Synthesis and properties of hydrazones bearing amide, thioamide and amidine functions

This review provides detailed methods for the synthesis, structures and chemical properties of hydrazones bearing carboxamide, thioamide and amidine functions. The main accent was put on the cyclization reactions leading to pyrazoles, thiazoles, 1,2,3-triazoles, 1,2,3-thiadiazoles, 1,2,4-triazines and other heterocyclic compounds. In addition, we have reviewed methods for the synthesis of substrates for pericyclic reactions from the hydrazones. © ARKAT USA, Inc

Synthesis and Reactivity of Azides Towards Enamines

T. V. Beryozkina thanks Russian Foundation for Basic Research, project №18-03-00715

Progress in intermolecular and intramolecular reactions of thioamides with diazo compounds and azides

Reactions of thioamides with nitrogen-rich 1,3-dipoles, diazo compounds and azides, have been known for long time already. However in recent years introduction of catalysts of different types (rhodium-, ruthenium- and copper-containing and Lewis acids) as well as highly electrophilic sulfonyl azides, allowed the development of new methods for the synthesis of heterocycles, enamines and N-sulfonyl amidines. Moreover, a new methodology in organic synthesis, based on generation and subsequent transformations of α-diazocarbonyl compounds was created. Reactions of sulfonyl azides with thioamides undergo readily in mild conditions to produce different sorts of N-sulfonyl amidines and represent a new type of click-type processes. Most of the cited works were published in the current decade. Earlier seminal papers are also reviewed when they constitute the background for new synthetic methods which were developed further. © 2019 Elsevier Lt

Synthesis and oxidative cyclization of 2-arylhydrazono-2-cyanoacetamidines to 5-amino-2-aryl-2H-[1,2,3]triazole-4-carbonitrile

A general and convenient method for the synthesis of 2-arylhydrazono-2- cyanoacetamidines, containing either a cytisine or tryptamine moiety, or other secondary and primary amines was elaborated. A series of 5-amino-2-aryl-2H-[1,2, 3]-triazole-4-carbonitriles was successfully prepared by oxidation of these amidines with copper acetate in pyridine. The screening of the biological activity of the synthesized triazoles and amidines have shown that, some of these compounds possess fungicidal activity at concentrations of 50 μg/mL against some fungi tested. © ARKAT USA, Inc

New Transformations of N-hetarylcyclopentano[d][1,2,3]triazoline Ring into 5-alkoxyvaleramidines

[Figure not available: see fulltext.] It was found that brief refluxing of N-hetarylcyclopentano[d][1,2,3]triazolines in methanol resulted in the elimination of nitrogen, accompanied by cyclopentane ring opening with the formation of N-hetarylvaleramidines. Amidines containing pyrimidine-2,4-dione ring were synthesized by a one-step procedure – the reaction of 5-azidopyrimidine-2,4-diones with endocyclic enamines containing a cyclopentene ring proceeded through an N-pyrimidyl-1,2,3-triazoline intermediate. Triazolines containing a 1,3,5-triazine ring at position 1 did not form valeramidines upon refluxing in methanol. N-(1,3,5-triazin-2-yl)cyclopenta[d][1,2,3]triazoline containing a morpholine ring at position 6a underwent a different type of transformation upon dissolving in acetic acid, resulting in the formation of N-(1,3,5-triazin-2-yl)diaminoalkene. Mechanisms for these transformations are proposed. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.This work was performed with financial support from the Russian Foundation for Basic Research (grant No. 18-03-00715)

A Base-Controlled Reaction of 2-Cyanoacetamidines (3,3-Diaminoacrylonitriles) with Sulfonyl Azides as a Route to Nonaromatic 4-Methylene-1,2,3-triazole-5-imines

Reactions of 2-cyanoacetamidines with sulfonyl azides were shown to take place via two different pathways to form a mixture of 1-substituted 5-amino-1,2,3-triazoles 3 and novel 4-methylene-1H-1,2,3-triazole-5(4H)-imine derivatives 4–14. In the absence of a base, 5-amino-1,2,3-triazoles 3 are formed as the only products. The presence of 1.2 equiv. of sodium ethoxide or DBU switches the reaction outcome while involving the cyano group, resulting (after a 1,5-protic shift) in triazoles 4–14 as the only products. The methods were elaborated for the selective and efficient synthesis of triazoles 3 and 4-methylene-1,2,3-triazole-5-imines 4–14 including one-pot synthesis from sodium azide and sulfonyl chlorides. The unusual structure of 4–14 compounds was confirmed by X-ray data and 2D 1H–15N and 1H–13C NMR spectra. The formation of the products was explained by the presence of two strong hydrogen bonds N···H and O···H in these molecules. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimWe gratefully acknowledge financial support of this work by the Russian Science Foundation (18‐13‐00161)

Molecular recognition of nitrogen–containing bases by Zn[5,15-bis-(2,6-dodecyloxyphenyl)]porphyrin

© 2016 Informa UK Limited, trading as Taylor & Francis Group.By means of spectrophotometric titration and 1H NMR spectroscopy, the selective binding ability of the Zn-5,15-bis-(2,6-dodecyloxyphenyl)porphyrin towards nitrogen containing organic molecules of various nature has been studied. It has been found that the presence of long alkoxy substituents at the ortho-positions of the Zn-porphyrin phenyl rings prevents the axial coordination of tertiary amines and, conversely, creates favourable conditions for binding of a primary diamine due to the presence of additional binding sites, namely the oxygen atoms of the ortho–ortho′- dodecyloxy substituents of the meso phenyl groups. The formation of stable complexes with multiple binding sites has been confirmed by DFT quantum chemical calculations and two-dimensional NMR experiments

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4- carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5-arylamino- 1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. © 2020 Ilkin et al.The authors thank the Russian Science Foundation (project №18-13-00161)

Synthesis of heterocyclic N-sulfonylamidines from heteroaromatic thioamides and sulfonyl azides

The authors thank the Russian Foundation for Basic Research (project № 18-13-00161)

QSAR-derived affinity fingerprints (part 1): fingerprint construction and modeling performance for similarity searching, bioactivity classification and scaffold hopping.

Funder: FP7 People: Marie-Curie Actions; doi: http://dx.doi.org/10.13039/100011264; Grant(s): 238701, 238701An affinity fingerprint is the vector consisting of compound's affinity or potency against the reference panel of protein targets. Here, we present the QAFFP fingerprint, 440 elements long in silico QSAR-based affinity fingerprint, components of which are predicted by Random Forest regression models trained on bioactivity data from the ChEMBL database. Both real-valued (rv-QAFFP) and binary (b-QAFFP) versions of the QAFFP fingerprint were implemented and their performance in similarity searching, biological activity classification and scaffold hopping was assessed and compared to that of the 1024 bits long Morgan2 fingerprint (the RDKit implementation of the ECFP4 fingerprint). In both similarity searching and biological activity classification, the QAFFP fingerprint yields retrieval rates, measured by AUC (~ 0.65 and ~ 0.70 for similarity searching depending on data sets, and ~ 0.85 for classification) and EF5 (~ 4.67 and ~ 5.82 for similarity searching depending on data sets, and ~ 2.10 for classification), comparable to that of the Morgan2 fingerprint (similarity searching AUC of ~ 0.57 and ~ 0.66, and EF5 of ~ 4.09 and ~ 6.41, depending on data sets, classification AUC of ~ 0.87, and EF5 of ~ 2.16). However, the QAFFP fingerprint outperforms the Morgan2 fingerprint in scaffold hopping as it is able to retrieve 1146 out of existing 1749 scaffolds, while the Morgan2 fingerprint reveals only 864 scaffolds