Reduction of Organic Compounds by Lithium in Amines of Low

Reduction of Organic Compounds by Lithium in Amines of Low Molecular Weight ROBERT A. BENKESER

Downloaded by UNIV OF IOWA on September 3, 2016 | http://pubs.acs.org Publication Date: January 1, 1959 | doi: 10.1021/ba-1959-0023.ch005

Department of Chemistry, Purdue University, Lafayette, Ind.

Lithium dissolved in amines of low molecular weight is a stronger reducing agent than sodium in ammonia. This reagent does not require addition of an acid such as alcohol to initiate the reaction. The mechanisms of the 1,4-reductions produced by the lithium-amine system are explained. Even at dry ice temperatures, compounds capable of conjugation are isomerized partially by the lithium alkylamides produced in the lithium-amine reductions. This is shown by inspection of the ultraviolet absorption spectra of the products.

The r e d u c t i o n o f o r g a n i c c o m p o u n d s b y a l k a l i o r a l k a l i n e e a r t h m e t a l s d i s s o l v e d i n l i q u i d a m m o n i a h a s been discussed e x t e n s i v e l y a n d i s t h e s u b j e c t o f s e v e r a l excellent r e v i e w s ( 5 , 11,12). T h e a m m o n i a b r i n g s r e l a t i v e l y h i g h c o n c e n t r a t i o n s of electrons a n d o r g a n i c m a t e r i a l i n t o close p r o x i m i t y , p e r m i t t i n g a s m o o t h t r a n s f e r o f t h e e l e c t r o n s t o t h e organic compound. T h e exact m e c h a n i s m b y w h i c h this electron transfer occurs has not been determined. T h e f o r m a t i o n of a n organometallic intermediate m a y be envisioned w i t h relatively covalent carbon-metal bonds o r s i m p l y electronic transfer, p r o d u c i n g r a d i c a l ions ( o n e - e l e c t r o n t r a n s f e r ) o r d i a n i o n s ( t w o - e l e c t r o n t r a n s f e r ) , d e p e n d i n g o n t h e n u m b e r of electrons c a p t u r e d i n i t i a l l y b y t h e o r g a n i c m a t e r i a l . T h e s e finer p o i n t s o f t h e m e c h a n i s m a r e u n d e t e r m i n e d , b u t t h e gross f e a t u r e s o f t h e r e d u c t i o n s c a n b e expressed as a t w o - s t e p p r o c e s s : e l e c t r o n t r a n s f e r r e v e r s i b l y f r o m the solvent o r m e t a l atoms t o t h e organic compounds, a n d solvolysis of t h e resulting i n t e r m e d i a t e , w i t h f o r m a t i o n of a r e d u c e d p r o d u c t a n d a n a l k a l i o r a l k a l i n e - e a r t h a m i d e . T h u s , n a p h t h a l e n e i s r e d u c e d b y s o d i u m i n a m m o n i a t o T e t r a l i n (13) :

(1) A v a r i e t y o f m e t a l s s u c h as l i t h i u m , s o d i u m , p o t a s s i u m , c a l c i u m , b a r i u m , a n d s t r o n t i u m h a v e b e e n u s e d as r e d u c i n g agents i n c o n j u n c t i o n w i t h a m m o n i a as t h e s o l v e n t . H o w e v e r , s o d i u m i n a m m o n i a h a s been t h e m o s t p o p u l a r c o m b i n a t i o n . 58

METAL-ORGANIC COMPOUNDS Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

59

BENKESER—REDUCTION OF ORGANIC COMPOUNDS BY LITHIUM

O f t e n a n a c i d s u c h as m e t h a n o l , e t h a n o l , o r a m m o n i u m c h l o r i d e m u s t b e a d d e d t o effect r e d u c t i o n i n t h i s s y s t e m . S o d i u m i n a m m o n i a does n o t r e d u c e benzene, t o l u e n e , x y l e n e , a n d o t h e r a r o m a t i c c o m p o u n d s , b u t r e d u c t i o n o f these m a t e r i a l s w i l l o c c u r i n t h e presence o f a l c o h o l (12) w i t h the f o r m a t i o n o f 1 , 4 - d i h y d r o p r o d u c t s .

+

NaOEt

(2)


T h e 1,4-nature o f these r e d u c t i o n s c a n b e r a t i o n a l i z e d b y a s s u m i n g a d i a n i o n intermediate. E n e r g e t i c a l l y , a double negative charge w o u l d be more favorable i n a 1,4- t h a n i n a 1,2-position. T h u s , 1,4-reduction s h o u l d p r o c e e d m u c h m o r e r a p i d l y

Less stable

More

stable

t h a n a 1,2-reduction. B e c a u s e r e d u c t i o n occurs o n l y i n t h e presence of e t h a n o l , e q u i l i b r i u m a i n E q u a t i o n 2 should l i e f a r t o the left. T h e a d d i t i o n of ethanol, a s t r o n g e r a c i d t h a n a m m o n i a , shifts t h i s e q u i l i b r i u m t o t h e r i g h t b y p r o t o n a t i n g t h e dianion intermediate. S o d i u m ethoxide is formed concomitantly. T h e latter is n o t effective a t — 3 3 ° i n c a u s i n g a n i s o m e r i z a t i o n o f the 1 , 4 - d i h y d r o p r o d u c t t o a c o n j u g a t e d s y s t e m . H e n c e , t h e r e d u c t i o n e s s e n t i a l l y stops a t t h i s p o i n t because o f t h e slowness o f 1,2-reductions. L i t h i u m dissolved i n certain low molecular amines is a more powerful reducing m e d i u m t h a n s o d i u m i n l i q u i d a m m o n i a (1, 3, 4 ) . I s o l a t e d benzene r i n g s are r e d u c e d s e l e c t i v e l y t o m o n o - o l e f i n s b y t h i s reagent (3). T h u s , benzene i t s e l f i s r e d u c e d t o c y c l o h e x e n e (3), b i p h e n y l t o 1 - c y c l o h e x y l c y c l o h e x e n e (3), n a p h t h a l e n e t o A » - o c t a l i n (1,2,3,4,5,6,7,8-octahydronaphthalene) (3), e t h y l b e n z e n e t o 1 - e t h y l c y c l o h e x e n e (3), a n d fluorene t o 1,2,3,4-tetrahydrofluorene (2). 9

10

A r o m a t i c c o m p o u n d s c o n t a i n i n g r e d u c i b l e f u n c t i o n a l g r o u p s are also a t t a c k e d b y the l i t h i u m - a m i n e reagent. Acetophenone is reduced t o α-Δ'-cyclohexenylethyl alcohol (1), 2 - p h e n y l e t h a n o l t o β - Δ ' - c y c l o h e x e n y l e t h y l a l c o h o l (1), a n d b e n z y l n i t r i l e t o β - Δ ' c y c l o h e x e n y l e t h y l a m i n e ( 1 ). T h i s r e a c t i o n h a s been a p p l i e d i n s t e r o i d a n d ferrocene c h e m i s t r y (10). I n the latter instance, i t holds promise f o r p r e p a r i n g substituted cyclopentadiene d e r i v a tives. N o a c i d s u b s t a n c e s u c h as a l c o h o l needs t o b e a d d e d t o t h e l i t h i u m - a m i n e reagent t o b r i n g a b o u t r e d u c t i o n . A possible e x p l a n a t i o n i s t h a t e q u i l i b r i u m α i n E q u a t i o n 2 lies f a r t h e r t o t h e r i g h t i n t h e l i t h i u m - a m i n e s y s t e m . U n d o u b t e d l y t h e l i t h i u m ions p r o d u c e d i n e q u i l i b r i u m a w o u l d b e m o r e h i g h l y s o l v a t e d t h a n w o u l d s o d i u m ions because o f t h e i r s m a l l e r a t o m i c r a d i u s a n d the m o r e b a s i c n a t u r e o f t h e solvent ( R N H vs. N H ) . A s a consequence of t h i s h i g h e r c o n c e n t r a t i o n , t h e i n t e r m e d i a t e is p r o t o n a t e d r a p i d l y b y t h e s o l v e n t , f o r m i n g 1 , 4 - d i h y d r o p r o d u c t s a n d a l i t h i u m a l k y l a m i d e . T h e l a t t e r , because of i t s h i g h s o l u b i l i t y a n d s t r o n g l y b a s i c n a t u r e , r e a d i l y c a n cause i s o m e r i z a t i o n of t h e 1,4-products t o c o n j u g a t e d dienes w h i c h a r e t h e n r e d u c e d f u r t h e r b y t h e reagent. 2

3

T w o pieces o f e v i d e n c e i n d i c a t e t h e 1,4-nature of t h e l i t h i u m - a m i n e r e d u c t i o n s . A n i s o l e was treated w i t h t w o equivalents of l i t h i u m , a n d the m i x t u r e was h y d r o l y z e d q u i c k l y a n d w o r k e d u p . U l t r a v i o l e t absorption i n d i c a t e d t h a t 4 7 % of the p r o d u c t w a s 2 , 3 - d i h y d r o a n i s o l e a n d 5 3 % w a s t h e 2,5-isomer ( j f ) . T h u s , e v e n u n d e r t h e f a v o r a b l e i s o m e r i z i n g c o n d i t i o n s w h i c h p r e v a i l e d , a p r e p o n d e r a n c e o f t h e 1,4-isomer


ADVANCES IN CHEMISTRY SERIES

60


was observed. T h e r e d u c t i o n o f 2 , 3 - d i m e t h y l - l , 3 - b u t a d i e n e gave a l m o s t e x c l u s i v e l y 2 , 3 - d i m e t h y l - 2 - b u t e n e (2). T h a t t h i s c o m p o u n d r e s u l t e d f r o m a 1 , 4 - r e d u c t i o n w a s i n d i c a t e d w h e n a n a u t h e n t i c s a m p l e of t h e 1-olefin was n o t i s o m e r i z e d a p p r e c i a b l y u n d e r t h e r e a c t i o n c o n d i t i o n s of t h e r e d u c t i o n . T h e i m p o r t a n c e o f t h e i s o m e r i z i n g p o t e n t i a l o f t h e l i t h i u m - a m i n e s y s t e m was demonstrated b y 1,4,5,8-tetrahydronaphthalene. E v e n at d r y ice temperatures this c o m p o u n d w a s i s o m e r i z e d , a t least i n p a r t , t o a c o n j u g a t e d s y s t e m b y t h e l i t h i u m a l k y l a m i d e s p r o d u c e d i n the l i t h i u m - a m i n e reductions. B u t even a saturated solution of s o d i u m a m i d e i n l i q u i d a m m o n i a was n o t as effective a n i s o m e r i z i n g agent a t — 7 8 ° C , as j u d g e d b y a n u l t r a v i o l e t a b s o r p t i o n s p e c t r u m o f t h e p r o d u c t (2). W h e n i e r i - b u t y l b e n z e n e w a s r e d u c e d w i t h t h e l i t h i u m - a m i n e reagent, a m i x t u r e of m o n o - o l e f i n s was p r o d u c e d (2). B u t t h e r e d u c t i o n o f t o l u e n e u n d e r c o m p a r a b l e conditions gave almost exclusively 1-methylcyclohexene. T h i s difference i n p r o d u c t m a y b e associated w i t h t h e i n a b i l i t y of t h e basic m e d i a t o effect i s o m e r i z a t i o n o f t h e olefin m i x t u r e t o t h e m o r e t h e r m o d y n a m i c a l l y stable 1-isomer i n t h e presence o f t h e bulky ieri-butyl group.

Experimental T h e g e n e r a l r e d u c t i o n p r o c e d u r e e m p l o y e d i n e a r l i e r w o r k (13) w a s u s e d t h r o u g h out. 1,2,3,4-Tetrahydrofluorene. T h e c r u d e p r o d u c t f r o m t h e r e d u c t i o n o f fluorene was r e c r y s t a l l i z e d t w i c e f r o m 9 5 % e t h a n o l . A n 8 3 % y i e l d o f m a t e r i a l m e l t i n g a t 5 5 - 6 ° C . was realized (literature 5 7 ° C ) . A picrate melted at 71-2°C. (literature 72°C). T h e i n f r a r e d s p e c t r u m of the 1 , 2 , 3 , 4 - t e t r a h y d r o f l u o r e n e i n d i c a t e d t h e presence of a n a r o m a t i c r i n g ( p e a k a t 6.25 m i c r o n s ) a n d of a d o u b l e b o n d c o n j u g a t e d w i t h a n a r o m a t i c r i n g ( p e a k a t 6.15 m i c r o n s ) . 2,3-Dimethyl-2-butene. 2 , 3 - D i m e t h y l b u t a d i e n e (17.1 g r a m s ; 0.207 m o l e ) w a s r e d u c e d i n c o n v e n t i o n a l f a s h i o n . F r a c t i o n a t i o n of t h e p r o d u c t y i e l d e d 5.99 g r a m s , b o i l i n g p o i n t , 7 0 - 4 ° C . , n™, 1 4 0 7 ; 1.8 g r a m s , b o i l i n g p o i n t 7 5 - 9 ° C , n ° 1.409; a n d h i g h e r b o i l i n g m a t e r i a l . A l l f r a c t i o n s b o i l i n g a b o v e 7 0 ° C . gave a s o l i d b r o m i n e a d d i t i o n c o m p o u n d w h i c h i s c h a r a c t e r i s t i c o f 2 , 3 - d i m e t h y l - 2 - b u t e n e b u t n o t of t h e 1-isomer. 2,3-Dimethyl-2-butene has a boiling point of 7 2 - 3 ° C . (9), n f ? 1.411. 2 , 3 - D i m e t h y l - l - b u t e n e b o i l s a t 5 5 ° C . a n d has a n i n d e x o f r e f r a c t i o n a t 2 0 ° C . o f 1.389 (9). A n a u t h e n t i c s a m p l e o f 2 , 3 - d i m e t h y l - l - b u t e n e ( 4 . 5 g r a m s ) w a s s t i r r e d f o r 30 m i n u t e s w i t h a s o l u t i o n o f l i t h i u m m e t h y l a m i d e i n m e t h y l a m i n e . A f t e r w o r k ing u p the product, little i f any isomerization occurred. T h e recovered m a t e r i a l boiled a t 5 5 - 7 ° C . (n l 1.3904). 2

D

2

Isomerizations of 1,4,5,8-Tetrahydronaphthalene. A n authentic sample of 1 , 4 , 5 , 8 - t e t r a h y d r o n a p h t h a l e n e ( m e l t i n g p o i n t 5 6 ° C . ) was p r e p a r e d b y t h e m e t h o d o f H u c k e l ( 7 ) . T h e ultraviolet s p e c t r u m of this c o m p o u n d ( 0 . 0 0 1 M solution i n 9 5 % ethanol) showed n o peaks for a conjugated o r aromatic system. L i t h i u m Methylamide. A 3 - n e c k e d flask (200 m l . ) w a s fitted w i t h a d r y i c e condenser, a s t i r r e r , a n d a D r i e r i t e - s o d i u m h y d r o x i d e d r y i n g t u b e ; 100 m l . o f m e t h y l a m i n e was condensed i n t h i s , a n d 0.14 g r a m of l i t h i u m a n d 4 g r a m s o f benzene were a d d e d . A f t e r a l l t h e l i t h i u m h a d r e a c t e d , t h e s o l u t i o n was c o o l e d w i t h a d r y ice b a t h ( — 7 8 ° C ) . T o t h e c o o l e d s o l u t i o n , 2.44 g r a m s o f 1 , 4 , 5 , 8 - t e t r a h y d r o n a p h t h a l e n e i n 2 0 m l . of e t h e r w a s a d d e d . I n a b o u t 15 m i n u t e s , t h e s o l u t i o n t o o k o n a r e d c o l o r w h i c h d e e p e n e d t o w a r d t h e v i o l e t . A f t e r 1.5 h o u r s , t h e m i x t u r e w a s h y d r o l y z e d w i t h a b o u t 100 m l . o f w a t e r . T h e r e a c t i o n p r o d u c t was e x t r a c t e d w i t h s e v e r a l p o r t i o n s o f e t h e r . T h e e x t r a c t s were w a s h e d w i t h w a t e r a n d d r i e d o v e r D r i e r i t e . T h e ether was e v a p o r a t e d a n d the residue was placed u n d e r 5 m m . of p r e s s u r e a t r o o m t e m p e r a t u r e t o r e m o v e r e s i d u a l v o l a t i l e m a t e r i a l ; 1.9 g r a m s o f h y d r o c a r b o n was obtained, m e l t i n g p o i n t 47-51 ° C . A n u l t r a v i o l e t s p e c t r u m showed m o d e r ate a b s o r p t i o n i n t h e areas o f c o n j u g a t e d d o u b l e b o n d s ( T a b l e I ) .


BENKESER—REDUCTION OF ORGANIC COMPOUNDS BY LITHIUM Table I.

61

Isomerization of 1,4,5,8-Tetrahydronaphthalene e* Χ 10~

3

Base System* LiMeNH—MeNH 1

NaNH2—NHs

2

Sample Wt., G . 1.0 2.4 1.0 0.64

Temp., °C.«> -36 -78 -36 -78

Time, Hr. 1.0 1.5 1.0 1.5

M . P . Prod., °C. liq. 47-51 38-43 54-5

221 τημ 15.10 4.86 14.00 1.89

Reduction of Organic Compounds by Lithium in Amines of Low

Recommend Documents