t y l c h l o r i d e was found to s p l i t i n t o butylene and hydrogen c h l o r i d e by the a c t i o n o f aluminum c h l o r i d e . A d d i t i o n of benzene would then r e s u l t i n formation of t-butylbenzene, the phenyl group, i n accordance w i t h the Markownikoff r u l e , a t t a c h i n g I t s e l f t o the carbon atom which possesses the l e a s t number of hydrogen atomss (CH3) 2CHCH 2C1 A l C l i f r (CH3) 2C=CH 2 + HC1 The production of sec-butylbenzene from n-b u t y l c h l o r i d e was expla i n e d i n analogous f a s h i o n . Wertyporoch and F i r l a (86) explained the d i f f e r e n c e s i n c o n d u c t i v i t i e s of s e v e r a l a l k y l h a l i d e s o l u t i o n s by assuming a dehydrohalogenation of such a l k y l h a l i d e s as pro p y l and i s o - p r o p y l c h l o r i d e or chlorocyclohexane t o the corresponding o l e f i n , and subsequent formation of h i g h l y i o n i z e d olefin-aluminum c h l o r - i d e complexes. However, previous t o these c o n d u c t i v i t y s t u d i e s the a l k y l a t i o n by means of o l e f i n s , c a t a l y z e d by aluminum c h l o r i d e , has been observed not to take place unless HC1 was present and, a c c o r d i n g l y M i l l i g a n and Reid (^9) suggested that t h i s would i n d i c a t e that i n o l e f i n a l k y l a t i o n the r e a c t i o n proceeds 6 . through the p r i o r formation of an a l k y l h a l i d e . I f o l e f i n s are i n v o l v e d i n the mechanism of the rearrange- ment of a l k y l h a l i d e s , the o l e f i n s should act I n much the same way as the h a l i d e s , themselves, hut when benzene was a l k y l a t e d w i t h propylene c a t a l y z e d by aluminum c h l o r i d e ( 3 ) , boron t r i - f l u o r i d e ( 7 6 , 8 9 ) , h y d r o f l u o r i c a c i d (7 1*) and f e r r i c c h l o r i d e ( 6 0 ) , only isopropylbenzene(s) was formed. A l c o h o l s w i l l a l k y l a t e aromatic compounds i n the presence of a c t i v e metal h a l i d e s or other Lewis a c i d s . I s o p r o p y l a l c o h o l gave isopropylbenzene and secondary b u t y l a l c o h o l gave secondary butylbenzene. Pentanol - 2 was reported to give 2-phenylpentane, while 2-methylbutanol - 3 gave 2-methyl - 3-phenylbutane. No evidence other than b o i l i n g point was given f o r any of these s t r u c t u r e s ( 3 5 ) . A number of t e r t i a r y h e p t y l a l c o h o l s have been shown to react w i t h phenol and aluminum c h l o r i d e to give t-heptylphenols ( 3 ^ ) . I s o m e r i z a t i o n i s common i n the r e a c t i o n s of a l i p h a t i c a l c o h o l s w i t h aromatic hydrocarbons. Thus, w h i l e i s o p r o p y l a l c o h o l and secondary b u t y l a l c o h o l reacted w i t h benzene and toluene t o give the unisomerized products ( 8 3 ) , isoamyl a l c o h o l w i t h 1 , 2 , 3 , ^ -tetrahydronaphthalene catalyzed-by aluminum c h l o r i d e , z i n c c h l o r i d e and phosphoric a c i d r e s p e c t i v e l y , was shown i n a l l cases to y i e l d the t e r t i a r y isomer ( 7 8 ) . Meyer and Bernhauer (M3) a l k y l a t e d benzene, toluene, phenol, and other aromatic compounds w i t h a l c o h o l s i n 80% s u l f u r i c a c i d a t 6 5 ° . Both i s o p r o p y l a l c o h o l and normal p r o p y l a l c o h o l w i t h benzene were reported to give isopropylbenzene. I s o b u t y l a l c o h o l and t e r t i a r y b u t y l a l c o h o l both y i e l d e d t e r t i a r y butylbenzene, i d e n t i f i e d as i t s bromo d e r i v a t i v e . Both secondary b u t y l a l c o h o l and normal b u t y l a l c o h o l gave secondary butylbenzene ( 3 8 ) . N i g h t i n g a l e and Smith (52) obtained l^-dimethyl-V-s-butylbenzene from xylene and secondary b u t y l or normal b u t y l a l c o h o l s w i t h s u l f u r i c a c i d . Neopentyl a l c o h o l w i t h benzene and s u l f u r i c a c i d produced t e r t i a r y amylbenzene, i d e n t i f i e d as i t s diacetamino d e r i v a t i v e ( 5 9 ) . Isoamyl a l c o h o l gave t e r t i a r y amylbenzene ( 3 8 ) . Normal amyl a l c o h o l y i e l d e d a monoamylbenzene f r a c t i o n of which 6 0 - 6 5 $ was 2-phenylpentane and 3 5 - ^ 0 $ was 3-phenylpentane, when t r e a t e d w i t h benzene and 80$ s u l f u r i c a c i d at 7 0 ° f o r s i x hours. Apparently, 1-phenylpentane was absent. With boron t r i f l u o r i d e , both p r o p y l a l c o h o l s gave isopropylbenzene; normal b u t y l a l c o h o l and- secondary b u t y l a l c o h o l y i e l d e d sec- ondary butylbenzene. I s o b u t y l a l c o h o l and t e r t i a r y b u t y l a l c o h o l gave t e r t i a r y butylbenzene ( V 6 ) . Sowa ( l +6, l f7»57) proposed that the mechansm f o r a l k y l a t i o n r e a c t i o n s using boron t r i f l u o r i d e as c a t a l y s t , w i t h e s t e r s and ethers as w e l l as w i t h a l c o h o l s , c o n s i s t s p r i m a r i l y I n the formation of an o l e f i n i c hydrocarbon t o which the aromatic compound then adds under the i n f l u e n c e of the c a t a l y s t . This was r e f u t e d by the work of P r i c e and Ciskowski ( 6 2 ) who found that cyclohexanol, which r e a c t s r e a d i l y w i t h naphthalene could be recovered q u a n t i t a t i v e l y a f t e r treatment w i t h boron t r i - f l u o r i d e under c o n d i t i o n s c o n s i d e r a b l y more d r a s t i c than those r e q u i r e d f o r a l k y l a t i o n . Not even t r a c e s of the o l e f i n were detected. Furthermore, i t was pointed out that formation of an o l e f i n i s impossible i n the case of the benzyl group, which may be introduced as r e a d i l y as any secondary or t e r t i a r y a l k y l 8 . group. A l k y l a t i o n s of benzene w i t h cycloheptanol and c y c l o - heptene r e s p e c t i v e l y , c a t a l y z e d by s u l f u r i c a c i d , e x h i b i t e d markedly d i f f e r e n t behavior. For the monoalkylated f r a c t i o n , c y cloheptanol gave a ko% y i e l d of cycloheptylbenzene w h i l e the corresponding y i e l d from cycloheptene was 9 5 $ . The sole b a s i s f o r the s u p p o s i t i o n of intermediate o l e f i n formation i s t h a t the products obtained i n a l k y l a t i o n s can be explained by a d d i t i o n of the aromatic nucleus t o the supposed o l e f i n , i n accordance w i t h Markownikoff's r u l e . Numerous authors have endorsed t h i s mechanism. The a l k y l a t i o n of aromatic hydrocarbons w i t h v a r i o u s a l c o h o l s c a t a l y z e d by aluminum c h l o r i d e ( 8 2 ) , s u l f u r i c a c i d ( ^ 6 ) , phosphorus pent- oxide ( 8 1 ) , phosphoric a c i d ( 5 0 , 6 7 ) , z i n c c h l o r i d e (*+3), and z i n c c h l o r i d e on aluminum oxide ( 7 2 ) have i n a l l cases shown the expected product on the b a s i s of intermediate o l e f i n formation. The a l k y l a t i o n of benzene w i t h methyl and e t h y l a l c o h o l s was i n v e s t i g a t e d by N o r r i s and Ingraham ( 5 3 ) . They suggested th a t a l c o h o l s react w i t h aluminum c h l o r i d e to form compounds having the formula RO&lClg which decompose when heated t o produce RC1 plus A10C1, w i t h subsequent r e a c t i o n of the a l k y l h a l i d e . This work was extended by N o r r i s and S t u r g i s (5*0 who showed the formation of methyl c h l o r i d e and e t h y l c h l o r i d e from contact of the corresponding a l c o h o l w i t h aluminum c h l o r i d e . However, when secondary b u t y l a l c o h o l wqs placed i n contact w i t h aluminum c h l o r i d e at room temperature f o r f i f t e e n hours, o n l y t r a c e s of a l c o h o l , and no a l k y l h a l i d e was obtained ( 6 3 ) . Tzukervanik ( 8 2 ) suggested that an alkoxy aluminum c h l o r i d e 9. forms, f o l l o w e d by decomposition t o y i e l d an o l e f i n and hydroxy- aluminum c h l o r i d e . I t i s of s i g n i f i c a n c e that diphenylmethyl bromide and phenol, or benzyl c h l o r i d e w i t h d i p h e n y l , benzene, toluene, o-xylene or mesitylene w i l l y i e l d , a t elevated temperatures, without a c a t a l y s t , normal condensation products (12,5D. Th i s emphasizes the f a c t that the a l k y l a t i o n by metal h a l i d e s i s e s s e n t i a l l y an a c t i v a t i o n r e a c t i o n o c c u r r i n g when s u i t a b l e a c t i v a t i o n of the nuclear hydrogen and a l i p h a t i c halogen are r e a l i z e d . Walker (85) and Dougherty (17) found that c e r t a i n meta- t h e t i c a l r e a c t i o n s occur between c e r t a i n types of a l i p h a t i c halogen compounds In the presence of aluminum c h l o r i d e . On t h i s b a s i s , the l a t t e r i n v e s t i g a t o r suggested that i o n i z a t i o n of an a l k y l h a l i d e I s induced by aluminum c h l o r i d e J RX + A I C I 3 ==> R X . A l C l 3 v = ^ R +(X41C1 3) Such an i o n i z a t i o n agreed w i t h P r i n s 1 theory (6V) who assumed that aluminum c h l o r i d e i o n i z e s benzene i n such a way that i t produces a phenyl i o n and a hydrogen i o n . The F r i e d e l - C r a f t s r e a c t i o n was then regarded as a r e a c t i o n of the negative phenyl i o n w i t h the p o s i t i v e a l k y l i o n . Wertyporoch and F i r l a (86) d i d not b e l i e v e that any f u r t h e r a c t i v a t i o n of the aromatic nucleus was necessary. S u b s t a n t i t a t i o n f o r t h i s b e l i e f was obtained from the k i n e t i c study of a l k y l a t i o n by U l i c h and Heyne (8V) who found d e f i n i t e evidence f o r the formation of the complex between a l k y l h a l i d e and metal h a l i d e , and i n f a c t were able t o determine the e q u i l i b r i u m constant f o r i t s formation. The r a t e of a l k y l a t i o n was d i r e c t l y p r o p o r t i o n a l t o the c o n c e n t r a t i o n of t h i s complex and of the hydrocarbon, i n d i c a t i n g that any f u r t h e r f u n c t i o n of the c a t a l y s t i n a c t i v F a i r b r o t h e r ( 18) proposed that an i n i t i a l and necessary step i n the r e a c t i o n i s the t r a n s i t i o n of the mainly covalent carbon-halogen bond of the a l k y l h a l i d e i n t o an i o n i c bond through complex formation w i t h the metal h a l i d e c a t a l y s t . Evidence f o r h i s proposal was the observed r a d i o - i s o t o p i c exchange of halogen atoms between the organic and i n o r g a n i c h a l i d e s , an exchange which has r e c e n t l y been demonstrated to a l s o occur between naphthyl h a l i d e s CgH^X and stann i c h a l i d e s SnYu, ( 3 1 ) , and by the observed l a r g e increment i n d i e l e c t r i c p o l a r i z a b i l i t y when aluminum bromide and e t h y l bromide were d i s s o l v e d together i n cyclohexane. I n c o n t r a s t , a mixture of bromobenzene and aluminum bromide showed no increment, the p o l a r i z a b i l i t y of the mixture being very n e a r l y the sum of the p a r t i a l p o l a r i z a b i l i t i e s of i t s components. P r i c e (61) concluded that s u b s t i t u t i o n proceeds through an e l e c t r o n - r d e f i c i e n t intermediate which acquires an e l e c t r o n p a i r from a double bond of the aromatic nucleus: Rearrangement of a l k y l h a l i d e s by aluminum c h l o r i d e was explained by Whitmore's theory of rearrangements ( 8 7 ) , i . e . the e l e c t r o n d e f i c i e n c y i n the a l k y l i o n migrates from a primary t o a secondary to a t e r t i a r y carbon atom, to give a a t i n g the l a t t e r i s n e g l i g i b l e . H 11. carbonium i o n of minimum energy. J u s t i f i c a t i o n of the i o n i c theory of r e a c t i o n has been advanced by stereochemical evidence. An a l k y l a t i o n of benzene w i t h o p t i c a l l y a c t i v e secondary b u t y l a l c o h o l , c a t a l y z e d by aluminum c h l o r i d e and boron t r i f l u o r i d e r e s p e c t i v e l y , gave a product which was completely racemized i n the f i r s t case and over 99% racemized i n the second ( 6 3 ) . This work was sub- s t a n t i a t e d and extended by B u r w e l l and Archer (lh) to hydro- f l u o r i c a c i d and phosphoric a c i d c a t a l y z e d r e a c t i o n s . They showed that the a l c o h o l could not have been racemized before i t reacted since w i t h phosphoric a c i d and a l c o h o l alone the recovered a l c o h o l had the same r o t a t i o n as the o r i g i n a l . However, w i t h h y d r o f l u o r i c a c i d and a l c o h o l alone, the recovered a l c o h o l was 23$ racemized ( 1 3 ) . The extensive r a c e m l z a t i o n was a t t r i b u t e d to the r e s u l t of a planar carbonium i o n in t e r m e d i a t e . Racemlzation of o p t i c a l l y a c t i v e oc-phenylethyl c h l o r i d e has been observed by the a c t i o n of v a r i o u s metal s a l t s which act as c a t a l y s t s f o r the F r i e d e l - C r a f t s r e a c t i o n (h). While the i o n i c mechanism of a l k y l a t i o n was at one time w i d e l y accepted, s e v e r a l p o i n t s arose which could not be s a t - i s f a c t o r i l y explained by such a scheme. Pea r l s o n and Simons (58) were able to c a l c u l a t e the r a t e of r e a c t i o n between toluene and t e r t i a r y b u t y l c h l o r i d e as c a t a l y z e d by hydrogen f l u o r i d e and showed that the maximum r a t e so c a l c u l a t e d on the b a s i s 4 of formation of an intermediate carbonium i o n , was slower than the experimental r a t e to such an enormous extent, a f a c t o r of IQH,- that the assumption of intermediate carbonium Ion form- a t i o n was untenable. These authors a l s o demonstrated the v e r y s i m i l a r e f f e c t s on promotion of the r e a c t i o n by the very d i s s i m i l a r compounds, water, methanol, d i e t h y l e t h e r , and hexamethylacetone and pointed out that on the b a s i s of a mechanism which r e q u i r e s two or more consecutive r e a c t i o n s and a c t i v e intermediates, i t i s d i f f i c u l t to e x p l a i n the s i m i l a r i t y of the observed e f f e c t s . The proposal of a one-step condensed phase, c a t a l y z e d , and promoted r e a c t i o n as the e s s e n t i a l f a c t o r i n the mechanism was shown to be s a t i s f a c t o r y from k i n e t i c c o n s i d e r a t i o n s and reasonable from energy c o n s i d e r a t i o n s . A recent i n v e s t i g a t i o n of the a l k y l a t i o n of phenols w i t h o p t i c a l l y a c t i v e <*-phenylethyl c h l o r i d e i n acetone-potassium carbonate medium showed an observed i n v e r s i o n of c o n f i g u r a t i o n and high (at l e a s t 6k%) r e t e n t i o n of o p t i c a l p u r i t y . I t was suggested that the major r e a c t i o n path i s a n u c l e o p h i l i c displacement of halogen by phenoxide ions (28). I t was f u r t h e r demonstrated that r a c e m l z a t i o n occurred independently of a l k y l a t i o n at a r a t e comparable w i t h i t (30). The independence of rearrangement and a l k y l a t i o n has been demonstrated. Contact of propyl c h l o r i d e w i t h aluminum c h l o r i d e has been observed to cause n e a r l y complete i s o m e r i z a - t i o n t o I s o p r o p y l c h l o r i d e i n f i v e minutes, c o n s i d e r a b l y l e s s time than i s r e q u i r e d f o r an a l k y l a t i o n w i t h t h i s reagent I n which at l e a s t some normal propyl benzene i s u s u a l l y formed. When propyl c h l o r i d e was s t i r r e d w i t h AlCl^SOb,, no Isomer- i z a t i o n occurred. Yet, when benzene was a l k y l a t e d w i t h p r o p y l c h l o r i d e w i t h t h i s c a t a l y s t , the y i e l d of propylbenzenes con- s i s t e d of 22$ normal propylbenzene and 78$ lsopropylbenzene (79)• In a r e a c t i o n between t e r t i a r y b u t y l c h l o r i d e and phenol, 13. the a c t i v a t i o n energy was determined to be 13-17 kcals./mole. For a carbonium i o n mechanism i t was c a l c u l a t e d that the energy r e q u i r e d would be 28 kcal./mole. I n a d d i t i o n , a very high order r a t e dependency upon c o n c e n t r a t i o n of phenol was observed Topchiev (80) s t u d i e d the r e l a t i o n s h i p between c a t a l y s t a c t i v i t y and e l e c t r i c a l c o n d u c t i v i t y of v a r i o u s F r i e d e l - C r a f t s c a t a l y s t s . The absence of any c o r r e l a t i o n l e d t o the c o n c l u s i o n t h a t complex formation w i t h the c a t a l y s t r a t h e r than carbonium i o n formation was the source of c a t a l y t i c a c t i o n . Brown and Grayson (7) concluded that i n view of the supposed very high r e a c t i v i t y of carbonium ions and the observed progression of v a r i o u s a l k y l a t i o n r e a c t i o n s a t moderate, measurable r a t e s , that the f i r s t step of the r e a c t i o n , the i o n i z a t i o n of the a l k y l h a l i d e must represent the r a t e - determining stage and t h e r e f o r e r a t e of r e a c t i o n should be independent of the c o n c e n t r a t i o n or n u c l e o p h i l i c c h a r a c t e r - i s t i c s of the aromatic c o n s t i t u e n t undergoing a l k y l a t i o n . These authors were able to demonstrate that f o r a l k y l a t i o n s w i t h benzyl c h l o r i d e , the r a t e was dependent both on the s t r u c - t u r e and c o n c e n t r a t i o n of the aromatic reactant and i n t e r p r e t e d t h e i r r e s u l t s as being more c o n s i s t e n t w i t h a mechanism i n v o l v i n g a rate-determining n u c l e o p h i l i c a t t a c k by the aromatic component on a p o l a r benzyl halide-aluminum c h l o r i d e compound. (29). The t r a n s i t i o n s t a t e i n the displacement step was represented as a o— complex co n t a i n i n g a p a r t i a l l y formed carbon-carbon bond and a p a r t i a l l y broken carbon-chlorine bond. T h i s theory was t e s t e d by extension of the study to the a l k y l - a t i o n of benzene and toluene w i t h v a r i o u s methyl h a l i d e s w i t h aluminum bromide c a t a l y s t . I t was found that n e i t h e r the isomer d i s t r i b u t i o n nor r e l a t i v e r e a c t i v i t i e s were independent of the h a l i d e used,8). With increased branching of the a l k y l h a l i d e there should be observed an increased tendency f o r the formation and r e a c t i o n of I o n i c intermediates. In order t o o b t a i n evidence on t h i s i u > p o i n t , Brown and Jungk (9) undertook an examination of the a l k y l a t i o n of aromatic compounds w i t h e t h y l , i s o p r o p y l , and t e r t i a r y b u t y l bromides. The r e s u l t s i n d i c a t e d that the r a t e s o f a l k y l a t i o n , i s o m e r i z a t i o n , and d i s p r o p o r t i o n a t i o n a l l increase sharply w i t h increased branching of the a l k y l group. I n view of the f a c t that s t a b i l i t y of carbonium ions a l s o i n c r e a s e s w i t h increased branching, the r e s u l t s i n d i c a t e carbon- ium Ion formation. However, i f carbonium ions are i n v o l v e d i n the a l k y l a t i o n r e a c t i o n , the toluene/benzene r e a c t i v i t y r a t i o should be expected to increase w i t h i n c r e a s i n g s t a b i l i t y of the carbonium i o n (10). The r e a c t i v i t y r a t i o as determined by Brown and Jungk showed the opposite t r e n d . In c o n t r a s t , i t was pointed out that i f the r e a c t i o n were p r i m a r i l y a n u c l e o p h i l i c displacement by the aromatic component, the r a t e o f a l k y l a t i o n would be expected to decrease i n the order: methylation> e t h y l a t i o r i > i s o p r o p y l a t i o n > t - b u t y l a t i o n . The r e s u l t s showed the opposite t r e n d . These authors maintain that the t r a n s i t i o n s t a t e i s best d e s c r i b e d i n terms of a n u c l e o p h i l i c a t t a c k by the aromatic on a s t r o n g l y p o l a r i z e d a l k y l bromide-aluminum bromide a d d i t i o n compound and i n accordance w i t h the i n t e r p r e t a t i o n of W i n s t e i n (88) suggested that as the a l k y l group i s changed to e t h y l , i s o p r o p y l , and f i n a l l y to t e r t i a r y b u t y l , the carbon-halogen bond must become more and more i o n i c i n the t r a n s i t i o n s t a t e w i t h a correspondingly decreasing covalent c o n t r i b u t i o n from the aromatic, and expected at some point i n the s e r i e s t o approach the " l i m i t i n g " c o n d i t i o n w i t h the r e a c t i o n proceeding through an e s s e n t i a l l y f r e e carbonium i o n . Several anomalous r e s u l t s w i t h regard to the s t r u c t u r e of products has a l s o cast doubt on the theory of intermediate carbonium i o n formation* The i o n i c mechanism does not account f o r the high y i e l d s of normal propylbenzene obtained i n the a l k y l a t i o n of benzene w i t h normal pr o p y l c h l o r i d e (38) and the s o l e formation of the normal propyl Isomer i n the a l k y l a t i o n of benzene w i t h normal propyl a l c o h o l and aluminum c h l o r i d e . Moreover, i t was found that neopentylbenzene i s formed i n the a l k y l a t i o n of benzene wi t h neopentyl a l c o h o l and aluminum c h l o r i d e (59). I f the carbonium i o n theory i s v a l i d , then i t i s to be expected that a l k y l a t i o n w i t h t e r t i a r y h a l i d e s should y i e l d e x c l u s i v e l y t e r t i a r y a l k y l benzenes. However, not more than about 20% of the pentylbenzene obtained w i t h t e r t i a r y p e n t y l c h l o r i d e at 2 5 - 3 0 ° was t e r t i a r y pentylbenzene, the remainder being a mixture of Isomeric compounds b e l i e v e d t o c o n s i s t c h i e f l y of l-phenyl - 2-methylbutane and 2-methyl - 3-phenylbutane ( 3 7 ) . On the other hand, when e i t h e r aluminum c h l o r i d e d i s s o l v e d i n nitromethane or f e r r i c c h l o r i d e was used as c a t - a l y s t , the product c o n s i s t e d of v e r y pure t e r t i a r y p e n t y l - benzene. The non-formation of t e r t i a r y alkylbenzenes as the p r i n c i p a l product i n the presence of aluminum c h l o r i d e has been shown to be the general r u l e r a t h e r than the exception, A l k y l a t i o n of benzene w i t h a t e r t i a r y h e x y l c h l o r i d e , 2 - c h l o r o - 2 , 3-dimethylbutane, I n the presence of aluminum c h l o r i d e a t 1° r e s u l t e d i n a 62% y i e l d of hexylbenzene which c o n s i s t e d of the secondary hexylbenzene, 2 , 2-dimethyl - 3-phenylbutane, mixed w i t h about 10% of the t e r t i a r y isomer, 2 , 3 - d i m e t h y l - 2 - phenylbutane. This rearrangement a l s o occurred w i t h zirconium c h l o r i d e . Again, when the r e a c t i o n was c a r r i e d out a t room temperature i n the presence of f e r r i c c h l o r i d e or of a n i t r o - methane s o l u t i o n of aluminum c h l o r i d e , the product was the p r a c t i c a l l y pure t e r t i a r y isomer ( 6 9 ) , The formation of the secondary isomer can be explained without using carbonium ions by assuming that the r e a c t i o n occurs by way of a concerted b i m o l e c u l a r n u c l e o p h i l i c d i s p l a c e - ment r e a c t i o n . I t i s suggested that s u b s t i t u t i o n takes place at the secondary carbon atom r a t h e r than the t e r t i a r y atom because backside a t t a c k by the approaching phenyl group i s more d i f f i c u l t at a t e r t i a r y carbon atom. 1 7 . H CI A H CH3 HCL-r-AlClo (^VC-C-CH- V The displacement was expected to proceed through a bim o l - e c u l a r r e a c t i o n i n v o l v i n g the r e a c t i o n of the a l k y l c h l o r i d e w i t h a complex of benzene and aluminum c h l o r i d e (68) or of benzene wi t h a complex of the a l k y l c h l o r i d e and c a t a l y s t ( 6 ) . The proponents of t h i s theory (69), however, themselves objected to i t on the b a s i s that such a displacement mechanism i n v o l v e s two simultaneous SN displacements, i . e . , two Walden i n v e r s i o n s on adjacent carbon atoms. The benzene d i s p l a c e s a hydride i o n from one carbon atom and the hydride i o n d i s p l a c e s the c h l o r i d e i o n from the adjacent carbon atom. Since the bulky entering and l e a v i n g groups are adjacent, r e a c t i o n by t h i s mechanism was stated to be u n l i k e l y . The authors suggested t h a t i n view of the ease w i t h which t e r t i a r y a l k y l ions are b e l i e v e d t o be formed i n the presence of c a t a l y s t s of the F r i e d e l - C r a f t s type, that a more l i k e l y mechanism was the intermediate formation of the t e r t i a r y alkylbenzene by r e a c t i o n w i t h the t e r t i a r y a l k y l i o n , f o l l o w e d by i s o m e r i z a t i o n of t h i s i n termediate. A recent I n v e s t i g a t i o n of the a l k y l a t i o n of benzene w i t h n lh ethyl-B-C c h l o r i d e showed that there was no i s o m e r i z a t i o n of the e t h y l group (66). Ethylbenzene was prepared by the i n t e r a c t i o n of ethyl-^-C^ 1 1 , c h l o r i d e , benzene, and aluminum c h l o r i d e . O x i d a t i o n of the p u r i f i e d ethylbenzene gave non- r a d i o a c t i v e benzoic a c i d , i n d i c a t i n g that no i s o m e r i z a t i o n of the e t h y l group had occurred during condensation. On the other hand, when e t h y l - ^ - C ^ c h l o r i d e was placed i n contact w i t h aluminum c h l o r i d e f o r one hour at room temperature, d i s t i l l e d and then used to a l k y l a t e benzene by the same procedure, almost complete i s o m e r i z a t i o n was i n d i c a t e d by an almost equal d i s t r i b u t i o n of C between the two p o s i t i o n s . I t was pointed out that while the n u c l e o p h i l i c displacement mechanism was the most probable, the a l t e r n a t i v e mechanism of formation of an intermediate carbonium i o n could not be excluded since the p o s s i b i l i t y e x i s t s that the ethylc a r b o n - ium i o n i s produced but no hydrogen s h i f t occurs before the e t h y l group r e a c t s w i t h the aromatic nucleus. The formation of an intermediate o l e f i n i s d e f i n i t e l y excluded. 19. THE PROPOSED WORK In view of the m u l t i p l i c i t y of t h e o r i e s and i n t e r p r e t a t i o n s set f o r t h on the F r i e d e l - C r a f t s a l k y l a t i o n , no proposed r e a c t i o n mechanism can yet c l a i m general and unequivocal acceptance. I n the hope of shedding f u r t h e r l i g h t on the mechanism of t h i s r e a c t i o n , a study of the a l k y l a t i o n of a n i s o l e w i t h 2-phenylethyl- 1-C c h l o r i d e and 2-phenylethanol-l-C i n the presence of aluminum c h l o r i d e was undertaken. In r e a c t i o n s where carbonium ions are l i k e l y i n v o l v e d as intermediates, rearrangements of C - l a b e l e d atoms from C - l to C-2 p o s i t i o n s i n the phenylethyl c a t i o n have been observed, e i t h e r through the 1,2-phenyl s h i f t * or i t s e q u i v a l e n t , a " n o n - c l a s s i c a l " phenonium i o n (W , l +5,65) . Should the a l k y l a t i o n r e a c t i o n under study i n v o l v e the carbonium i o n , analogous rearrangements should be observable: CHg---—C. Hg (OH) A1C1 3 unrearranged rearranged 20. Permanganate o x i d a t i o n of the a l k y l a t i o n product, .p_-methoxydIbenzyl, should a f f o r d a n i s i c and benzoic a c i d s . From the content of these degradation products, the degree of rearrangement, i f any, may be c a l c u l a t e d . In the present study, pure benzoic a c i d could not be i s o l a t e d a f t e r the o x i d a t i v e degradation. The degree of rearrangement was determined from the r a d i o a c t i v i t y assays of jj-methoxydibenzyl and a n i s i c a c i d , the a c t i v i t y t h e o r e t i c a l l y present i n the benzoic a c i d being c a l c u l a t e d by d i f f e r e n c e . 21 RESULTS AND DISCUSSION 2-phenylethanol-l-C - L was prepared by the l i t h i u m alum- inum hydride r e d u c t i o n of phen y l a c e t i c a c i d - l - C l l + (56). Conversion of the a l c o h o l to the c h l o r i d e was e f f e c t e d w i t h t h i o n y l c h l o r i d e i n p y r i d i n e (*f5)» That a l l the C1** a c t i v i t y was l o c a t e d at the C - l p o s i t i o n was shown by the permanganate o x i d a t i o n of both the a l c o h o l and the c h l o r i d e to give non- r a d i o a c t i v e benzoic a c i d . The a l k y l a t i o n of a n i s o l e w i t h e i t h e r 2 - p h e n y l e t h y l - l - C l l f c h l o r i d e or 2-phenylethanol-l- was e f f e c t e d using an excess of a n i s o l e as solvent and s l i g h t l y over one and a h a l f molar eq u i v a l e n t s of anhydrous aluminum c h l o r i d e at 100° f o r s e v e r a l hours. The j>-methoxydibenzyl obtained was assayed f o r r a d i o - a c t i v i t y and then o x i d i z e d w i t h potassium permanganate to y i e l d a n i s i c a c i d . As a check on the t o t a l a c t i v i t y , the 2 - p h e n y l e t h y l - l - c l 1 * c h l o r i d e was converted to hydrocinnamic a c i d whose r a d i o a c t i v i t y was found t o be e s s e n t i a l l y i d e n t i c a l w i t h that of the cor- responding o-methoxydibenzyl. I n the a l c o h o l runs, the r a d i o - a c t i v i t y of the phenylurethan of 2-phenylethanol-l-C l l f was a l s o shown to be the same as the corresponding p,-methoxydibenzyl products. I f there were no rearrangement i n the r e a c t i o n s s t u d i e d , 100$ of the t o t a l r a d i o a c t i v i t y i n the j>-methoxydibenzyl should be recovered i n the a n i s i c a c i d . The r e s u l t s from d u p l i c a t e c h l o r i d e and a l c o h o l runs are ta b u l a t e d i n Table I , the $ r e a r - rangement being the d i f f e r e n c e between 100$ and the $ of t o t a l a c t i v i t y a c t u a l l y recovered i n the a n i s i c a c i d . TABLE I REARRANGEMENTS IN THE ALKYLATION OF ANISOLE A l k y l a t i n g Agent Compound Counted a Observed A c t i v i t y D (cts/min/sample) Corrected A c t i v i t y c (cts/min/mole) % A c t i v i t y i n % r e a r - A n i s i c A c i d rangement Run I Run I I Run I Run I I Run I Run I I Run I Run C 6H^CH 2C l l +H20H CgH^NHCOOCH^CH^CgHj 590 590 8850 8850 ^-CH 30C 6H 1 +CH 2CH 2C 6H 5 59>+ 592 8910 8880 J2-CH30C6HL.COOH 567 565 ^536 ^520 5 0 . 9 5 0 . 8 ^ 9 . 1 ^ 9 . 2 C 6 H ^ C H 2 C I 1 4 H 2 C I C 6 H 5 < ; H 2 C H 2 C O O H 1929 t 1010 17360 9090 ^ - C H 3 0 C 6 H I , . C H 2 C H 2 C 6 H 5 1152 595 17280 8925 £ - C H 3 0 C 6 H L C 0 0 H 1073 537 8580 ^296 ^ 9 * 7 1+8.2 5 0 . 3 5 1 . 8 (a) A l l compounds were converted to barium carbonate and counted as i n f i n t e l y t h i c k samples of constant geometry i n a windowless gas flow counter. (b) A l l samples were counted f o r a s u f f i c i e n t l e n g t h of time to insure s t a t i s t i c a l d e v i a t i o n of not more than 1-2 %. (c) Corrected f o r the d i l u t i o n by non-labeled C atoms. Equals the observed a c t i v i t y m u l t i p l i e d by the number of C-atoms i n the compound counted. ro ro 2 3 . These r e s u l t s c l e a r l y i n d i c a t e that e s s e n t i a l l y 50$ rearrangement has taken place i n the a l k y l a t i o n of a n i s o l e , i n the presence of aluminum c h l o r i d e , by both 2 - p h e n y l e t h y l - l - C A c h l o r i d e and 2-phenylethanol-l-C l l +. Such a complete e q u i l - i b r a t i o n of the l a b e l e d atoms i n the C - l and C-2 p o s i t i o n s of the o r i g i n a l c h l o r i d e and a l c o h o l may best be accounted f o r by the assumption that the phenylethyl c a t i o n i s i n v o l v e d at some stage of the r e a c t i o n process or processes, the r e a r - rangement being the r e s u l t of a 1 , 2-phenyl s h i f t or the formation of a phenonium i o n as p r e v i o u s l y i n d i c a t e d . I t i s very tempting, t h e r e f o r e , to simply conclude that the F r i e d e l - C r a f t s a l k y l a t i o n of a n i s o l e w i t h 2-phenylethyl c h l o r i d e or 2-phenylethanol proceeds by way of a carbonium i o n mechanism, i . e . , the a l k y l a t i n g agent f i r s t gives r i s e to the a l k y l c a t i o n which then e f f e c t s an e l e c t r o p h i l i c a t t a c k on the aromatic hydro- carbon to give the f i n a l product. However, the observed r e s u l t s merely demonstrate that under the experimental c o n d i t i o n s used, there i s a rearrangement of the C ^ - l a b e l e d atoms which most probably r e s u l t s from the formation of the phenylethyl c a t i o n . These f i n d i n g s do not i n d i c a t e what exact r o l e such a c a t i o n would play i n the F r i e d e l - C r a f t s a l k y l a t i o n . I t i s a f a c t t h a t , i n many cases, rearranged products have been obtained from F r i e d e l - C r a f t s a l k y l a t i o n r e a c t i o n s ( 2 0 , 2 2 , 2 3 , 2 5 , 2 7 , 3 2 , 3 6 , 3 8 , ^ 2 , ^ 8 , 5 2 , 5 9 , 7 8 ) . These rearrangements are g e n e r a l l y explained by assuming the formation of a c a r - bonium i o n from the a l k y l a t i n g agent (61) f o l l o w e d by subsequent rearrangement t o a more s t a b l e carbonium i o n ( 8 7 ) . By analogy w i t h g e n e r a l l y accepted c a t i o n i c organic r e a c t i o n processes ( 1 ) , one may assume that i n a carbonium i o n mechanism f o r the F r i e d e l - C r a f t s a l k y l a t i o n , the rat e determining step may be formation of the i o n , the subsequent r e a c t i o n of the c a t i o n w i t h the aromatic hydrocarbon being f a s t : RC1 -f A1C1 3 s l o w > R+ 4 AlCl£ ArH 4 f 9 s t > RArH 4" RArH +-J- AlCl£ f a s t > A l C l ^ - f HC1 - j - RAr For such a mechanism, one would expect that the o v e r a l l rate of r e a c t i o n would be independent of the concent r a t i o n of the aromatic hydrocarbon. Brown and co-workers r e c e n t l y found t h a t i n the F r i e d e l - C r a f t s a l k y l a t i o n w i t h s e v e r a l benzyl, methyl and e t h y l h a l i d e s , the r e a c t i o n r a t e showed f i r s t order dependency on the a l k y l h a l i d e , aluminum h a l i d e , and aromatic hydrocarbon (7,*+l), Consequently, these workers suggested th a t the F r i e d e l - C r a f t s r e a c t i o n of aromatic n u c l e i w i t h primary h a l i d e s may proceed by a displacement mechanism, with the aromatic c o n t r i b u t i n g to vie breaking of the carbon-halogen bond i n the t r a n s i t i o n s t a t e : RX - j - AIX^ s - RX r A l X 3 ArH-f Rx:AlX 3 - S l ^ R A r r t l X ^ RArH +AlX^ v ^ RAr + HX +• AIX^ On the other hand, Hine (33) has pointed out that the observed k i n e t i c data of Brown et a l . may a l s o be accounted f o r by assuming a rat e c o n t r o l l i n g a t t a c k of the carbonium i o n or i o n p a i r on the aromatic r i n g : RX +- A1X, v s R+" -f- AIX^ R + + ArH s l o w > RArH + RArH +-4- Aixj^ > RAr + HX -f- A1X In t h e i r most recent papers, Jungk and Brown (^0,^1) pointed out that the r a t e s of a l k y l a t i o n of benzene increase s h a r p l y w i t h increased branching of the a l k y l groups i n the s e r i e s where R represents methyl, e t h y l , i s o p r o p y l and t e r t i a r y b u t y l groups. They the r e f o r e proposed that methylation proceeds e s s e n t i a l l y by a displacement mechanism i n v o l v i n g n u c l e o p h i l i c a t t a c k by the aromatic nucleus on the p o l a r i z e d a l k y l h a l i d e - aluminum h a l i d e a d d i t i o n compound. As the a l k y l group becomes b e t t e r able to accommodate a p o s i t i v e charge, i . e . , methyl<C e t h y l < i s o p r o p y l < t e r t i a r y b u t y l , there w i l l be an increase i n the amount of i o n i c character i n the carbon-halogen bond i n the t r a n s i t i o n s t a t e , accompanied by a decrease i n the nucleo- p h i l i c . c o n t r i b u t i o n by the aromatic. They speculated that i s o p r o p y l a t i o n may represent the l i m i t i n g case where the aromatic w i l l no longer c o n t r i b u t e s i g n i f i c a n t l y to the breaking of the carbon-halogen bond. I n such an event, the mechanism w i l l become e s s e n t i a l l y one of the f r e e carbonium i o n type and the r e a c t i o n r a t e w i l l t h e r e f o r e be independent of the aromatic hydrocarbon. However, Brown and co-workers were unable to v e r i f y such c o n j e c t u r e s , f o r they were not able to make d e t a i l e d k i n e t i c measurements of the ve r y f a s t i s o p r o p y l a t i o n and t e r t i a r y b u t y l a t i o n r e a c t i o n s . To i n t e r p r e t the p r e s e n t l y observed rearrangement of the C A - l a b e l e d atoms i n the p h e n y l e t h y l a t i o n of a n i s o l e , f i r s t l y , one may subscribe to the i o n i c mechanism as suggested by Hine. 2 6 . On the other hand, i f one were to choose a n u c l e o p h i l i c d i s - placement mechanism as suggested by Brown, one may r a t i o n a l i z e the observed rearrangement by assuming that the rearrangement may have taken place during the formation of the p o l a r i z e d complex between the a l k y l a t i n g agent and the c a t a l y s t . There i s a t h i r d p o s s i b i l i t y which may a l s o account f o r the present r e s u l t s . One may p o s t u l a t e that rearrangements i n the F r i e d e l - C r a f t s a l k y l a t i o n a r i s e from a process separate from the a l k y l a t i o n r e a c t i o n i t s e l f . The f a c t that the a l k y l - a t i o n of benzene w i t h ethyl-^-C 1* 4 - c h l o r i d e r e s u l t s i n no r e a r - rangement, whereas simple contact of t h i s c h l o r i d e w i t h aluminum c h l o r i d e r e s u l t s i n the complete e q u i l i b r a t i o n of the l a b e l e d atoms (66) appears to be q u i t e dramatic evidence that a l k y l a t i o n and rearrangement can be independent of each Cther, Rearrangement of normal propyl t o i s o p r o p y l c h l o r i d e by contact w i t h aluminum c h l o r i d e has a l s o been demonstrated ( 7 9 ) . Moreover, the work of Hart and others (28 ,30) has shown that i n the a l k y l a t i o n of phenol w i t h o p t i c a l l y a c t i v e oC-phenylethyl c h l o r i d e , r a c e m i z a t i o n occurred independently of a l k y l a t i o n , an a p p r e c i a b l e part of the observed l o s s of o p t i c a l p u r i t y being due t o r a c e m i z a t i o n p r i o r to a l k y l a t i o n . On the b a s i s that separate processes account f o r r e a r - rangement and a l k y l a t i o n i n the F r i e d e l - C r a f t s a l k y l a t i o n r e a c t i o n s , the 50% rearrangement observed i n the present s t u d i e s may be v i s u a l i z e d as r e s u l t i n g from the a c t i o n of aluminum c h l o r i d e on the 2 - p h e n y l e t h y l - l - C l l + c h l o r i d e or 2-phenyl- e t h a n o l - l - C ^ . The aluminum c h l o r i d e , being a strong Lewis a c i d , promotes the formation of the l a b e l e d phenylethyl c a t i o n , a f f o r d i n g an opportunity f o r the 1,2-phenyl s h i f t . The r a t e of t h i s c a t a l y s t promoted rearrangement must he f a s t e r or at l e a s t comparable to the r a t e of a l k y l a t i o n ; thus, the phenyl- e t h y l system would have the opportunity of a t t a i n i n g complete e q u i l i b r a t i o n before y i e l d i n g the f i n a l a l k y l a t i o n product. As a f u r t h e r t e s t of such a p o s t u l a t e , p o s s i b l e rearrangement of 2 - p h e n y l e t h y l - l - C l l f c h l o r i d e and 2-phenylethanol-l-C l l + on simple contact w i t h aluminum c h l o r i d e i s c u r r e n t l y being i n v e s - t i g a t e d . I n i n t e r p r e t i n g t h e i r r e s u l t s obtained from ethyl - | 2-C l l + c h l o r i d e , Roberts et a l . (66) suggested that the non-rearrangement i n the e t h y l a t i o n of benzene may mean e i t h e r a displacement mechanism without the formation of the e t h y l c a t i o n , or that a carbonium i o n mechanism i s oper a t i v e but that no hydride s h i f t takes place i n the e t h y l c a t i o n during the e t h y l a t i o n of benzene. However, since these same workers showed.that contact of e t h y l - ^ - C ^ c h l o r i d e w i t h aluminum c h l o r i d e alone r e s u l t e d i n the complete Ik e q u i l i b r a t i o n of the C a c t i v i t y i n both oC and p carbons, one may v i s u a l i z e , on the ba s i s of separate processes governing the rearrangement and a l k y l a t i o n r e a c t i o n s , that i n t h i s case, the a l k y l a t i o n r e a c t i o n i s f a s t e r than the aluminum c h l o r i d e promoted rearrangement. Non-rearranged ethylbenzene i s t h e r e f o r e formed before the c a t a l y s t can e f f e c t a rearrangement of the l a b e l e d e t h y l system. Brown and Jungk (8) have found that the r a t e of a l k y l a t i o n of benzene w i t h methyl i o d i d e i s much slower than that w i t h methyl c h l o r i d e . Should the same d i f f e r e n c e e x i s t between e t h y l c h l o r i d e and i o d i d e , i t may be p o s s i b l e t h a t , i f rearrangement and a l k y l a t i o n do take placd by separate processes, e t h y l a t i o n of benzene w i t h ethyl-^-C i o d i d e may le a d . t o some rearranged product, because the expected slower'rate of e t h y l a t i o n w i t h the i o d i d e would a l l o w the c a t a l y s t promoted rearrangement to take place, at l e a s t to some exte n t , before the f i n a l formation of the end a l k y l a t i o n product. The work w i t h C ^ - l a b e l e d e t h y l i o d i d e i s th e r e f o r e a l s o under current i n v e s t i g a t i o n (39). EXPERIMENTAL 2 -Phenvle tha n o l - l - C l l f A s o l u t i o n of 5 . 7 gm ( 0 . 1 5 moles) of l i t h i u m aluminum hydride i n 200 ml of sodium-dried ether was placed i n a one l i t r e three-necked f l a s k equipped w i t h condenser, dropping f u n n e l , and mercury-sealed s t i r r e r . Through the dropping f u n n e l , a s o l u t i o n of 1 3 . 9 gm ( 0 . 1 0 moles) of p h e n y l a c e t i c lh acid-l-C - 1" was added at such a r a t e as to maintain gentle r e f l u x . One h a l f hour a f t e r complete a d d i t i o n , the r e a c t i o n v e s s e l was immersed i n an i c e - b a t h and water added dropwise to the contents of the f l a s k i n order to decompose excess anhydride. With continued s t i r r i n g , 200 ml of d i l u t e s u l f u r i c a c i d wa,s added, when a c l e a r s o l u t i o n r e s u l t e d . The organic l a y e r was then separated, the aqueous l a y e r e x t r a c t e d w i t h three 25 ml p o r t i o n s of ether and the combined e t h e r e a l s o l u t i o n s washed w i t h sodium bicarbonate s o l u t i o n and water. A f t e r drying over anhydrous magnesium s u l f a t e , the ether was removed by simple d i s t i l l a t i o n and the residue d i s t i l l e d under reduced pressure. Average y i e l d f o r the v a r i o u s t r i a l and r a d i o a c t i v e runs was 1 0 . 9 gm ( 8 8 $ ) , b.p. 2 1 1 1 ^ . 5 - 1 1 5 . 5 ° . * L i t . (56) y i e l d 9 2 $ , b.p # 1g 1 1 2 ° . To recover t r a c e s of r a d i o - a c t i v e product, 10 gm of pjienyethanol was added to the pot, d i s t i l l e d , and combined w i t h the product. lh O x i d a t i o n of 2-Phenylethanol-l-C J- i L _ P h e n y l e t h a n o l - l - C x ( 1 gm), together w i t h 8 gm potassium permanganate, 5 gm sodium hydroxide and 50 ml of d i s t i l l e d water was placed i n a 125 ml erlenmeyer f l a s k and heated on * A l l b o i l i n g p o i n t s are uncorrected A l l melting p o i n t s are c o r r e c t e d f o r stem Axnaan a b o i l i n g water bath f o r three hours, w i t h frequent s t i r r i n g . The f l a s k and contents were then cooled, f i l t e r e d by s u c t i o n , and the p r e c i p i t a t e of manganese d i o x i d e washed thoroughly w i t h d i s t i l l e d water. The combined f i l t r a t e and washings were a c i d i f i e d w i t h d i l u t e s u l f u r i c a c i d and t r e a t e d w i t h s o l i d sodium b i s u l f i t e u n t i l the c o l o r of the permanganate was d i s - charged. The r e s u l t i n g mixture was e x t r a c t e d repeatedly w i t h e t h e r , the e x t r a c t s d r i e d , the ether removed by evaporation and the residue r e c r y s t a l l i z e d from water. The y i e l d of benzoic a c i d was 0 . 7 0 gm ( 7 0 $ ) , m.p. 1 2 0 - 1 2 1 ° . L i t . (hk) y i e l d ( 7 0 - 8 0 $ ) , m.p. 1 2 1 ° . Phenvlurethan of 2-phenylethanol-l-C^ l f A mixture of 1 gm 2 - p h e n y l e t h a n o l - l - C l l f , 1 gm p h e n y l i s o - cyanate and 2 drops of p y r i d i n e were placed i n a 5 ml beaker and heated on a low temperature hot p l a t e f o r twenty minutes. The mixture was then cooled by r e f r i g e r a t i o n and the r e s u l t i n g s o l i d t r a n s f e r r e d t o a funnel and washed ten times w i t h l i g h t petroleum e t h e r . R e c r y s t a l l i z a t i o n from chloroform-petroleum ether y i e l d e d 1 .7 gm (82$) of product, m.p. 7 8 . 5 - 8 0 ° . L i t . (hh) 7 9 - 8 0 ° . 2 - P h e n y l e t h v l - l - C l I f c h l o r i d e A s o l u t i o n of 1 7 . 5 gm of 2 - p h e n y l e t h a n o l - l - C l l t i n 80 ml o f p y r i d i n e was placed i n a 500 ml f l a s k and cooled i n an i c e - bath. T h i o n y l c h l o r i d e ( 3 5 ml) was added dropwise over a p e r i o d of one-half hour. The r e a c t i o n mixture was then heated on a b o i l i n g water bath f o r 10 minutes. The r e s u l t i n g b l a c k s o l u t i o n was allowed to stand a t room temperature f o r one-half 3 1 . hour and then poured s l o w l y , w i t h r a p i d s t i r r i n g , i n t o an i c e - water mixture. The product was e x t r a c t e d w i t h f o u r 100 ml p o r t i o n s of ether and the combined e x t r a c t s washed s u c c e s s i v e l y w i t h d i s t i l l e d water, d i l u t e h y d r o c h l o r i c a c i d , saturated sodium bicarbonate s o l u t i o n , and d i s t i l l e d water. A f t e r d r y i n g over anhydrous magnesium s u l f a t e , the ether was removed by d i s t i l l a t i o n and the residue d i s t i l l e d under reduced pressure. Average y i e l d f o r the v a r i o u s runs was 1 3 . 1 gm ( 6 5 $ ) , D » P » 1 3 8 2 - 8 3 ° . L i t . (1+5) y i e l d 6 6 $ , b . p . ^ 8 5 - 8 7 ° . To recover t r a c e s of r a d i o a c t i v e product, 10 gm of phenylethyl c h l o r i d e was added t o the pot, d i s t i l l e d , and combined w i t h the product. O x i d a t i o n of 2-Phenylethvl-l-C 1 1* c h l o r i d e lh 2 - p h e n y l e t h y l - l - C A c h l o r i d e ( 3 gm) was placed i n a 500 ml f l a s k attached to a r e f l u x condenser. The c h l o r i d e was heated w i t h a f r e e flame to the b o i l i n g point and then a s a t - urated s o l u t i o n of potassium permanganate was added sl o w l y . A f t e r a t o t a l of 10 gm of permanganate as a saturated s o l u t i o n had been added, the mixture was r e f l u x e d f o r 3 0 minutes, cooled, f i l t e r e d by s u c t i o n , and the p r e c i p i t a t e of manganese d i o x i d e washed thoroughly w i t h d i s t i l l e d water. The combined f i l t r a t e and washings were a c i d i f i e d and t r e a t e d w i t h s o l i d sodium b i s u l f i t e u n t i l c l e a r . The r e s u l t i n g s o l u t i o n was e x t r a c t e d repeatedly w i t h ether, the combined e x t r a c t s d r i e d over anhydrous magnesium s u l f a t e and evaporated to dryness. The s o l i d residue was taken up i n d i l u t e sodium hydroxide and washed twice w i t h e t h e r . The a l k a l i n e s o l u t i o n was then a c i d i f i e d w i t h d i l u t e h y d r o c h l o r i c a c i d , the r e s u l t i n g mixture e x t r a c t e d w i t h ether and the combined e x t r a c t s d r i e d over anhydrous magnesium s u l f a t e Removal of the ether and r e c r y s t a l l i z a t i o n of the residue from water y i e l d e d 1 .6 gm (61$) of benzoic a c i d , m.p. 1 2 1 - 1 2 2 ° . Hydrocinnamlc acld - 2-C A mixture of . 6 8 gm (.028 moles) magnesium t u r n i n g s , 1 . 5 gm ( . 0 1 1 moles) 2 - p h e n y l e t h y l - l - C l l f c h l o r i d e and 3 ml of ether was ..placed i n a 200 ml three-necked f l a s k equipped w i t h conden- s e r , mercury-sealed s t i r r e r and dropping f u n n e l . The mixture was s t i r r e d and heated g e n t l y to i n i t i a t e r e a c t i o n . A s o l u t i o n of 2 . 5 gm ( . 0 1 7 moles) of 2 - p h e n y l e t h y l - l - C l l f c h l o r i d e d i s s o l v e d i n 15 ml of ether was added dropwise at j u s t the r a t e to maintain gentle r e f l u x ( 2 0 minutes f o r a d d i t i o n ) . The mixture was then g e n t l y r e f l u x e d f o r one hour and the r e s u l t i n g Grignard reagent poured s l o w l y onto 10 gm of "dry i c e " S t i r r i n g was continued u n t i l a l l of the "dry i c e " had evap- orated and a s t i f f mass r e s u l t e d . A mixture of 10 gm of crushed i c e and 8 ml of d i l u t e h y d r o c h l o r i c a c i d was then added and the mixture s t i r r e d u n t i l the s o l i d had decomposed. The r e s u l t i n g mixture was e x t r a c t e d w i t h three 10 ml p o r t i o n s of ether. The combined e x t r a c t s were washed w i t h water and then e x t r a c t e d w i t h three 10 ml p o r t i o n s of 5$ sodium hydroxide. The combined a l k a l i n e e x t r a c t s were then r e a c i d i f i e d w i t h d i l u t e h y d r o c h l o r i c a c i d . This s o l u t i o n was then e x t r a c t e d w i t h ether, the e x t r a c t s d r i e d , the ether removed and the residue r e c r y s t a l l i z e d from l i g h t petroleum e t h e r . The y i e l d s o f hydrocinnamlc a c i d f o r the v a r i o u s runs averaged 2 . 0 gm ( ^ 7 $ ) , m.p. ^ 8 - ^ 9 ° . L i t . ( L 5 ) y i e l d 7 0 - 8 0 $ , m.p. h8-h9°. A l k y l a t i o n of A n i s o l e w i t h 2-Phenylethanol-l-C 1 1* A n i s o l e ( 130 gm, 1 . 2 0 moles) was placed i n a three-necked 250 ml f l a s k equipped w i t h s t i r r e r , dropping f u n n e l and condenser. Aluminum c h l o r i d e ( 3 0 gm, 0 . 2 3 moles) was added and the mixture lh s t i r r e d u n t i l s o l u t i o n was e f f e c t e d . Phenylethanol-l t-C J- ( 1 7 gm, O.lh moles) was added and the r e s u l t i n g s o l u t i o n , w i t h vigorous s t i r r i n g , heated on a b o i l i n g water bath f o r eight hours. The wine-coloured s o l u t i o n was then poured i n t o an i c e - h y d r o c h l o r i c a c i d mixture, the organic l a y e r separated and the aqueous l a y e r e x t r a c t e d w i t h two 100 ml p o r t i o n s of e t h e r . The combined organic s o l u t i o n s were then e x t r a c t e d w i t h f i v e 100 ml p o r t i o n s of % sodium hydroxide ( u n t i l a c i d - i f i c a t i o n of the a l k a l i n e l a y e r a f t e r e x t r a c t i o n no longer produced an a p p r e c i a b l e p r e c i p i t a t e ) . The organic s o l u t i o n was then r e a c i d i f i e d w i t h d i l u t e h y d r o c h l o r i c a c i d and washed s u c c e s s i v e l y w i t h d i l u t e sodium bicarbonate s o l u t i o n and water. A f t e r drying overnight over anhydrous magnesium s u l f a t e , the solvents were removed and the residue f r a c t i o n a t e d i n vacuo. The product was c o l l e c t e d over the range 1 5 7 - 1 6 3 ° at a pressure of 6 mm. L i t . (77) b.p.g 1 6 6 - 1 6 7 ° . On s t o r i n g f o r s e v e r a l days i n a r e f r i g e r a t o r , the l i q u i d product p a r t i a l l y s o l i d i f i e d . I t was then r e c r y s t a l l i z e d three times from 95$ methanol. Y i e l d s of jD-methoxydibenzyl f o r the v a r i o u s runs ranged between 2 . 8 2 and 2 . 9 6 gm ( 9 . 7 - 1 0 . 2 $ ) , m.p. 5 9 . 5 ° - 6 0 . 5 ° . L i t , (77) 6 0 - 6 1 ° , (11) 6 1 - 6 2 ° . A l k y l a t i o n of A n i s o l e w i t h 2 - P h e n v l e t h v l - l - C l I t c h l o r i d e A n i s o l e ( 130 gm, 1 .2 moles) was placed i n a three-necked 250 ml f l a s k equipped w i t h mercury-sealed s t i r r e r , dropping f u n n e l and condenser. Aluminum c h l o r i d e (30 gm, 0.23 moles) was added and the mixture s t i r r e d u n t i l s o l u t i o n was e f f e c t e d . 2-phenylethyl-l-C c h l o r i d e (19.3 gm, 0.1V moles) was then added and, w i t h continued vigorous s t i r r i n g , the r e s u l t i n g mixture heated on a b o i l i n g water bath f o r s i x hours. The r e a c t i o n mixture was hydrolyzed and worked up as described i n the a l c o h o l run. Y i e l d s of jD-methoxydibenzyl f o r the v a r i o u s runs ranged between 2.63 and 2.86 gm (9.0-9.8$), m.p. 59.5-60.5°. O x i d a t i o n of p-Methoxvdibenzyl In a two-necked 1000 ml f l a s k equipped w i t h condenser and s t i r r e r were placed 500 ml of 3»2$ potassium permanganate s o l u t i o n , 3*5 gm potassium hydroxide, and 2.0 gm of p-methoxy- d i b e n z y l . The mixture was r e f l u x e d , w i t h s t i r r i n g , f o r 120 hours, a f t e r which the f l a s k and contents were cooled and the manganese d i o x i d e f i l t e r e d o f f by s u c t i o n . The water white f i l t r a t e was s l o w l y evaporated t o a volume of about 200 ml before a c i d i f y i n g w i t h d i l u t e s u l f u r i c a c i d . The r e s u l t i n g mixture was e x t r a c t e d repeatedly w i t h ether and the combined e x t r a c t s d r i e d and evaporated to dryness. The residue was d i s s o l v e d i n d i l u t e sodium hydroxide, washed w i t h ether, and r e a c i d i f i e d . Repeated e x t r a c t i o n w i t h e t h e r , f o l l o w e d by drying and removal of the ether and two r e c r y s t a l l i z a t i o n s of the r e s u l t i n g residue y i e l d e d pure a n i s i c a c i d , m.p. 182.5- 183.5°. L i t . (71) 18V°. Y i e l d s f o r the v a r i o u s runs averaged 0.15 gm (10$). 35, BIBLIOGRAPHY 1 . Alexander, E. R. 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