3－嘧啶胺基或三嗪胺基甲酰基－4－羟基－2H－1，2－苯并噻嗪－1，1－二氧化物的合成及活性

通过３－乙氧甲酰基－４－羟基－２－氢（甲基）－２Ｈ－１，２－苯并噻嗪－１，１－二氧化物与取代嘧啶胺或均三嗪胺的胺解反应，合成了标题化合物。生物活性测定结果表明多数化合物具有较好的除草活性，部分化合物显示好的植物生长调节活性和抗炎免疫活性。     

Overview of the synthetic routes of 2-alkyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamides-1,1-dioxides (oxicams) and their analogues

The biological and medicinal properties of oxicams and its analogues have prompted enormous research aimed at developing synthetic routes to these heterocycles. This review focuses on the chemical properties associated with this system.     

13C NMR Analysis of some 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides

The ¹³C nmr spectra of some 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides I have been recorded and analyzed. Spectroscopic assignments were made on the basis of chemical shift theory, APT and fully coupled ¹³C nmr spectra. Spectral data support the enolic structure of these compounds.     

4-hydroxy-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide-oxalohydrazide (1:1): X-ray structure and DFT calculations

The title compound, 4-hydroxy-2H-1,2-benzothiazine-3-carbohydrazide 1,1-dioxide-oxalohydrazide (1:1), is determined using X-ray diffraction techniques and the molecular structure is also optimized at the B3LYP/6-31G(d,p) level using density functional theory (DFT). The asymmetric unit consists of four independent molecules. The oxalohydrazide molecules have the centre of symmetry at the mid-point of the central C-C bond. Each thiazine ring adopts a half-chair conformation. Intermolecular C-H...O, N-H...O and N-H...N hydrogen bonds produce R ₂ ² (10), R ₂ ² (13), R ₃ ³ (12) and R ₃ ³ (15) rings, which lead to one-dimensional polymeric chains. An extensive three-dimensional supramolecular network of N-H...N, N-H...O, C-H...O and O-H...O hydrogen bonds is responsible for crystal structure stabilization.     

New synthetic approaches to 3-carhoxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide

Two new synthetic approaches to the title compounds are reported. In the first of these, starting with N-carbobenzyloxysarcosine, four synthetic steps are employed to finally assemble the C³? C⁴ bond of the 1,2-benzothiazine ring. In the second approach, an enol ether is employed as a protecting group to allow formation of the 3-carboxamide function, which is followed by cleavage of the ether function to yield the desired 4-hydroxy-1,2-benzothiazine-3-carboxamide 1,1-dioxide.     

Synthesis of 4-substituted 3-hydroxy-and 3-amino-6H-1,2,6-thiadiazine 1,1-dioxides

Reaction of sulfamide with ethoxymethylene derivatives yielded 4-ethoxycarbonyl-, 4-cyano-, and 4-nitro-2H,6H-1,2,6-thiadiazine 1,1-dioxide. In some cases, the corresponding open chain sulfamidomethylene derivatives were isolated. Preparation of 4-amino- and 4-amino-5-methyl-2H,6H-1,2,6-thiadiazin-3-one 1,1-dioxide is also described. Reaction of sulfamide with ethyl 3,3-ethoxypropionate afforded 3,7-bis(etlioxycarbonylmethyl)perhydro-1,5,2,4,6,8-dithiatetra-zocine 1,1,5,5-tetroxide.     

4－羟基－3－酰基（酯基）－2H－1，2－苯并噻嗪－1，1－二氧化物衍生物的合成及生物活性

利用４－羟基－３－酰基（酯基）－２Ｈ－１，２－苯并噻嗪－１，１－二氧化物分别与芳基异氰酸酯、苯肼、氯甲酸甲酯和乙二醇反应合成了２０种新衍生物，研究了其与异氰酸酯在不同摩尔比碱作用下的加成反应。生物活性测定结果表明，大部分化合物具有较好的除草活性和植物生长调节活性。     

Synthesis and properties of 3-substituted 2h-1,2,4-benzothiadiazine 1,1-dioxides

The ethyl ester and amides of 2H-1,2,4-benzothiadiazine-3-carboxylic acid 1,1-dioxide were obtained by reaction of 2-aminobenzenesulfonamide with diethyl oxalate or oxamic acid esters in the presence of sodium methoxide. The hydrolysis, animation, and hydrazinolysis of the ester were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 479–483, April, 1976.     

Synthesis and absorption spectra of 2-substituted 5,8-dimethoxy-4H-1-benzothiopyran-4-one 1,1-dioxides

2,3-Dibromo-5,8-dimethoxy-4H-1-benzothiopyran-4-one (thiochromone) 1,1-dioxide which was a starting material to prepare sulfone analogues of 1,4-naphthoquinone dyes was easily prepared from 5,8-dimethoxythiochroman-4-one by oxidation and bromination. The reactions of 2,3-dibromo-5,8-dimethoxythiochromone 1,1-dioxide 4 with aliphatic and aromatic amines in ethanol below 20° gave 2-substituted derivatives 12a-e and at higher reaction temperature the amination gave 2-arylamino derivatives 13c-e debrominated at C -3. The visible absorption spectra of these derivatives were investigated by the PPP MO method.     

Direct electrosynthesis of Cu,Cd, Zn complexes of piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1,-dioxide) and isoxicam (4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide) in nonaqueous media by in-situ generation of supporting electrolyte

The direct electrosynthesis of Cu, Cd and Zn complexes of the anti-inflammatory drugs piroxicam (4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1,-dioxide=H-pir) and isoxicam (4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide=H-isox) was accomplished by electrochemical dissolution of sacrificial metallic anodes in an acetonitrile solution of the ligand. The chemical and electrochemical in-situ generation of supporting electrolyte was used as a means to obtain pure coordination compounds without the use of supporting electrolytes such as tetraalkylammonium or lithium salts in nonaqueous media. Characterization of the complexes obtained by direct synthesis and comparison with those obtained by traditional synthesis shows that a new copper–piroxicam complex was synthesized.     

Studies on the reaction of 3-substituted-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides with aryl isocyanates and the synthesis of corresponding derivatives

The reaction of 3-substituted-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxides with aryl isocyanate under different equivalents of strong base NaH was studied.Seventeen of new derivatives were obtained whose structures were characterized by 1H NMR,IR,MS,elementary analysis and FeCl3 test.     

Synthesis of 3-substituted 4,1,2-benzothiadiazine 4,4-dioxides and 2 or 3-substituted 1,4-benzothiazine 1,1-dioxides

The title compounds were prepared starting from the synthones 6 using two different synthetic approaches: 3-substituted 1,4-benzothiazine 1,1-dioxides were synthesised by cyclisation with phosphorus oxychloride as the Vilsmeier reagent, while 4,1,2-benzothiadiazine 4,4-dioxides and 3-substituted 1,4-benzothiazine 1,1-dioxides were obtained by direct diazotisation or by cyclisation with triethyl orthoformate.     

On the synthesis of 3,4-dihydro-2H-1,2-benzothiazine 1,1-dioxides

The 3,4-dihydro-2H-1,2-benzothiazine 1,1-dioxides were prepared by reduction of the corresponding 1,2-benzothiazin-2-ones with diborane. The latter were obtained by the action of primary amines on 4,5-dimethoxy-2-carbomethoxymethylbenzenesulfonyl chloride followed by basic hydrolysis and cyclization of the formed 4,5-dimethoxy-2-carbomethoxymethylbenezenesulfonamides.     

Preparation of some 4-hydroxyl-1-methyl-1H-2,1-benzothiazine-3-carboxanilide 2,2-dioxides

An improved, 3-step synthesis of 3,4-dihydro-1-methyl-1H-2,1-benzothiazin-4-one 2,2-dioxide has been developed. This general method offers a more facile entrance into the 2,1-benzothiazine 2,2-dioxide heterocyclic system than was heretofore available. Preparation of several 3-carbox-anilides was accomplished by interaction of this ring system with various isocyanates. The resulting carboxanilides are moderately strong, enolic acids.     

Synthesis of new 3-substituted-2H-1,2-naphthothiazin-4(3H)-one 1,1-dioxides via directed ortho-metalation reaction

The reaction of compounds 6a–i, readily available from α-amino acids, with an excess of lithium diisopropylamide, leads to new 3-substituted-2H-1,2-naphthothiazin-4(3H)-one 1,1-dioxides 7a–i, with yields ranging between 21 and 70%. The key steps are: the naphthylsulfonyl ortho-deprotonation based on the directed ortho-metalation reaction followed by a regiospecific intramolecular cyclisation reaction. Lithiation–deuteration experiments carried out on the naphthylsulfonamides 8 and 9 using n-BuLi and LDA demonstrated the regioselectivity of the deprotonation of the H-3 over the H-1 one of the naphthalene ring.     

New approach to the synthesis of 3-amino-1,2-benzothiazine 1,1-dioxides

The possibility of obtaining 3-amino-1,2-benzothiazine 1,1-dioxides by nucleophilic substitution of the chlorine atom in 5-nitro-2-chlorobenzenesulfonamides by carbanions generated from substituted acetonitriles was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 264–266, February, 1992.     

Synthesis of 3,4-Dihydro-2-methyl-3-oxo-N-aryl-2H-[1]benzothieno[3,2-e1,2-thiazine-4-carboxamide 1,1-Dioxides

A novel synthesis of the title compounds, representing a new heterocyclic ring system, is described. Chlorosulphonation of 3-methylbenzo[b]thiophene followed by reaction with methylamine gave sulfonamide, 4 . Lithiation of 4 , followed by quenching with carbon dioxide yielded acetic acid, 5 . Cyclodehydration of 5 to benzothienothiazine 6 followed by reaction with aryl isocyanates afforded the desired benzothieno[3,2-e]-1,2-thiazine-4-carboxamides 1a-f.