E. E. Rumyantseva

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.

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 hydroxyderivatives of 4-methylcoumarin

7-Hydroxy-4-methylcoumarin (V) was reported to produce a choleretic [1] and hepatoprotectve [2] action. This compound is also used as an intermediate for the synthesis of compounds with antibacterial [3] and spazmolytic [4] properties. Coumarin V and some other hydroxyderivatives of 4methylcoumarin are usually obtained by the Pechman reaction, involving polycondensation of twoand three-atomic phenols with acetoacetic ester (AE) in the presence of H2SO4 [I, 5]. A disadvantage of this method is the comparatively low and unstable yield of the target coumarins V and VIII. In this work we propose new efficient twoand threecomponent systems for for the Pechman reaction with resorcinol (1), orcin (I1), pyrogallol (Ill), and hydroquinone (IV): CISiMe3 -CdClz AcOH (A); CISiMe3 -ZnC! 2 -AcOH (B); ClSiMe3 CdCI2 CF3COOH (C); ClSiMe3 ZnCl2 (D) CISiMe 3 H 2 S O 4 (E ) . Cyclocondensations are performed by mixing phenols and AE with reagents at room temperature, and the coumarins ( V VIII) formed during the reaction are extracted by treating the reaction mixture with water.

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

Synthesis of N-aroyl hydrazones

N-Aroyl hydrazones exhibit antibacterial activity [1] and are used as precursors for synthesis of 1,3,4-oxadiazoles [2]. N-Aroyl hydrazones are usually obtained by prolonged heating o f hydrazides of carboxylic acids with carbonyl compounds (CC) in MeOH [3, 4] or in an excess of CC [1]. In this work we have demonstrated for the first time that a CISiMe3 HCONMe2 system can be used for synthesis of Naroyl hydrazones; this system allows us to carry out synthesis o f hydrazones at room temperature and over a short period o f time. For instance, hydrazides o f benzoic (Ia) and m-nitrobenzoic (lb) acids react under these conditions with corresponding CC to give N-aroyl hydrazones ( I I a f ) in 70 9 0 % yields (see Table 1). RC6H4CONHN=CR l R 2 (IIa f), R = H (Ila d), NO2-3 (lie, f ) ; R t --Me (IIa, b, e, f ) , Et (IIc); R ~ = Ph (Ila, c, e); C6H4Br-4 (lib, f ) ; R I + R 2 = (CH2)s (lid)

Synthesis of N-aryl enamino ketones

Dihydroresorcinol and dimedone are condensed with aromatic amines at room temperature under the action of CiSiMe3-DMFA system to give 3-anilino-2-cyclohexene derivatives in 70–90% yield.

1-Bromoalkan-2-ones in organic synthesis (review)

The development of selective and preparatively suitable means for obtaining l-bromoalkan-2-ones (BK) from methylketones [i] and terminal olefins [2-4] opened up many possibilities for using BK in the syntheses of biologically-active compounds. Effective syntheses of pterines [5], 8-aminolevulinic acid hydrochlorides (I) biological precursors to heam, chlorophyll, and vitamin Bl2 [6, 7], imidazole derivatives [8], and pheromones [9] have already been carried out using BK as starting material. Most of these syntheses are characterized by multistep procedures, satisfactory yields of the desired products, and the accessibility of starting materials and reagents.