Molecules, Volume 5, Issue 7 (July 2000) – 24 articles , Pages 916-991, Articles M162-M171

A mixture of 4.28 mmol (1.1328 g) bibenzil-4,4-di-yl-diisocyanate (1) [1] and 84 mmol (6.14 g) of redistilled N,N-dimethylformamide (2) was refluxed under stirring using a magnetically stirring-bar for 12 h, with complete absorption for any carbon dioxide in aqueous potassium hydroxide solution [2].[...] Full article

Selective cyclooxygenase inhibitors have attracted much attention in recent times in the design of new non-steroidal anti-inflammatory drugs (NSAID). 3D-QSAR studies have been performed on a series of 1,5-diarylpyrazoles that act as selective cyclooxygenase-2 (COX-2) inhibitors, using three different methods: comparative molecular field analysis (CoMFA) with partial least squares (PLS) fit; molecular field analysis (MFA) and; receptor surface analysis (RSA) with genetic function algorithms (GFA). The analyses were carried out on 30 analogues of which 25 were used in the training set and the rest considered for the test set. These studies produced reasonably good predictive models with high cross-validated and conventional r² values in all the three cases. Full article

Thiols and amines were benzamidomethylated in water solution at room temperature with (benzamidomethyl)triethylammonium chloride (1) in the presence of a small quantity of triethylamine (pH>9). Benzamidomethyl thioethers (3a-d) and (benzamidomethyl) amines or di(benzamidomethyl)amines (5) were obtained in high yields (>90%) as well as S(CH₂NHBz)₂ in a reaction of 1 with Na₂S. Benzamidomethyl esters RCOOCH₂NHBz were obtained (60-75%) in reactions of carboxylic acids with 1 in chloroform or dioxane. Full article

Reaction of dimethyl disulfide (1) with cyclohexene (2a) in AcOH in the presence of Pd(OAc)₂ yields trans-1-acetoxy-2-methylcyclohexane (3a). The equivalent reactions with hex-1-ene (2b) and 2-methylpent-1-ene (2c) or 1-methylcyclohex-1-ene (2d) preferentially give anti-Markovnikov and Markovnikov adducts 4 and 3, respectively, by acetoxymethylthiolation of the alkene. The Markovnikov regioselectivity 3b/4b for the reaction with 2b is higher than that for the reaction using AgOAc instead of Pd(OAc)₂, which proceeds via a thiiranium ion. Addition of a polar solvent (MeCN or MeNO₂) to the reactions with 2b or 2c using Pd(OAc)₂ abnormally decreases the Markovnikov regioselectivity. The total yield of 3 and 4 increases with an increased concentration of AcOH. Compounds 3 and 4 are also formed and the reactions in MeCN or MeNO₂ not containing AcOH. A solution of Pd(OAc)₂ in 1 exhibits λ_max 380 nm (log ε 3.6) assigned to the absorption of a relatively stable sulfonium salt. These indicate that the reactions using Pd(OAc)₂ proceed by S_N2 ringopening of a new type of thiiranium radical cations paired with −OAc via the sulfonium salts. The insensitivity of the 3/4 ratios to the reaction time at 25-60°C in the reactions with 2c-d shows the ring-opening to be controlled kinetically, but the increased ratio with reaction time at 116°C in the reaction with 2b suggests that the ring-opening is thermodynamically governed. The reaction product with 2d also undergoes a skeletal rearrangement to a thietanium radical cation to give 1-acetoxymethyl-2-methylthiocyclohexane. Full article