REGIOSELECTIVE BROMINATION OF N-ACYL-~-AMINO KETONES

S. I. Zav'yalov and G. I. Ezhova UDC 542.944.546.14:547.447.5

For the first time we have established the possibility of the regioselective bromina- tion of N-acyl-a-amino ketones (I) [i] at CI and C3. The application of Br2 to I (R = Me) in AcOH and to I (R = Ph) in AcOH or conc. HCI in the presence of NiCI2 or LiCI (70 h, 20~ results in the formation of oily l-acylamino-3-bromo ketones (II) according to the scheme

- , RCONHCH2COCHBrR' !

Br, ~ (II) 60--70% RCONHCH~COCH2R' "'~ RCONHCIHBrCOCH~R'-- / (1) HCl, ~,o

----+ 0CHCOCH~R' R ---- Me, P h , R ' ---- I-I, Me (IV)

50--60%for dioximes (IV)

The conversion of I into II may be treated as a two-step process involving the initial bro- mination of I at CI followed by the rearrangement of the intermediate kinetic-control prod- ucts (III) to form the "thermodynamic" 3-bromo ketones (II). Such chemistry of the bromina- tion of I to II is supported by the course of the reaction of I (R = Me, R' = H, Me) with

Br2 in conc. HCI in the presence of LiCI (4 h, 20~ The reaction is accompanied by the formation of unstable l-bromo ketones (III, R = Me), which are hydrolyzed by conc. HCI to ~- keto aldehydes (IV) without managing to be rearranged to form 3-bromo ketones (II). The 3- bromo ketones (II) react with nucleophilic reagents with or without the 3,1 displacement of the bromine atom. For example, the reactions of II (R = Me, R' = H) with AcSNa in H=O and II (R = Ph, R' = Me) with piperidine (24 h, 20~ yielded l-acetamido-3-acetylmercaptoace- tone, mp 66-68~ and l-benzamido-l-piperidino-2-butanone, mp I19-120~ respectively. The structures of the compounds obtained were proved by elemental analysis, as well as the IR, PMR, and mass spectra.

LITERATURE CITED

i. S. I. Zav'yalov, N. I. Aronova, and I. N. Makhova, Reactions and Methods of Investiga- tion of Organic Compounds [in Russian], Vol. 22, Khimiya (1971), p. 9.

N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Original article submitted August i0, 1977.

SOLID-PHASE HYDROLYSIS OF THE p-NITROANILIDE OF N-SUCCINYL-L-

PHENYLALANINE IN THE PRESENCE OF CHYMOTRYPSINOGEN

N. V. Medvedeva and Yu. I. Khurgin UDC 542.938:547.9:577.15

Chymotrypsinogen displays a catalytic activity which is lower by a factor of 107 to 104 than that of chymotrypsin in the hydrolysis of substrates of the ester type. We have dis- covered the chymotrypsinogen hydrolysis of a chymotrypsin substrate of the amide type, viz., the p-nitroanilide of N-succinyl-L-phenylalanine (NSP) when the reaction was carried out without a solvent in the solid phase according to the method in [I], which has previously been developed for studying the chymotrypsin hydrolysis of NSP.

The chymotrypsinogen was freed from any possible admixture of chymotrypsin by affinity chromatography on an immobilized chymotrypsin inhibitor from Phaseolus beans [2]. The reac-

N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. i0, pp. 2392-2393, October, 1977. Original article submitted August 24, 1977.

2226 0568-5230/77/2610- 2226507.50 �9 1978 Plenum Publishing Corporation