Syntheses of 2-(2-arylethyl)imidazoles

Condensation of 2-methylimidazole with arylaldehyde 4 and subsequent reduction of the intermediate 5 with Raney-nickel gave 2-[2-(2,4-dichlorophenyl)ethyl]imidazole 2 . Compound 11 was prepared from compound 10 similarly. Reaction of compound 2 with methylsulfonyl chloride gave 1-methylsulfonyl-2-[2-(2,4-dichlorophenyl)ethyl]imidazole ( 7a ) in moderate yield. Nitration of compound 11 (Ar = 3-pyridyl) gave the desired nitro compounds 14 and 15 .     

Synthesis of Chloramphenicol via a new Intermediate 4-para-Nitrophenyl-5-formamido-1,3-dioxane

4-Phenyl-5-amino-1,3-dioxane 4, obtained from β-bromo styrene 2 was protected as formamido derivative 5. Nitration of 5 followed by regioselective acylative cleavage of the nitro product 12 gave N-formyl-N-acetyl hemiacetal diacetate 16, which on sequential base and acid hydrolysis followed by dichloroacetylation gave chloramphenicol 1.     

Influence of the heterocyclic side ring on orientation during nitrations of 1,2-alkylenedioxy-annelated benzenes and their mononitro derivatives

Nitration of 1,2-alkylenedioxybenzenes 1 furnished the respective nitro derivatives 3 and 4 in the relative ratios: 4a:3a /100:trace, 4b:3b /98:2.4, 4c:3c /86:14, 4e:3e /91:9 and 4f:3f /99:1.3. Nitration of 4 gave 5a:6a:8a /0:0:100, 5b:6b:8b /7.7:3.2:89, 5c:6c:8c /23:12:65, 5d:6d:8d /14:74:12, 5e:6e:8e /27:18:55 and 5f:6f:8f /23:7.0:70. Nitration of the isomeric 3 afforded the dinitro products 5, 6 and 7 in the following relative ratios: 5a:6a:7a /92:8:0, 5b:6b:7b /80:20:0, 5c:6c:7c /69:20:1 1, 5d:6d:7d /45:19:36, 5e:6e:7e /37:57:5.9 and 5f:6f:7f /64:36:0. Nitration of 3-nitro-1,2-dimethoxybenzene ( 9 ) furnished: 10:11 /63:37. Orientation as a function of the heterocyclic ring-size is discussed.     

On the nitration of 2-benzylthiophene and the spectroscopic behaviour of nitro-2-benzylthiophenes

Nitration of 2-benzylthiophene with nitric acid (molar ratio 1:1) in acetic anhydride gave only nitro-2-benzylthiophenes, indicating the benzene ring is unreactive to this electrophilic substitution. The main reaction product was 2-benzyl-5-nitrothiophene (about 87%) the amounts of the 3-nitro and 4-nitro isomers were about 10% and 3%, respectively. These percentages, determined by glc and nmr techniques, were found to be constant using various nitration conditions. The syntheses of the nitro-2-benzylthiophenes are described, together with some spectroscopic properties. The uv spectra confirm that the conjugation of the nitro group in the α position is greater than in the β position. The isomer structures have been assigned by nmr chemical shifts and coupling constant of the thiophene protons. Also infrared spectra are briefly considered.     

1-Aminoisoindole as a useful π-system elongation unit

Nitration of 4,7-ethanoisoindoles gave 1-nitro derivatives in moderate yields. Reduction of a nitro to amino group was successfully performed by sodium hydrosulfite in the case of ethyl 3-nitro-4,7-ethanoisoindole-1-carboxylate. The amino derivative was converted to benzylidenaminoisoindoles based on the retro Diels-Alder reaction. Their UV-vis spectra showed strong absorptions at 500-700 nm.     

Orientation and mechanism of reactions of aromatic amines with sulfur monochloride

The reaction of m-substituted anilines with sulfur monochloride has been studied. It has been shown that cyclization with the formation of 1, 3, 2-benzothiazathiolium compounds takes place in the position para to the substituent. The introduction of methoxy groups into o-nitroanilines interferes with the displacement of the nitro group by the chlorine atom. A nucleophilic reaction mechanism has been proposed according to which the nitro group is displaced after the formation of the thiathioniaazine ring.     

Nitration of dithieno[3,2-b:3′,2′-d]pyridine and dithieno[3,2-b:3′,4′-d]pyridine

Nitration of dithieno[3,2-b:3′,2′-d]pyridine ( 4 ) and dithieno[3,2-b:3′,4′-d]pyridine ( 5 ) has been studied. Nitration of 4 occurred in both positions of the C ring, while 5 was predominantly substituted on the 3,4-fused ring. The structures of the nitro derivatives were proven by extensive use of ¹H and ¹³C nmr spectroscopy.     

Nucleophilic substitution in 4-bromo-5-nitrophthalodinitrile: VIII. Synthesis of 4-(benzotriazol-1-yl)-5-[4-(1-methyl-1-phenylethyl)phenoxy]phthalodinitrile and phthalocyanines on its basis

Nucleophilic aromatic substitution of the bromine atom in 4-bromo-5-nitrophthalodinitrile by a 2-aminophenylamine residue followed by conversion of the resulting compound to 4-(1-benzothiazol-1-yl)-5-nitrophthalodinitrile and nucleophilic substitution of the nitro group by a 4-(1-methyl-1-phenylethyl)-phenoxy group gave 4-(benzotriazol-1-yl)-5-[4-(1-methyl-1-phenylethyl)phenoxy]phthalodinitrile. The latter product was reacted with certain metal acetates and chlorides to obtain the corresponding metal complexes of octasubstituted phthalocyanines. Spectral properties of the complexes were studied.     

Nucleophilic substitutions in some derivatives of 4- and 5-nitroimidazoles

Hydrogen, as well as the halogen atom, at the 4 or 5 position in some 5- and 4-nitroimidazoles were displaced by various nucleophiles such as the amino, cyano, hydroxy, and alkoxy groups. The greater reactivity of the departing group in the 4 position, which was regularly observed, is ascribed to the double activating effect of the azo and nitro groups. Cyanide ion in alcoholic solution reacted peculiarly with both 4- and 5-nitroimidazoles giving o-cyanoazoxyimidazoles as the only products. In some of the nucleophilic displacements at the 4 position of 5-nitroimidazoles the formation of intermediate S?-complexes was observed.     

A study of some quinolizone derivatives

The condensation of methyl 2-pyridylacetate and ethyl phenylpropiolate has been found to be a simple and convenient method for the preparation of 4-quinolizone derivatives. Upon hydrolysis and decarboxylation, the initial condensation product, l-carbethoxy-2-phenyl-4H-quinolizin-4-one (V) was converted to 2-phenyl-4H-quinolizin-4-one (VII). Nitration and bromination of these quinolizones were affected under mild conditions. Nitration of V displaced the carbethoxy group, while bromination did not and 1,3-dinitro-4H-quinolizin-4-one and 1-carbeth-oxy-2-phenyl-3-bromo-4H-quinolizin-4-one were obtained, respectively.     

Nitro derivatives of the thiophene series. 3. Study of the nitration of thiophene α,β-unsaturated ketones in the presence of protic and aprotic acids

The nitration of 4-(5-R-2-thienyl) but-3-en-2-ones (R = H, CH₃, C₂H₅) with a nitrating mixture and group I and III metal nitrates in concentrated sulfuric and trifluoroacetic acids, as well as in the presence of aluminum chloride, was investigated. Nitration with a nitrating mixture and potassium, sodium, lithium, copper, and aluminum nitrates in sulfuric acid takes place in the heterocyclic ring to give a mixture of nitro ketones. Nitration in trifluoroacetic acid and in the presence of aluminum chloride proceeds with the formation of a single -nitro ketone. The structures of the substances obtained were proved by means of the IR and PMR spectra. A possible mechanism of the reaction is discussed.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–757, June, 1981.     

Nitration in the carbazole series

Nitration of9-tosylcarbazole in acetic anhydride solution gives l-nitro (28%), 2-nitro (19%) and 3-nitro (53%) derivatives. The mixture of the nitro compounds obtained from 9-acetylcarbazole contains 10%, 48% and 42% of the isomers, respectively. Under similar conditions 9-nitrosocarbazole shows a different isomer distribution: 34% of 1-nitro and 66% of 3-nitrocarbazole. Nitration of carbazole is a two step process involving formation and rearrangement of 9-nitrocarbazole. The hypothesis was supported by the results of 1,3,6,8-tetrachlorocarbazole nitration and oxidation of 9-nitrosocarbazole and rearrangement of 9-nitrocarbazole in the nitration conditions.     

Synthesis of 2,3,8,9-Dibenzo-5,6-(substituted)benzo-1,4-dithio-7-oxacyclonona-2,5,8-trienes and some electrophilic substitution reactions

Treatment of 5-(2-hydroxyaryl)thianthreniumyl perchlorates 1 with sodium hydride in tetrahydrofuran at reflux gave the title compounds 5 in excellent yields. For the reactivities of the compounds 5 , the selected compounds 5 were subjected under the conditions of electrophilic substitution reactions. Bromination of 5,6-{3-(2-butyl)benzo}-2,3,8,9-dibenzo-1,4-dithio-7-oxacyclonona-2,5,8-triene ( 5f ) in acetic acid at 60° afforded two bromo compounds 9 (22%) and 10 (69%), which were oxidized by m-chloroperbenzoic acid to give tetraoxides 11 (95%) and 12 (97%), respectively. Treatment of 5f with acetyl chloride in the presence of aluminum chloride in carbon disulfide at 0° gave an acetylated compound 13 (58%). Nitration of 5f with nitric acid in acetic acid at 50° gave a nitro compound 17 (15%) together with 1,4-dioxide 7e (22%) and a 5-oxide 18 (3%) whose regiochemistry has not been established. On the other hand, 5,6-(3-methylbenzo)-2,3,8,9-dibenzo-1,4-dithio-7-oxacyclonona-2,5,8-triene ( 5a ) reacted with acetyl chloride under the same conditions to give two acetylated compounds 15 (33%) and 16 (18%). The mechanism for the formation of 5 and the structural elucidation of these compounds are discussed.     

Furopyridines. XXVII. Reactions of 2-methyl and 2-cyano derivatives of furo[2,3-b]-, -[3,2-b]-, - [2,3-c]- and -[3,2-c]pyridine

Bromination of 2-methylfuropyridines 1a-d-Me gave the 3-bromo derivatives 2a-d , while the 2-cyano compounds 1a-d-CN resulted in the recovery of the starting compounds. Nitration of 1a-d-Me and 1a-d-CN did not yield the corresponding nitro derivative, except for 1-c-CN giving 3-nitro derivative 3c in 7% yield. N-Oxidation of 1a-d-Me and 1b-d-CN with m-chloroperbenzoic acid yielded the N-oxides 4a-d-Me and 4b-d-CN , whereas 1a-CN did not afford the N-oxide. Cyanation of N-oxides 4a-d-Me and 4b-d-CN with trimethylsilyl cyanide gave the corresponding α-cyanopyridine compounds 5a-d-Me and 5b-d-CN . Chlorination of 4a-d-Me and 4b-d-CN with phosphorus oxychloride also gave the α-chloropyridine compounds 6b-d-Me and 6b-d-CN , accompanying formation of γ-chloropyridine 6a-Me, 6′b-Me and 6′b-CN , β-chloropyridine 6′b-CN , and α'-chloropyridine derivatives 6′c-Me and 6′c-CN . Acetoxylation of 4a-d-Me and 4b-d-CN with acetic anhydride yielded α-acetoxypyridine compounds 7a-Me and 7b-CN , pyridone compounds 11d-Me, 11c-CN and 11d-CN , 3-acetoxy compounds 8, 9b, 9c , and 2-acetoxymethyl derivatives 10b and 10c.     

Nucleophilic substitution in nitrofluorenones

The reaction of 2,4,5,7-tetranitrofluorenone with amines, thiols, and phenol in a polar aprotic solvent led to the preferable substitution of the nitro group in the position 2, and in the reaction of 2,4,7-trinitrofluorenone first the nitro group in the position 4 was replaced. The different regioselectivity is due evidently to the steric hindrances to the nucleophilic attack on the atom C⁴ caused by the nitro group in the position 5 of tetranitrofluorenone.     

The reactions of pyranylidenemethylpyrylium salts with sodium sulfide

Symmetrical pyranylidenemethylpyrylium salts react with sodium sulfide to give, after acidification, pyranylidenemethylthiapyrylium salts. In the case of unsymmetrical salts in which the methylene group is joined at the 2-position of one ring and the 4-position of the other, the ortho oxygen atom is displaced by sulfur. An unsymmetrical dye which is substituted in the 2,6-positions of one ring with phenyl groups and with alkyl groups in the other ring gave a product which contained the sulfur atom in the aryl-substituted ring.     

SnCl2/EtOH-Mediated Synthesis of Novel 4-Ethoxy- and 4-Chloroindazoles Bearing Sulfonamide Moieties

Abstract

The treatment of N-alkyl-5-nitroindazole with stannous chloride in ethanol, aftercoupling of the obtained amines with arylsulfonyl chloride in pyridine, gave the new 4-ethoxy- and 4-chloroindazoles bearing sulfonamide in moderate to good yields. Chlorination and ethoxylation of indazole were observed during the reduction of the nitro group with anhydrous SnCl₂ in ethanol. The influence of the N-alkylation in N-1 and N-2 position of 5-nitroindazole on the reduction was investigated. The presence ofethoxy group and chlorine atom at position C-4 of indazole was confirmed by x-ray diffraction analysis of compounds 7a and 8a.     

N-nitration of secondary amines with 4-chloro-5-methoxy-2-nitropyridazin-3-one

N-Nitration of 4-chloro-5-substituted-pyridazin-3-one with copper nitrate trihydrate in acetic anhydride gave the corresponding 4-chloro-2-nitro-5-substituted-pyridazin-3-one. 4-Chloro-5-alkoxy-2-nitropyridazin-3-ones such as 5-methoxy (2b) and 5-ethoxy (2d) derivatives showed excellent nitro group transfer potentiality. N-Nitration of some secondary amines with 2b gave the corresponding N-nitramines under mild neutral condition in good yields.     

Behavior of 6-cyclopropyl- and 6-bromo-7-cyclopropyl-1,4-benzodioxanes under electrophilic substitution reaction conditions

Bromination of 6-cyclopropyl-1,4-benzodioxane occurs with concerted orientation of the ethylenedioxy group and the cyclopropyl radical for the least sterically hindered position of the aromatic ring. Nitration of 6-bromo-7-cyclopropyl-1,4-benzodioxane does not lead to products of substitution of the hydrogen atom in the 5 or 8 position of the 1,4-benzodioxane, but rather to the nitrodebromination product: 7-nitro-6-cyclopropyl-1,4-benzodioxane. The anomalous behavior of the bromo-substituted benzodioxane is explained by the predisposition of the carbon atom bonded to the bromine towardipso attack by an electrophile.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 618–620, May, 1998.     

α-Nitro chalcones: Structure and reaction with pyrrole

According to the ¹H NMR, IR, and electronic absorption spectra and X-ray diffraction data, 2-aryl-1-benzoyl-1-nitroethenes have E configuration with predominant s-cis conformation, where the nitro group lies in the plane of the double carbon-carbon bond, while the carbonyl group deviates from that plane. Reactions of 2-aryl-1-benzoyl-1-nitroethenes with pyrrole and N-methylpyrrole gave the corresponding alkylation products at the C² atom in the heteroring.