Acylation of 2-aminothiobenzamide or 2-methylaminothiobenzamide with substituted benzoyl chlorides has been used to synthesise the corresponding 2-benzoyl-aminothiobenzamides whose subsequent sodium methoxide-catalysed ring closure gives the corresponding quinazoline-4-thiones. These compounds were characterised by means of their 1H- and 13C-NMR spectra. The preferred tautomeric form of selected compounds has been discussed on the basis of their 13C-NMR, IR and Raman spectra. It has been found that in the given medium 1-methyl-quinazoline-4-thiones undergo a replacement of the sulphur substituent by oxygen giving 1-methyl-quinazoline-4-ones. In strong acid media, 2-benzoylaminothiobenzamide is cyclised through its sulphur atom to give 2-phenylbenzo[d-1,3]thiazin-4-one.

Twelve new substituted S-(1-phenylpyrrolidin-2-on-3-yl)isothiuronium bromides and twelve corresponding 2-imino-5-(2-phenylaminoethyl)thiazolidin-4-ones have been prepared and characterised. Kinetics and mechanism of transformation reaction of S-[1-(4-methoxyphenyl)pyrrolidin-2-on-3-yl]isothiuronium bromide and its N,N-dimethyl derivative 5a into corresponding substituted thiazolidin-4-ones 2a and 6a have been studied in aqueous solutions of amine buffers (pH 8.1-11.5) and sodium hydroxide solutions (0.005-0.5 mol l(-1)) at 25 degrees C and at I= 1 mol l(-1) under pseudo-first-order reaction conditions. The kinetics observed show that the transformation reaction is subject to general acid-base, and hydroxide ion catalyses. Acid catalysis does not operate in the transformation of 1a; the rate-limiting step of the base-catalysed transformation is the decomposition of bicyclic tetrahedral intermediate In(+/-) and the Brønsted dependence is non-linear (pK(a) approximately 9.8). In the case of derivative 5a both base and acid catalyses make themselves felt. In the base catalysis, the rate-limiting step consists of the decomposition of bicyclic intermediate In, and the Brønsted dependence is linear (beta = 0.9; pK(a) > 11.5). The acid-catalysed transformation of 5a also proceeds via the intermediate In, and the reaction is controlled by diffusion (alpha approximately equal to 0). With compound 5a in triethylamine and butylamine buffers, the general base catalysis changes into specific base catalysis. The effect of substitution in aromatic moiety of compounds 1a-h and 3a-h on the course of the transformation reaction has been studied in solutions of sodium hydroxide (0.005-0.5 mol l(-1)) at 25 degrees C by the stopped-flow method. The electron-acceptor substituents 4-NO(2) and 4-CN do not obey the Hammett correlation, which is due to a suppression of cross-conjugation in the ring-closure step of the transformation reaction.

Dedicated to Professor Jaromír Kaválek on the occasion of his 65th birthday Substituted S‐(1‐phenylpyrrolidin‐2‐on‐3‐yl)isothiuronium salts in weakly basic media undergo intramolecular recyclisation reaction in which the γ‐lactam cycle is split and a thiazolidine cycle is formed. A series of six substituted 2‐imino‐5‐[2‐(phenylamino)ethyl]‐thiazolidin‐4‐ones have been prepared by this reaction.

A study of chemical behaviour of substituted 4‐chloro‐N‐phenylbutanamides in aqueous solutions of sodium hydroxide showed that the substrate first undergoes ring closure to give substituted 1‐phenylpyrrolidin‐2‐ones, which are subsequently hydrolysed to substitution derivatives of sodium 4‐amino‐N‐phenylbutanoates. Kinetic measurements provided the values of dissociation constants pKa and cyclization rate constants kc in water at 25 °C for 2‐bromo‐4‐chloro‐N‐(4‐nitrophenyl)butanamide [pKa = 11.64 ± 0.01; kc = (1.94 ± 0.03) × 10−2 s−1], 4‐chloro‐N‐(4‐nitrophenyl)butanamide [pKa = 13.35 ± 0.02; kc = (1.60 ± 0.02) × 10−2 s−1] and 4‐chloro‐2‐methyl‐N‐(4‐nitrophenyl)butanamide [pKa = 13.55 ± 0.03; kc = (7.61 ± 0.11) × 10−2 s−1]. The pKa and kc values of individual derivatives differ depending on the substitution at the α‐position of the butanamide skeleton. In methanolic sodium methoxide solutions, the course of ring closure of 2‐bromo‐4‐chloro‐N‐(4‐nitrophenyl)butanamide is of similar nature but slower [K = 60.10 ± 0.08 and kc = (6.52 ± 0.05) × 10−3 s−1]. The subsequent hydrolyses of substituted 1‐phenylpyrrolidin‐2‐ones to substituted 4‐aminobutanoic acids also have different courses with different derivatives and depend on the substituents in the aromatic and/or heterocyclic moiety. The rate‐limiting step of hydrolysis of 1‐(4‐nitrophenyl)pyrrolidin‐2‐one consists of the non‐catalysed decomposition of the tetrahedral intermediate. In the case of 3‐bromo‐1‐(4‐nitrophenyl)pyrrolidin‐2‐one at sodium hydroxide concentrations below 0.1 mol l−1, the rate‐limiting step is the second reaction pathway, i.e. the hydroxide ion‐catalysed decomposition of the tetrahedral intermediate. At sodium hydroxide concentrations above 0.1 mol l−1, the rate‐limiting step shifts to formation of the tetrahedral intermediate. This formation of the intermediate is 140 times slower than its hydroxide ion‐catalysed decomposition [k3/k−1 = (1.40 ± 0.04) × 102 l mol−1]. Introduction of a 3‐bromo substituent into 1‐(4‐nitrophenyl)pyrrolidin‐2‐one results in acceleration of all the reaction steps of hydrolysis and increases the acidity of the intermediate. Copyright © 2002 John Wiley & Sons, Ltd.

The paper deals with a simple and sufficient synthesis of key precursor of Lasofoxifene. The 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene was prepared by a sequence of five reactions steps: first 1-(4-benzyloxyphenyl)-6-methoxy-3,4-dihydronaphthalene was prepared (70%), and this was quantitatively epoxidized to 7b-[4-(benzyloxy)phenyl]-5-methoxy-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene. Catalytic (ZnI 2 ) isomerization of the epoxide gave 1-(4-benzyloxyphenyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-2-one (75%). Its subsequent reaction with phenylmagnesium bromide gave 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydro-2-naphthol (87%). Acid-catalysed dehydration of this alcohol by polyphosphoric acid (25°C) provides 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,4-dihydronaphthalene (80%). Dehydration in the system of acetic anhydride/polyphosphoric acid gives 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-3,4-dihydronaphthalene (66%).