Similarities between thermolysis and mass spectrometric fragmentation of tetrazoles (review)

KAMETANI T.

Könnecke A., Lippmann E., Kleinpeter E.

Antonowa A., Herzschuh R., Hauptmann S.

Löster H., Herzschuh R., Lippmann E.

The mass spectra of S-(1-aryltetrazol-5-yl)-monothiocarbonic acid esters have been studied. The stability of the ester molecular ions is lower than the stability of the corresponding 1-aryl-5-mercaptotetrazoles. Substituents at the phenyl group increase the stability, whereas the influence of the ester alkyl groups is very small. The esters undergo fragmentation via four different fragmentation pathways. The elimination of carbon dioxide is influenced by an ‘ortho effect’ of the substituents.

Green M.M.

Gilchrist T.L., Moody C.J., Rees C.W.

Gilchrist T.L., Gordon P.F., Pipe D.F., Rees C.W.

Holm A., Carlsen L., Larsen E.

Glish G.L., Cooks R.G.

Wentrup C., Damerius A., Reichen W.

Ruccia M., Vivona N., Cusmano G.

Addition reactions of 1,2-dimethylpyrrole and 1-methyl-2-carbomethoxypyrrole with C-acetyl-N-phenylnitrilimine, have been investigated. 1,2-Dimethylpyrrole gives three different types of adducts: i.e. bis-cycloadducts (Vc) and (VIc), spirocycloadduct (IX), and non cyclic bis-adduct (XII). On the other hand, 1-methyl-2-carbomethoxypyrrole gives the bis-cycloadduct (VIb) only. Compound XII arises probably through a double 1,3-addition reaction, whereas the formation of cycloadducts Vc, VIc, and IX depends on the substituents present at C2 of the pyrrole ring and consequentially on the intermediary occurence of mono-cycloadduct (IIIc), its methylenic tautomer VII, VIc, and XL The behaviour of the cycloadducts towards heating or acidic treatment showed a termal cleavage of the pyrazoline ring and acidic cleavage of the pyrrolidine ring.

Könnecke A., Dörre R., Lippmann E.

Grigg R., Kemp J., Thompson N.

Kallury R.K., Rao P.L.

The mass spectra of nine aryl heteryl ketoximes indicated that a gaseous phase Beckmann rearrangement occurs to a significant extent, as confirmed by the exact mass measurements of the resulting aroyl cation peaks. Loss of oxygen, hydroxyl radical and migration of the oxime hydrogen to the heterocycle is observed to take place in varying proportions.

Butler R.N.

This chapter discusses the development of tetrazole chemistry from 1965 to 1975. Over the years, it has been noted that the field has grown rapidly, with regard to the industrial interest that the tetrazoles command. Some of the significant areas in this field include the applications of modern physical techniques to tetrazole derivatives and studies of pharmacologically active tetrazoles, particularly, replacement of the carboxylic acid group in known active molecules by its analog—the tetrazole ring. Tetrazole essentially is an aromatic azapyrrole nucleus, which exist in two tautomeric forms. The chapter also describes physicochemical studies. These studies include nuclear magnetic resonance spectroscopy and theoretical calculations, mass fragmentation, tetrazole complexes and crystal structures, and photolysis and tetrazole radicals. Tetrazole can be synthesized by several methods that are also presented in the chapter. In the context of azide-tetrazole isomerism, it is observed that polar solvents tend to favor the tetrazole form and nonpolar solvents the azide form. Another factor that influences this isomerism is the syn-anti isomerism about the C=N moiety.

Lucero P.L., Peláez W.J., Moyano E.L.

The present study, deals with the synthesis of 2-substituted-6-phenyl-imidazo[2,1-b][1,3,4]thiadiazoles from 2-amino-5-substituted-1,3,4-thiadiazoles and 2-bromo-1-phenylethanone, which was carried out applying a microwave-assisted aqueous procedure. Furthermore, the gas-phase thermal behaviour of these imidazothiadiazoles in flash vacuum pyrolysis reactions has been studied. It has been shown that thermolysis conditions induce thiadiazole fragmentation to give indole-carbonitriles and other nitriles. The quantum chemical calculations support a stepwise mechanism for the fragmentation of imidazothiadiazoles to afford products.

Ostrovskii Vladimir A., Chernova Ekaterina N., Zhakovskaya Zoya A., Pavlyukova Yulia N., Ilyushin Mikhail A., Trifonov Rostislav E.

Rapid processes of tetrazole decomposition serve as sources of chemical energy stored in the five-membered ring, as well as gaseous products, primarily molecular nitrogen. Due to these properties, energetic tetrazole derivatives have found applications in various fields of science, engineering and technology, for example as components of energetic materials and products, as well as in emergency rescue equipment. The review presents an alternative view of the processes of tetrazoles decomposition, focusing on the diversity, differences, and similarities of the mechanisms and degradation products formed under the action of external energy sources. Some of these products are valuable reagents for the synthesis of previously inaccessible substances, as well as promising objects of analytical, medical, and bioorthogonal chemistry.The bibliography includes 140 references.

Ershov I.S., Esikov K.A., Nesterova O.M., Skryl’nikova M.A., Khramchikhin A.V., Shmaneva N.T., Chernov I.S., Chernova E.N., Puzyk A.M., Sivtsov E.V., Pavlyukova Y.N., Trifonov R.E., Ostrovskii V.A.

3-(5-Phenyl-2H-tetrazol-2-yl)pyridine was synthesized by treating 5-phenyl-1H-tetrazole with pyridin-3-ylboronic acid under Chan–Evans–Lam coupling conditions. The structure and identity were confirmed by 1H, 13C-NMR spectroscopy, IR spectroscopy, UV–Vis spectroscopy, high-resolution mass spectrometry, and TLC. The molecular structure was studied experimentally by sequential X-ray diffraction analysis and theoretically by DFT B3LYP quantum chemistry calculation.

Testen A., Plevnik M., Štefane B., Cigić I.K.

Abstract Development of safe and effective drugs requires complete impurity evaluation and, therefore, knowledge about the formation and elimination of impurities is necessary. During impurity profiling of a key intermediate during synthesis of candesartan cilexetil (1-(((cyclohexyloxy)carbonyl) oxy)ethyl 1-((2’-(2H-tetrazol-5-yl)-[1,1’-biphenyl]-4-yl) methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylate, TCV-116), a novel compound, which had not been reported previously, was observed. Structural elucidation of impurity was achieved by liquid chromatography hyphenated to different high resolution mass analyzers. Based on exact mass measurements and fragmentation pattern, a chloro alkyl carbonate ester analogue of the intermediate was identified. Structure of the impurity was confirmed by mass spectro-metric and NMR analyses of the target substance. Identified impurity could represent a hazard if it is transferred to the final API stage and its presence should be kept below allowed limits. Further investigation could reveal whether bis(1-chloroethyl) carbonate is a precursor to impurity formation. Therefore, synthesis should be regulated so as to minimize impurity production. Analysis of the final product indicated that the amount of impurity did not exceed 50 mg L−1, which represents the detection limit, determined according to the signal/noise ratio.

Velikorodov A.V., Stepkina N.N., Ionova V.A., Melent’eva E.A.

Reactions of methyl(ethyl) N-(2-cyanophenyl)carbamates with sodium azide in dimethylformamide at 80–90°C in the presence of anhydrous CdCl2 afforded the corresponding N-arylcarbamates with a 1,2,3,4-tetrazole fragment. The acylation of methyl N-[2-(1H-1,2,3,4-tetrazol-5-yl)phenyl]carbamate with acetic anhydride followed by the condensation of the obtained N-acyl derivative with thiophene-2-carbaldehyde in the KOH methanol solution led to the formation of methyl N-(2-{1-[3-(2-thienyl)-2-propenoyl]-1H-1,2,3,4-tetrazol-5-yl}phenyl)carbamate. The reaction of cyclohexyl N-(4-aminophenyl)carbamate with a triethyl orthoformate and sodium azide in glacial AcOH yielded cyclohexyl N-[4-(1H-1,2,3,4-tetrazol-1-yl)phenyl]carbamate.

Moderhack D.

Transformations of heterocycles into tetrazoles as well as conversions of the latter into other rings are reviewed. The literature is covered through early 1998 (material that has been surveyed by Van der Plas [1] and Benson [2] is resumed in abridged fashion). From the wide variety of interconversions accumulated in this overview a great many processes emerge that are of prime importance preparatively; moreover, quite a number of reactions will arouse interest in their mechanisms.