5-甲基-2，3-二苯基-1，5-苯并硫氮杂卓-4(5H)-酮的合成

以2-甲硫基苯胺为原料,通过酰化、碘环化以及Suzuki交叉偶联反应,合成了5-甲基-2,3-二苯基-1,5-苯并硫氮杂卓-4(5H)-酮。 分别考察了催化剂对酰化反应、溶剂对碘环化反应的影响,以及催化剂、配体、碱和温度等因素对Suzuki交叉偶联反应的影响,在最佳的反应条件下,反应总收率为68.5%,中间产物和目标产物的结构经IR、NMR和MS等测试技术得以确证。     

Solution-phase parallel synthesis of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

Practical and efficient parallel methods have been developed for the synthesis of 7,8-disubstituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones and 3,7,8-trisubstituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones. This benzothiazepin-4(5H)-one skeleton possesses three or four diversity points. Furthermore, three novel tricycles integrating a benzothiazepin-4(5H)-one scaffold with other privileged structures, such as benzimidazole, benzimidazolone, and thio-benzimidazole, were also developed. The synthetic strategy provides an efficient way to access the benzothiazepinone core, starting from commercially available 1,5-difluoro-2,4-dinitrobenzene (DFDNB), and also allows further derivation of the strategically anchored functionalities.     

Electron impact-induced fragmentation of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

The electron impact-induced fragmentations of 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones and some related compounds were investigated. On the basis of low- and high-resolution measurements, metastable ion studies by means of mass-analysed ion kinetic energy spectroscopy and collision-induced dissociation experiments, the main fragmentation pathways were established. The effect of methyl and phenyl substituents at the C(2) and C(3) positions of the heterocyclic ring on the fragmentations was also studied. The (1,3) ring splitting was investigated in some detail, using semi-empirical molecular orbital calculations.     

Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position.

In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action.     

3-碘-5-甲基-1,5-苯并硫氮杂(艹卓)-4(5H)-酮的合成

以2-甲基硫代苯胺为原料,通过酰化反应、碘环化反应合成了3-碘-5-甲基-1,5-苯并硫氮杂(艹卓)-4(5H)-酮,总收率86.3%,其结构经NMR,IR和MS表征.     

2-甲基-1,5-苯并硫氮杂的基态和激发态反应的研究III:2-甲基-1,5-苯并硫氮杂4-(5H)-酮与-4-甲基-1,5-苯并硫氮杂-2(3H)-酮间的互变异构

用化学反应和光谱分析证实了2-甲基(1,5)苯并硫氮杂环庚三烯-4(5H)-酮和4-甲基(1,5)苯并硫氮杂环庚三烯-2(3H)-酮是作为互变异构混合物存在的.     

Oxazepines and thiazepines. XIX Synthesis of optically active 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones

Optically active 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones (14–17) have been synthesizedvia resolution and chemical transformation of nitrocarboxylic acids6–9. Starting from the latter various optically active substances have been synthesized as well. Optical purity was checked by NMR spectroscopy.Dedicated to Prof. Dr.G. Snatzke on the occasion of his 60th birthday.     

Novel syntheses of 2,3-dihydro-1,5-benzothiazepin-4(5h)-ones and 2h-1,4-benzothiazin-3(4h)-ones

Nucleophilic additions of alpha-mercaptoalkanoate esters and beta-mercaptoalkanoate acids to benzoquinone diimines, followed by cyclization with trifluoroacetic acid or 1,3-dicyclohexylcarbodiimide (DCC), provide novel, high-yielding syntheses of 2H-1,4-benzothiazin-3(4H)-ones (3a-f) and 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones (5a-c), respectively.     

Synthesis and Absolute Configuration of (2S,3S,3aS,6S,7aR)-2,3-Dihydroxy-2-((R)-1-hydroxy-3-methylbutyl)-3,6-dimethylhexahydrobenzofuran-4(2H)-one

To investigate the anti-ulcer effect of bisabolangelone reduction derivatives, the sesquiterpene was further proceeded with dihydroxylation reaction. The structure of the target compound was characterized by IR, ESI-MS, 2D NMR and elemental analysis, and its absolute configuration was confirmed with a Flack parameter of 0.08(16) by X-ray crystallography using a Cu radiation source. Compound(3), C_(15)H_(26)O_5, crystal data: monoclinic system, space group P2_1, a = 11.467(2), b = 6.0303(12), c = 11.711(2) ?, β = 99.70(3)°, V = 798.3(3) ?~3, Z = 2, F(000) = 312, D_c = 1.191 g/cm~3, μ = 0.723 mm~(-1), R = 0.0303 and wR = 0.0797 for 2590 independent reflections(Rint = 0.0164) and 2563 observed ones(I 2σ(I)).     

Oxazepines and thiazepines,XXI: CD-spectra of optically active 2-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-ones and related 3-phenylthio-butyric acid derivatives

Summary Chiroptical properties of the title compounds have been studied. The influence of the substitution pattern of the aromatic ring and the configuration of the centre of chirality on the Cotton effects appearing in various wavelengths ranges are discussed.

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Oxazepine und Thiazepine, 21. Mitt.: CD-Spektren optisch aktiver 2-Methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one und verwandter 3-Phenylthio-buttersäure-Derivate

Zusammenfassung Die chiroptischen Eigenschaften der im Titel genannten Verbindungen wurden studiert. Der Einfluß des Substitutionsmusters des aromatischen Rings und der Konfiguration des Chiralitätszentrums auf die Cotton-Effekte, die in verschiedenen Wellenlängenbereichen auftreten, werden besprochen.

     

Structural assignment of regioisomeric 3-[2- or 5-anilino-2-(alkylamino)phenyl]propanoic acids, 2H-1,4-benzothiazin-3(4H)-ones and 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones by 1D NOE and gHMBC NMR techniques

The 1H and 13C NMR spectra of compounds 1-11 and 16-22 in CDCl3 and DMSO-d6 solutions allowed structural assignment to regioisomers 1/5 and 2/6 and their regioselective cyclization products 16-18 utilizing one- and two-dimensional NMR techniques (APT, DEPT, NOE difference, COSY, NOESY, HETCOR and gHMQC, gHMBC). Temperature-dependent 1H NMR spectra of 8-anilino-5-(4-methyl-2-pentyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (18) indicated a free energy of activation (deltaG++) of ca 17 kcal mol(-1) for interconversion between rotamers. The 1H and 13C NMR spectra of 20 and 22 containing two chiral centers exhibit duplication of several signals, indicating the existence of two diastereomeric forms. The structure of 4 was unambiguously confirmed by x-ray crystallography.     

Chlorination of 4-methyl-8-methoxy-2,3-dihydro-1H,1,5-benzodiazepin-2-one

The results of the chlorination of 4-methyl-8-methoxy-2,3-dihydro-1H,1,5-benzodiazepin-2-ones are compared with the results of quantum-chemical calculations of 4-methyl-2,3-dihydro-1H-1,5-benzodiazepin-2-ones with various substituents in the benzene ring in the case of homolytic halogenation. The chlorination of 4-methyl-8-methoxy-2,3-dihydro-1H-1,5-benzodiazepin-2-one (I) with N-chlorosuccinimide leads to 3-chloro- and 3,3-dichloro-4-methyl-8-methoxy-2,3-dihydro-1H-1,5-benzodiazepin-2-ones, whereas chlorination with sulfuryl chloride leads to 4-chloromethyl and 3,3-dichloro-4-methyl derivatives. The IR, PMR, and mass spectra of the synthesized compounds are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1272–1274, September, 1981.