Investigation on the Ring-Opening Reactions of 3-(1H-1,2,4-Triazol-1-yl)1,5-benzothiazepines with Arylonitrile Oxides

Abstract

Novel ring opening compounds, (Z)-2-((Z)-((E)-1,3-diaryl-2-(1H-1,2,4-triazol-1-yl)allylidene)amino)aryl N-hydroxybenzimidothioates 4a–r, were obtained from the reaction of 2,4-diaryl-3-(1H-1,2,4-triazol-1-yl)-2,5-dihydro-1,5-benzothiazepines 3a–f and arylonitrile oxides. The structure of these products has been elucidated by spectroscopic analysis and, in one case, X-ray crystallographic analysis. According to the result, it was presumed that this reaction did not proceeded through 1,3-dipolar cycloaddition reaction.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

GRAPHICAL ABSTRACT      

A structurally diverse heterocyclic library: A benzothiazepine-fused β -lactam library derived from reaction of 2,3-dihydro-1,5-benzothiazepines and acyl chlorides: Synthesis and stereochemistry

A 1H-azeto[2,1-d][1,5]benzothiazepin-1-one, -lactam derivatives of dihydrobenzothiazepines library derived from reactions of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines and acyl chlorides, including phthalimidoacetyl chloride, chloroacetyl chloride, dichloroacetyl chloride and phenoxyacetyl chloride, was built up through parallel solution-phase synthesis. Stereochemistry of 1H-azeto[2,1-d][1,5]benzothiazepin-1-ones in the reaction process is discussed.     

4-苯基-2-对甲氧基苯基-1,5-苯并硫氮杂卓-α,α-二甲基-β-内酰胺的合成及晶体结构

合成了标题化合物并测定了其晶体结构。该化合物的化学式为C26H25NO2S, Mr = 415.53。晶体为三斜晶系,P 空间群,晶胞参数为:a = 9.299(3), b = 10.134(3), c = 12.455(4) ? a = 98.457(5), b = 106.143(5), g = 103.843(5), V = 1065.7(6) 3, Z = 2, Dc = 1.295 g/cm3, F(000) = 440, m = 0.175 mm-1, R = 0.0406, wR = 0.1064。晶体结构显示,化合物中七员环呈类椅式构象,b-内酰胺环近似梯形。     

Studien zur Chemie von O,N- und S,N-haltigen Heterocyclen, 14. Mitt. Tricyclische 1,5-Benzothiazepine aus 2,3-Dihydro-1,5-benzothiazepin-4-amin

Summary Starting from 2,3-dihydro-1,5-benzothiazepin-4-amine (1) tricyclic 1,5-benzothiazepines were obtained. Reaction with ethyl bromopyruvat and ethyl aminoacetate hydrochloride led to the imidazo[2,1-d][1,5]benzothiazepines3 and6, respectively. The triazolo derivative8 was prepared by treatment of1 with triethyl orthoacetate/ammonia, followed by oxidative cyclization with sodium hypochlorite.

     

3-甲基-1a-(4-甲氧基苯基)-1,1-二氯-1,1a,2,3-四氢-吖丙啶并[2,1-d][1,5]苯并硫氮杂的合成和晶体结构

通过2-甲基-4-(4-甲氧基苯基)-2,3-二氢-1,5-苯并硫氮杂与二氯卡宾的[2 1]环加成反应制备了标题化合物,用X射线单晶衍射测定了其晶体结构.分子式C_(18)H_(17)Cl_2NOS,分子量366.30,晶体属正交晶系,空间群P_(bca),晶胞参数:a=1.2246(3)nm,b=1.5219(4)nm,c=1.9272(9)nm,V=3.592(2)nm~3,Z=8,D_c=1.355g·cm~(-3).位于中心的1,5-硫氮杂环为扭曲的类船式构象,船头与苯环并合,船底与吖丙啶环并合.     

Structure Comparison of Benzothiazepine Derivatives

ＳｔｒｕｃｔｕｒｅＣｏｍｐａｒｉｓｏｎｏｆＢｅｎｚｏｔｈｉａｚｅｐｉｎｅＤｅｒｉｖａｔｉｖｅｓＬｉＧｅｎ－ＰｅｉＪｉａｎｇ；Ｌｉ－ＨｏｎｇＬｉＰｉｎｇ－Ｗｅｉ（ＩｎｓｔｉｔｕｔｅｏｆＰｈｙｓｉｃａｌＣｈｅｍｉｓｔｒｙ，ＰｅｋｉｎｇＵｎｉｖｅｒｓｉｔｙ...     

Cycloaddition of benzoheteroazepine II Reactions and conformations of cycloadducts on1,5-benzothiazepines and 1,5-benzodiazepines with nitrile imine and nitrile oxides

Benzodiazepine and benzothiazepine derivatives have been well known as therapeutically important compounds. Four new tricyclic heterocyclic compounds, 3a,4,5,11-tetrahydro-3H-1,2,4-triazolo[4,3-d] [1, 5]benzothiazepines (3), 3a,4,5,11-tetrahydro-3H,6H-1,2,4-triazolo[4,3-d][1,5]benzodiazepine (4), 3a, 4,5,11-tetrahydro-1,2,4-oxadiazolo[4,5-d] [1,5]benzothiazepines (5, 6) and 3a,4,5,11-tetrahydro-6H-1, 2,4-oxadiazolo[4, 5-d] [ 1, 5 ] benzodiazepines (7,8), have been synthesized by 1,3-dipolar cycloaddition reactions of 2, 3-dihydro-1, 5-benzothiazepines and 2, 3-dihydro-1H-1, 5-benzodiazepine with benzonitrile N-phenylimine and benzonitrile oxides, respectively. The conformations of some cycloadducts and cycloaddition mechanism are described.     

ELEGANT SYNTHESIS OF SOME NOVEL SPIRO [BENZOTHIAZEPINE-INDOLE] DERIVATIVES

Abstract

The synthesis of some novel sulfur-containing spiroindole derivatives is reported, 2,3-Dihydrospiro [cycloalka[3,4][1,5] benzothiazepine-2,3′-[3H]indole]-2′-(1′H)-ones (V) were prepared by the reaction of 1,3-dihydro-3-(2-oxocycloalkylidene)indole-2(1H)-one (II) with 2-aminothiophenol in dry toluene. The compounds have been characterized on the basis of elemental and spectral studies.     

PHOSPHORORGANISCHE VERBINDUNGEN 901

Abstract

Aus Allylamido-phosphoniumsalzen wird durch trockenes Tetrabutylammoniumcyanid in Methylenchlorid die Allylgruppe unter Erhaltung der Konfiguration und Bildung von Phosphinigsäureamiden abgespalten (P-C-Cyanolyse). Allyl-O-alkyl-phosphoniumsalze reagieren unter den oben genannten Bedingungen nach Arbusov, Allyl-S-alkyl-phosphoniumsalze aber unter Spaltung der P-S-Bindung ab. (P-S-Cyanolyse).

Das System: Tetrabutyl-ammoniumcyanid in Methylenchlorid kann ohne Nachteil für die Ausbeute durch KCN und katalytische Mengen 18-Krone-6 in Methylenchlorid ersetzt werden. Optisch aktives Benzyl-methyl-phenyl-phosphinsulfid kann auf diese Weise unter Erhaltung der Konfiguration desulfuriert werden.

Auch Dithiophosphinsäureester und Thiophosphinsäureamide werden nach vorausgehender S-Alkylierung (Überführung in die entsprechenden Quasiphosphoniumsalze) mit Tetrabutylammoniumcyanid unter Bildung von Thiophosphinigsäureestern bzw. Phosphinigsäureamiden desulfuriert. Thiophosphinsäure-O-alkylester R₂P(S)OR' liefern über diese Reaktionsfolge nach Arbusov Thiophosphinsäure-S-alkylester R₂P(O)SR′.

Die P-C-Cyanolyse von Allyltriphenyl-phosphoniumbromid mit KCN/18-Krone-6 oder Tetrabutyl-ammoniumcyanid bleibt im aprotischen Medium auf der rotgefärbten Ylidstufe stehen. Erst nach Zugabe eines Protonendonators läuft die Isomerisierung zum Propenyl-phosphoniumsalz ab.

Treatment of allylamido-phosphorlum salts with dry tetrabutylammonium cyanide in methylenechloride delivers after removal of the allyl group phosphinous acid amides with retention of configuration (P-C-cyanolysis).

Allyl-O-alkylphosphonium salts undergo the Arbusov reaction under the above conditions, while allyl-S-alkyl phosphonium salts undergo fission of the P[sbnd]S bond (P-S cyanolysis).

Equally good results were obtained using KCN in methylene chloride accompanied by catalytic amounts of 18-crown-6 ether; thus optically active benzyl-methyl-phenyl-phosphine-sulfid gave the corresponding phosphine with retention of configuration.

Dithiophosphinic acid esters and thiophosphinic acid amides, after conversion to the corresponding quasiphosphonium salts via S-alkylation and subsequent treatment with tetrabutylammonium cyanide in methylenechloride, also give the corresponding thiophosphinous acid ester and phosphinous acid amide respectively. Thiophosphinic acid O-alkyl esters (R₂P(S)OR′) give however the thiophosphinic S-alkyl ester (R₂P(O)SR′) via an Arbusov reaction.

The P-C cyanolysis of allyl-triphenylphosphoniumbromide using KCN/18-crown-6 or tetrabutylammonium cyanide in aprotic medium stops at the stage of the intermediary red-coloured ylide; addition of a proton-donor then results in the subsequent rearrangement to the corresponding propenyl-phosphonium salt.