Phase-transfer-catalysed Additions of Methyl N-(Diphenylmethylidene)glycinate to Azomethines$ Donka Tasheva, a Olyana Angelova b and Veneta Dryanska* a a Department of Chemistry, University of So®a, 1126 So®a, Bulgaria b Bulgarian Academy of Sciences, Institute of Applied Mineralogy, 1000 So®a, Bulgaria Methyl 3-aryl-3-arylamino-2-[(diphenylmethylidene)amino]propanoates are prepared by phase-transfer-catalysed reactions of methyl N-(diphenylmethylidene)glycinate with arylmethylideneanilines. Glycine ester Schi bases have been widely used in recent years as anionic glycine synthons in reactions with a variety of electrophiles to prepare higher, or possessing another functional group a-amino acids. 7±14 However, reactions with azomethines, giving access to a,b-diamino acids, have not received any attention. 1 We now report on the preparation and stereochemistry of methyl 3-aryl-3-arylaminopropano- ates 3 by phase-transfer-catalysed reactions of methyl N- (diphenylmethylidene)glycinate (1) with the azomethines 2. The reaction of 1 and 2a was investigated using dierent solvents, catalysts and bases, at both room temperature and 0 8C in order to optimize the yields and the stereo- selectivities (Scheme). In general, low to moderate yields and low stereoselectivities were observed in all cases. Somewhat better results were obtained when performing the reaction in MeCN using 50% NaOH and benzyltriethylam- monium chloride (TEBA) at both room temperature and 0 8C for 10 min: 54±60% yield of the diastereoisomers of 3a from which, after recrystallization, syn-3a was isolated in a yield of 40±45%. Prolonging the reaction time to 60 min did not change the yield of syn-3a when carried out at 0 8C (40%); however, after 60 min at room temperature no 3a was detected. In addition, small amounts of the sodium salt 4a was isolated, indicating that cleavage of the azomethine bond, beside retro-addition and hydrolysis reactions, was also taking place. HPLC analysis of the reaction of 1 and 2a within 1 h con®rmed these results (Table 4). Similar behaviour was observed when 1 was reacted with substituted arylmethylideneanilines 2 except for N-(2- methylphenyl)methylideneaniline (2f ). At room temperature and 0 8C using the standard procedure (50% NaOH± TEBA±MeCN) the diamino esters 3 were obtained in low to moderate yields (Table 5). In the case of the reaction of 1 with 2f, the cleavage of the azomethine bond and hydrolysis of the ester function was observed even at shorter reaction times. After 10 min the sodium salt 4b was isolated in a yield of 22%, while the corresponding protected diamino ester 3f was obtained at 0 8C. Low yields of compounds 3 were also obtained when performing the reaction in the DMSO±NaOH system (Table 5). A lower yield of syn-3a (28%) was also observed upon performing the reaction without any catalyst. Attempts to convert 3a into the free acid failed owing to degradation processes. However, its sodium salt (4a) and potassium salt (4c) were easily prepared in good yields (72 and 85%, respectively) by re¯uxing an ethanol solution of 3a with aqueous sodium hydroxide or solid potassium hydroxide, respectively. J. Chem. Research (S), 1998, 428±429 J. Chem. Research (M), 1998, 1933±1951 Scheme 1 Reagents and conditions: i, 50% NaOH, TEBA, MeCN, room temperature or 0 8C; ii, 4% NaOH, DMSO Table 4 Ratio of anti 3a/syn 3a obtained at r.t. under standard conditions a Anti/syn b Reaction time r.t. 0 8C 10 s 35:65 37:63 30 s 32:68 33:67 60 s 32:68 32:68 2 min 32:68 31:69 5 min 31:69 30:70 10 min 25:75 27:73 30 min Ð c 25:75 60 min Ð d Ð e a 50% NaOH±TEBA±MeCN, 10 min. b Measured by HPLC. c Only traces of 3a were detected. d No 3a was detected. e Not measured. Table 5 Yields of compounds 3a±k prepared Yield (%) a r.t. 0 8C NaOH, DMSO 3a 45 40 36 3b 56 64 21 3c 66 64 55 3d 28 Ð b 33 3e 52 51 41 3f Ð c 28 9 3g 12 12 5 3h 27 22 Ð d 3i 18 37 13 3j 15 22 Ð d 3k 9 Ð b 6 a Yield of pure syn diastereoisomer. b The reaction was not carried out at 0 8C because of crystallization of the azomethine. c The sodium salt 4b was isolated in yield of 22%. d No product was isolated. $Part 15. For Part 14 see ref. 1. *To receive any correspondence. 428 J. CHEM. RESEARCH (S), 1998 Published on 01 January 1998. Downloaded on 28/10/2014 21:31:24. View Article Online / Journal Homepage / Table of Contents for this issue