Research on heterocyclic compounds. XXI. Synthesis of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]thiazole derivatives

The reaction of some 2-aminobenzothiazoles and 2-aminothiazoles with ethyl 3-bromo-4-oxopentanoate was investigated with the aim to obtain the corresponding imidazo[2,1-b]benzothiazole and imidazo[2,1-b]-thiazole derivatives, respectively. In some cases, two unexpected side products were obtained together with the required compound and their structures were elucidated: e.g., 2-aminobenzothiazole reacted with ethyl 3-bromo-4-oxopentanoate to give ethyl 2-methylimidazo[2,1-b]benzothiazole-3-acetate together with ethyl imi-dazo[2,1-b]benzothiazole-2-propionate and ethyl 3-(benzothiazol-2-yl)amino-4-oxopentanoate.     

2,1-benzisothiazoles. XIII. Intermediates and products in the sulfur extrusion reaction of 2,1-benzisothiazolin-3(1H)-one. A new synthesis of 11H-pyrido[2,1-b]quinazolin-11-one (“pyracridone”)

Triethyl phosphite abstracts sulfur from 2,1-benzisothiazolin-3(1H)-one (1); a reaction intermediate is the spirocyclic compound 11 , and products include the benzoxazine 6 and polyanthraniloyl compounds. In the presence of pyridine, pyracridone ( 13 ) is formed. The ketene-imine 9 is probably not an intermediate in these reactions. The reactions of other nucleophiles with 1 and with its N-methyl derivative 15 , have been examined.     

2,1-benzisothiazoline 2,2-dioxide. I. Some 3-substituted derivatives

A number of 3-mono- and 3,3-disubstituted derivatives of 1-methyl 2,1-benzisothiazoline 2,2-dioxide (IIa), a unique benzosultam, were synthesized. Starting materials for the condensation and aminoalkylation reactions utilized were IIa and the 3-methyl compound IIb, which were prepared by cyclization of the 2′-chloro-N-methylalkylsulfonanilides, Ia and b, respectively.     

2,1-Benzisothiazoles. XII. . The use of n-substituted-2,1- benzisothiazolium salts as synthetic equivalents of o-aminobenz- aldehydes. A simple synthesis of some 2-Quinolones

N-Substituted-2,1-benzisothiazolium salts 2 react with ethyl cyanoacetate in pyridine solution to give substituted 3-cyano-2-quinolones 5.     

Pyrrolo[2,1-c][1,4]benzoxazepines. 2. Synthesis of 5-phenyl derivatives

A series of 5-phenylpyrrolo[2,1-c][1,4]benzoxazepines with basic substituents at the 11-position has been synthesized utilizing a nucleophilic aromatic fluoride displacement-cyclization. Piperidinyl derivatives were prepared by Vilsmeier formylation of the key 1-[(2-fluorophenyl)phenylmethyl]pyrrole ( 4 ) followed by addition of a piperidinyl Grignard reagent and cyclization of the resulting carbinol. A (dimethylamino)methyl derivative was prepared via an analogous cyclization of α-(dimethylamino)methyl-1-[(2-fluorophenyl)phenyl-methyl]-1H-pyrrole-2-methanol ( 10 ), obtained by the Hoeben-Hoesch acylation of 4 with chloroacetonitrile, addition of dimethylamine to the resulting α-chloroketone 8 , and reduction of the α-(dimethylamino)ketone 9 with sodium borohydride to give 10 .     

A new synthesis of 2,1-benzisothiazoles

A novel synthesis of 2,1-benzisothiazoles is described. When an o-toluidine or N-sulfinyl-o-toluidine is allowed to react with an N-sulfinylsulfonamide, a 2,1-benzisothiazole is formed.     

The 2,1-benzisothiazolo[2,3-b]-2,1-benzisothiazole system,synthesis and properties

2,2′-Diaminodiphenylmethane and its 4,4′-dibromo-derivative both react with N-sulfinylmethanesulfon-amide to form 2,1-benzisothiazole derivatives. Methylation or acetylation of these provides examples of the hypervalent sulfur 2,1-benzisothiazolo[2,3-b]-2,1-benzisothiazole system. The nmr spectra of these compounds are discussed.     

Synthese von pyridylphenyl-imidazo[2,1-b]thiazolen

The synthesis of the isomeric 6(5)-phenyl-5(6)-pyridyl-2,3-dihydroimidazo[2,1-b]thiazoles are described. Only the synthesis of 5-phenyl-6-(2-pyridyl)-2,3-dihydroimidazo[2,1-b]thiazole failed.     

Substituted benzimidazo[2,1 -h]pteridine-2,4-diones

5-Alkyl-5,6-dihydrobenzimidazo[2,1 -h]pteridine-2,4(1H,3H)-diones (4 a–d) have been synthesised by the condensation of 2-(alkyl-aminomethyl)benzimidazole dihydrochloride (1 a–d) with 5-bromobarbituric acid (2). Similarly, 5-alkyl-5,6-dihydro-4 a-nitrobenzimidazo[2,1 -h] pteridine-2,4(3H,4aH)-diones (10 a–d) have also been synthesised by the condensation of1 a–d with 5-bromo-5-nitrobarbituric acid (8) followed by cyclisation of the intermediate 5-[(benzimidazol-2-ylmethyl)alkylamino]-5-nitrobarbituric acid (9 a–d) with 5% NaOH. Thermal cyclisation of the intermediates9 a–d have also been studied. Methylation of the compound10 a has been carried out with CH₃I and K₂CO₃ usingD M F as solvent to confirm cyclisation. The structures are supported by elemental analyses, IR and PMR spectra.

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Substituierte Benzimidazo[2,1 -h]pteridin-2,4-dione

Zusammenfassung Die 5-Alkyl-5,6-dihydrobenzimidazo[2,1 -h]pteridin-2,4(1H,3H)-dione4 a-d wurden mittels Kondensation von 2-(Alkylaminomethyl)benzimidazolidhydrochloriden1 a–d mit 5-Brombarbitursäure (2) dargestellt. In ähnlicher Weise wurden die 5-Alkyl-5,6-dihydro-4a-nitrobenzimidazo[2,1 -h]pteridin-2,4(3H,4aH)-dione10 a–d über die Kondensation von1 a–d mit 5-Brom-5-nitrobarbitursäure (8) und nachfolgender Cyclisierung der intermediären 5-[(Benzimidazol-2-ylmethyl)alkylamino]-5-nitrobarbitursäuren9 a–d mit 5% NaOH dargestellt. Die thermische Cyclisierung der Produkte9 a–d wurde ebenfalls untersucht. Die Verbindungen wurden mittels Elementaranalyse, IR und PMR charakterisiert.

     

Studies on 2,1-benzisoxazoles. Behaviour towards electrophilic substitution and cycloaddition reactions

The behaviour of 2,1-benzisoxazoles (anthranils) towards electrophilic substitutions has been studied. Nitration of 5-chloro-2,1-benzisoxazole (VII) exclusively gives 4-nitro-5-chloro-2,1-benzisoxazole (XII). However, 5-chloro-3-phenyl-2,1-benzisoxazole (VIII) gives dinitrated products XIII, one nitro group entering at position C₇ instead of C₄ of the carbocyclic ring and the other at the 4′ position of the 3-aryl ring. When 6-nitro-3-carbalkoxy-2,1-benzisoxazoles (X and XI) are nitrated, 4-nitroisomers XV and XVI are obtained exclusively. The substituents already present in the carbocyclic ring exert decisive directing influence. While the parent 2,1-benzisoxazole (Ia) fails to react with dimethyl acetylenedicarboxylate, 6-nitro-2,1-benzisoxazole (XVII) and 5-chloro-2,1-benzisoxazole (VII) react to give 1,4-cycloadducts XIX and XX, respectively. These results suggest that 2,1-benzisoxazoles possess benzenoid as well as ortho-quinonoid character.     

Luminescent nitro derivatives of benzotriazolo[2,1a]benzotriazole

Fluorescence was enhanced and laser activity introduced by substitution in 5,11-dehydro-5H,11H-benzotriazolo[2,1-a]benzotriazole 6 to give 2-nitro, 2,8-dinitro, 2,4,8-trinitro, and 2,4,8,10-tetranitro derivatives 9a–d . Luminescence for compounds 6 and 9a–d and the 2,8-dinitro-3,9-dimethyl and 2,3,8,9-tetramethyl-4,10-dinitro derivatives 11a,b was erratically solvent dependent when examined in ethyl acetate, acetonitrile, and acetone and was most efficient in the 2,8-dinitro derivative 9b [λ_f 479 nm (ethyl acetate) Φ 0.98, λ_f 501 nm (acetonitrile) Φ 0.58, and λ_f 494 nm (acetone) Φ 0.61] and in the tetranitro derivative 9d [λ_f 509 nm (acetonitrile) Φ 0.81 and λ_f 511 nm (acetone) Φ 0.66]. With laser activity at 560–590 nm (acetonitrile) the dye 9b was 30% as efficient as rhodamine 6G (ethanol) in power output. Luminescence was quenched by the reduction of nitro groups to give 2-amino and 2,8-diamino derivatives 9e,f and by the conversion of the tetranitro compound 9d to an unassigned diazido dinitro derivative 9g . Luminescence was not detected in 2,5-dimethyl-3,6-dinitro-1,3a-4,6a-tetraazapentalene 14 and ethyl 2,5-dimethyl-1,3a,4,6a-tetraazapentalene-3,6-dicarboxylate 15 . Azidoazobenzenes were obtained from 4-methyl- and 4,5-dimethyl-1,2-phenylene diamines via oxidation with lead dioxide to aminoazobenzene derivatives followed by treatment of the diazotized amines with sodium azide and thermolysis of azido intermediates to give 3,9-dimethyl and 2,3,8,9-tetramethyl derivatives 10a,b of the triazolotriazole 6 . Nitration converted the triazole 6 to the 2,4,8-trinitro derivative 9c and the alkyltriazoles to their dinitro derivatives 11a,b .     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

Synthesis of 3a,6,6,9a-tetramethyl-trans-perhydronaphtho [2,1-b]furan and 4a,7,7,10a-tetramethyl-trans-perhydronaphtho [2,1-b]pyran

The compounds 3a,6,6,9a-tetramethyl-trans-perhydronaphtho[2,1-b]furan (ambrox or ambroxide) and 4a,7,7,10a-tetramethyl-trans-perhydronaphtho[2,1-b]pyran (homofixator) — substances important in the perfume industry — have been synthesized by superacid cyclization of E,E-homofarnesol and E,E-bishomofarnesol or mixtures of the isomeric bicyclohomofarnesenes or bicyclobishomofarnesenols. Superacid cyclization of these alcohols was shown to be an effective structurally selective and stereospecific method of obtaining ambroxide and homofixator.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 896–901, July, 1990.     

Synthesis of a new bridgehead nitrogen heterocyclic system. Pyrrolo [2,1-f]-1,2,4-triazine derivatives

1-Ureidopyrroles of type 6a,b prepared by the general method previously described (2), readily cyclized under basic conditions giving pyrrolo [2,1-f]-1,2,4-triazine-2,4(1H, 3H)dione derivatives.     

Nitrogen Bridgehead Compounds. Part 79. Synthesis and structure elucidation of benzimidazolo[2,1-f][1,6]naphthyridine aza-derivatives

6-Substituted 1,6-naphthyridine-5(6H)-ones were prepared from diethyl 2-[2-(dimethylamino)vinyl]-6-methylpyridine-3,5-dicarboxylate 1 [2] by ring closure with aromatic and heteroaromatic diamines (o-phenylenediamine, 2,3-diaminopyridine, 3,4-diaminopyridine and 4,5-diaminopyrimidine, respectively). 1,6-Naphthyridine-5(6H)-ones were cyclised in phosphoryl chloride to yield nitrogen bridgehead tetracycles 6-9 . The structure of the products was established by nOe difference spectroscopy. A complete ¹H and ¹³C nmr assignment was achieved by different 2D carbon-proton correlation measurements.     

Intramolecular capture of pummerer rearrangement intermediates. I. Synthesis of pyrrolo[2,1-c][1,4]benzothiazines

Treatment of 1-(2-alkylsulfinylphenyl)pyrroles with trifluoroacetic acid in refluxing toluene gives 4-substituted pyrrolo[2,1-c][1,4]benzothiazines in good yield when the alkyl group bears an electron withdrawing substituent on the α-carbon. In the absence of such a group, starting material is recovered. The sulfoxides are prepared by oxidation (mCBPA) of the corresponding sulfide. The sulfides are prepared from 2-aminobenzenethiol either by S-alkylation followed by conversion to the pyrrole using 1,4-dimethoxytetrahydrofuran in glacial acetic acid or by S-alkylation of 1-(2-phenylmercapto)pyrrole followed by oxidation to the sulfoxide.     

New Synthetic Approach to 4-N-Arylaminoazuleno[2,1-d]pyrimides

1-Cyano-2-N,N-dimethylformamidinylazulenes as new synthons directed to heterocycle-fused azulenes were obtained by the condensation of 2-amino-1-cyanoazulenes and N,N-dimethylformamide dimethyl acetal (DMFDMA). 1-Cyano-2-N,N-dimethylformamidinylazulene (2a) and 1-bromo-3-cyano-2-N,N-dimethylformamidinylazulene (2b) reacted with anilines (3a–h) to give 4-N-arylaminoazuleno-[2,1-d]pyrimidines in moderate yields. This reaction provides a new procedure for synthesis of pyrimidine-fused azulenes.     

Synthesis of pyrrolo[2,1-c][1,4]benzoxazepines. 1. A novel heterocyclic ring system

The synthesis of a novel pyrrolo[2,1-c][1,4]benzoxazepine ring system (II) by a nucleophilic aromatic fluoride displacement-cyclization is described. Aminoalkyl derivatives were prepared by either the Mannich reaction, or Vilsmeier formylation to provide the 3-formyl derivative which was further elaborated.     

Some derivatives of indeno[2,1-g]pteridine

The condensation of indantrione monohydrate (ninhydrin) with ortho-diamines derived from pyridine and pyrimidine led to the synthesis of several new indeno[2,1-g]pteridine derivatives. The structure of these compounds is discussed and their physical properties described.     

Fluorocontaining Heterocycles: IX. Derivatives of Imidazo[2,1-b][1,3]benzothiazine

The heating of derivatives of benzimidazole-2-thione and imidazolidine-2-thione with tetra(penta)fluorobenzoyl chlorides in toluene or pyridine gave rise to fluorocontaining derivatives of imidazo[2,1-b][1,3]benzothiazine. The latter were studied in reactions of nucleophilic substitution of fluorine for amino groups.