Synthesis and Polymerization of Propanesultam

Abstract

A typical duplicate run yielded 52.5% of VII, b.p. 94-97' (0.10 mm.), 71% 1.4853. E. Proof of Structure for the Cyclic Formal of cis-3,a-Dihydroxycyclohexylmethanol (IV). 1. Methylation of 5-Hydroxymethylhexahydrobenzo-cis-1,3-dioxole (VII) .-In a microreaction flask waa heated 0.6 g. (0.026 g.-atom) of sodium metal in 30 ml. of toluene. To the sodium at reflux was added dropwise over 45 min. a solution of 4.00 g. (0.0254 mole) of VI1 in 20 ml. of toluene (Nz atmosphere). The formation of the alkoxide waa allowed to proceed overnight. After 14 hr., dimethyl sulfate, 3.2 g . (0.025 mole) in 10 ml. of toluene, waa added over 15 min. and the reaction mixture allowed to reflux 2 hr. Methanol, 10 ml., waa added and the resulting toluene solution washed with dilute ammonia water and dried over anhydrous sodium sulfate. After removal of the solvent the residue waa distilled. One main fraction was collected, 3.0 g. (73q;b yield), of 5-methoxymethylhexahydrobenzo-cis-l,3-dioxole, b.p. 58' (0.1 mm.), n * '~ 1.4605.Anal. Calcd. for CoHieOj: C, 62.76; H, 9.34. Found: C , 62.45; H, 9.37. 2. Hydrolysis of the Methylated Formal of IV and Determination of 1,2-Glycol Content.-A 0.2811-g. sample of the methylated formal of IV, 50 ml. of water, and 5 drops of concentrated HC1 were heated on a steam bath overnight. The reaultant homogeneous solution waa diluted quantitatively to 100 ml. and the concentration of 1,2-glycol structure determined by periodic acid titration.' Aliquota of the hydrolyzed glycol took up 98-110% of the theoretical amount of periodic acid after a 1-hr. reaction time a t 25'.Acknowledgment.-The trans-hexahydrobenzo-l,3dioxole wm synthesized for the first time by Dr. Newman M.Propanesultam has been prepared by addition of thiolacetic acid to allyl chloride, oxidation of the adduct with aqueous chlorine to 3-chloropropanesulfonyl chloride, reaction with ammonia, and cyclization of the resulting 3chloropropanesulfonamide in alcoholic base. Chromatographically pure propanesultam had m.p. 23.1-23.2', b.p. 156-157 (2 mm.), n% 1.4826; the N-benzoyl derivative melted a t 171-172'. Polymerization of propanesultam of 99.17, purity has been investigated using a variety of catalysts. Basic catalysts such aa sodium hydride, sodium and potassium hydroxides, potassium phenoxide, or tetramethylguanidine are effective in producing polymer of high molecular weight, m.p. 257-260°, [ q ] 0.77 dl./g., particularly when used with an N-alkane-or N-arenesulfonyl-l,3-propaneaultam aa cocatalyst, as for example, N-(p-toluenesulfonyl)-1,3-propanesultam.Octadecylamine hydrochloride, aniline hydrochloride, picric acid, p-toluenesulfonic acid, mesitylenesulfonic acid, and benzenesulfonyl chloride effected polymerization, but only polymer of low molecular weight waa produced.Lewis acids were ineffective under a variety of conditions.

Design and Synthesis of 8-Hydroxy-[1,6]Naphthyridines as Novel Inhibitors of HIV-1 Integrase in Vitro and in Infected Cells

“…The resultant aldehyde was re-duced with sodium borohydride to afford benzyl alcohol 16 in 77% yield. Alcohol 16 was converted to its corresponding bromide, which was then reacted with γ-sultam 16 to give 17 in 74% yield. Compound 17 was subjected to Heck reaction conditions with butyl vinyl ether followed by acid hydrolysis to provide methyl ketone 18 in 90% yield.…”

Practical Synthesis of Sultams via Sulfonamide Dianion Alkylation: Application to the Synthesis of Chiral Sultams

“…The reported syntheses of 1,4-butanesultam and 1,3-propanesultam, which utilized chloroalkanesulfonyl chloride intermediates, required multistep sequences and inconvenient reagents such as PCl 5 and chlorine . Although various protocols for synthesis of the substituted sultams have been developed using as a key ring formation step either C−N bond formation or C−C bond formation, these methods have been limited to a specific class of substrates.…”

Preparation and reactions of .alpha.-lithiobutanesultams

“…B. Preparation of 2H-2-Methyl-6-(diphenylhydroxymethyl)tetrahydro-1,2-thiazine 1,1-Dioxide (10). Condensation with Benzophenone.…”