5-Aryloxymethyl-2-oxazolidinones

Abstract

passed through the reaction mixture and then through 3% hydrochloric acid for 15 hours. The acid solution was evaporated to dryness in DQCUO and the white, crystalline residue identified as a mixture of methylamine hydrochloride, m.p. 225O, and ammonium chloride, no m.p. t o 300°, by recrystallization from methanol-ether and by vapor phase chromatography. For the latter a Perkin-Elmer model 154 Vapor Fractometer with a 1-m. triethanolamine impregnated Celite column wasused a t 79". The mixture of amines was introduced in methanol solution after liberation from their hydrochlorides by addition of methanolic potassium hydroxide.Four sharp maxima were obtained corresponding to control peaks obtained for ammonia, methylamine, methanol and water. The area under the ammonia peak was smaller than that from methylamine. Control Experiments.-(a)The above procedure was repeated with 1 g. (0.0032 mole) of 4-ami110-6-cliloro-N,X'dimethyl-nt-benzenedisulfonainide (Yh). Onlv a sm,lll amount of ammonium chloride WAS isolated in this case. S o trace of methylamine could be detected by vapor phase chromatography.A suspension of 0.50 g. (0.0016 mole' of X wds refluxed for 2 hours in 60 ml. of 10yc hydrochloric acid, cooled and made strongly basic with saturated sodium hydroxide solution. A stream of nitrogen T V~T passed through the solution and through a trap of 3y0 hydrochloric acid for 15 hours Evaporation of the acid to tiryneqs did not le tve any residue.SUMMIT, N. J. (b) [CONTRIBUTION FROM THE CHEMICAL RESEARCH LABORATORY, A. H. ROBISS Co., INC.] When (a) 3-(o-methoxyphenoxy)-1,2-propanediol (11) is fused at 180-200O with two molar equivalents of urea or when (b) 2-hydroxy-3-(o-methoxyphenoxy)-propyl carbamate (I) and one molar equivalent of urea are similarly fused, the major product is 5-(o-methoxyphenoxymethyl)-2-oxazolidinone (IIIa). A sequence of reactions by which the oxazolidinone ring is formed under these conditions has been investigated and these reactions are discussed. Following method (a) twentyfive 5-aryloxymethyl-2-oxazolidinones, in which the substitution in the aryl nucleus is alkyl, alkyloxy and/or halogen, have been prepared for pharmacological testing. A total of nineteen corresponding N-substituted-5-aryloxymethyl-2-oxazolidinones, prepared by condensation of l-amin0-3-aryloxy-2-prop~1101~ with ethyl carbonate or phosgene, are also reported.In an effort to develop other processes of preparing the skeletal muscle relaxant 2-hydroxy-3-(o-methoxyphenoxy)-propyl carbamate (I) the reaction between 3-(0-methoxyphenoxy) -1,2-propanediol (11) and urea was studied. Instead of yielding the desired carbamate, the fusion of these 0 J-FHd I1 i OCHi CHCH? OCKH, \= I

Solubility and Some Crystallization Properties of Conglomerate Forming Chiral Drug Guaifenesin in Water

“…For example, it can be used in treatment of cough, rhinitis, gout, fibromyalgia, and primary dysmenorrhea . Diol 1 is a valuable precursor in the synthesis of the skeletal muscle relaxant and spasmolytic methocarbamol and the muscle relaxant and tranquilizer agent mephenoxalone …”

“…21,22 Diol 1 is a valuable precursor in the synthesis of the skeletal muscle relaxant and spasmolytic methocarbamol 23 and the muscle relaxant and tranquilizer agent mephenoxalone. 24 Recently, based on the identity of the IR spectra of the racemic and scalemic crystalline samples, thermochemical studies, and X-ray diffraction analysis, the conglomerate nature of rac-1 has been established. [25][26][27] Also a separation procedure based on entrainment (i.e., preferential crystallization) of slightly enantiomerically enriched aqueous solution was introduced.…”

New synthesis of mephenoxalone

“…(o-Methoxy)phenoxyacetaldehyde diethyl acetal (9). Guaiacol (2.00 g, 16.1 mmol) was dissolved in 60 mL of HMPA, a NaOH aqueous solution (1.28 g, 32.2 mmol, 10 mL) was added drop wise and stirred at 0 o C for 15 minutes, bromoacetaldehyde diethyl acetal (3.00 g, 16.1 mmol) was added drop wise at 0 o C and the mixture was refluxed for 6 hours.…”

“…9 This method consisted in the fusion of one equivalent of urea with one equivalent of 3-o-methoxyphenoxy-1,2-propanediol at 180-200 o C to produce the crude oxazolidinone which was further purified by fractional distillation and crystallization to gave a 67% isolated product yield. There are only a few reports in literature about the synthesis of Mephenoxalone.…”

Partial and Complete Reduction of Heterocycles Containing More than One Heteroatom

“…Metal hydrides react with pyrimidines (68) to give 3,4-dihydropyrimidines (69),29 but electrochemical reduction of the analogs (70) gives radical anions (71) which may dimerize or, in the presence of a proton source, yield dihydro derivatives (72). The latter exist in equilibrium with acyclic tautomers (73),30 and at high potentials further reduction produces anions (74) and (75) which may then be protonated to give pyrroles (76).31 N-Benzyldihydropyrimidines (77; R =Bn) are reduced by sodium borohydride in ethanol to give hexahydro derivatives (78), but if the N-substituent is a phenyl group excess reagent leads to diamines (79; Scheme 3).32 Similar products form when dihydropyrimidinium salts (80) are treated with this reagent, although reduction with LAH yields amino imines (81).…”