Reaction of 4,5-dichloro-3-trichloromethylisothiazole with heterocyclic amines

4,5-Dichloro-3-trichloromethylisothiazole reacted with piperidine, morpholine, pyrrolidine, and piperazine in DMF to give 81–96% of the corresponding 5-amino-4-chloro-3-trichloromethylisothiazoles as a result of selective nucleophilic replacement of the 5-chlorine atom. Acylation of 4-chloro-5-(piperazin-1-yl)-3-trichloromethylisothiazole with acetyl chloride gave 4-chloro-5-(4-acetylpiperazin-1-yl)-3-trichloromethyl-isothiazole.     

Homolytic ethoxycarbonylation of 3-nitropyridines

The homolytic ethoxycarbonylation of alkyl-3-nitropyridines has been accomplished for the first time by the action of ethyl pyruvate and hydrogen peroxide in the presence of ferrous sulfate. M. V. Lomonosov Moscow State University, 119899 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1502–1503, November, 1997.     

Nucleophilic alkylations of 3-nitropyridines

3-Nitropyridine and 4-substituted-3-nitropyridines were reacted with chloroform, methyl chloroacetate and ethyl 2-chloropropionate under vicarious nucleophilic substitution (VNS) conditions. Substitution was obtained in the ortho or para position to the nitro group with acceptable to good yields and regioselectivity. With potassium 5-nitropyridine-2-sulfonate the substitution took place in the 4-position. Further substitution of the sulfonate group proved to be possible.     

Analysis of heterocyclic aromatic amines

Heterocyclic aromatic amines are formed in protein and amino acid-rich foods at temperatures above 150 °C. Of more than twenty heterocyclic aromatic amines identified ten have been shown to have carcinogenic potential. As nutritional hazards, their reliable determination in prepared food, their uptake and elimination in living organisms, including humans, and assessment of associated risks are important food-safety issues. The concentration in foods is normally in the low ng g⁻¹ range, which poses a challenge to the analytical chemist. Because of the complex nature of food matrixes, clean-up and enrichment of the extracts are also complex, usually involving both cation-exchange (propylsulfonic acid silica gel, PRS) and reversed-phase purification. The application of novel solid-phase extraction cartridges with a wettable apolar phase combined with cation-exchange characteristics simplified this process—both the polar and apolar heterocyclic aromatic amines were recovered in one fraction. Copper phthalocyanine trisulfonate bonded to cotton (“blue cotton”) or rayon, and molecular imprinted polymers have also been successfully used for one-step sample clean-up. For analysis of the heterocyclic aromatic amines, liquid chromatography with base-deactivated reversed-phase columns has been used, and, recently, semi-micro and capillary columns have been introduced. The photometric, fluorimetric, or electrochemical detectors used previously have been replaced by mass spectrometers. Increased specificity and sub-ppb sensitivities have been achieved by the use of the selected-reaction-monitoring mode of detection of advanced MS instrumentation, for example the triple quadrupole and Q-TOF instrument combination. Gas chromatography, also with mass-selective detection, has been used for specific applications; the extra derivatization step needed for volatilization has been balanced by the higher chromatographic resolution.     

Convenient synthesis of fused heterocycles from α-ketohydroximoyl chlorides and heterocyclic amines

Nitroso derivatives of imidazo[1,2-a]pyridine ( 11, 13, 14 ), imidazo[1,2-a]pyrimidine ( 15 ), imidazo[1,2-a]pyrazine ( 16 ), imidazo[1,2-b]pyrazole ( 17 ), and imidazo[1,2-b]-1,2,4-triazole ( 19 ) were obtained in good yields from α-ketohydroximoyl chlorides 3 and 2-aminopyridines ( 4–6 ), 2-aminopyrimidine ( 7 ), 2-aminopyrazine ( 8 ), 5-amino-3-phenylpyrazole ( 9 ), and 3-amino-2H-1,2,4-triazole ( 10 ), respectively. Under different conditions, the reaction of 3 with 3-amino-2H-1,2,4-triazole ( 10 ) and 2-aminopyrazine ( 8 ) afforded the noncyclized substitution products 18 and 22 , respectively. The structures of the products were assigned and confirmed on the basis of their elemental analyses, spectral data, and alternate synthesis wherever possible.     

Tertiary amines and quaternary salts derived from alpha-substituted stilbenes and heterocyclic nitrogen bases

N-bromosuccinimide and -methylstilbenes, p-methyl--chlorostilbene, and p-methyltolan give bromomethyl derivatives, which react with piperidine to give tertiary amines. The latter and methyl iodide give quaternary salts.With pyridine, -picoline, and quinoline, the p-bromomethyl-d-chlorostilbenes synthesized give quaternary bromides which are readily soluble in water and converted into perchlorates by KClO₄.     

Synthesis and conformational properties of 2,6-bis-anilino-3-nitropyridines

The synthesis of 2,6-bis-anilino-3-nitropyridines that are alkylated or acylated at the anilino nitrogen atoms is described. These derivatives show characteristic differences in the 1H-NMR spectra compared with the unsubstituted parent compound. These differences are used to determine structure-conformation relationships of this type of compounds. The conclusions drawn from the 1H-NMR spectra in this respect are supported by X-ray crystallographic data and by 1H-NMR data of conformationally restricted analogues. Preliminary investigations indicate that these relationships can in principle be extended to other diarylamines.     

A heterocyclic arene oxide. 5,6-Diphenylbenz[c]acridine 5,6-oxide

The first synthesis of a benz[c]acridine 5,6-oxide is described. Treatment of 5,6-benz[c]-acridinequinone with phenylmagnesium bromide results in the formation of a trans-diol, which gives the title compound upon dehydration with dimethylformamide dimethylacetal. In sulfuric acid, the epoxide rearranges mainly into 6,6-diphenyl-5-benz[c]acridone.     

Preparative synthesis of heterocyclic and aromatic N-benzyl amines

A simple and highly efficient procedure has been proposed for the synthesis of heterocyclic and aromatic N-benzyl amines via reductive amination of substituted aromatic aldehydes in the presence of sodium tetrahydridoborate-acetic acid system generating reactive sodium triacetoxyhydridoborate.     

Reaction of pyrylium salts with heterocyclic amines

It has been established that in the reaction of 2, 4, 6-trimethylpyrylium perchlorate with 2-, 3-, and 4-aminopyridines, cytosine, adenine, guanine, and the corresponding nucleosides, and also with 2-amino-1-methylbenzimidazole, 2-amino-4-methylthiazole, 2-amino-4-phenylthiazole, 2-amino-6-bromobenzo-thiazole, and 2-amino-6-methoxybenzothiazole, either the corresponding quaternary pyridinium salt is formed or the pyrylium ring opens, depending on the basicity of the amino group.     

Spontaneous conversion of 2-azido-3-nitropyridines to pyridofuroxans

Several pyridofuroxans were obtained by spontaneous N₂ elimination from the corresponding 2-azido-3-nitropyridines. In this particular case, the presence of nitrogen in the pyridine ring must facilitate a cyclic extrusion mechanism. The pyridofuroxans prepared in this study did not present tautomerism as evidenced by NMR.     

Blue chitin columns for the extraction of heterocyclic amines from cooked meat

The identification of the in vitro metabolites of dehydroepiandrosterone formed from human prostate homogenate was investigated by hyphenated techniques using the stable-isotope dilution method. A mixture of dehydroepiandrosterone and [2H4]dehydroepiandrosterone was incubated with hypertrophied human prostate tissue homogenate in the presence of NAD, NADH and NADPH. The metabolites were extracted with AcOEt-hexane, purified by solid-phase extraction, and then analyzed by LC-atmospheric pressure chemical ionization MS and/or GC-MS. Androst-5-ene-3beta,17beta-diol (major product), androst-4-ene-3,17-dione, testosterone, 5alpha-dihydrotestosterone, androsterone, and 7alpha-hydroxydehydroepiandrosterone were identified in comparison with authentic samples based on their chromatographic behavior and mass spectra.     

Unusual pathway of vicarious nucleophilic substitution for methyl-containing 3-nitropyridines

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 136–137, January, 1993.     

NitropyridineS. 9*. Synthesis of substituted 3-amino-5-nitropyridines

Substituted 3-amino-5-nitropyridines have been synthesized by the Curtius, Schmidt, and Hofmann reactions.     

Reactions of alkali metal derivatives of some heterocyclic amines

Procedures are described for converting 2-amino-1,3,4-oxa- and thiadiazoles into various products in one-pot syntheses. The preparative method employs alkali metal derivatives of the heterocyclic amines as the reactive species.     

Complexing of some heterocyclic analogs of diphenylpicrylhydrazine with amines

The complexing of-(6-methyl-2-benzothiazolyl)--phenyl--picrylhydrazine and-(6-methyl-2-benzothiazolyl)--phenyl--(2,6-dinitrophenyl)hydrazine with ammonia and trimethylamine in both the solid state and in solvents (benzene, acetone, hexafluorobenzene, and heptane) was investigated. It was demonstrated that complexing does not depend on the donor and acceptor characteristics of the molecules but is determined by the structural peculiarities of the substance in solution and in the crystalline state.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1200–1201, September, 1972.     

Thermal characterization of modified phyllosilicates with aromatic heterocyclic amines

Vermiculite with the general formula of [Si_6.85Al_1.15][Mg_4.68Al_0.51Fe_0.63]O₂₀(OH)₄Ca_0.128Na_0.032K_0.094 was made to react with heteroaromatic amines α-, β- and γ-picolines in aqueous solution. The products were characterized by elemental analysis, infrared spectroscopy, X-ray diffraction and thermogravimetry. The intercalated nanocompounds maintained the crystallinity which changed the original interlayer distance of 1422 to 1474, 1456 and 1474 pm, for the sequence of the guest picoline molecules. Thermogravimetry data suggested the intercalation reactions were governed by basicity of amines.     

Nucleophilic addition of heterocyclic amines to conjugated enyne ketones

Nucleophilic addition of secondary heterocyclic amines (morpholine, piperidine, and piperazine) to the double or triple bond of (E)-1,5-diarylpent-2-en-4-yn-1-ones is controlled by the kinetic and thermodynamic factor, respectively. The regioselectivity of the addition of piperazine to these enynones is determined by the substituent nature in the benzene rings. Conjugated ketones with electron-donating substituents take up piperazine molecule at the double bond, and those with electron-withdrawing groups, at the triple bond.