Microwave-Assisted Rapid and Simplified Hydrogenation

7/30/2019 Microwave-Assisted Rapid and Simplified Hydrogenation

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Microwave-Assisted Rapid and Simplified Hydrogenation1,

B i m a l K . B a n i k, K h a l e d J . B a ra k a t , Dilip R. Wagle, M a g h a r S . M a n h a s , a n d A ja y K . B o s e*

George B arasch B i oorgani c Research L aborat ory, D epart m ent of Chemi st ry and Chemi cal B i ol ogy,Stevens I nstit ute of T echnology, H oboken, N ew J ersey, 07030

Received July 30, 1998

Ca ta lytic tra nsfer hydrogenat ion ha s b een conducted under microwa ve irradia tion in open vessels

using high-b oil ing solvents such as ethylene glycol (b p 198 C) a s the microwave energy tra nsf era gent. Reduction of double bonds a nd hy drogenolysis of several functiona l groups were carried out

s a f e ly a n d r a p i d ly (3-5 m i n ) a t a b o u t 1 1 0-130 C with 10% P d/C as an ef ficient cata lyst a ndam monium f ormat e as the hyd rogen donor. Diverse types of -lacta m synt hons were prepar ed b yt h e r e du ct i on of r i n g s u bs t i t u en t s co nt a i n in g a l k en e a n d a l k y l id e n e g r o up s or co nju g a t e d

u n s a t u r a t e d e s t er s . C l e a v a g e o f t h e -lactam ring b y hydrogenolysis of the N-C 4 bond of 4-a ryl-2-azetidinones w as a faci le reaction w ith 10%P d/C as the cata lyst ; b ut no r ing scission occurred

w h e n R a n e y n i ck el c a t a l y s t w a s e m pl oy e d . D e h a l og e n a t i on of a r om a t i c c om p ou n d s w a s a l s osuccessful with a mmonium forma te a nd P d/C ca ta lyst. H ydrogenolysis of phenylhydra zone of methyl

benzoylforma te ga ve th e methy l ester of phenylglycine in excellent yield. The techniqu es describedhere for microwa ve assisted hyd rogena tion are sa fe, rapid, and efficient a nd a re suita ble for resea rch

investigation as well as f or undergraduate and high school lab oratory exercises.

Introduction

La b ora tory-scale cata lytic hydrogenation2 plays a keyrole in chemical research and the synthesis of organic

intermediates. Any simplif ication of this operation is,therefore, potential ly useful provided t he tota l process

is safe and ecologically friendly. Industrial-scale hydro-g en a t i on , w h i ch h a s s p eci a l r e q u ir e m en t s , w i l l n o t b e

considered here.

In most organic lab oratories i t is a common practice

to conduct cata lytic reduction or hydrogenolysis under40 psi pressure in a commercial ly availab le apparatus.

P u r e h y d r o g e n g a s f r o m a c y l i n d e r f i t t e d w i t h a n a p -p rop ri a t e v a l ve s y st e m i s r eq u ir ed . Th e a i r i n t h ehydrogenator has to b e completely removed either b y

f lushing the syst em for several minutes w ith hydrogen,or , b y r e pe a t e d ly p u m pi n g t h e s y s t e m d o w n t o a l ow pressure and ref i l l ing with hydrogen. Lab oratories in

r e m ot e l oc a t i on s m a y n ot h a v e a l l of t h e s e f a c i li t i esava ilab le at short notice. M any teaching lab orat ories are

often not equipped w ith m ultiple units for f requent useb y groups of students.

Some hyd rogenat ion processes are more effective under

higher pressu re (1000 psi or more) a nd t hus req uire moreelaborate equipment. Considerable amounts of hydrogen

a r e w a s t e d d u ri n g t h e f lu s hi ng of s u ch e q ui pm en t .Hydrogen and air mixtures are potential ly hazardous i f

f lames or sparks are produced in the neighb orhood ofhydrogenators.

Results and Discussion

Catalytic Transfer Hydrogenation.In recent yearsa f ew l a bor a t o ri es h a v e s t a r t e d t o e mp loy ca t a l yt i c

tra nsfer hydrogena tion (CTH).3 This is a sa fe and simpleop er a t i on i n w h i ch a ca t a l ys t a n d h y d rog en g a s a r er e pl a c ed w i t h a c a t a l y s t a n d a h y d r og e n d on or s u c h a s

cyclohexane, 4 hydrazine, 5 formic acid,6 ammonium f or-m a t e ,7 cyclohexadiene, 8 an d phosphinic a cid,9 sodium

hypophosphite.10 This t ype of hydrogena tion is usuallyconducted in f lasks f i t ted w ith a ma gnetic st irrer an d a

reflux condenser. Ethyl alcohol is a widely used solventfor CTH.

De di c at e d t o Prof . Sasanka C . Bhat t ac hary y a on t he oc c asi on ofhi s 8 0t h bi rt hday .

Pre se nt addre ss: U ni ve rsit y of Te x as, M. D. Ande rson C a nc erCenter, Houston, TX 77030.

Pre se nt a ddre ss: Me rck C om pany , Ra hwa y , N J 0 70 65 . P resent ad dress: Alteon Inc., Ramsey, NJ 07446.(1) Microwa ve-induced organ ic reaction enha ncement (MORE) chem-

i st ry . Part 1 3. For Part 1 2, se e: Ba ni k, B. K. ; J ay a ram a n, M.; Srirajan,V.; Manha s, M. S. ; B ose, A. K. J. Ind. Chem. Soc. 1997, 74, 951. For

Pa rt 1 1 , se e : Bose , A. K. ; Ba ni k, B. K. ; L avl i nskai a, N .; J ay a ram a n,M . ; M a n h a s , M . S . Chemtech 1997, 27 (9), 18.(2) For some heterogeneous hydr ogenation met hods, see: (a) Ry-

l ande r, P. N .; H ydrogenati on M ethods; Academic Pr ess: Orland o, FL,1985. (b) J ohnstone, R. A. W.; Wilby, A. H.; Entwistle, I . D. Chem.Rev. 1985, 85, 1 2 9 . ( c ) We i r, I . R. ; Pat e l , B . A.; H e c k, R. F. J . O r g .Chem. 1980, 45, 4926. (c) Brown, C. A. J. Org. Chem. 1970, 35, 1900.For some homogeneous hydrogenat ion methods, see: (d) Gr eenspoon,N.; Keinan, E. J . J . Org. Chem. 1988, 53, 3723. (e) Tsuji, J .; Suguira,T.; Mai na m i , I . S ynthesis 1987, 603. (f) Grigg, R.; Mitchell , T. R. B.;S u t t h i va i y a k it , S . Tetrahedron L ett. 1979, 1 06 7. (g ) J am e s, B. R.H omogeneous H ydr ogenat ion; Wiley: New York, 1973 and referencestherein. Use of finely dispersed metal particles or colloids in a polymerm at ri x ha s at t rac t e d a t t e nt i on re ce nt l y for hy drog e nat i on. Se e : Tour,J . M.; C oope r, J . P. ; Pe ndal war, S . L . J . O r g . C h em . 1990, 55, 3452and references therein.

(3 ) (a) Ra jag opal , S . ; Anwe r, M. K. ; S pat ol a, A. F . I n Peptides:Design, Synth esis and Bi ological Acti vity; Basava , C . , Anant ha ram ai ah,G. M., Ed s.; Birkha user: Boston, 1994; Chapter 2, p 11. (b) Ra o, H. S.P . ; R ee dy , K . S . Tetrahedron Lett. 1994, 35, 1 71 . ( c) R a m , S . ;E hre nkaufe r, R. E . Synthesis 1988, 91.

(4) (a) Viswa na tha , V.; Hruby, V. J. Org. Chem. 1980, 45, 2010. (b)J ackson, A. E.; J ohnst one, R. A. W. Synthesis 1977, 685. (c) Brieger,G.; Nestr ick, T. J . Chem. Rev. 1974, 74, 567. (d) Braude, E. A.; Listead,R . P . J. Chem. Soc. 1954, 3544.

( 5 ) ( a) Anwe r, M. K. ; Khan, S. A.; Si vanandai ah, K. M. Synthesis1978, 751. (b) Furst , A.; Berlo, R. C.; Hooton, S. Chem. Rev. 1965, 65,51.

(6) (a) Gray, B. D.; J effs, P. W. J. Chem. Soc. Chem. Commun. 1987,1 32 9. ( b) E l am i n, B. ; Anant ha ram a i ah, G . M.; Roy er, G. P. ; Me an s, G.E . J . O r g . C h em . 1979, 44, 3442.

5746 J . O r g . C h em . 1999, 64 , 5746-5753

10.1021/jo981516s CC C: $18.00 1999 American C hemica l SocietyP ub lis h ed on Web 07/20/1999


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Recently we11 h a v e d e m on s t r a t e d t h a t ca t a l y t i c t r a n s -fer hydrogena tion can b e conducted very rapidly a nd inessential ly quanti tative yield inside an unmodif ied do-

mestic microwave oven. We present here details of ourtechnique and indicate the scope of reduction and hy-

drogenolysis a chieved under microwave irradia tion.

Microwave-Assisted Reactions. Tw o pioneering pa-pers 12 appeared in 1986 on remarkab le acceleration ofman y organic reactions upon irradiat ion w ith microwa ves

(2450 MHz). Since then, a number of la borat ories, includ-i n g ou r ow n , h a v e b ee n s t u d y i ng m i cr ow a v e-a s s i s t ed

chemical syn thesis.13 Some research groups conduct theirreactions in sealed tub es, which can withstand several

atmospheres of pressures, but occasional explosions havebeen reported due to the high pressure from a rapid risein temperature.

A few lab oratories 14a avoid t he r isk of explosions b y

con d u ct i n g m i cr ow a v e-a s s i s t e d r e a c t ion s a t a m b i e n tp r es s u r e b y i r r a d i a t i n g r e a ct a n t s a d s o r be d on s ol id

supports such a s clay, a lumina, or si l ica gel.

Special microwave ovens have been designed by someg r ou ps t o p r ev en t e xp los ion s ca u s e d b y r u n a w a yreactions. 14b We prefer to conduct experiments in open

vessels in inexpensive, unmodified, domestic microw a veovens. A wide variety of compounds ha ve b een synthe-

sized using our microwave-induced organic r eactionenhancement (MORE) chemistry techniques.15

These techniques are also very convenient f or rapidand saf e catalytic transfer hydrogenation experiments.

MORE Chemistry Techniques. We have developedan unconventional experimental set up for conductingorgan ic reactions to ta ke adva nta ge of the special na ture

of microwave energy.

Erlenmeyer f lasks or b eakers with loose covers arepreferred r eaction vessels for a mbient pressure rea ctionsin unmodif ied domestic microwave ovens. The upper

part s of these vessels remain cool since glass is tra nspar-

ent to microwa ves. The solvent (microwa ve energy t ra ns-

fer agent) should be polar a nd w ith a suitably high boilingpoint at least 20 or 30 higher than the projected reactiontemperature.

Domestic microwave ovens produce 2450 MHz radia-tion at a rat e tha t is controlled to a moderate degree bya n o n-off cycle. F or f iner control of the microwave

energy input int o sma ll-scale reaction mixtures, i t isconvenient to use a hea t sinksa beaker of water placed

next to the reaction vessels inside the oven. This heats in k w i t h a p pr op ri a t e a m o un t s of w a t e r ca p t u r es as i gn i fi ca n t a m o u n t of t h e m i cr ow a v e e n e r g y t h e r eb y

reducing t he energy supplied to t he rea ction mixture.Since microwa ve energy is absorbed by all of the polar

m ol ecu le s a n d i on s a t t h e s a m e t i m e, n o s t i r r er i srequired for reaction mixtures in sha llow layers. Fla sks

with ground glass joints, heat ing man tles, and the otherstandard equipment of a conventional organic laboratorya re not needed. Reflux condensers ar e unnecessary since

liquids are maintained well b elow their b oil ing pointswhen M ORE chemistry techniques are used.

Microwave-Assisted CTH. Ethylene glycol (bp 198 C) or m ore eco-friendly 1,3-propan ediol, bp 210-212 C,

as the solvent and ammonium formate as the hydrogendonor form an excellent combination for catalytic transferhydrogenation under microwave irradiation. Hydrazine

h y d r a t e w a s u s ed a s t h e h y d r o g en d o n or i n a f ew ca s e sb ut am monium forma te proved to b e more convenient.

M ost of our studies on CTH reactions have b een con-ducted w ith P d/C (10%) ca ta lyst . A few experiments w ere

ca t a l y z ed w i t h R a /N i c a t a l y s t . S i n ce P d /C c a t a l y s t i ssometimes a pyrophoric powder, a specific protocol forCTH experiments w a s developed for ensuring sa fety (see

the Experimenta l Section). Representa tive examples ofCTH experiments are described below.

Reduction and Hydrogenolysis of-Lactams. Atthe beginning of these studies, test runs w ith a mmonium

format e reduction in th e presence of 10%P d/C showedt h a t ol ei c a n d l in ol ei c a c i ds (on a 1-2 g s c a l e ) , w e r ecompletely reduced to stearic acid in only 1-2 m i n a t

ab out 110-130 C. We were, therefore, encouraged toundertake a detai led examination of CTH experiments

of various types.In the course of studies on sub sti tuted -l a c t a m s a s

synthons for natural products, various -lactams withunsaturated sub sti tuents were prepared. Some of theseh a d b ee n r ed u ce d i n t h e p a s t b y con v en t i on a l l ow -

pressure hydrogenation in the presence of Raney nickelor P d /C c a t a l y s t s . N ow t h e m i cr ow a v e-a s s i s t ed C TH

technique was applied to several of these compoundsusing commercia lly ava ilable Raney nickel cat alyst wh en

reduction products were obtained in about 80%yield orb etter in a few minutes. Thus, 1 with an N-allyl groupwas reduced to 2 wit h a n N -propyl group (Scheme 1). Thev i n y l g r o u p a t C - 3 w a s c o n v e r t e d t o t h e e t h y l g r o u pduring t he reduction of 3 t o 4 (S cheme 2).

When 10%Pd /C w a s used as t he cata lyst t he -lactam5 underwent selective hydrogenolysis of the O-benzyl

(7) (a) Anwer M. K.; Spatola, A. F. Synthesis 1980, 9 29 , and l at e rpublicat ions. (b) Adger, B . M.; OFar rell , C.; Lew is, N. J .; Mitchell , M.B . Synthesis 1987, 53. (c) Carpino, L.; Tunga, A. J. Org. Chem. 1986,11, 1 9 3 0 . ( d) Ram , S. ; E hre nkaufe r, R. E . Synthesis 1986, 133. (e)O ve r m a n , L . E . ; S u g a i , S . H e l v . C h i m . Ac t a 1985, 68, 745. (f) For are ce nt re vi ew se e : Ranu, B . C . ; Sarka r, A.; Guc hhai t , S . K. ; Ghosh, K.J. Ind. Chem. Soc. 1998, 75, 690.

(8) (a) Bajwa, J . S. Tetrahedron Lett. 1992, 33, 2299. (b) Felix, A.M.; Heimer, E. P.; Lambros, T. J .; Tzougraki, C.; Meienhofer, J . J . O r g .Chem. 1978, 43, 4194.

(9) (a) E ntw istle, I . D.; Gilkerson, T.; J ohnst one, R. A. W.; Telford,R . P . Tetrahedron1978, 34, 313. (b) Entw istle, I . D.; J ohnstone, R. A.W.; Telford, R. P. J. Chem. Res. (S) 1977, 117.

(1 0) Marq ue s, C . A.; Se l va, M.; Tundo, P. J. Chem. Soc., PerkinT r a n s . I 1993, 529.

(11 ) (a ) B o se , A . K . ; B a n i k , B . K . ; B a r a k a t , K . J . ; M a n h a s , M . S .Synlett 1993, 5 7 5 . ( b) Bose , A. K. ; Manhas, M. S. ; Ghosh, M.; Shah,M.; Raju, V. S. ; Bari , S . S . ; N e waz , S . N .; Ba ni k, B. K. ; C haudha ry , A.

G . ; B a r a k a t , K . J . J. Org. Chem. 1991, 56, 6968.(1 2) (a) G e dy e , R. N .; S m i t h, F. ; We st awa y , K. ; Al i , H . ; B al di se ra,L . ; L abe rg e , L . ; Roussel l , J . Tetrahedron Lett. 1986, 27, 279. (b)Gi g ue re , R. J . ; Bra y , T. L . ; Dunc an, S. M.; Ma jet i ch, G . TetrahedronLett. 1986, 27, 4945.

(1 3) For a re ce nt re vie w, se e : C addi c k, S. Tetrahedron 1995, 51,10403.

(14) (a) Villemin, D.; Labiad, B. Sy n t h . C om m u n . 1990, 20, 3213.(b ) C s i b a , M . ; C l eop h a x , J . ; L ou p y, A. ; M a l t h et e , J . ; G e r o, S . D .Tetrahedron Lett. 1993, 34, 1787. (c) Pilard, J . F.; Klein, B.; Texier-boullet, F.; H am elin, J . Synlett. 1992, 3, 219. (d) Var ma , R. S.; Da hiya,R. ; Kum ar, S . Tetrahedron Lett. 1997, 38, 203. (e) Ca blewsk i, T.; Fa ux,A. F. ; St rauss, C . R. J. Org. Chem. 1944, 59, 3408.

(1 5) (a) B ose, A. K. ; B ani k, B . K. ; L avl i nskai a, N .; J ay a ram a n, M.;M a n h a s , M . S . Chemtech 1997, 27, 1 8 . ( b) Bani k, B. K. ; Manhas, M.S.; Robb, E. W.; B ose, A. K. H eterocycles1997, 44, 405. (c) Bose, A. K .;Manha s, M. S. ; B ani k, B. K. ; Robb, E . W. Res. Chem. Intermed. 1994,20, 1 . (d ) B a n i k , B . K . ; M a n h a s , M . S . ; B a r a k a t , K . J . ; B o s e, A . K .Tetrahedron Lett. 1992, 33, 3603.

Scheme 1

Microwa ve-Assisted Hy drogenat ion J. Org. Chem., Vol. 64, No. 16, 1999 5747


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g r ou p a n d r ed u ct i on of t h e u n s a t u ra t e d e st e r t o asaturated ester side chain to give the -lactam 6 whichretained the N-benzyl group intact (Scheme 3).

Using conventiona l cat alyt ic hydrogena tion (amb ient

pressure of hydrogen at 50 C in metha nol with P d/C a sthe cata lyst), Ojima et al . 16 have cleaved N-C 4 bonds in4-phenyl-2-a zetidinones t o produce phenyla lan ine deriva -tives (for example, see Scheme 4) in a convenient fashion

and in high yield. We17 had observed earl ier tha t , in thepresence of a large excess of Ra ney nickel cata lyst a nd

hydrogen, 3-methoxy-1,4-diphenyl-2-azetidinone under-w e n t -lactam scission to provide a small amount of thea nilide of R-methoxy--pheny lpropionic a cid (Scheme 5).However, under m ilder conditions, clea vag e of the -lac-t a m s r i n g d o es n ot occu r . F o r s ev er a l y e a r s n ow m i ld

ca t a l y t i c h y d r og e na t i on (5-10% Pd/C cata lyst , roomtemperature) under conventiona l conditions ha ve b een

the sta nda rd method in our lab oratory for th e reduction

of R-azido--lactam s to R-amino--lacta ms (for example,see Scheme 6).

Recently we11 h a v e s t u d i ed m i cr ow a v e a s s i s t e d c a t a -

lytic tra nsf er hydrogenolysis a t 120-130 C using 10%P d /C a s t h e ca t a l y s t . R a p i d s ci s si on o f 4 -p h en y l -2 -

azetidinones was observed in every case. The N-benzylgroup of the -lactam 9 wa s not hydrogenolyzed, but t heO-B n g r ou p a t C -3 w a s con v er t ed t o a n O H g r ou p;

alkenes (11, 13, a n d 15) were reduced to alkyl groups(Scheme 7). The reduction product w a s obta ined in h igh

yield and in a few m inutes. It is useful to note tha t underthese conditions Ra-N i d i d n o t c a u s e c l e a v a g e o f t h e

-lactam ring in 3 (See Scheme 2).

The hydr ogenat ion of 4-sty ryl-2-a zetidinones (17 a n d19) showed an interesting patt ern (Scheme 8): the alkenegroups were reduced b ut th ere wa s only partia l -lactamring scission under t he condit ions used w ith P d/C cat a -

lyst . Thus, the two products (18a,b), n a m e ly , t h e s a t u -r a t e d -lactam and the open chain amide, were f ormedi n a p pr ox im a t e ly 6: 4 r a t i o. I t w o ul d a p pe a r t h a t t h e

vinylogous aryl group led to the scission of the C 4-N

b o n d , b u t i f t h e s t y r y l g r o u p w e r e r e d u c e d f i r s t , r i n gcleavage was of course no longer possible. The relativera tes of reduction of the st yryl group an d hyd rogenolysis

o f t h e -l a c t a m r i n g ca n t h e r ef or e b e e x pe ct e d t o b einfluenced by the level of microwave irradiation.

Stereoselective Preparation of -Lactam Syn-thons. A convenient procedure ha s been d eveloped in ourlab oratory19 for resolving hy droxy--lactams (e.g., 23) b ythe formation of two diastereomeric glycosides via the

Ferrier rea ction involving a glucal (e.g., 22) (Scheme 9).The determ ina tion of the st ereochemistr y of the glycosidic

linkages in these compounds was necessary. The problemappeared to ha ve a r el iab le solution i f the unsat urat ioncould be easily removed, and the 1H NMR spectra of the

chair-shaped pyranosides could be studied. CTH reactionusing 10% Pd /C wa s tested on 24a a n d f o u n d t o b es u cce s sf u l: t h e u n s a t u r a t i on i n t h e s u g a r m o ie t y w a sremoved without r ing fission of the -lacta m to give 25a.Allylic dea cetoxylat ion also occurred t o a limited extent

a n d g a v e 25b.

Microwave-assisted CTH reaction of 26 resulted in theformation of a reduced and deacetylated product 27. Theproton NMR spectrum of this compound was useful forassigning the stereochemistry of the glycosidic bond.

In the course of studies on carb apenem synthons, a

series of monocyclic -l a c t a m s w e r e g en e r a t e d w i t h a nexo-alkene group at C-3. 15b,20 These conjugated doublebonds could be reduced easily un der microwa ve-a ssisted

CTH reaction (Scheme 10). Fur therm ore, because of th eessentia lly plana r sha pe of the -lacta m ring a nd the bulkof the sub sti tuent at C4, the hydrogenation was stereo-specific: only cis -lactams were ob tained b ecause theca t a l ys t s u rf a ce w a s a l w a y s p la c ed t r a n s t o t h e l a r g esub sti tuent at C4. S uch st ereospecif icity is of coursehighly desira ble from t he point of view of a tom economy.

(16) (a) Ojima, I.; Suga, S.; Abe, R. Chem. Lett. 1980, 853. (b) Ojima ,I. Acc. Chem. Res. 1995, 28, 383, and references therein.

(1 7) Bose A. K. ; Manha s, M, S. ; C hi b, J . S . ; C haw l a, H . P . S . ; Da y al ,B . J . O r g . C h em . 1974, 39, 2877.

(1 8) Bose, A. K. ; Anjane y ul u, B. ; B hat t ac hary a , S . K. ; Man has, M.S . Tetrahedron 1967, 23, 4769.

(19) (a) Ba nik, B, K .; Manh as, M. S.; B ose, A. K. J. Or g. Chem. 1994,59, 4 7 1 4 . ( b) Bani k, B. K. ; Manhas, M. S. ; Bose , A. K. TetrahedronLett. 1997, 38, 5 0 7 7 . ( c ) Bani k, B. K. ; Ze g roc ka, O .; Manhas, M. S. ;Bose A. K. H eterocycles1987, 46, 173.

(20) Banik, B. K.; Manhas, M. S.; Newaz, S. N.; Bose, A. K. Biomed.Chem. Lett. 1993, 3, 2363.

Scheme 2

Scheme 3

Scheme 4

Scheme 5

Scheme 6

5748 J. Org. Chem., Vol. 64, No. 16, 1999 B a n i k et a l .


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Dehalogenation Reaction. Rajagopal and Spatola 21

h a v e s t u d i ed C TH m e t h od s f or t h e d e h a l og e n a t i on of

a romat ic compounds. They ha ve observed tha t t he ordero f a d d i t i o n o f r e a g e n t s p l a y s a n i m p o r t a n t r o l e i n t h e

deha logena tion process. According to them, th e ca ta lytic

activi ty of the P d/C cata lyst is improved signif icantlywhen i t is a ctivat ed b efore the addition of the hydrogen

a cceptor. Thus, th e d echlorina tion of 4-chlorotoluene isc o m p l e t e d i n 9 0 m i n a t r o o m t e m p e r a t u r e w h e n a m -

m on iu m f or m a t e i s a d d ed t o t h e ca t a l y st a f t er t h eintroduction of the substr at e. In contra st it required only

15 min for complete reduction i f the sequence of thea d d i t i o n o f t h e f o r m a t e a n d t h e h a l o - c o m p o u n d w e r ereversed.

We22 have ob served, however, that when microwave-assisted CTH reactions are used for dehalogenation, the

end products and the t ime f or complete reduction arei n d ep en d e n t o f t h e o r d er o f a d d i t i on of t h e r e a c t a n t s .

Several -lactams (such as, 28 a n d 33) and isoquinoline

derivatives (e.g., 31 were smoothly deha logenat ed (Scheme11) in a few minutes.

During microwave-assisted dehalogenation of chloro-b enzene an d p-bromoa nisole, t he forma tion of biphenyls

(Scheme 12) in a bout 10%yield wa s detected. No couplingto dimeric products was observed during the dehalogen-

ation of 1-bromonaphthalene and 9-bromoanthracene.

R a j a g o p a l a n d S p a t o l a 23 s t u d ie d t h e k in e t ic s o f t h e

dehalogenation of o-chlorotoluene by HC O2Na-E t O H-H 2O a n d D C O2Na-E t O D-D 2O a n d n ot ed a k in et ic

isotope ef fect . On the b asis of these f indings they sug-gested tha t tra nsfer of the formyl hydrogen of the donor

t o t h e c a t a l y s t s u r f a c e i s t h e r a t e -d e t er m i n in g s t e p.Wiener et a l,23 have observed a significant kinetic isotope

effect in t he decomposition of sodium forma te (HCO 2Na -

H 2O v s D C O2Na-D 2O) cata lyzed b y 5% P d/C a t 35 C.B u t , t h e y 24 concluded from their study on the reduction

of nitro-toluene with formate that there was no kineticisotope effect.

Synthesis of Amines. H y d r a z o n es a r e f or m e d i nexcellent yield in m inutes under microwave irradia tion

of ketones such as 35 a n d w i t h h y d r a z i n e o r p h e n y l -hydra zine in ethylene glycol solution. S uch hydra zones

can be converted to amines by microwave-assisted CTHreaction. Thus, methyl b enzoylforma te (35) g a v e t h ephenylhydra zone (36) in 90%yield in 6 min. Reductionof (36) d u r i n g 4 m i n o f m i c r o w a v e i r r a d i a t i o n i n t h epresence of ammonium forma te a nd 10%Pd /C led t o the

amine (37) which wa s a cetylat ed to give methyl N-acetyl

phenylglycinat e (38) in excellent yield (Scheme 13).22

Summary and Outlook

In summary, we have devised safe, rapid, and efficient

techniques for conducting catalytic hydrogenation andh y d r o g e n o l y s i s u s i n g j u s t b e a k e r s a n d f l a s k s a n d u n -

m od i fi ed d om e s t ic m i cr ow a v e o ve n s . R u n a w a y r e a c -tions under microwave irradiation leading to possib leexplosion ar e prevented b y opera ting under a mb ient

pressure in open sys tems . The source of hydrogen for th iscata lytic transfer hydrogenation method w as amm onium(21) Rajagopal, S.; Spatola, A. F. J . O r g . C h em . 1995, 60, 1347.

(22) Bar aka t, K. J . Ph.D. Dissertat ion, St evens Institute of Technol-ogy, Hoboken, New J ersey, 1992.

(23) Wiener, H .; S ass on, Y.; B lum, J . J . M o l . C a t a l . 1986, 35, 277. (24) Wi en er , H . ; B l u m, J . ; S a s s on , Y . J. Org. Chem. 1991, 56, 4481.

Scheme 7



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f o r m a t e , w h i c h i s i n e x p e n s i v e a n d e a s y t o s t o r e a n dtransportsunlike pure hydrogen ga s under pressure in

cylinders.

F i el d t e s t s a t S t e v en s I n s t i t u t e of Te ch n ol og y a n dneighboring inner city high schools have shown that the

microwa ve-a ssisted techniques described here for reduc-tion and hydrogenolysis are sa fe and suita ble for resear ch

investigations as well as laboratory exercises for collegeand pre-college students. With minor modifications thesetechniques could a lso b e used for ma ny industr ial proc-

esses.

Recent pub lications show increasing use of catalytictransfer hydrogenation methods. Thus, Albanese et al.25

have found th ese methods t o b e the b est for the hy dro-genolysis of 4-nitrobenzyl esters of cephalosporin anti-b iotics w ithout isomerizing or reducing t he conjugated

double bond. Knochel and co-workers 26 have reported newef ficient cat alyst s f or ena ntioselective tr an sf er hydro-

genat ions. There is every rea son to believe tha t t hese andother new developments27 c a n b e e n h a n c e d b y t h e a p -

plica tion of microwa ve-a ssisted techniques d escribed byus here.

Experimental Section

Melting points were determined with a Mel-temp apparatusand are uncorrected. IR spectra were recorded on a Perkin-Elmer Model 1310 instrument. NMR spectra were recordedon a Bruker AC-20 spectrometer using TMS as an internalsta nda rd. Chemical ionization ma ss spectra were recorded ona Biospect. instrument using CH 4 as t he r e ag e nt g a s. Thi n-layer chromatography was performed with Whatman plates,a n d t h e s po t s w e r e d e t ect e d b y U V . M icr oa n a l y s es w e r eperformed by S chwar tzkopf Microana lytical L aborat ory, NY.Compounds described h ere ar e ra cemat es.

General Procedure for -Lactams. The r e ac t ion ofsub st i t ut e d ac e t y l c hl or i d e s w i t h S c hi f f b ase s and t e r t i ar yamines (triethylamine for conventional experiments; N-meth-ylmorpholine for rea ctions under microwave irra diation) wa sused for the synthesis of acetoxy-, benzyloxy-, methoxy-, and

(25) Albanes, D.; Leone, M.; Penso, M.; Seminati , M.; Zenoni, M.;Tetrahedron Lett. 1998, 39, 2405.

(26) P unt ener, K. ; Schw ink, L.; Kn ochel, P. Tetrahedron Lett. 1996,37, 8165.

(27) Stins on, S. C. Chem. Eng. News1998, J une 1, 21-22.

Scheme 8 Scheme 9



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phenoxy-substituted -lacta ms (for example, 1, 5, 17, and 28).

For the preparation ofR

-vinyl--lactams (for example, 3 a nd19), R, -unsa tura ted acid chlorides were substituted for acetylchlorides and the reaction was conducted under microwaveirradiation. 28

Schiff bases were prepared by the reaction of an aldehydewith an am ine in methylene chloride solution in the presenceof molecular sieves.29

Almost al l of the - l ac t am s use d as s t ar t i ng m at e r i al forthis study are known compounds described in the l i terature.M any of t he se -lactams have been reported in our earl ierpublications. 30

General Procedure for CTH Reaction. On the basis ofse ve r al y e ar s of e xpe r ie nce , w e have found t he fol low ingprotocol to be safe for conducting cat alyt ic tran sfer hydrogena-tion. Ca ution must be exercised, however, since some of th e

c at al y st s ar e py r ophor i c; a l so m i xt ur e s of hy d r og en and ai rc an c ause a n e xplosi on i f i g nit e d b y a spar k or a f lam e . Anunmodified domestic microwa ve oven (600-1000 W) pla ced ina h ood should be used. The rea ction vessel should be a beakeror an Erlenmeyer flask of fairly large size. A beaker of wat ershould be placed near t his reaction vessel to serve as a heatsink to provide a finer control on the amount of microwaveenergy input into th e hydrogenation mixture. Wat er absorbsmicrowave energy very efficiently and thereby reduces theam ount of e ne r gy ab sor be d b y t he r e ac t ion m i xt ur e. Theappr oxi mat e am ount of w a t e r t o b e use d c an b e d e t er m i nedw i t h a t r i al r un i nvol vi ng onl y t he sol ve nt and w i t hout t hec at al y st .

The desired tempera tur e of the solvent should r ise to 110-120 C i n a b ou t 3 m i n . Th e ca t a l y s t s h ou ld b e q u i ck lyi nt r od uce d i nt o t he r e act i on vessel and cove r ed w i t h t he

solvent (such a s ethylene glycol , bp 198 C) an d ma de into aslurry by gentle swirl ing motion of the beaker or the conicalflask. The compound to be reduced is diss olved in the solvent(ethylene glycol or 1,3-propanediol) and then added to ther e act i on ve sse l. The hy d r og en d onor (such as am m oni umfor m at e ) i s ad d e d now . M i c r ow ave i r r ad i at i on for t he pr e -determined period of time to reach a temperature of 110-130C should be applied. The microwave oven door should beopened, and the temperature of the reaction mixture shouldbe checked to be in the desired ra nge.

Th e ov en d oor s h ou ld b e cl os ed a n d i r ra d i a t i on w i t hm i cr ow ave shoul d b e r e sum e d for anot he r 3-4 m i n. T hemicrowa ve oven should be switched off, and t he reaction vessel

(28) Manhas, M. S.; Ghosh, M.; Bose, A. K. J. Org. Chem. 1990, 55,575.

(2 9) Bose , A. K. ; Anjane y ul u, B. ; B hat t ac hary a , S . K . ; Manha s, M.S .; Tetrahedron 1967, 23, 4769.

(30) Banik, B. K.; J ayaraman, M.; Srirajan, V.; Manhas, M. S.; Bose,A. K. J. Ind. Chem. Soc. 1997, 74, 943-947, and references therein.

Scheme 10

Scheme 11

31 32

Scheme 12

Scheme 13



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removed from the oven. Careful decantation of the reactionmixture after cooling followed by the addition of glycol to ther e act i on vesse l w ould pr ese r ve t he c at al y st for t he ne xtexperiment.

It is customa ry in our la boratory to place a beaker cover ora f il t er funnel on t op of t he r e ac t ion ve ssel t o pr event anya c ci de n t a l s pi ll a g e. S i n ce g la s s i s n e a r ly t r a n s p a r en t t omicrowaves, th e upper pa rts of th e beaker of flask serves as acondenser for any small a mounts of va pors formed. After thehy d r og e nat i on t he r e act i on m i xt ur e w as c oole d a nd t he nfiltered. The filtrate was diluted with water and extracted withe t hy l ac et at e , and t he or g ani c l ay e r w as w a she d w i t h w a t e r .Eva pora tion of the solvent from t he organic layer (dried overanhy d r ous Na 2S O4) followed by crystal l ization ga ve the pureproduct in 80-90%yield. We ha ve observed th at the optimalra tio of the cata lyst (10%P d/C) to substr a te is 0.3:1 by weightfor e ac h r e d uc ib le g r oup. Fi ve e q ui val ent s of a m m oni umformate for each reducible group gave good results.

2: yield 75%; m p 108 C ; I R (CH 2C l2) 1740 cm-1; 1H NM R7.30-6.69 (m, 10H), 5.43 (d, J ) 4.30 Hz, 1H), 4.93 (d, J )4.32 Hz, 1H), 3.53-3.39 (m, 1H), 3.00-2.86 (m, 1H), 2.03-1.82 (m, 2H), 1.11 (t, J ) 7.37 Hz, 3H); CIMS (CH 4 g a s ) m/z282 (M + H )+; Anal . Calcd for C 18H 19NO 2: C, 76.84; H, 6.80;N, 4.97. Foun d: C, 76.67; H , 6.67; N, 4.89.

4a: yield 80%; mp 118 C; I R (CH 2C l2) 1740 cm-1; 1H NMR7.35-6.99 (m, 10H), 4.67 (d, J ) 2.34 Hz), 3.10-3.01 (m, 1H),2.03-1.82 (m, 1H), 1.11 (t, J ) 7.37 Hz, 3H); CIMS (CH 4 g as)m/z252 (M + H )+. Ana l. Ca lcd for C 17H l7NO: C, 81.24; H, 6.81;N, 5.57. Foun d: C, 80.99; H , 6.67; N, 4.89.

4b: yield 85%; mp 109 C; IR (CH 2C l2) 1740 cm-1; 1H NMR7.32 (s, 5H), 7.15 (d, 2H), 6.69 (d, 2H), 4.54 (d, J ) 2.27 H z,1H), 3.74 (s, 3H ), 2.94-2.90 (m, 2H), 2.07-1.69 (m, 2H), 1.04(t, 3H). Anal. Ca lcd for C 18H 19NO 2: C, 76.84; H, 6.80; N, 4.97.Found: C, 76.62; H, 6.92; N, 5.0.

4c: yield 85%, oil; I R (nea t) 1740 cm-1; 1H NMR 7.37 (brs,1H), 7.25 (d, J ) 8.9 Hz, 2H), 6.7 (d, J ) 8.9 Hz, 2H), 6.38-6.29 (m, 2H), 4,66 (d, J ) 2.38 Hz, 1H), 3.71 (s, 3H), 3.30-3.31 (m, 1H), 2.01-1.72 (m, 2H), 1.05 (t, J ) 7.4l Hz, 3H);CIMS (CH 4 g as) m/z 272 (M + H )+. Anal . C a l cd for C 16H 17-NO 3: C, 70.83; H, 6.31 N, 5.16. Found: C, 70.59, H, 6.11; N,5.02.

6a: yield 90%; m p 109-110 C ; I R (Nujol) 3300, 1730 cm-1;1

H NMR 7.41 (d, 2H), 6.92 (d, 2H), 5.04 (d, J)

4.9 Hz, 1H),4.37 (m, 1H), 3.82 (s, 3H), 3.72 (s, 3H ), 2.61 (m, 2H), 2.12 (m,2H); CIMS (NH 3 r e ag ent g a s) m/z 297 (M + 18)+. Anal . Ca lcdfor C 14H l7NO 5; C, 60.20; H , 6.10; N, 5.01. Found: C, 59.61, H,6.26, N, 5.00.

6b:yield 85%; oil, IR (Nujol) 3350, 1730 cm-1; 1H NMR 7.40(s, 5H), 5.23 (m, 1H), 4.94 (t, 1H), 4.67 (d, J ) 15.4 H z, 1H),4.20 (d, J ) 15.4 Hz, 1H), 3.75 (s, 3H), 3.24 (m, 1H), 2.41 (m,2H), 2.0 (m, 2H); CIMS (NH 3 r e ag ent g a s) m/z 281 (M + 18)+.

8: yiel d 84%; m p 123-125 C ; I R (Nujol) 3300, 1640 cm-1;1H NMR 7.80 (brs, 1H) 7.00 (m, 14H ), 4.93 (dd, J1 ) J2 ) 3.91Hz, 1H), 3.8 (s, 3H), 3.33 (d, J1 ) J2 ) 14.16 Hz , 2H ); 13C NMR168.80, 157.25, 136.40, 129.84, 128.32, 126.28, 122.42, 122.14,115.82, 114.23, 80.16, 55.49, 38.97. Ana l. C a lcd for C 22H 2lNO 3;C, 76.00; H , 6.05; N, 4.03. Found: C, 75.55; H ,6.12; N, 3.99.

10a: yield 83%; m p 89 C; IR (Nujol) 3300, 1630 cm-1; 1H

NMR 7.25 (m, 10H), 4.23 (m, 2H), 3.40 (brs, 1H), 3.12 (dd, 2H),2.64 (dd, 1H); CIMS (NH 3 r e ag e nt g as) m/z 273 (M + 18)+.Ana l . Ca lcd for C 26H 17NO 2: C 75.29; H, 6,66; N, 5.49. Found:C, 75.13, H, 6.69; N, 5.58.

10b: yield 80%; m p 128 C; IR (Nujol) 3300, 1640 cm-1; 1HNMR 8.20 (brs, 1H), 7.51-6.80 (m, 9H), 4.4 (m, 1H), 3.85 (s,3H), 3.42 (dd, J1 ) 7.80 H z, J2 ) 7.80 Hz, 1H), 3.09 (dd, J1 )8.30 Hz, J2 ) 14.10 H z, 1H ), 2.63 (d, J ) 8.30 Hz, 1H); CI MS(NH 3 r e ag ent g a s) m/z 289 (M + H )+. Anal . Ca lcd for C 16H 17-NO 3: C, 66.43; H , 6.51; N, 4.48. Found C, 66.65; H, 5.84; N,4.76.

12a: yield 83%; m p 113-115 C; IR (Nujol) 1640 cm-1; 1HNMR 7.10-6.65 (m, 9H), 3.73 (s, 3H), 2.82 (m, 2H), 2.21 (m,1H), 1.75 (m, 2H), 0.90 (t, 3H); CI MS (NH 3 r e ag e nt g as) m/z301 (M + 18)+. Anal . Ca lcd for C 18H 21NO 2: C, 76.32; H, 7.42;N, 4.84. Foun d: C, 75.80; H , 7.79; N, 4.84.

12b: yield 80%; mp 107 C; I R (CH 2C l2) 1640 cm-1; 1H NMR7.58 (s, 1H), 7.34-7.15 (m, 3H), 6.81 (d, J ) 6.61 Hz, 2H),6.25-6.22 (m, 1H), 6.02-6.01 (m, 1H), 3.73 (s, 3H), 3.05-2.68(m, 2H), 2.58-2.44 (m, 1H), 1.87-1.43 (m, 2H), 0.97 (t, J )7.35 Hz, 3H); CI MS (CH 4 g as) m/z 258 (M + H )+. Anal . Ca lcdfor C 16H 19NO 2: C, 74.68; H, 7.44; N, 5.44. Found C, 74.01; H,7.38; N, 5.19.

14: yield 80%; I R (Nu jol) 1650 cm-1; 1H NMR 7.18-7.02 (m,H), 6.71-6.64 (m, 2H), 3.67 (s, 3H), 2.85 (d, J ) 6.81 Hz, 1H),2.06-1.93 (m 2H), 1.03 (d, J ) 6.26 Hz, 3H), 0.97 (d, J ) 6.18Hz, 3H); CIMS (CH 4 g as) m/z 258 (M + H )+.

16: yield 87%; mp 69 C; IR (Nujol) 3350, 1730 cm-1; 1HNMR 8.30 (brs, 1H), 7.51-6.81 (m, 9H), 4.02 (dd, J1 ) 3.5 Hz,J2 ) 7.59 Hz, 1H), 3.85 (s, 3H), 3.42 (m, 2H), 3.03 (dd, J1 )7.7 Hz, J2 ) 3.9 Hz, 2H ), 1.59 (m, 2H), 0.90 (t, 3H); CI MS (NH3r e ag ent g a s) m/z 314 (M + H )+.

18a: yield 60%; m p 70 C; IR (Nujol) 1740 cm-1; 1H NM R7.09 (m, 14H), 5.90 (d, J ) 4.9 Hz, 1H), 4.72 (m, 1H), 3.84 (s,3H), 2.63 (m, 2H), 1.81 (m, 2H); CIMS (NH 3 r e ag ent g a s) m/z399 (M + 18)+. Anal . Ca lcd for C 24H 23NO 3: C, 77.21; H, 6.16;N, 3.75. Found : C, 76.39; H, 6.61; N, 3.81.

18b: yield 30%oil; IR (CH 2C l2) 3300, 1640 cm-1; 1H NM R7.42-7.16 (m, 13H), 6.84 (d, J ) 8.95 Hz, 2H), 3.77 (s, 3H),2.64 (t, J ) 7.19 Hz, 1H), 2.33 (t, J ) 6.97 Hz, 2H), 1.72 (m,4H); CIMS (CH 4 r e ag e nt g as) m/z 376 (M + H )+. Anal . Ca lcdfor C 24H 25NO 3: C, 76.76; H, 6.71; N, 3.73. Found: C, 76.51;H, 6.53; N, 3.81.

20a: yield 40%; mp 72 C; I R (CH 2C l2); 1740 cm-1; 1H NMR7.36-7.17 (m, 7H), 6.86 (d, J ) 8.81 H z, 2H), 4.15-4.08 (m,1H), 3.78 (s, 3H), 3.42-3.20 (m, 1H), 2.83-2.57 (m, 2H), 2.32-1.67 (m, 4H), 1.17 (t, J ) 7.43 Hz, 3H); CIMS (CH 4 g as) m/z326 (M + H )+. Anal . Calcd for C 20H 23NO 2: C, 77.64; H, 7.49;N, 4.52. Found : C, 77.76; H, 7.40; N, 4.57.

20b: yield 35%; mp 50 C; I R (CH 2C l2) 1740 cm-1; 1H NMR7.36 (m, 7H), 6.85 (d, J ) 6.7 Hz, 2H), 4.16 (dd, J1 ) 5.54 Hz,J2 ) 11.23 Hz, 1H), 3.84 (s, 3H), 3.08 (dd, J1 ) 5.63 H z, J2 )10.00 Hz, lH), 2.82-2.65 (m, 2H), 2.27-1.88 (m, 3H), 1.28 (d,J ) 6.54 Hz, 3H), 1.06 (d, 6.39 Hz); C IMS (CH 4 g as) m/z 324(M + H )+. Anal . Calcd for C 2lH 25NO 2: C, 77.98; H, 7.79; N,4.33. Found: C, 77.71; H , 7.64; N, 4.39.

21a: yield 40%; mp 87 C; IR (CH 2C l2) 3320, 1640 cm-1; 1HNMR 7.79 (s, 1H), 7.43 (d, J ) 8.9 Hz, 2H), 7.32-7.15 (m, 5H),6.85 (d, J ) 8.9 Hz, 2H), 3.79 (s, 3H), 2.63 (t, J ) 6.78 Hz,

2H), 2.08-2.06 (m, 1H), 1.79-1.50 (m, 6H), 0.94 (t, J ) 7.34Hz, 3H); CIMS (CH 4 g as) m/z 312 (M + H )+. Anal . Calcd forC 20H 25NO 2: C, 77.13; H, 8.09; N, 4.49. Found: C, 77.00; H,8.37; N, 4.34.

21b: yield 35%; mp 12l C; I R (CH 2C l2) 3350, 1650 cm-1; 1HNMR 7.41 (d, J ) 8.77 Hz, 2H), 7.35-7.14 (m, 6H), 6.83 (d, J) 9 Hz, 2H), 3.78 (s, 3H), 2.63 (t, J ) 7.07 Hz, 2H), 1.91-1.51(m, 6H), 0.98 (d, J ) 5.76 Hz, 3H); CIMS (CH 4 g as) m/z 326(M + H )+. Anal . Calcd for C 21H 27NO 2: C, 77.49; H, 8.36; N,4.30. Found: C, 77.77; H , 8.35; N, 4.44.

29: mp 108 C ; IR (CH 2C l2) 1740 cm-1; 1H NMR 7.30-6.60(m, 10H), 5.43 (d, J ) 4.31 Hz, 1H), 4.93 (d, J ) 4.32 Hz, 1H),3.53-3.39 (m, 1H), 3.00-2.86 (m, 1H), 1.57-1.46 (m, 2H), 0.89(t , J ) 7.32 Hz, 3H); CIMS (CH 4 g a s ) m/z 282 (M + H )+. Anal.C al c d for C 18H 19NO 2: C, 76.84; H, 6.80; N, 4.97. Found C,76.67; H, 6.67; N, 4.89.

30: IR (CH 2C l2) 1650 cm-

1; 1H NMR 7.40-6.51 (m, 11H),4.83 (dd, J1 ) 6.80 Hz, J2 ) 10.70 Hz , 1H ), 2.99-2.48 (m, 3H),2.52-2.48 (m, 1H), 1.43-1.28 (m, 2H), 0.75 (t, J ) 7.42 H z,3H).

32: IR (Nujol) 1660 cm-1; 1H NMR 8.37-8.32 (m, 1H), 7.59-7.22 (m, 8H), 5.49 (brs, 1H), 4.36-4.19 (m, 1H), 4.12 (brs, 1H),3.69 (s, 3H), 3.01-2.87 (m, 1H), 1.93-1.74 (m, 2H), 1.08 (t, J) 7.33 Hz, 3H). Anal. Calcd for C 20H 21NO 3: C, 74,28; H 6.54;N, 4,33. Found C, 74.39; H , 6.41; N , 4.38.

34: oil; IR (Nujol) 1750 cm-1; 1H NMR 7.2 (s, 5H ), 4.75 (d,J ) 16.0 Hz, 1H), 4.20 (d, J ) 16.0 Hz, 1H ), 4.0 (m, 1H ), 3.65-3.40 (m, 2H), 3.01 (dd, J1 ) 5 Hz, J2 ) 16 Hz, 1H), 2.55 (dd, Jl) 5 Hz, J2 ) 16 Hz, 1H ), 1.30 (s, 3H ), 1.20 (s, 3H ); CIMS (NH 3r e ag ent g a s) m/z 279 (M + 18)+.

Methyl Phenylglycinate (37). Methyl benzoyl formate(35) (6.1 mmol), phenyl hyd ra zine (7 mmol) and ethy lene glycol



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(5 mL) were placed in an Erlenmeyer flask (125 mL). Themixture wa s heat ed for 6 min at low power sett ing. The desiredphenyl hydrazone (36) precipitated out on scratching underice cold condition. I t was fi l tered, washed with hexane, anddried (yield 90%, m p 86-88 C).

Ammonium forma te (200 mg) a nd 10%P d/C (100 mg) wereadded to phenylhydra zone (36) (2 mmol) in ethylene glycol (5mL). The mixture was irradiated for 4 min. After the usualworkup, the amine (37) wa s isola ted (92%): IR 1710 cm-1; 1HNMR (CDCl3) 7.40 (s, 5H), 4.6 (s, 1H), 3.61 (s, 3H), 2.0 (brs,2H): 13C NMR 174.19, 140.11, 128.56, 127.77, 126.69, 59.15,

52.11; CIMS (NH 3 r e ag ent g a s) m/z 183 (M + 18)+. A port ionof (37) w as ac e t y lat e d w i t h a c et i c anhy d r i d e and py r id i ne t oafford (38): mp 85-86 C ; I R (Nujol) 1700 cm-1; 1H NMR 8.9(brs, 1H ), 7.31 (s, 5H ), 5.60 (d, J ) 8.24 Hz, 1H), 3.70 (s, 3H),2.0 (s, 3H); 13C NMR 168.79, 138.02, 128.83, 127.15, 119.98,

61.90, 56.56, 24.33; CIMS (NH 3 r e ag e nt g as) m/z 225 (M +18)+.

Acknowledgment. This resear ch wa s supported byStevens Insti tute of Technology (in part) and by theHoward Hughes Medical Insti tute [ through a grant toour C hemical B iology E ducation E nha ncement (CBEE )P rogram ]. For technica l help we tha nk Keiko Tabei a ndRaza Naqvi , undergraduate research part icipants Gre-gory Morriel lo, Kavita Mistry, and Ma dhumeeta P at el ,and pre-college research trainees Ingrid Cal lejas andVa rs h a Va l e ch a (s u pp ort e d b y P ro je ct S E E D of t h eAmerican Chemical Society).

J O981516S


Microwave-Assisted Rapid and Simplified Hydrogenation

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