116196-83-9

Basic information

• Product Name: 4,4'-bis(tetrahydro-2H-thiopyran)
• Synonyms: 4,4'-bis(tetrahydro-2H-thiopyran)
• CAS NO: 116196-83-9
• Molecular Formula: C₁₀H₁₈S₂
• Molecular Weight: 202.37992
• Mol File: 116196-83-9.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 4,4'-bis(tetrahydro-2H-thiopyran)(CAS DataBase Reference)
• NIST Chemistry Reference: 4,4'-bis(tetrahydro-2H-thiopyran)(116196-83-9)
• EPA Substance Registry System: 4,4'-bis(tetrahydro-2H-thiopyran)(116196-83-9)

Safety Data

• Hazardous Substances Data: 116196-83-9(Hazardous Substances Data)

Upstream product

• 1622-55-5 9,10-dihydro-4H-benzo<4,5>cyclohepta<1,2-b>thiophen-4-one 
• 32358-88-6 4-Bromotetrahydrothiopyran 
• 86-39-5 2-Chlorothioxanthone 
• 1531-77-7 dibenzo[b,e]thiepin-11(6H)-one 
• 1210-35-1 10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-one 
• 5202-11-9 2-methyldibenzothiepin-11(6H)-one 

Relevant articles and documents

4H-BENZOCYLOHEPTATHIOPHENES AND 9,10-DIHYDRO DERIVATIVES-SULFONIUM ANALOGUES OF PIZOTIFEN AND KETOTIFEN; CHIRALITY OF KETOTIFEN: SYNTHESIS OF THE 2-BROMO DERIVATIVE OF KETOTIFEN

Reaction of ketone IX with 4-tetrahydrothiopyranylmagnesium bromide and the following dehydration with thionyl chloride afforded the sulfide III which was transformed to the methiodide II (sulfonium analogue of pizotifen).Similar sequence starting from ketone XXIV and concluded by dehydration of the alcohol XX, cleavage of the enol ether, and by treatment with methyl iodide resulted in the formation of the sulfonium analogue of ketotifen (V).Three modified routes leading to ketotifen (IV) are being described.The chirality of ketotifen was proven by (1)H NMR spectrscopy with the help of,optically active NMR shift reagent.The resolution of racemic ketotifen (IV) was achieved by crystallization of salts with optically active O,O'-diacyltartaric acids and homogenous anantiomers were obtained.The X-ray crystallographic analysis of (+)-IV-O,O'-di(p-toluoyl)-(R)-tartrate led to the three- dimensional structure of the molecule of (+)-ketotifen which enabled to determine its absolute configuration to be (R).One of the products of bromination of the ketone IX, the following methanolysis and dehydrobromonation, identified as XXVII, was transformed by reaction with 1-methyl-4-piperidylmagnesium chloride, by the following acid-catalyzed dehydration, and cleavage of the enol ether to the 2-bromo derivative of ketotifen XXXIV. (R)(+)-Ketotifen (IV) was found to be the more active ketotifen enantiomer but the stereoselectivity of its action is only a partial one.The 2-bromo derivative of ketotifen (XXXIV) is much less active than ketotifen in the line antihistamine activity.

POTENTIAL ANTIHISTAMINE AGENTS: 4-(6,11-DIHYDRODIBENZOTHIEPIN-11-YLIDENE)-1-METHYLTETRAHYDROTHIOPYRANIUM IODIDE AND SIMILAR SULFONIUM SALTS DERIVED FROM RELATED TRICYCLIC SYSTEMS

Thioxanthone, 10,11-dihydrodibenzocyclohepten-5-one, dibenzothiepin-11(6H)-one, its 2-methyl derivative, and thieno-2-benzothiepin-4(9H)-one were reacted with 4-tetrahydrothiopyranylmagnesium bromide and the obtained tertiary alcohols IVabc, VIc, and XIX were dehydrated to the olefinic sulfides IXabc, Xc, and XXI.Addition of methyl iodide afforded the title compounds XIabc, XIIc, and XXII.The Grignard reactions were accompanied by the 1,6-addition giving the ketones XVI-XVIII as by-products.The reductive properties of tetrahydrothiopyranylmagnesium bromide were most striking in the case of reaction with 2-chlorothioxanthone; the isolation of thioxanthene and thioxanthone showed that nuclear dehalogenation took also place.Reactions of 11-chloro-6,11-dihydrodibenzothiepin and benzhydryl chloride with tetrahydrothiopyran-4-ol gave the sulfides XXV and XXVIII; whereas the latter reacted with methyl iodide under the formation of sulfonium salt XXIX, the former was cleaved and gave 4-hydroxyl-1-methyltetrahydrothiopyranium iodide (XXVI).The sulfonium salts are free of the central effects but their antihistamine activity is rather low.