GB668562A - Improvements in or relating to diaryl-tertiary-aminoalkyl-methyl alkyl or cycloalkyl sulfones and their preparation - Google Patents

Improvements in or relating to diaryl-tertiary-aminoalkyl-methyl alkyl or cycloalkyl sulfones and their preparation

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Publication number
GB668562A
GB668562A GB12684/49A GB1268449A GB668562A GB 668562 A GB668562 A GB 668562A GB 12684/49 A GB12684/49 A GB 12684/49A GB 1268449 A GB1268449 A GB 1268449A GB 668562 A GB668562 A GB 668562A
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GB
United Kingdom
Prior art keywords
sulphone
ethyl
dimethylamino
diphenylbutyl
piperidyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB12684/49A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
STWB Inc
Original Assignee
Sterling Drug Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sterling Drug Inc filed Critical Sterling Drug Inc
Publication of GB668562A publication Critical patent/GB668562A/en
Expired legal-status Critical Current

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Abstract

Basic sulphones of the formula B-X-C(Ar)(Ar1)-SO2-R, where B is a dialkylamino group (the alkyl groups containing 1-4 carbon atoms) or an N-piperidino, N-morpholino or N-pyrrolidino radical, Ar and Ar1 are benzene nuclei (which may be linked to form a fluorene ring), X is an alkylene group of 2-6 carbon atoms and R is an alkyl or cycloalkyl group of 1-8 carbon atoms (if cyclic, containing 3-6 ring carbon atoms), are prepared by condensing CH(Ar)(Ar1)-SO2-R with B-X-halogen in the presence of a basic condensing agent. The aryl radicals may be substituted by non-interfering atoms or groups, e.g. hydroxy, alkyl, alkoxy, dialkylamino, chlorine, bromine or iodine. Sodium amide is the preferred condensing agent (others are listed) and an inert solvent such as toluene is preferably used. The product may be isolated as the free base or as a salt with a non-toxic acid, e.g. hydrochloric, hydrobromic, sulphuric, sulphamic, phosphoric, tartaric, citric, succinic, acetic, oleic or benzoic. Alternatively, a quaternary salt may be formed, by reaction with, e.g., methyl iodide, ethyl bromide or benzyl chloride. Examples show the preparation of the following sulphones: 3 - (1 - piperidyl) - 1 : 1 - diphenylpropyl ethyl sulphone, 3-(1-piperidyl)-1 : 1-diphenylpropyl methyl sulphone, 3-dimethylamino-1 : 1 - diphenylbutyl ethyl sulphone, 3 - diethylamino - 1 : 1 - diphenylpropyl ethyl sulphone, 9 - (2 - (1 - piperidyl) ethyl) - 9 - fluorenyl ethyl sulphone, 4-(1-piperidyl)-1 : 1-diphenylbutyl ethyl sulphone, 3-dimethylamino-1 : 1-diphenylbutyl n-propyl sulphone, 3-dimethylamino-1 : 1-diphenylbutyl isopropyl sulphone, 3 - dimethylamino - 1 : 1 - diphenylpropyl ethyl sulphone, 3 - dimethylamino - 1 : 1 - diphenylbutyl cyclopentyl sulphone, 3-(1-piperidyl)-1 : 1-diphenylpropyl isobutyl sulphone and 3-(1-piperidyl)-1 : 1-diphenylbutyl ethyl sulphone. Other products are mentioned, including those with dimethylaminophenyl, anisyl and phenetyl groups, and other suitable groups are given for B, X and R. 3-Dimethylamino-1 : 1-diphenylbutyl ethyl sulphone may be resolved into its optically active forms with the aid of d-tartaric acid. In connection with establishing the structure of the products, the following reactions are carried out: (1) diphenylmethane thiol is condensed with 1-bromo-3-chloropropane to give diphenylmethyl 3-chloropropyl sulphide, which is oxidized to diphenylmethyl 3-chloropropyl sulphone; the latter is treated with piperidine yielding diphenylmethyl 3-(1-piperidyl)-propyl sulphone; (2) 3-dimethylamino-1 : 1-diphenylbutyl ethyl sulphone is refluxed with Raney nickel to give 3-dimethylamino-1 : 1-diphenylbutane; the latter is also obtained from 3-dimethylamino - 1 : 1 - diphenyl - 1 - cyanobutane by heating with sodamide. Sulphones CH(Ar)(Ar1)-SO2-R are obtained by (1) oxidizing the corresponding sulphides, or (2) treating CH(Ar)(Ar1).OH or CH(Ar)(Ar1) Hal with a sulphinic acid R.SO2H. Examples show the preparation of the following benzhydryl sulphones: methyl, ethyl, propyl, isopropyl, isobutyl and cyclopentyl; also of 9-fluorenyl ethyl sulphone and bis-(4-methoxyphenyl)-methyl n-propyl sulphone. Sulphides CH(Ar)(Ar1)-SR are obtained from (1) the corresponding thiol and R-Hal; or (2) RSH and CH(Ar)(Ar1)-Hal. Examples show the preparation of the following benzhydryl sulphides: methyl, ethyl, propyl, isopropyl, isobutyl and cyclopentyl; also of 9-fluorenyl ethyl sulphide. Diphenylmethane thiol is prepared by treating benzhydryl chloride with thiourea to give the isothiouronium salt and hydrolysing this with alkali. 9-Fluorene thiol is prepared similarly. According to the Specification as open to inspection under Sect. 91, Ar and Ar1 may be joined through atoms such as carbon, oxygen, sulphur or nitrogen, to give such rings as those of 9 : 10-dihydroanthracene, xanthene, thioxanthene and acridane. A typical product is 10 - (2 - dimethylamino - 1 - propyl) - 10 - thioxanthenyl ethyl sulphone. The Specification also refers to compounds of the formula B-X-SO2-CH(Ar)(Ar1), the symbols having the same meaning as above. These may be made by (1) condensing CH(Ar) (Ar1)SH with a dihalo-paraffin to give CH(Ar) (Ar1)-S-X-Hal, oxidizing to the sulphone and reacting with the appropriate secondary amine, or (2) condensing CH(Ar)(Ar1)SH with B-X-Hal and oxidizing. The products may be converted into salts as above. In further examples, benzhydryl mercaptan is condensed with ethylene chlorobromide and the product oxidized to benzhydryl 2-chloroethyl sulphone. This may then be condensed with dimethylamine, di-n-butylamine, piperidine, 2-methylpiperidine and morpholine. Other products mentioned are benzhydryl 2-diethylaminoethyl sulphone, di - p - anisylmethyl 4 - dimethylaminobutyl sulphone, 3 - (1 - piperidyl) - propyl 9-fluorenyl sulphone, benzhydryl 3-(4-morpholinyl)-propyl sulphone and phenyl-(3-ethoxyphenyl) - methyl 2 - di - n - butylaminoethyl sulphone. This subject-matter does not appear in the Specification as accepted.
GB12684/49A 1948-05-18 1949-05-12 Improvements in or relating to diaryl-tertiary-aminoalkyl-methyl alkyl or cycloalkyl sulfones and their preparation Expired GB668562A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US668562XA 1948-05-18 1948-05-18

Publications (1)

Publication Number Publication Date
GB668562A true GB668562A (en) 1952-03-19

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ID=22072154

Family Applications (1)

Application Number Title Priority Date Filing Date
GB12684/49A Expired GB668562A (en) 1948-05-18 1949-05-12 Improvements in or relating to diaryl-tertiary-aminoalkyl-methyl alkyl or cycloalkyl sulfones and their preparation

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GB (1) GB668562A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2047881A1 (en) * 1969-06-18 1971-03-19 Delalande Sa
EP0373836A1 (en) * 1988-12-14 1990-06-20 Eli Lilly And Company Improvements in or relating to serotonin and norepinephrine uptake inhibitors

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2047881A1 (en) * 1969-06-18 1971-03-19 Delalande Sa
EP0373836A1 (en) * 1988-12-14 1990-06-20 Eli Lilly And Company Improvements in or relating to serotonin and norepinephrine uptake inhibitors

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