Tetraethylene sulfoxide

Dimethyl sulfoxide oxidizes certain thlo ethers to the sulfoxides in reasonable yield. The ether is heated with a 50% molar excess of DMSO at 160-175° for several hours and the dimethyl sulfide is removed by distillation as formed. The suifoxides were isolated in high purity by distillation and there was no evidence of sulfone formation. Di-n-butyl sulfoxide and tetraethylene sulfoxide were obtained in similar yield, but several sulfides did not react to an appreciable extent. DMSO is a superior reagent for the oxidation of thiols to disulfides. A solution of the thiol in NHj MHj... 

The physical properties of the anhydrate form and two polymorphic monohydrates of niclosamide have been reported [61], The anhydrate form exhibited the highest solubility in water and the fastest intrinsic dissolution rate, while the two monohydrates exhibited significantly lower aqueous solubilities. In a subsequent study, the 1 1 solvates of niclosamide with methanol, diethyl ether, dimethyl sulfoxide, N,/V -dimethyl formamide, and tetrahydrofuran, and the 2 1 solvate with tetraethylene glycol, were studied [62], The relative stability of the different solvatomorphs was established using desolvation activation energies, solution calorimetry, and aqueous solubilities. It was found that although the nonaqueous solvates exhibited higher solubilities and dissolution rates, they were unstable in aqueous media and rapidly transformed to one of the monohydrates. 

The chemical and physical stability of aqueous and nonaqueous suspensions of a number of solvatomorphs of niclosamide has been evaluated in an effort to develop pharmaceutically acceptable suspension formulations [90]. Studied in this work was the anhydrate, two polymorphic monohydrates, the 1 1, Y, A"-dimethyI I ormam ide solvatomorph, the 1 1 dimethyl sulfoxide solvatomorph, the 1 1 methanol solvato-morph, and the 2 1 tetraethylene glycol hemisolvate. All of the solvatomorphs were found to convert initially to one of the polymorphic monohydrates, and over time converted to the more stable monohydrate phase. The various solvatomorphs could be readily desolvated into isomorphic desolvates, but these were unstable and became re-hydrated or re-solvated upon exposure to the appropriate solvent. 

Note 1,2-BC 1,2-dunethylethylene carbonate 1,3-DOL 1 -dioxolane AC acetonitrile A.N. acceptor number BC butylene carbonate BEC butyl ethyl carbonate BMC butyl methyl carbonate CF3-EC trifluoromethyl ethylene carbonate QEC chloroethylene carbonate DBC dibutyl carbonate DEC diethyl carbonate DEE 1,2-diethoxyethane DGM diethyleneglycol dimethyl ether DIPC di-isopropyl carbonate DMC dimethyl carbonate DME 1,2-dimethoxyethane DMSO dimethyl sulfoxide D.N. donor number DPC di-n-propyl carbonate EC ethylene carbonate EIPC ethyl isopropyl carbonate EMC ethyl methyl carbonate EPC ethyl propyl carbonate MeTHF 2-methyl tetrahydrofuran MIPC methyl isopropyl carbonate MFC methyl propyl carbonate PC propylene carbonate TEGM tetraethylene glycol dimethyl ether TGM triethylene glycol dimethyl ether TFIF tetrahydrofuran. 

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