Reduction of Aroma tic A ldehydes and Ketones w ith Acyloxy Substituen t a t the O r tho-position by NaBH4 in the Presence of W a ters 3

Size: px

Start display at page:

Download "Reduction of Aroma tic A ldehydes and Ketones w ith Acyloxy Substituen t a t the O r tho-position by NaBH4 in the Presence of W a ters 3"

Christine Butler
5 years ago
Views:

1 V o l. 15 N o Chem ical R esearch in Ch inese U niversities Reduction of Aroma tic A ldehydes and Ketones w ith Acyloxy Substituen t a t the O r tho-position by NaBH4 in the Presence of W a ters 3 W AN X in2hua, ZHOU Hong2b ing, X IE R en, ZHAN G Dong FEN G X in2de and ZHOU Q i2feng 3 3 (D ep artm ent of P olym er S cience & E ng ineering, P ek ing U niversity, B eij ing, ) (R eceived June 5, 1998) A n unusual reduction of som e arom atic aldehydes and ketones by sodium bo rohydride w as discovered. In a TH FgH 2O o r DM SO gh 2O so lvent system the arom atic aldehydes and ketones w ith acyloxy substituent on the ortho2po sition to the carbonyl group can be reduced to the co rresponding alkyl pheno lṡ T h is unusual reduction is app licable also to the co rresponding alcoho ls of all the above aldehydes and ketoneṡ A putative m echanism w as suggested. In addition to the above aldehydes, ketones and benzyl alcoho ls, certain 42acyloxybenzyl esters (p robably also the 22substituted analogues) such as 42benzoyloxybenzyl benzoate w as also found to be reduced to m ethylpheno l by th is unusual reduction. Ke yw o rdsr eduction, Sodium bo rohydride, Benzaldehyde, A rom atic ketone In troduction A s a m ild reductan t, sodium bo rohydride (N abh 4) is w idely u sed in o rgan ic syn thesis to p repare alcoho ls from aldehydes and ketones. Certain diaryl ketones m ay undergo fu rther reduction to give diaryl m ethane as the final reduction p roduct under special condition s such as in a strong acidic acid ( F 3CH ) o r reflux ing in a strong basic m edium (N aoh g H 2O ) [13 ]. R ecen tly, in the study of liqu id crystalline po lym ers, 2, 52b is[ (42m ethoxybenzoyl)oxy ]2 benzaldehyde w as reacted w ith N abh 4 w ith the aim of ob tain ing their co rresponding benzyl a lcoho l ( Schem e 1, react ion 1 ). U nder the d ry cond it ion s ( react ion 1 ) the aldehyde w as, as expected, reduced to the alcoho lic p roduct ( g ), w hereas to ou r su rp rise the p roduct under the w et condition s ( reaction 2 ) w as 22m ethyl242( 42 m ethoxybenzoyl)oxypheno l [4, 5 ]. A s the reaction ( 2) w as unu sual, w e decided to have a fu rther study. T he model reaction s of a series of benzaldehydes w ere designed and carried ou ṫ It w as also found that th is unu sual reaction w as app licab le to som e arom atic ketones and their co rresponding 3 Suppo rted by the N ational N atural Science Foundation of Ch ina (N o ). 3 3 To w hom co rrespondence should be addressed.

2 N o. 2 WAN X in2hua, ZHOU Hong2bing, X IE R en et al. 183 a lcoho ls w ith acyloxy sub st ituen t s on the ortho2po sit ion in good yield s. A p u ta t ive m echan ism w as suggested. CH 3O OOC OCH 3 N abh 4 OOC OCH 3 (1) THFgCH 3OH CH 3O CH 2OH CH 3O OOC OCH 3 N abh 4 OH (2) THFgH 2O o r DM SO gh 2O CH 3O CH 3 Schem e 1 Results and D iscuss ion Tw o m odel com pound s A and B w ere first stud ied to invest iga te the effect of the sub stitu tion po sition. Fo r each compound tw o reaction condition s as tho se in the reaction s (1) and (2) w ere app lied. CH 3O CH 3O (A, m eta2) (B, ortho2) R educing A yielded on ly the no rm a l p roduct, i. e., 32( 42m ethoxybenzoyl) oxybenzyl alcoho l, no m atter w hether w ater w as u sed o r no ṫ How ever, the reduced p roduct of the ortho2sub stitu ted aldehyde B depended on the reaction condition s: in the ab sence of w ater the no rm al alcoho lic p roduct w as ob tained; bu t in the p resence of w ater the unu sual p roduct 22m ethyl p heno l w a s ob ta ined. It seem ed tha t the p resence of w a ter and the acyloxy sub st itu t ion on the ortho2po sit ion to the ca rbonyl g roup w ere tw o key facto rs fo r th is reduct ion. In o rder to b ring in to general u se of th is unu sual reaction, w e studied the reduction of a series of arom atic aldehydes and ketones w ith acyloxy sub stituen ts on the o rtho2po sition to the carbonyl group. R ep resen tative resu lts are show n in T ab les 1 and 2. A ll the aldehydes and ketones w ere reduced to the co rresponding alcoho lic p roducts (p roduct g s) under condition s A. T hey all gave 22alkyl pheno ls (p roduct g s) under cond it ion B and, in addition, benzo ic acid w as iso lated in sto ich iom etric yield from the reaction m edia of 22 benzoyloxy sub stitu ted aldehyde g 22 and ketones g 22, g 24 and g 26. It imp lied that under condition B the ester bonds ortho to the aldehyde o r ketone group in the mo lecu les w ere hyd ro lyzed a t the sam e t im e a s the reduct ion of the a ldehydes o r ketones g roup. It is reasonab le to assum e that the in term ediates of the unu sual reduction s repo rted here are the co rresponding alcoho ls. If th is is the case, the co rresponding alcoho ls w ill also be reduced under condition B to give alkyl sub stitu ted pheno ls. T he resu lts co llected in T ab le 3 shou ld verify th is assump tion. T able 1R eduction of 22substituted benzaldehydes A ldehydes Substituents Conditions 3 P roducts 3 3 Yield (% ) g 21 A cetyloxy2 A g g 21 A cetyloxy2 B g g 22 Benzoyloxy2 A g g 22 Benzoyloxy2 B g Condition A : dry TH FgCH 3OH; condition B: DM SO gh 2O, 0, 56 h. 3 3 P roducts g 21, g 22 and g 21 are 22acetyloxybenzyl alcoho l, 22benzoyloxybenzyl alcoho l and 22m ethylpheno l

3 184 Chem ical R esearch in Ch inese U niversities V o l. 15 respectively. T able 2R eduction of 22acyloxyaryl ketones 3 Ketones Conditions P roducts 3 3 Yield (% ) R 1 R 2 g 21 CH 3 CH 3 B g g 22 Phenyl CH 3 B g g 22 Phenyl CH 3 A g g 23 CH 3 Phenyl B g g 24 Phenyl Phenyl B g g 25 CH 3 CH 2CH 3 B g g 26 Phenyl CH 2CH 3 B g g 26 Phenyl CH 2CH 3 A g General fo rm ula of the ketones: OOCR 1, in w h ich R 1 and R 2 of different ketones are show n in T able 2; COR 2 reduction conditions A and B are the sam e as defined under T able P roducts g 23, g 24, g 22, g 23 and g 24 are 22(12hydroxyethyl) phenyl benzoate, 22(12hydroxyp ropyl) 2phenyl benzoate, 22ethylpheno l, 22benzyl pheno l and 22p ropylpheno l respectively. T able 3R eduction of 22acyloxy substituted benzyl alcoho ls 3 A lcoho ls Conditions P roducts Y ield (% ) A lcoho ls Conditions P roducts Y ield (% ) g 21 B g g 24 B g g 22 B g g 25 B g g 23 B g R efer to T ables 1 and 2 fo r the structures of the alcoho ls (g s, p repared under condition A ) and p roducts (g s); the alcoho l g 25 is 22(hydroxybenzyl) phenyl benzoate: OOC. H Based on the experim en tal resu lts: ( 1 ) no hydro lysis w as found fo r 2, 52b is [ ( 42 m ethoxy2benzoyl) oxy ] benzaldehyde 6 hou rs after it w as disso lved in a basic so lu tion of N a2co 3gDM SO gh 2O at 0, the basicity of th is m edium is equ ivalen t to that of the reduction condition B; (2) on ly the ortho2, bu t no t the m eta2 o r p a ra2 acyloxy2sub stitu ted carbonyl group is reduced in the p resence of w ater to the alkyl group; (3) the ortho acyloxy2 sub stitu ted benzylalcoho l is reducib le under condition B to yield the co rresponding m ethyl com pound s; and the in t ram o lecu la r t ran sesterifica t ion of 22acyloxybenzyla lcoho l m akes reaction (3) lean ing tow ards righ t (Schem e 2) [6, 7 ] : OOCR CH 2OH OH - gh 2O OH CH 2OOCR Schem e 2 T hu s w e suggest the fo llow ing m echan ism fo r th is unu sual reduction (Schem e 3). 22 A cyloxy benzaldehyde 1 is reduced by sodium bo rohydride to benzyl alcoho l 2, w h ich is the no rm al reduction p roduct. In the p resence of w ater an in tramo lecu lar m igration of the ester group occu rs in 2, yielding 3 w h ich in tu rn yields 4 becau se the acyloxy group of 3 is a good leaving group and 4 is stab ilized by resonance effectṡ T he fu rther reduction of 4 by N abh 4 leads to the fo rm ation of 22m ethylpheno l as the final p roducṫ A sim ilar m echan ism m ay be p ropo sed fo r the reduct ion of the 22acyloxy sub st itu ted a ryl ketones. In con t ra st, no equ ivalen t resonance stab ilization fo r in term ediates can be expected if a m eta2sub stitu ted (3)

4 N o. 2 WAN X in2hua, ZHOU Hong2bing, X IE R en et al. 185 derivative is sub ject to the reduction under the sam e condition s. T he reduction is therefo re un likely to be driven beyond the first step and the alcoho l ( in stead of alkyl pheno l) w ill be p rincipal p roduct. Schem e 3 P resum ab ly becau se the m igration of the ester group (to fo rm 42hydroxybenzyl benzoate a s the requ ired in term ed ia te ) is d ifficu lt, if po ssib le, 42benzoyloxybenza ldehyde can be reduced to on ly 42benzoyloxybenzyl alcoho l under the condition s bo th A and B. How ever, 42benzoyloxybenzyl benzoa te (p rep a red from 42benzoyloxybenzyl a lcoho l) can be reduced under condition B to 42m ethylpheno l w ith a yield of 80% (Schem e 4). 1M a ter ia ls CH 2OOC N abh 4 DM SO gh 2O Schem e 4 Exper im en tal HO CH H Comm ercial2grade so lven ts and reagen ts w ere u sed w ithou t fu rther purification un less o therw ise sta ted. T et rahyd rofu ran w a s d ist illed from ca lcium hyd ride after 8 h reflux. M ethano l w as dried w ith anhydrou s N a2so 4. 2Character iza tion T he m elting po in ts w ere m easu red on a po larizing m icro scope w ith L eitz2350 ho t2stage. T he 1 H NM R spectra w ere ob tained on a V arian FT 280 spectrom eter. determ ined by an A E Ig50 m ass spectrom eter. 3Genera l Syn thesis Procedure 3. 1Prepara tion of Aryl A ldehydes and Ketones with Acyloxy Substituen t T he m ass spectra w ere T he p reparation of 32( 42m ethoxybenzoyl ) oxybenzaldehyde (A ) w ill serve as an examp le. O ther aldehydes and ketones w ere p repared acco rding to th is general p rocedu re. To a m ix tu re of 32hydroxybenzaldehyde (6 g, 0105 mo l), E t3n (10 ml ) and TH F (30 ml ) w as added slow ly a so lu tion of p 2m ethoxybenzoyl ch lo ride (10 g, 0106 mol ) in TH F (20 ml ). T he m ix tu re w as stirred fo r 4 h in an ice2w ater bath, and after filtering off the E t3n salt, the residual so lu tion w as pou red in to 200 ml of w ater. T he pow der p roduct w as filtered off and w ashed in tu rn by w ater, 5% N a2co 3 so lu tion, and w ater. R ecrystallization from to lueneghexane gave 12 g of a w h ite crystal. Y ield 95%, m. p Reaction of Aroma tic A ldehydes, Ketones and The ir Correspond ing A lcohols

5 186 Chem ical R esearch in Ch inese U niversities V o l (42M ethyloxybenzoyl)oxybenzaldehyde (B ) (10 g, 3818 mmo l) disso lved in 100 ml of DM SO w as in troduced in to a flask p laced in an ice2w ater bath, to w h ich a so lu tion of N abh 4 (3 g, 80 mmol ) in w ater (30 ml ) w as added dropw ise under stirring. A fter ano ther 6 hou rs the m ix tu re w as pou red in to 200 ml of w ater. T he so lu tion w as acidified by HC l(6 mo lgl ) to co llect p 2m ethoxybenzo ic acid as by2p roduct. T he residual so lu tion w as ex tracted fou r tim es w ith 50 ml of ether each. A fter dried by anhydrou s N a2so 4, the ether in the ex tract w as evapo rated and the p roduct w as iso lated by co lum n ch rom atography ( 80 g silica gel, petro leum etherether= 83, R f= 0145). A fter the evapo ration of the so lven t and vacuum distillation, 215 g of 22m ethylpheno l w as ob tained. Y ield 54%, m. p T he reduction s of o ther aldehydes, ketones and alcoho ls w ere sim ilar to w hat has been described above. A ldehydes 1 H NM R, M S and elem en tary analysis data are listed in T ab les 47 respectively. T able 4Characterization of aldehydes 1 H NM R (CDC l3) M S A (1H, s, - ), (8H, m, phenyl), (3H, s, - OCH 3) B (1H, s, - ), (8H, m, phenyl), (m gz ) Calcd. 256 C H C (3H, s, - OCH 3) H g (4H, m, phenyl), (3H, s, - CH 3) 164 C H g (1H, s, - ), (9H, m, phenyl) 226 C Ketones T able 5Characterization of Ketones Elem entary analysis (% ) H H NM R (CDC l3) M S g (4H, m, phenyl), (3H, s, - CH 3), (3H, s, Found (m gz ) Calcd. 178 C CH 3) H g (9H, m, phenyl), (3H, s, - CH 3) 240 C H g (9H, m, phenyl), (3H, s, - CH 3) 240 C H g (14H, m, Phenyl) 302 C g (4H, m, phenyl), (2H, q, - CH 2- ), (3H, s, - CH 3), (3H, t, - CH 3) g (9H, m, phenyl), (2H, q, - CH 2- ), (3H, t, - CH 3) T able 6Characterization of alcoho ls Compd. 1 H NM R (CDC l3) M S g (11H, m, phenyl), (2H, s, - CH 2O - ), (3H, s, - OCH 3), (3H, s, - OCH 3) g 2a (8H, m, phenyl), (2H, s, - CH 2O - ), (3H, s, - OCH 3) Continued to next page. (m gz ) Calcd. 3 C H C H C H C m. p. g Elem entary analysis (% ) H Elem entary analysis (% ) H Found Found m. p. g

6 N o. 2 WAN X in2hua, ZHOU Hong2bing, X IE R en et al. 187 Compd. 1 H NM R (CDC l3) M S Elem entary analysis (% ) m. p. (m gz ) Calcd. Found g g 2b (8H, m, phenyl), (2H, s, - CH 2O - ), (3H, s, - OCH 3) 258 C H g (4H, m, phenyl), (2H, s, - CH 2O - ), (3H, s, - CH 3) 166 C H g C (9H, m, phenyl), (2H, s, - CH 2O - ) H g ( 9H, m, phenyl), ( 1H, q, 242 C CH - ), (3H, d, - CH 3) H g ( 9H, m, phenyl), ( 1H, q, 256 C CH - ), (2H, m, - CH 2- ), H (3H, t, - CH 3) g ( 14H, m, phenyl), ( 1H, m, 304 C CH - ) H N o m gz w as found fo r th is compound. How ever, its reaction p roduct w ith m ethacryloyl ch lo ride gave m gz 476, equivalent to calculated value. 3 3 A lcoho ls g 2a and g 2b are 32(42m ethoxybenzoyl) oxybenzyl alcoho l and 22(42m ethoxy2benzoyl) oxybenzyl alcoho l respectively. T able 7Characterization of alkyl pheno ls Pheno ls 1 H NM R (CDC l3) M S Elem entary analysis (% ) m. p. (m gz ) Calcd. Found g g (4H, m, phenyl), (1H, s, - OH ), (3H, s, - CH 3) 108 C H g (4H, m, phenyl), (1H, s, - OH ), (2H, q, - CH 2- ), (3H, t, - CH 3) g (9H, m, phenyl), (1H, s, - OH ), (2H, s, - CH 2- ) 184 C H g (4H, m, phenyl), (1H, s, - OH ), (2H, t, - CH 2- ), (2H, m, - CH 2- ), (3H, t, - CH 3) 136 Re fe re nce s [ 1 ]Sm ith, M. B., O rganic Chem istry, M cgraw 2H ILL, Inc., 1994: 368 [ 2 ]Gribbe, G. W., Kelly, W. J. and Em ery S. E., Synthesis, 763 (1978) [ 3 ]Gribbe, G. W., L eese, R. M. and Evans, B. E., Synthesis, 172 (1977) [ 4 ]Jutaitis, C. F. and Bernardo, J. E., Synth. Comm un., (487) 1990 [ 5 ]Bell, K. H., A usṫ J. Chem., 22, 601 (1969) [ 6 ]Zhou, H. B., X ie, R., D eng, C. et al., A cta Ch im ica Sinica, 50, (1992) [ 7 ]Zhou, Q. F., L i, H. M. and Feng, X. D., M acromo lecules, 20, 233 (1987) [ 8 ]H elferich, B. and M uler, H. O., Chem. Beṙ, 86, (1953) [ 9 ]W ak selm an, M., Comp ṫ R end., Ser. C, 262, 770 (1966)

(IGBP) km 2,? PRO GR ESS IN GEO GRA PH Y. V o l. 20, N o. 4 D ec., 2001 : (2001) m m 3,

(IGBP) km 2,? PRO GR ESS IN GEO GRA PH Y. V o l. 20, N o. 4 D ec., 2001 : (2001) m m 3, 20 4 2001 12 PRO GR ESS IN GEO GRA PH Y V o l. 20, N o. 4 D ec., 2001 : 100726301 (2001) 0420355209, (, 100101) :, 501 mm 502 mm, 765 10 8 m 3 638 10 8 m 3, 127 10 8 m 3,,, ;, : ; ; : P42616; P343 : A