Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: 8-Substituted 6-(4-piperidyl)-6H-dibenz[b,e]-1,4-oxathiepins

1982 ◽  
Vol 47 (11) ◽  
pp. 3077-3093 ◽  
Author(s):  
Karel Šindelář ◽  
Jiřina Metyšová ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Jiří Protiva ◽  
...  
Keyword(s):  
Secondary Amine ◽  
Amino Alcohol ◽  
Sodium Hydride ◽  
Amino Alcohols ◽  
Central Ring ◽  
Psychotropic Agents ◽  
High Degree ◽  
By Products ◽  
Antiapomorphine Effect ◽  
Central Depressant

2-(2-Fluorophenylthio)benzaldehydes IXa-c and 5-chloro-2-(2-fluorophenylthio)acetophenone were treated with 1-methyl-4-piperidylmagnesium chloride and 3-dimethylaminopropylmagnesium chloride, respectively, and the resulting amino alcohols VIa-c, XVII and XVIII were cyclized with sodium hydride in dimethylformamide. In addition to the title compounds Ia-c, XIX and XX, several types of by-products were obtained. Demethylation of compound Ib by the chloroformate method afforded the secondary amine IIb which was transformed to the amino alcohols IIIb and Vb. Compounds Ia-c are very potent neuroleptics with a high degree of central depressant and cataleptic activity. The amino alcohol Vb exhibits a very strong antiapomorphine effect in rats.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: 2-Fluoro-8-substituted 6-(4-piperidyl)-6H-dibenz[b,e]-1,4-oxathiepins

1982 ◽  
Vol 47 (11) ◽  
pp. 3114-3133 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Sodium Hydroxide ◽  
Sodium Hydride ◽  
Central Ring ◽  
Highly Active ◽  
Psychotropic Agents ◽  
Triethylbenzylammonium Chloride ◽  
Depot Neuroleptic ◽  
Boron Tribromide ◽  
Long Acting ◽  
By Products

The aldehydes VIa and VIb were transformed by treatment with chloroform and sodium hydroxide in the presence of triethylbenzylammonium chloride to the α-chloro acids VIIa and VIIb which were demethylated with boron tribromide and the products were cyclized with sodium hydroxide in dimethyl sulfoxide to 2-fluoro-6H-dibenz[b,e]-1,4-oxathiepin-6-carboxylic acids Ia and Ib. Syntheses of the aldehydes XVIIbcd were carried out and the products treated with 1-methyl-4-piperidylmagnesium chloride to give the amino alcohols XVIbcd. Cyclizations with sodium hydride in dimethylformamide afforded the title compounds XIIbcd; compounds XVIIIbc and XIX were isolated as by-products and characterized. Compound XIIb was transformed via the secondary amine XIIIb to the amino alcohol XIVb which was esterified to the decanoate XVb. Substances XIIbcd are highly active neuroleptic agents with an important prolongation of the central depressant effect. The decanoate XVb revealed the properties of a medium long acting depot neuroleptic.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Synthesis of 11-(dimethylaminoalkyl) derivatives of 11H-dibenzo[b,e]-1,4-dioxepin and 11H-dibenzo[b,e]-1,4-dithiepin

1982 ◽  
Vol 47 (1) ◽  
pp. 72-87 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Emil Svátek ◽  
Antonín Dlabač ◽  
...  
Keyword(s):  
Liquid Ammonia ◽  
Sodium Hydride ◽  
Central Ring ◽  
Simultaneous Formation ◽  
Alternative Synthesis ◽  
Psychotropic Agents ◽  
Reserpine Hypothermia ◽  
The One ◽  
High Degree ◽  
Derivatives Of

1-[2-(2-Fluorophenoxy)phenyl]-4-dimethylaminobutanol (XI) was synthesized from 2-(2-fluorophenoxy)benzoic acid (VIII) in three steps and cyclized with sodium hydride in dimethylformamide to the title compound V. Reaction of 5-chloro-2-(methylthio)thiophenol (XIV) with sodium and liquid ammonia afforded benzene-1,2-dithiol (XIII) which was treated with 2-bromobenzyl bromide and gave 11H-dibenzo[b,e]-1,4-dithiepin (II). An alternative synthesis of compound II consisted in the cyclization of 2-(2-bromophenylthiomethyl)thiophenol (XVIII) and was accompanied by the simultaneous formation of 6H, 12H-dibenzo[b,f]-1,5-dithiocin (XIX) and thianthrene (XX). Reaction of compound II with n-butyllithium and the following treatment with dimethylaminoalkyl chlorides or with carbon dioxide resulted on the one hand in two further title compounds VI and VII, and in the carboxylic acid XXI on the other. 2-Chloro-11H-dibenzo[b,e]-1,4-dithiepin (XXII) was obtained by a further synthesis alternative using in the first step the cyclization of 2-(4-chloro-2-chloromethylphenylthio)thiophenol (XXV). Compound VI and VII showed a high degree of activity in the test of antagonization of reserpine hypothermia in mice.

Tricyclic psychotropic agents containing two chalcogen atoms in the central ring: Derivatives of 11H-dibenz[b,f]-1,4-oxathiepin

1982 ◽  
Vol 47 (3) ◽  
pp. 967-983 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Holubek ◽  
Miroslav Ryska ◽  
Antonín Dlabač ◽  
Jiřina Metyšová ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Sodium Hydride ◽  
Sulfuryl Chloride ◽  
Side Chains ◽  
Central Ring ◽  
Lithium Compounds ◽  
Psychotropic Agents ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of

Reactions of 2-bromobenzyl bromide and its analogues XVII and XXV with 2-hydroxythiophenol resulted in 11H-dibenz[b,f]-1,4-oxathiepin (Ia) and its 2-chloro (Ib) and 2-trifluoromethyl derivative (IC). Treatment of the lithium compounds derived from Ia and Ib with carbon dioxide and dimethylaminoalkyl chlorides gave compounds IIa, Va and VIab; modification of side chains led to amines IVa, VIIa and VIIIa. 11-(1-Methyl-4-piperidyl) derivatives Xbc were obtained by chlorination of compounds Ibc with sulfuryl chloride or N-chlorosuccinimide and the following treatment with 1-methyl-4-piperidylmagnesium chloride. Compound Ib was transformed by oxidation to the sulfone XX affording by treatment with sodium hydride and tert-aminoalkylchlorides the basic sulfones XXI and XXII. While the nuclearly unsubstituted amines with the aliphatic side chains (IVa and VIIa) have intensive antireserpine activity and are potential antidepressants, the 11-(1-methyl-4-piperidyl) derivatives with a substituent in position 2 of the skeleton (Xbc) are potential neuroleptics; the trifluoromethyl derivative Xc especially has outstanding cataleptic and antiapomorphine efficacy.

8-Chloro and 8-methylthio derivatives of 10-piperazino-10,11-dihydrodibenzo[b,f]thiepins; New compounds and new procedures

1983 ◽  
Vol 48 (3) ◽  
pp. 906-927 ◽  
Author(s):  
Jiří Jílek ◽  
Josef Pomykáček ◽  
Zdeněk Prošek ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
...  
Keyword(s):  
Amino Alcohol ◽  
Amino Alcohols ◽  
Water Soluble ◽  
Amino Ketone ◽  
Piperazine Derivatives ◽  
Neuroleptic Agent ◽  
New Compounds ◽  
High Degree ◽  
Derivatives Of ◽  
New Procedures

The resolution of racemic clorothepin (Ia) was repeated and the water-soluble methanesulfonates of (S)(+)-clorothepin and (R)(-)-clorothepin were prepared which were used in recent studies of the stereoselectivity of action of this neuroleptic agent. Alkylation of the secondary amine VIa with 2-chloroethyl decanoate resulted in noroxyclothepin decanoate IVa whose basically catalyzed ethanolysis afforded smoothly the amino alcohol IIa. Reactions of amines VIa and VIb with 1,2-butene oxide gave the amino alcohols VIIab. Alkylation of the amine VIa with 5-bromopentan-2-one and the following reduction of the amino ketone IXa formed gave the amino alcohol VIIIa. Amino alcohols IIa and IIIb were transformed by treatment with thionyl chloride to the chloroalkylamines Xa and XIb which were used for the synthesis of mandelates XIIa, XIIIb and benzilates XIVa, XVb derived from noroxyclothepin IIa and oxyprothepin IIIb. A substitution reaction of 2,11-dichloro-10,11-dihydrodibenzo[b,f]thiepin with 1,4-diazabicyclo[4,3,0]nonane led to the clorothepin analogue XVI. From 2-chlorodibenzo[b,f]thiepin-10(11H)-one XVII via the 11-bromo derivative XVIII the amino ketone XIX was prepared. While its reduction with sodium borohydride gave the cis-amino alcohol XXI, the reduction with diborane gave the trans-amino alcohol XXII. The pharmacological properties of the new piperazine derivatives are described; some of them showed a high degree of neuroleptic activity of various profile.

ChemInform Abstract: Synthesis of 1,2- and 1,4-Amino Alcohols from 1,3-Dienes via Oxazines. Rearrangements of 1,4-Amino Alcohol Derivatives to Oxazolines.

ChemInform ◽  
2010 ◽  
Vol 41 (37) ◽  
pp. no-no
Author(s):  
Lukas Werner ◽  
Jason Reed Hudlicky ◽  
Martina Wernerova ◽  
Tomas Hudlicky
Keyword(s):  
Amino Alcohol ◽  
Amino Alcohols

scholarly journals Continuous and convergent access to vicinyl amino alcohols

2015 ◽  
Vol 51 (82) ◽  
pp. 15133-15136 ◽  
Author(s):  
Tomoya Nobuta ◽  
Guozhi Xiao ◽  
Diego Ghislieri ◽  
Kerry Gilmore ◽  
Peter H. Seeberger
Keyword(s):  
Amino Alcohol ◽  
Amino Alcohols ◽  
Assembly System

A four module convergent chemical assembly system delivers two classes of vicinyl amino alcohol and five APIs.

Synthesis of 1,2-amino alcohols via catalytic C–H amidation of sp3 methyl C–H bonds

2014 ◽  
Vol 50 (81) ◽  
pp. 12073-12075 ◽  
Author(s):  
Taek Kang ◽  
Heejeong Kim ◽  
Jeung Gon Kim ◽  
Sukbok Chang
Keyword(s):  
Amino Alcohol ◽  
Amino Alcohols ◽  
Chelating Groups

A new route to 1,2-amino alcohols is presented by C–H amidation of sp3 methyl C–H bonds as a key step. Various alcohols were employed after converting them to removable ketoxime chelating groups. Iridium-catalyzed C–H amidation and following LAH reduction furnished β-amino alcohol products.

Phosphanchalkogenide und ihre Metallkomplexe. IV. Halogenierungsprodukte der Gold(I)halogenidkomplexe einiger Diphosphanmonochalkogenide

2016 ◽  
Vol 71 (3) ◽  
pp. 249-265 ◽  
Author(s):  
Christina Taouss ◽  
Peter G. Jones
Keyword(s):  
Membered Ring ◽  
Quantitative Yield ◽  
X Ray Diffraction ◽  
Central Ring ◽  
X Ray ◽  
Hydrolysis Products ◽  
Related Product ◽  
Hydrolysis Of ◽  
By Products

AbstractDiphosphanegold(I) complexes of the form dppmEAuX [dppm = bis(diphenylphosphano)methane, E = S, Se; X = Br, I], dppeEAuX [dppe = 1,2-bis(diphenylphosphano)ethane; E = O, S; X = Br, I] and dppbzEAuX [dppbz = 1,2-bis(diphenylphosphano)benzene; E = S, Se, X = Br, I] were treated with elemental X2. With dppm, the three products [dppmEAuX2]+X3– (E = S, X = Br (1), I (2); E = Se, X = I (3) were obtained in quantitative yield. These are gold(III) complexes involving a five-membered ring . With dppe, the only related product was [dppeEAuBr2]+Br3– (4), in which the central ring is six-membered with two carbon atoms. These dppe systems are very sensitive to oxidation/hydrolysis of the ligand, and several such unintended products were isolated and identified. The reaction of dppbzSAuBr with bromine leads to [dppbzS]2+[AuBr4]–Br– (5), the dication of which is formally 1,1,3,3-tetraphenylbenzo[d]-2-thia-1, 3-diphosphol-1,3-diium and contains a central five-membered ring . The dications are associated with the bromide anions via S…Br contacts of ca. 3.1 Å to form inversion-symmetric S2Br2 rings. The halogenation of the dppbzSe derivatives leads to loss of selenium and formation of dppbzAuBr3 (6), with [4+1] coordination at gold, or the known compound [dppbzAuI2]+I3– (7). All products 1–6 were subjected to X-ray diffraction analyses, as were four hydrolysis products 4a–d and two further by-products [5(thtBr+)·2Br3–·3(AuBr4–)] (1a) and (tht)AuBr3 (1b). Compound 1a displays unusually short Br…Br contacts of 3.2398(8) Å between neighbouring tetrabromidoaurate(III) ions.

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