1,2,4-benzothiadiazine 1,1-dioxides 3. Reactions of 2-aminobenzenesulfonamide with chloroalkyl isocyanates

Reactions of 2-aminobenzenesulfonamide ( 1 ) with allyl, methyl, 2-chloroethyl aor 3-chloropropyl isocyanates gave 2-(methylureido)-, 2-(allylureido)-, 2-(2′-chloroethylureido)- and 2-(3′-chloropropylureido)-benzene sulfonamides 3a,b and 7a,b in excellent yields. Treatment of 3a,b at refluxing temperature of DMF afforded 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide ( 4 ) in good yield. However, when compounds 7a,b were refluxed in 2-propanol, 3-(2′-aminoethoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 11a ) and 3-(3′-aminopropoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 11b ) were obtained in a form of the hydrochloride salts 10a,b in 87% and 78% yields respectively. Heating 11b in ethanol gave a dimeric form of 2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide and 3-(3′-aminopropoxy)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 12 ) in 55% yield. Treating of 7a,b or 11a,b with triethylamine at the refluxing temperature of 2-propanol afforded 3-(2′-hydroxyethylamino)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 2a ) and 3-(3′-hydroxypropylamine)-2H-1,2,4-benzothiadiazine 1,1-dioxide ( 2b ) via a Smiles rearrangement.     

The mass spectrometic fragmentation patterns of some biologically active derivatives of 2H-1,2,4-benzothiadiazine 1,1-dioxides

The mass spectra of some twenty-six derivatives of 2H-1,2,4-benzothiadiazine 1,1-dioxide are discussed. All compounds studied follow relatively simple fragmentation routes; as a consequence the fragmentation pattern gives a clear guide to the structure of the compound under investigation.     

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 structure of 1,1-dioxides of 3-allyl(styryl)-4H-1,2,4-benzothiadiazine

The reaction of o-aminobenzenesulfonamides with acids of crotonic and cinnamic acids in dioxane yielded the corresponding anilides, which were cyclized to derivatives of 1,2,4-benzothiadiazine 1,1-dioxide. The structure of the end products is discussed in connection with the possibility of tautomeric equilibrium of the 2H- and 4H-forms on the basis of the spectral data.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 907–911, July, 1984.     

Facile Synthesis of 4H-1,2,4-Benzothiadiazine-1,1-dioxides

A short and efficient synthesis of the title compound based on racemate resolution is described.     

Synthesis of 4-methyl-2H-1,2,3-benzothiadiazine 1,1-dioxides and their further transformation via alkylation and reduction steps

Abstract

Ortho lithiation of acetophenone ketals followed by introduction of the chlorosulphonyl group and subsequent ring closure with hydrazine monohydrate or acetohydrazide gave rise to the formation of variously substituted 4-methyl-1,2,3-benzothiadiazine 1,1-dioxides. N(2)-Alkylation and reduction of the C=N double bond were carried out successfully to give N(2)-alkyl-4-methyl-3,4-dihydro-1,2,3-benzothiadiazine 1,1-dioxides. Finally, N(3)-alkylation was accomplished by reductive alkylation with aldehydes. Certain unsaturated and also some 3,4-dihydro derivatives exhibited a significant anxiolytic effect in vivo. Detailed NMR studies and DFT calculations supported the structure elucidation of the compounds.     

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.     

Design and Synthesis of Novel 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides-based Strobilurins as Potent Fungicide Candidates

To discover novel strobilurins analogues with good and broad spectrum activity, a series of novel 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides-based strobilurins was designed, synthesized, and tested against various phytopathogenic fungi. Compounds 7b, 7c, and 7k exhibited substantial and broad spectrum antifungal activities against the tested phytopathogenic fungi, especially compound 7b, which showed 100%, 80%, 90%, and 90% antifungal activity(in virto) against Erysiphe graminis(E. graminis), Puccinia sorghi Schw.(P. sorghi Schw.), Colletotrichum lagenarium(C. lagenarium), and Pseudoperonospora cubensis(P. cubensis) at 300 μg/mL, respectively, better or comparable to the positive control azoxystrobin. Moreover, compound 7b exhibited 85% greenhouse inhibition activity(in vivo) against E. graminis even at 0.2 μg/mL, equal to azoxystrobin(90%) and trifloxystrobin(90%). Meanwhile, compound 7b against P. cubensis displayed 70% and 55% greenhouse inhibition activity(in vivo) at 1.56 and 0.2 μg/mL, respectively, much better than those of azoxystrobin and trifloxystrobin(both 0% at 1.56 and 0.2 μg/mL). Therefore, compound 7b could be considered as the most promising fungicidal candidate for further study. Furthermore, based on the effective concentration(EC₅₀) against C. arachidicola, the built CoMSIA model provided the useful reference for the further structural optimization design.     

The structure of 1,2,4-benzothiadiazine-1,1-dioxides

The structure of N-unsubstituted 1,2,4-Benzothiadiazine-1,1-dioxides has been investigated by means of NMR spectroscopy. ¹³C NMR spectra obtained in DMSO-d₆, solution show the actual tautomeric form to be the 4H tautomer.     

2H-1,2,4-苯并噻二嗪-1,1-二氧类化合物的简便合成

2H- 1 ,2 ,4 -苯并噻二嗪 - 1 ,1 -二氧类化合物在药物化学中有广泛的应用。常作为利尿剂 ,促进肾脏对尿的排泄 ,和其他药物混合使用还具有一定的降压作用 ,常作为高血压病的辅助治疗药物。本世纪五十年代发现的氯噻嗪 ( )和双氢氯噻嗪( ) ,利尿作用很强 ,成为利尿药和降压药的重大突破。此外这类化合物还具有抗菌、消炎、刺激毛发生长 [1] 等作用。在这类化合物的合成中 ,关环反应是关键步骤 ,文献报道过的主要方法为 :( 1 )用甲酸或原甲酸乙酯关环 [2 ] ;( 2 )用醛关环 [3 ] ;( 3)高温 (～ 2 0 0℃ )关环[4] 。当磺酰胺 (氮 )上的氢未…     

A one-pot, non-catalytic approach to 1,2,4-benzothiadiazine-1,1-dioxides

Condensations of o-halo-substituted benzenesulfonyl chlorides with 2-aminopyridines and amidines may give the corresponding 1,2,4-benzothiadiazine-1,1-dioxides under mild, non-catalytic conditions in nearly quantitative yields. The successful one-pot cyclization depends on three factors: (i) the nature of the o-halogen, (ii) the electronic character of the benzene ring substituent, and (iii) the steric load around the amidine unit. O-Fluorobenzenesulfonyl chlorides bearing methylcarboxyl- or nitro-group and o-chloro- and o-bromobenzenesulfonyl chlorides bearing nitro-group are reactive enough to give the desired 1,2,4-benzothiadiazine-1,1-dioxides in a one-pot base-promoted reaction. In all other cases, open-chain sulfonylated amidine intermediates are isolated. The latter are converted to the title compounds either in the presence of potassium carbonate or upon the addition of a copper(I) catalyst.     

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.     

Alkylation of 2H-1,2,3-benzothiadiazine 1,1-dioxides. Formation of a new family of mesoionic compounds

Alkylation of 2H-1,2,3-benzothiadiazine 1,1-dioxide and its aromatic ring substituted derivatives was studied in detail. It was found that alkylation took place both at N(2) and N(3) atoms. In the latter case, a series of interesting mesoionic compounds was prepared. Various alkylation conditions were tried, and due to the substantially different solubility of the two products formed in the reactions, the target compounds could be selectively isolated without chromatographic separation.     

Synthesis of 3-disubstituted 3H-4,1,2-benzothiadiazines and 3-disubstituted 3H-4,1,2-benzothiadiazine 4,4-dioxides

3H-4,1,2-Benzothiadiazines 8 and 9 have been prepared by cyclization of the key intermediates 6 and 7 . The diazotisation of 2-aminophenylthio and 2-aminophenylsulfone derivatives could represent a new convenient synthetic way to obtain 4,1,2-benzothiadiazines.