Vd. 18%. 6 CHINESE JOURNAL OF CIIEMISLaY uloo 0

Synthesis of the B-keto acids from benzimidazolium iodides and ethyl malonate

It has been re@ that Fketo acid and some of its derivatives showed signdicant activities in the metabolism of cahoqlic acid. PKeto acid has been syntheaized in several ways. Matsunma et al . prkparad the pketo acid fmn the reaction of &n dioxide carri- er 2-morpho l ino idazo l in~a ium amplex with ac- tive methylcne canpund.' Milton et d. claimed the preparation of p keto acid fnm the hydrolysis of the cor- responding eatex by glacial acetic acid and concentrated

hydrochloric acid .2 Bamick et al . develapd a new method for the synthesis of the Pketo acid, the car- bcnrylic acids were converted into acid chlorides and sub- jected to tmatmmt with the mono-anion of bis (trimethylsiyl) donate at oc, followed by the short treatment with water at "Xn temperature leading to hy- drolysis and decaTboxylation of the inte.xmediate triacyl compound to yield the kketo acid.3

We quuted the addition-hydrolysis reacticn of benzimihle methiodide salts with nucleophile such as Grigna~d reagents, and a new method for the preparation of aldehydes and ketones was p~wided .~ In thia peper, the reactim of benzimidezolium salts with nucleophile ethyl d o n a t e anion was studied, and a new convenient and useful synthetic method of the pketo acid waa pm- vided (schane 1)

2CH3I a N y R - - H 2 0

+ RCOOH - A N H

la-c

Urn' NHz

CHI 0

I ) CH2(COZEt)2, EON& EtOH II RCCH2COOH

2) H+, HzO I CHI

29- c

39- c

Benzimidamle la-c was prepad fnm 1,2-ben- zenediarnine and carboxylic acid,' and the benzimida- zalium iodide 20-c was obtained via q~aterisation.~

The procedure for the preparation of the kketo acid 3 m : 15 mL of a n h y h ethanol and 0.46 g (0.02 ml) of sodium cut in small pieces were plaoed in a W)

Vol. 18 No. 6 2ooo C h i l l f X J a u n a l O f ~ 941

d three necked mund-bottamed flask fitted with a can- denserand a mechanical stirrer, 3 .2 g (0.02 mol) of ethyldonate was added until all the sodium was dis- solved. The stirring was started and the solution was heated to gentle boiling. To the boiling solution 0.02 mol of benzimihlium iodide was added over a pexiod o f h t 3 O m i n . TherenuXandstirringweremtinued for 16-18 h, then a 10% solution of hydrochloride was added slowly, and the resulting mixture was heated at

moved, and after the residue was dissolved in glacial acetic acid, concentrated hydmchloride was added drop- wise until the solution became slightly tubid. The mix- ture was allowed to stand at room temperature for45-48 h, and the resulting white crystals were collected, and recrystallized from acetone to give pure kketo acids. The eqmimental data tm listed in Table 1.

60-65g: for 30 min with stilling. Ihe solvent was re-

la GHIS 143-144(&: 144.5-145.0) 86.5 lb h H 3 1 98-loO(Ii?: 96.5-97.0) 85.4 IC Qb 1%-179(Ii?: 177-177.5) 78.5 tr GHu 210-211' 82.4 2b C15H31 181-188' 86.7

3. C7Hu =M(Lit': 83--84) 65.4 3b h H 3 1 101-102(&: 1-104) 54.5

2c cH3 U6258(Lit7:256) 76.4

lm-l04(Iig: 104-105)= 61.5 ' calod: C, 51.35; H, 6.68; N. 7.48. F d : C, 51.64; H, 6.92; N, 7.21. ' Calcd: C, 59.25; H, 8.44; N, 5.76. F d : C, 58.97; H, 8.35; N, 5.50. 'mpd0x.k.

I h e mechanism of the reaction for benzimidamlium iodide with nucleophile reagent has been proposed in our previous paper.' me d o n details described in this paper are d l y explaid by a similar addition re- actionof ethyl donate auhn with guatemary C = N bond d benzimihlium iodide, and the obtained be- naimihlidine can be converted into the corresponding pketo acid via hydrolysis.

In view ofpoor result obtained from the reaction of benzimidamle with nucleophile, it may be concluded that the formation of nuatemery ammonium salt probably assists the additim reaction by incxwsing the polarity of C = N bond being attacked by ethyl donate anion. Further studies of this reaction are being continued in our laboratory.

1. Matamnna, N.; Sakapbi, Y.; Ohba,T., J. Gem.

2. ~ , M . A . ; A r d r o d , A . E . ; H ~ , K . , J . A m .

3. Barnick, J .W.; h, J .L . ; Bickelhaupt. F . , S p k i s , 787(1979).

4. Shi, Z.; Gu, H . , sdmocinchino ( S a i a B ) , 3 9 , 654

5. Pool. W . O . , 1. Am. chan. Soc., 59, 178(1937). 6. F&, O., J. h b . Gem., 75, 88(1907). 7. El'bov, A.V., 2%. Org. h., 36, 1307(1%5). 8. StaJlegen, E., Ark. Kani., 3. 381(1951).

tim, New Yo&, Chapm cud Hall, 1982, p.9.

soc., Gun. conmarn., 326(1980).

chsn. soc., 72, 1231(1950).

(1996).

9. -9 J . , 4 Or@ -9 4th acb-

(m m G , X.H.; DONG, L . J . )