Investigation of the Structure of 5-R-3-Aryl-2,1-benzisoxazoles (Anthranils) Using <Superscript>1</Superscript>H NMR Spectroscopy

It has been shown that a feature of the ¹H NMR spectra of 5-R-3-aryl-2,1-benzisoxazoles is the large difference in chemical shift values for the H(4), H(6), and H(7) protons of the 2,1-benzisoxazole system in each of the compounds but with retention of the overall pattern for the series discussed. It was found that the effect of the heterocycle on the aryl residue in position 3 is equivalent to the effect of a moderately electron accepting group.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 732–736, May, 2005.     

Anil-Synthese 18. Mitteilung. Über die Herstellung von Styryl-Derivaten des 3-Phenyl-benzisoxazols

Preparation of styryl derivatives of 3-phenyl-benzisoxazole 3-(p-Tolyl)-1,2-or 2, 1-benzisoxazoles and 6-methyl-3-phenyl-1,2-benzisoxazoles react with anils of aromatic aldehydes in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding 3-(stilben-4-yl)-1,2- or 2,1-benzisoxazoles and the 3-phenyl-6-styryl-1,2-benzisoxazoles respectively (‘Anil Synthesis’). Further, the Schiff's bases derived form chloroanilines and 3-(p-formylphenyl)-1,2-benzisoxazoles yield, with methyl-and p-tolyl substituted heterocyles the corresponding heterocyclic substitued styryl and stilbenyl derivatives.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

The synthesis and reactions of certain 3-substituted-2,1-benzisothiazoles

A new and general synthesis of 2,l-benzisothiazolin-3-ones ( 2 ) is described from the corresponding isatoic anhydride ( 3 ) and potassium hydrogen sulfide which gives the thioanthranilic acid ( 4 ) which is readily oxadized and ring closed to 2 with hydrogen peroxide. Phosphorus oxy-chloride converted 3-hydroxy-2,1-benzisothiazole to 3-chloro-2,1-benzisothiazole which gave a number of different 3-substiluted 2,1-benzisothiazolesby nucleophilic substitution of the 3-chloro group. Rleetrophilie substitution of 1-methyl-2,1 -benzisothiazoIin-3-one ( 2i ) proceeded readily to give the corresponding 5-bromo-, 5-nitro-, and 5-chlorosulfonyl-1-methyl-2,1-benzisothiazolin-3-one. This appears to be a good synthetic route to such 2,1-benzisothiazole derivatives.     

Nitration of 2- and 4-[2-(2-furyl)vinyl]thiazole derivatives

Nitration of 4-methyl-2-[2-(nitro-2-furyl)vinyl]thiazole with a mixture of concentrated nitric and sulfuric acids leads to 4-methyl-5-nitro-2-[2-(3,5-dinitro-2-furyl)vinyl]thiazole. Under the same conditions 2-methyl- and 2-acetamido-4-[1-R-2-(5-nitro-2-furyl)vinyl]thiazoles (R=CH₃, Cl) are nitrated in the 3 position of the furan ring, 2-amino-4-[1-chloro-2-(5-nitro-2-furyl)vinyl]thiazole is nitrated in the 5 position of the thiazole ring and 2-acetamido-5-nitro-4-[2-(2-furyl)vinyl]thiazole undergoes profound changes. Under the influence of a mixture of of nitric acid and acetic anhydride the latter compound is converted quantitatively to the 5-nitro derivative (with respect to the furan ring), whereas 4-[2-(5-nitro-2-furyl)vinyl]thiazole derivatives do not undergo reaction.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 314–317, March, 1977.     

Zur Photochemie von 1, 2-Benzisoxazolen in stark saurer Lösung

On the Photochemistry of 1, 2-Benzisoxazoles in Strongly Acidic Solution The 1, 2-benzisoxazoles 1a, 1b and 1d when dissolved in 96% sulfuric acid and irradiated through a quartz filter with a mercury high-presure lamp yield, after work-up, mixtures of 2, 5- and 2, 3-dihydroxy-acylbenzenes ( 2 and 3 , respectively; cf. Schemes 1 and 3 and Table 1). Irradiation of 3, 5-dimethyl-1, 2-benzisoxazole ( 1c ) in 96% sulfuric acid leads to the formation of 2, 3-dihydroxy-5-methyl-acetophenone ( 3c ) in only 6% yield (cf. Table 1). It is assumed that the 1, 2-benzisoxazolium ions react in the excited singlet state by heterolytic cleavage of the N, O-bond to yield the corresponding aryl oxenium ions 7 in the singlet ground state (see Scheme 5). Reaction of 7 with HSO ₄ ? ions, present in 96% sulfuric acid, yields, after hydrolysis, the dihydroxy compounds 2 and 3 . Photolysis of 3-methyl-1, 2-benzisoxazole ( 1b ) in diluted sulfuric acid (0,5 to 9 M ) in methanol or water leads only to the formation of 2-amino-phenol ( 6 ; see Scheme 3), presumable via photo-isomerization of 1b to 2-methylbenzoxazole ( 5b ) which then is hydrolyzed to give 6 .     

Mannich bases and methiodides of 6-(2-furyl)imidazo[2,1-b]thiazole and its substituted derivatives

The Mannich reaction in a number of 6-(2-furyl)-substituted imidazo[2,1-b]thiazoles is realized initially in the 5 position of the imidazothiazole system, whereas it is also realized in the 5 position of the furan ring in the presence of excess reagents if the latter position is not substituted. Iodomethylation occurs at the N₇ atom of imidazothiazole. The Mannich bases of 6-(5-nitro-2-furyl)imidazo[2,1-b]thiazole are iodomethylated only at the aminomethyl group. The pK_a values of the series of compounds were measured.     

Alkenyl derivatives of 5-nitro-2-pyridone: Synthesis and halocyclization

Alkylation of 5-nitro-2-pyridone by alkenyl halides in acetone in the presence of K₂СО₃ proceeds with generation of a mixture of N- and О-derivatives with N-isomer prevailing. 1-Allyl- and 1-methylallyl-5-nitro-2-pyridone react with halogens with the formation of 2-halomethyl-6-nitro-2,3-dihydrooxazolo[3,2-a]-pyridinium halides. 1-Prenyl-5-nitro-2-pyridone reacts with bromine with the formation of 3-bromine-2,2-dimethyl-7-nitro-3,4-dihydro-2Н-pyrido[2,1-b][1,3]oxazinium bromide, and with iodine giving 2,2-dimethyl-7-nitro-3,4-dihydro-2Н-pyrido[2,1-b][1,3]oxazinium triiodide.     

Thermal Stability of 4-chloro-2-nitro- and 4-chloro-3-nitrobenzoates of Rare Earth Elements: Influence of substituent positions

The physico-chemical properties and thermal stability in air of rare earth element 4-chloro-2-nitro- and 4-chloro-3-nitrobenzoates of the general formulae Ln(C₇H₃NO₄Cl)₃2H₂O were compared and the influence of the position of the Cl and NO₂ substituents on their thermal stabilities was investigated. The complexes of both series are crystalline, hydrated salts with colours typical of Ln³⁺. The carboxylate group in these complexes is a bidentate, chelating ligand. The NO₂ group in the chloronitro complexes does not undergo isomerization. The thermal stabilities of the 4-chloro-3-nitrobenzoates of rare earth elements were studied in the temperature range 293–1173 K, but those of 4-chloro-2-nitrobenzoates of those elements were studied only at 293–523 K because they decompose explosively above 523 K. The positions of the Cl and NO₂ substituents on the benzene ring influence the thermal properties of the complexes and their decomposition mechanisms. The different thermal stabilities of the complexes are connected with various inductive and mesomeric effects of the Cl and NO₂ substituents on the electron density in benzene ring.This revised version was published online in November 2005 with corrections to the Cover Date.     

Oxidation of perfluoroaromatics

3,4,5,6-Tetrafluoro-2-nitroaniline (I), 2,3,5,6-tetrafluoro-4-nitroaniline (IV) and 2,5,6-trifluoro-4-nitro-1,3-phenylenediamine (VI) react with nitrous acid to give 3,4,5-trifluoro-6-nitro-1,2-diazo-oxide (III), 3,5,6-trifluoro-4-nitro-1,2-diazo-oxide and (V) 5-fluoro-6-nitro-bis-1,2:3,4-diazo-oxide (VII), respectively. Reduction of the diazo-oxide (III) with hypophosphorous acid gives 4,5,6-trifluoro-3-nitrophenol (VIII). Treatment of 2,3,4,6-tetrafluoroacetanilide with nitric acid affords trifluoro-p-benzoquinone (X), the reduction of which gives trifluorohydroquinone (XI). Proton and fluorine chemical shifts and coupling constants of the new compounds are reported.     

Oxidative cyclization of halobenzophenone oximes to 4,2′-iodonia-3-phenyl-1,2-benzisoxazole salts

It is shown that the syn oximes of o-iodo- and o-, m-, and p-bromobenzophenones, under the influence of K₂S₂O₈ in concentrated H₂SO₄, form the corresponding 3-aryl-1,2-benzisoxazoles as a result of oxidative cyclization. 3-(2-Iodophenyl)-1,2-benzisoxazole is oxidized by peracetic acid to the iodoso derivative which, upon heating in concentrated H₂SO₄, undergoes cyclization to the 4,2-iodonia-3-phenyl-1,2-benzisoxazole cation. The iodide, bromide, and tetrafluoroborate of this cation were isolated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 474–478, April, 1985.     

One-pot synthesis of 2,1-benzisoxazoles (anthranils) by a stannous chloride-mediated tandem reduction-heterocyclization of 2-nitroacylbenzenes under neutral conditions

Classically, 2,1-benzisoxazoles (anthranils) are prepared from 2-nitroacylbenzenes by a reductive heterocyclization reaction with Sn or SnCl₂ concentrated HCl. Acid sensitive functionalities are expected to be incompatible with these conditions; milder approaches to the synthesis of 2,1-benzisoxazoles would be welcomed. We demonstrate that SnCl₂·2H₂O in a 1:1 mixture of EtOAc/MeOH is capable of mediating the tandem reduction-heterocyclization of a variety of 2-nitroacylbenzenes to their corresponding 2,1-benzisoxazoles in good to excellent yields under essentially neutral conditions. Importantly, several commonly used acid-labile protecting groups, including Boc carbamate, tert-butyl ether, and tert-butyl ester, proved orthogonal to these reaction conditions.     

Synthesis and properties of 5-chloro-4-nitropyrazoles

The nitration of 5-chloropyrazoles with a mixture of 100% nitric acid and 65% oleum or a mixture of 60% nitric acid and polyphosphoric acid gave substituted 5-chloro-4-nitropyrazoles in 45–91% yield. The nitration of 3-aryl-5-halopyrazoles was accompanied by introduction of a nitro group into the aromatic ring. 4-Chloropyrazoles failed to undergo nitration under these conditions. The reaction of 5-chloro-1,3-dimethyl-4-nitropyrazole with ethyl cyanoacetate in DMSO in the presence of K₂CO₃ led to the formation of ethyl 2-cyano-2-(1,3-dimethyl-4-nitro-1H-pyrazol-5-yl)acetate.     

Photolyse des 3-Phenyl-2, 1-benzisoxazols und einiger seiner Derivate in Bromwasserstoffsäure

Photolysis of 3-phenyl-2, 1-benzisoxazole and some derivatives in hydrobromic acid The behaviour of 3-phenylanthranils (3-phenyl-2, 1-benzisoxazoles) towards photolysis in hydrobromic acid differs greatly from that in hydrochloric and sulfuric acid. Thus, reduction and substitution products are obtained. The formation of the reduction products involves hydrogen abstraction by a nitrenium ion species in the triplet state and that of the substitution products can be attributed to a subsequent S_E-bromination.     

Synthesis, biological activity and crystal structure of ethyl 6-amino-8-(4-methoxy phenyl)-9-nitro-2,3,4,8-tetrahydropyrido[2,1b][1,3]thiazine-7-carboxylate

The compound ethyl 6-amino-8-(4-methoxy phenyl)-9-nitro-2,3,4,8-tetrahydropyrido[2,1b][1,3]thiazine-7-carboxylate (C₁₄H₂₂N₄O₄S₂) has been synthesized by multicomponent reactions, and characterized by ¹H NMR, IR, and X-ray diffraction. The crystal structure analysis shows that the thiazinane ring displays a half-chair conformation. The benzene ring is almost vertical to the tetrahydro-pyridine ring. Intramolecular H-bonding of N–H···O type exists and completes an S (6) ring. In the crystal, the molecules are connected into a 3D network by a N–H···O and C–H···O intermolecular hydrogen bond. The bioassay indicates that the compound shows moderate insecticidal activity against Aphis craccivora.     

Über die Einwirkung von Ammoniak auf 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon

Zusammenfassung 5-Chlor-2-(N-methyl-jodmethansulfonamido)-benzophenon (6 b) reagiert mit flüss. NH₃ zu 6-Chlor-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (7), mit NH₃ in absol. Alkohol zu 6-Chlor-4-hydroxy-3-jod-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazin-2,2-dioxid (9). Der Mechanismus dieser Reaktionen wird diskutiert.

---

The reaction of ammonia with 5-Chloro-2-(N-methyl-iodo-methanesulfonamido)-benzophenone

The reaction of 5-chloro-2-(N-methyl-jodomethanesulfon-amido)-benzophenone (6b) with liquid or absol. alcoholic ammonia leads to 6-chloro-4-hydroxy-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (7) and 6-chloro-4-hydroxy-3-jodo-1-methyl-4-phenyl-3,4-dihydro-1H-2,1-benzothiazine-2,2-dioxid (9) resp. The mechanism of these reactions is discussed.

     

Nucleophilic substitution in 1-alkyl-4,5-dichloro-3-nitropyridazin-6-ones

Treatment of 1-alkyl-4,5-dichloro-3-nitropyridazin-6-one with C-nucleophiles and with ambident nucleophiles (2-azahetarylacetonitriles) leads to a selective substitution of a chorine atom by the quaternary carbon atom of the carbanion formed from a substituted acetonitrile. The pK_a of the CH-acid 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)malononitrile was determined by potentiometric titration. Reaction of 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)-2-hetarylacetonitriles with primary amines gives 6,7-dihydro-1H-pyrrolo[2,3-d]pyridazin-7-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 556–564, April, 2006.     

Photolyse des 3-Phenyl-2, 1-benzisoxazols und einiger seiner Derivate in Salzsäure bzw. Schwefelsäure

Photolysis of 3-phenyl-2,1-benzisoxazole and some derivates in hydrochloric and sulfuric acid The photolysis of 3-phenylanthranils (3-phenyl-2, 1-benzisoxazoles) in conc. hydrochloric or sulfuric acid leads to the formation of 5-substituted 2-amino-benzophenones wherein the 5-substituent is the anion of the acid employed. 5-Halo-substituted 3-phenylanthranils, however, show a differing reaction pattern in the two acids. Whereas 2-amino-3, 5-dihalo-benzophenones are obtained when photolysis is effected in conc. hydrochloric acid, irradiation in sulfuric acid causes the hydroxy group to substitute the halogen which migrates to the 4-position of the 2, 1-benzisoxazole to yield 2-amino-5-hydroxy-6-halo-benzophenones. A similar behaviour in sulfuric acid is also observed with 5, 7-dichloro-3-phenylanthranil. When the 5-position of the anthranil is blocked by a phenyl group, irradiation in conc. hydrochloric acid leads to entry of the halogen mainly in this 5-phenyl substituent, as can be expected from mesomeric structures. The reaction mechanisms for the photolytic behaviour of 3-phenylanthranils in both conc. hydrochloric and sulfuric acid is discussed.     

Coordination Compounds of Copper(II) with Benzoylhydrazones of Substituted Salicylaldehydes

Benzoylhydrazones of 5-nitro- (H₂L¹), 3-nitro- (H₂L²), 5-chloro- (H₂L³), 5-bromo- (H₂L⁴), and 3,5-dibromosalicylaldehydes (H₂L⁵) react in ethanol with copper acetate to form complexes CuL^1-5. In the presence of amines (A = C₅H₅N, 3-CH₃3C₅H₄N), the above reactions give complexes CuL^1-5A·nH₂O (n = 0, 1). When cuprous bromide or nitrate and benzoylhydrazone H₂L³ were used as starting materials, complexes Cu(HL³)X (X = Br^-, NO₃ ^-) were isolated. The resulting complexes all are polynuclear structures in which azomethines H₂L^1-5 behave as tridentate O,N,O-ligands. Thermolysis of the complexes involves the stages of dehydration (70-90°C), deaquation (120-150°C) or deamination (150-180°C), and complete thermal de- composition (350-500°C).     

Influence of substituents in salicylaldehyde molecule on interaction with 2-imino-3,5-dimethylthiazolidine

Salicylaldehyde, 5-chlorosalicylaldehyde, or o-vanillin will react with 2-imino-3,5-dimethylthiazolidine to form previously unknown bis(3,5-dimethylthiazolidin-2-ylideneamino)-2-hydroxyphenylmethanes. If strong electron-acceptor groups are present on the aromatic ring, an acid-base interaction takes place. Thus, 3-nitro-5-methoxy-, 3-nitro-5-chloro-, and 3-bromo-5-nitrosalicylaldehyde react with the heterocyclic base to form saltlike complexes, the structure of which has been confirmed by x-ray diffraction.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 420–425, March, 1993.