Synthesis of new substituted 5‐methyl‐3,5‐diphenylimidazolidine‐2,4‐diones from substituted 1‐(1‐cyanoethyl‐1‐phenyl)‐3‐phenylureas

Abstract

The reaction of substituted phenyl isocyanates with 2-amino-2-phenylpropanenitrile and 2-amino-2-(4-nitrophenyl)propanenitrile has been used to prepare substituted 1-(1-cyanoethyl-1-phenyl)-3-phenylureas. In anhydrous phosphoric acid the first products to be formed from 1-(1-cyanoethyl-1-phenyl)-3-phenylureas are phosphates of 4-methyl-4-phenyl-2-phenylimino-5-imino-4,5-dihydro-1,3-oxazoles, which on subsequent hydrolysis give the respective ureidocarboxylic acids. On prolongation of the reaction time, the phosphates of 4-methyl-4-phenyl-2-phenylimino-5-imino-4,5-dihydro-1,3-oxazoles rearrange to give phosphates of 5-methyl-4-imino-3,5-diphenylimidazolidin-2-ones, and these are subsequently hydrolysed to the respective substituted 5-methyl-3,5-diphenylimidazolidin-2,4-diones. The ureidocarboxylic acids were also prepared by alkaline hydrolysis of 5-methyl-3,5-diphenylimidazolidin-2,4-diones. The 5-methyl-3,5-diphenylimidazolidin-2,4-diones and ureidocarboxylic acids were characterised by their 1 H and 13 C NMR spectra. Structure of the 5-methyl-5-(4-nitrophenyl)-3-phenylimidazolidine-2,4-dione was verified by X-ray d i ffraction. The alkaline hydrolysis of individual imidazolidine-2,4-diones was studies spectrophotometrically in sodium hydroxide solutions at 25 °C. The rate-limiting step of the base catalysed hydrolysis consists in decomposition of the tetrahedral intermediate. The reaction is faster if electron-acceptor substituents are present in the 3-phenyl group of imidazolidine-2,4-dione cycle. The pK a values of individual 5-methyl-3,5-diphenylimidazolidine-2,4-diones have been determined kinetically.

2-Amino-2-alkyl(aryl)propanenitriles as key building blocks for the synthesis of five-membered heterocycles

“…49 The reaction of substituted phenyl isocyanates with 2-amino-2-phenylpropanenitrile and 2-amino-2-(4-nitrophenyl)propanenitrile was used for preparation of substituted 1-(1-cyano-1-phenylethyl)-3-phenylureas. 50 These substituted phenylureas react in anhydrous phosphoric acid giving first the phosphates of 5-imino-4-methyl-4-phenyl-2-phenylimino-4,5-dihydro-1,3-oxazoles, which on subsequent hydrolysis provide the corresponding ureidocarboxylic acids. An increase in reaction temperature and time results in rearrangement of the phosphates of 5-imino-4-methyl-4-phenyl-2-phenylimino-4,5-dihydro-1,3-oxazoles to phosphates of 4-imino-5-methyl-3,5-diphenylimidazolidin-2-ones, which on subsequent hydrolysis provide the corresponding substituted 5-methyl-3,5-diphenylimidazolidin-2,4-diones (Scheme 7).…”

“…The kinetically determined pK a values of individual 5-methyl-3,5-diphenylimidazolidin-2,4-diones varied in the range of 11.0-12.1 (water, 25 °C) (Scheme 7). 50 The recently published 51 one-pot methodology of synthesis of hydantoins was realized as a multi-component reaction starting directly from carbonyl compounds, ammonia and carbon dioxide (yields 47-94%). The first step produces the imine, the second step gives the aminonitrile, and the last step provides the required hydantoin.…”

Heterocycles from α‐Aminonitriles

“…Marco and co-workers developed a route starting from 2-aminoisobutyronitrile 145 and alkanesulfonyl chlorides. [79] Zhong and co-workers presented a synthesis of diversely functionalized imidazoles starting from N-acylated a-aminonitriles 154, which were reacted with triphenylphosphine and a carbon tetrahalide to afford 2,4-disubstituted 5-halo-1H-imidazoles 155 in a single step. [76] In a similar approach, Postel constructed spiro-[4.4]azaphospholenes 150 from carbohydrate-derived a-aminonitriles 149 by N-phosphonylation and intramolecular anionic cyclization (Scheme 30).…”

“…As in the Edman degradation, hydantoins (153) are the final and thermodynamically stable reaction products (Scheme 31). [79] Zhong and co-workers presented a synthesis of diversely functionalized imidazoles starting from N-acylated a-aminonitriles 154, which were reacted with triphenylphosphine and a carbon tetrahalide to afford 2,4-disubstituted 5-halo-1H-imidazoles 155 in a single step. Various further functional groups can be easily introduced in the latter compounds, and structural modifications can be carried out (Scheme 32).…”

“…Treatment of ureas 152 with anhydrous phosphoric acid results first in the kinetically favored ring closure by attack of the oxygen on the nitrile carbon to furnish phosphate salts of 4‐methyl‐4‐phenyl‐2‐phenylimino‐5‐imino‐4,5‐dihydro‐1,3‐oxazoles. As in the Edman degradation, hydantoins ( 153 ) are the final and thermodynamically stable reaction products (Scheme ) 79…”