Modern chemical disinfectants and antiseptics. Part I

Aim. To generalize and systematize information on the properties of modern chemical disinfectants and antiseptic agents (DA and AA).Results and discussion. The review provides generalized and systematized information on the properties of modern chemical DA and AA – alkylating reagents, aldehydes, amides, amidines, bisguanidines, dyes, halogenated reagents, halogens and their complexes, 2-nitrofuran derivatives. The classification of DA and AA by their chemical structure was carried out. The activity spectra, possible application ways and forms of DA and AA were given. Their toxicity and impact on the environment were described as well.Conclusions. On the basis of the analysis carried out it was shown that aldehydes, halogen-active compounds and halogen-containing complexes are modern effective DA and AA with a wide spectrum of biocidal action. Amides, amidines and bisguanidines are characterized by a narrow spectrum of activity. Dyes and 2-nitrofuran derivatives are old-fashioned antiseptics.

Halomethyl-Triazoles for Rapid, Site-Selective Protein Modification

Post-translational modifications (PTMs) are used by organisms to control protein structure and function after protein translation, but their study is complicated and their roles are not often well understood as PTMs are difficult to introduce onto proteins selectively. Designing reagents that are both good mimics of PTMs, but also only modify select amino acid residues in proteins is challenging. Frequently, both a chemical warhead and linker are used, creating a product that is a misrepresentation of the natural modification. We have previously shown that biotin-chloromethyl-triazole is an effective reagent for cysteine modification to give S-Lys derivatives where the triazole is a good mimic of natural lysine acylation. Here, we demonstrate both how the reactivity of the alkylating reagents can be increased and how the range of triazole PTM mimics can be expanded. These new iodomethyl-triazole reagents are able to modify a cysteine residue on a histone protein with excellent selectivity in 30 min to give PTM mimics of acylated lysine side-chains. Studies on the more complicated, folded protein SCP-2L showed promising reactivity, but also suggested the halomethyl-triazoles are potent alkylators of methionine residues.

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.

Synthesis, Antibacterial and Antifungal Activity of New 3-Aryl-5H-pyrrolo[1,2-a]imidazole and 5H-Imidazo[1,2-a]azepine Quaternary Salts

A series of novel 3-aryl-5H-pyrrolo[1,2-a]imidazole and 5H-imidazo[1,2-a]azepine quaternary salts were synthesized in 58–85% yields via the reaction of 3-aryl-6, 7-dihydro-5H-pyrrolo[1,2-a]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepines and various alkylating reagents. All compounds were characterized by 1H NMR, 13C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-1-ium chloride 6c possessed a broad activity spectrum towards Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Cryptococcus neoformans, with a high hemolytic activity against human red blood cells and cytotoxicity against HEK-293. However, compound 6c is characterized by a low in vivo toxicity in mice (LD50 > 2000 mg/kg).

Alkylation of Quinoxalin-2(1H)-Ones Using Phosphonium Ylides as Alkylating Reagents

A practical and efficient methodology for the construction of 3-alkylquinoxalinones through base promoted direct alkylation of quinoxalin-2(1H)-ones with phosphonium ylides as alkylating reagents under metal- and oxidant- free conditions was...

Homogeneous Catalytic C(sp3)–H Functionalization of Gaseous Alkanes

The conversion of light alkanes into bulk chemicals is becoming an important challenge as it avoids effectively the use of prefunctionalized alkylating reagents. The implementation of such processes is, however,...

Effect of surface acidity and basicity of supported Ni catalysts on the N-alkylation of isopropylamine with isopropanol

The N-alkylation of amines with alkylating reagents is widely used in the synthesis of aliphatic amines, which usually be catalyzed by homogeneous catalytic system. In this work, the heterogeneous catalysts...

Orthoamide und Iminiumsalze, IIC. Darstellung von N-(ω-Ammonioalkyl)-N,N′,N′,N″,N″-peralkylierten Guanidiniumsalzen und N-(ω-Aminoalkyl)-N′,N′,N″,N″-tetramethylguanidinen

N,N,N′,N′-Tetraalkylchlorformamidiniumchlorides 1a, b react with ω-dimethylaminoalkylamines 19, 20 to give mixtures of N-(ω-dimethylammonioalkyl)-guanidinium salts 12, 13 and N-(ω-dimethylaminoalkyl)-guanidinium salts 21, 22. These mixtures are transformed to mixtures of the ureas 15, 17 and N-(ω-dimethylaminoalkyl)-guanidines 23, 25 on treatment with aqueous sodium hydroxide. The reaction of N-(3-dimethylammoniopropyl)-guanidin 25a with dimethylsulfate in a molar ratio of 1:1 delivers a mixture of the N-(3-dimethylaminopropyl)-N,N,N′,N′,N″,N″-pentamethyl-guanidinium salt 29a and the N-(3-dimethylammoniopropyl)-N,N′,N′,N″,N″-pentamethyl-guanidinium-bis (methylsulfate) 33a. The action of dimethylsulfate on the guanidines 23a, 25a in a molar ratio of 2:1 affords the bisquarternary salts 32a, 33a. Alkylating reagents as methyliodide, benzylbromide, allylbromide and chloroacetonitrile attack N-(2-dimethylaminoethyl)-N′,N′,N″,N″-tetraethylguanidine (23b) in a molar ratio of 1:1 cleanly at the dimethylaminoethylgroup to give the ammonium salts 30a–d. As a strong base the guanidine 23b dehydrochlorinates β-Chlorpropionitrile and chloroacetone under formation of the guanidinium salt 21c. In contrast to this the reaction of ethyl bromoacetate with the N-(2-dimethylaminoethyl)guanidine 23b occurs at the guanidinogroup giving the guanidinium salt 28c. The methylation of the guanidinium chlorides 21a, 22a with dimethyl sulfate affords the bis-quaternary salts 35b, 36b with mixed anions. From the heterocyclic guanidines 14, 16 and the alkylating reagents benzylbromide and ethyl bromoacetate the heterocyclic guanidinium salts 37a, b, 39a, b can be obtained. The reactions with ethyl chloroformiate proceed in an analogous way giving the guanidinium salts 37c, 39c. The N-alkyl-N,N,N′,N′-tetramethyl-(3-ureidopropyl)guanidinium salts 41a, b can be prepared from the N′,N′,N″,N″-tetramethyl-N′′-(3-ureidopropyl) guanidine 17a and the alkylating compounds dimethyl sulfate and benzyl bromide. Several compounds obtained that way were transformed to the corresponding tetraphenyloborates and bis(tetraphenylborates), respectively.

Alkyl Tosylates as Alkylating Reagents in the Catellani Reaction

A cooperative catalytic system involving a Pd/XPhos complex and inexpensive 5-norbornene-2-carbonitrile that enables the use of alkyl tosylates as alkylating reagents in the Catellani reaction has been developed. This mild, scalable protocol is compatible with a range of readily available functionalized aryl iodides and alkyl tosylates, as well as terminating olefins (45 examples, up to 97% yield).

Epoxides as Dual-Functionalized Alkylating Reagents in Catellani Reactions for the Assembly of Heterocycles

Reported is a cooperative catalytic system consisting of a complex of Pd with dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos) and the potassium salt of 5-norbornene-2-carboxylic acid that permits the use of epoxides as dual-functionalized alkylating reagents in Catellani-type reactions for the assembly of heterocycles. Salient features of this research include readily available substrates, use of the potassium salt of 5-norbornene-2-carboxylic acid as a catalytic mediator as well as a base, and excellent regioselectivity for the cleavage of epoxides. This mild, chemoselective, scalable, atom- and step-economic protocol offers a straightforward approach for the assembly of isochroman and 2,3-dihydrobenzofuran scaffolds.