L. B. Kulikova

Synthesis of 2-aminothiazole derivatives

The optimum amount of urea for the selective bromination of ketones in DMF has been established. The obtained α-bromoketones have been used for the synthesis of 2-aminothiazoles in situ. A series of compounds with potential biological activity has been synthesized proceeding from chloroacetyl derivatives of 2-aminothiazoles.

1,3-Dihydro-2H-imidazol-2-one Derivatives: Synthesis and Applications (A Review)

1,3-Dihydro-2H-imidazol-2-ones possess biological activity of various types. For example, 1,3-dihydro-2H-imidazol-2-one (I) [1, 2], 1,3-dihydro-4-methyl-2H-imidazol2-one (II) [1], and 1,3-dihydro-4-methyl-5-(4-methylthiobenzoyl)-2H-imidazol-2-one (enoximone, III) [2, 3] exhibit antioxidant properties. Enoximone (III) and 1,3-dihydro-5isonicotinoyl-4-ethyl-2H-imidazol-2-one (piroximone, IV) were reported to possess pronounced cardiotonic activity [4 – 6].

Synthesis of N-Phthaloyl Derivatives of Amino Acids

N-Phthaloyl derivatives of amino acids are used as semiproducts in the synthesis of compounds possessing hypolipidemic [1], analgesic [2], antibacterial [3], and antitumor [4] activity. These N-phthaloyl amino acids (PAAs) are usually synthesized through cyclocondensation of amino acids with phthalic anhydride [5 – 8]. Some PAAs, representing the N-phthaloyl derivatives (VIII – X) of DL-alanine, -alanine, and -aminobutyric acid (GABA), can be also obtained by fusing phthalic acid (I) with the corresponding amino acids (III – V) at 170 – 190°C [9]. However, the possibility of using this method for the synthesis of other PAAs was not considered in [9]. Recently [10] we have demonstrated that glycine (II) can be brought into reaction with I in a medium of boiling propionic acid, which simultaneously performs the functions of solvent and condensing agent. The reaction yielded N-phthaloylglycine (VII) with a yield exceeding 80%. R = H, n = 1 (II, VII); R = CH3, n = 1 (III, VIII); R = H, n = 2 (IV, IX); R = H, n = 3 (V, X); R = H, n = 4 (VI, XI)

Synthesis of 4,5,6,7-tetrahydroindole derivatives

4,5,6,7-Tetraindole derivatives are used as semiproducts in the synthesis of acetylchotinesterase (ACE) inhibitors [ 1 ]. According to [2], tetraindole derivatives I and II (see the scheme below) can be synthesized by intramolecular cyclization of 2-phenacyldimedone (III) followed by amination of the intermediate 6,6-dimethyl-4-oxo-2-phenyl4,5,6,7-tetrahydrobenzofuran (IV) by aniline or 4-toluidine in AcOH.

Short communication. A region-selective method for the synthesis of 4-substituted 2-amino-6-methylpteridines

We provide here the first report of cyclic condensation of 5,6-diaminopyrimidines with 2-benzamidopropanal or 2,2-dihalogenpropanals for the highly selective synthesis of substituted 6-methylpteridines.

Natural Uracils: Synthesis and Chemical Properties (A Review)

The most important and best characterized representatives of natural uracils are unsubstituted uracil (I), thymine (II), and orotic acid (III). Uracil and thymine enter into the composition of nucleic acids, while orotic acid is a biological precursor of uracil [1]. Uracil and thymine were reported to potentiate the antitumor activity of 5-fluorouracil (IV) and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur, V) [2 – 8]. Orotic acid was reported to produce a therapeutic effect with respect to cardiological disorders [9 – 12].

Synthesis of N-substituted 3-nitrophthalimides

The N-substituted 3-nitrophthalimides are known to possess antibacterial [ 1], analgesic [2], and vasodilative [3] activity. These compounds can be synthesized by heating 3-nitrophthalic anhydride with amines either without solvent [4] or in acetic acid [5]. / Below we will show that N-substituted 3-Mitrophthalimides are conveniently obtained by cyclocondensation of 3-nitrophthalic acid (I) with amines in the presence of a two-component reagent system CISiMe3DMF. For example, the reaction of compound I with glycine (II), 5-aminovaleric acid (III), 4-aminobenzoic acids (IV), methyl ester of 4-aminobenzoic acid (V), aniline (VI), and p-toluidine (VII) lead to a high yield of the corresponding products (VIIIXIII). By the same token, the cyclocondensation of phthalic acid (XIV) with compounds II and III yield the N-substituted phthalimides XV and XVI:

Synthesis of N-haloacyl and N-hetarylthioacyl derivatives of 2-amino-5-aryl-6H-1,3,4-thiadiazine

Conditions for N-acylation of 2-amino-5-aryl-6H-1,3,4-thiadiazines with trifluoroacetic anhydride and halogen-substituted carboxylic acid halides with retention of the initial heterocyclic system were found. 5-Aryl-2-haloacylamino-6H-1,3,4-thiadiazines were obtained in preparative yields. Their reactions with hetarenethiols afforded N-hetarylthioacyl derivatives.

Regioselective chlorination of 6-(5-methyl-2-oxo-4-imidazolin-4-yl)-6-oxohexanoic acid ethyl ester: A new synthesis of biotin

Regioselective chlorination of a methyl group in 6-(5-methyl-2-oxo-4-imidazolin-4-yl)-6-oxohexanoic acid ethyl ester via reaction with sulfuryl chloride in methylene chloride has been performed for the first time. The synthesis of 5-(2-oxo-2,3-dihydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid methyl and ethyl esters (tetradehydrobiotin esters) — key compounds in biotin (vitamin H) synthesis — has been developed proceeding from 6-(2-oxo-5-chloromethyl-4-imidazolin-4-yl)-6-oxohexanoic acid ester.

Synthesis of hippuric acid amides and coumarin derivatives. Effect of N,N-diethylacetamide

Hippuric acid amides are used as semiproducts in the synthesis of oxazole derivatives possessing antidepressant activity [1]. According to [2 7], these compounds are obtained by azlactonation ofhippuric acid (I) under the action of acetic anhydride, followed by condensation of the intermediate product, 2-phenyl-2-oxazolin-5-one (II), with amines in tetrahydrofuran or benzene (or without solvent). The azlactonation of compound I is not a smooth process: the intermediate product II has to be recrystallized from butanol or absolute ethanol and the total yield of hippuric acid amides does not exceed 50%. We have established that hippuric acid amides can be obtained at a high yield without purification of the intermediate product II if both stages (azlactonation of compound I and condensation of compound II with amines) are performed in the presence ofN,N-diethylacetamide (DEAA). For example, by using this method and proceeding from compound I and the corresponding amines-aniline (III) and p-toluidine (IV) we have synthesized anitide (V) and p-toluidide (VI) with a total yield of 80 and 86%, respectively