Synthesis of Selenocyanates and Selenoethers of Amino Pyrazoles and Amino Uracils by In Situ Triselenium Dicyanide from Malononitrile and Selenium Dioxide.

Herein, we report an efficient method for synthesis of novel selenocyanates of amino pyrazole, amino uracil, and amino isoxazole derivatives using in situ triselenium dicyanide from the combination of malononitrile and selenium dioxide in DMSO medium. Using the same combination but changing the stoichiometry of reagents and sequence of addition and temperature, symmetrical selenoethers of amino pyrazoles and amino uracils were prepared in good yields. Furthermore, selenocyanates of amino pyrazoles were utilized for the synthesis of corresponding alkynyl selenides in the presence of CuI and Cs2CO3. The salient features of this methodology are inexpensive starting materials, short reaction time, and good to very good yields. This method is also applicable for the gram-scale synthesis of selenocyanates of amino pyrazoles and amino uracils.

Synthesis of styryl-linked fused dihydropyridines by catalyst-free multicomponent reactions.

Herein, we report a rapid catalyst-free three-component reaction of 2-hydroxy-1,4-naphthoquinone, cinnamaldehydes and 3-aminopyrazoles in ethanol medium under reflux conditions for the easy access of styryl-linked dihydropyridines fused with naphthoquinone and pyrazole moiety. A wide variety of cinnamaldehyde derivatives and 3-aminopyrazoles were found suitable for this three-component reaction. All the products were fully characterized by spectroscopic tools and by recording single crystal XRD of one of the product. Catalyst-free reaction conditions, short reaction time, good yields of the products, easy purification process, formation of three new bonds (Two C-C and one C-N) in one-pot and products having four different bioactive moieties are the notable features of this methodology.

Hydrogen Peroxide-Mediated Rapid Room Temperature Metal-Free C(sp2)-H Thiocyanation of Amino Pyrazoles, Amino Uracils, and Enamines.

A rapid metal- and additive-free room temperature method for C(sp2)-H thiocyanation of aminopyrazoles, aminoisoxazole, aminoisothiazole, amino uracils, and aliphatic enamines has been developed in an aqueous medium using hydrogen peroxide as a benign oxidant and ammonium thiocyanate as a thiocyanating agent. On the other hand, the reaction of hydrogen peroxide and ammonium thiocyanate followed by one-pot addition of NaOH provides the corresponding disulfides in the case of amino azoles, and pyrimidine-fused 2-amino thiazoles were observed in the case of aminouracils. The salient features of this method are the use of an eco-friendly oxidant, reaction tunability to access different products, wide substrate scope, and good to very good yields.

One-pot synthesis of pyrimidine linked naphthoquinone-fused pyrroles by iodine-mediated multicomponent reactions.

Herein we report iodine-mediated multicomponent reactions for the synthesis of naphthoquinone-fused pyrroles tethered with a pyrimidine moiety. The reaction of aryl methyl ketones (3) or terminal aryl alkynes (5) in the presence of molecular iodine in DMSO medium followed by sequential addition of barbituric acids (2) and 2-amino-1,4-naphthoquinone (1) provides the corresponding three-component hybrid molecules 4 having naphthoquinone-fused pyrroles tethered with a barbituric acid moiety. This three-component reaction proceeds via metal-free C-H oxidation followed by multi-component cyclization forming three new bonds (2 C-C, 1 C-N) in one pot. Alternatively, the same molecules can also be prepared from the reaction of arylglyoxals, 2-aminonaphthoquinone, and barbituric acids in the presence of a catalytic amount of iodine in methanol medium under reflux conditions. The salient features of these methodologies are: one-pot metal-free method, good yields, wide substrate scope, easy purification of products, and the presence of medicinally important naphthoquinone, pyrrole and pyrimidine moieties in the products.

Cs2CO3-Mediated Rapid Room-Temperature Synthesis of 3-Amino-2-aroyl Benzofurans and Their Copper-Catalyzed N-Arylation Reactions.

Cs2CO3 in dimethylformamide (DMF) is a perfect combination for the rapid room-temperature synthesis of 3-amino-2-aroyl benzofuran derivatives from the reaction of 2-hydroxybenzonitriles and 2-bromoacetophenones in good to excellent yields. Using this one-pot C-C and C-O bond-forming strategy, we prepared a series of 3-amino-2-aroyl benzofuran derivatives within a very short time (10-20 min). This method was also found suitable for gram-scale synthesis. Benzofurans (3) obtained by this Cs2CO3-mediated methodology were then further explored for the development of a tunable base- and ligand-free copper-catalyzed N-arylation methodology using arylboronic acids for the easy access of either mono- or bi-N-aryl derivatives of aminobenzofurans at ambient temperature. The reaction of 3 with malononitrile in DMF medium under microwave heating conditions provided highly fluorescent conjugated alkenes and novel pyridine-fused benzofurans.

I2/DMSO mediated multicomponent reaction for the synthesis of 2-arylbenzo[d]imidazo[2,1-b] thiazole derivatives.

Synthesis of a series of 2-arylbenzo[d]imidazo[2,1-b] thiazoles tethered with barbituric acid moiety has been reported from the three component reaction of 2-aminobenzothiazoles, barbituric acids and terminal aryl acetylenes or aryl methyl ketones in the presence of I2 in DMSO medium. Both conventional and microwave heating conditions can be used for this multicomponent reaction. The salient features of this methodology are: (i) formation of one C-C and two C-N bonds in one-pot under metal-free oxidation followed by cyclization, (ii) selective formation of the fused imidazole ring, (iii) wide substrate scope, (iv) easy purification of the products, (v) products having more than one pharmaceutically important motifs and (vi) gram scale synthesis possible.

Synthesis of fused pyrroles containing 4-hydroxycoumarins by regioselective metal-free multicomponent reactions.

The reaction of arylglyoxals, 4-hydroxycoumarin, and aromatic amines such as 7-amino-2-methylchromone, 6/7-aminoflavone, 7-amino-4-methylcoumarin, 1-amino-9-fluorenone, 1-aminoanthraquinone and aniline derivatives in acetic acid medium under microwave conditions provides the corresponding regioselective fused pyrroles having hydroxycoumarin and aryl substituents. Alternatively, we have developed another method using in situ arylglyoxals from acetophenone derivatives by I2/DMSO promoted C-H oxidation followed by one-pot three component cyclization reactions to provide similar fused pyrroles. Using both the methods a series of novel pyrroles fused with pharmacologically important chromone, flavone, coumarin, fluorenone, and anthraquinone moieties were synthesized under metal-free reaction conditions in good to very good yields within a short reaction time. The structures of the synthesized fused pyrroles have been unambiguously confirmed by spectroscopic techniques, mass analysis and single crystal XRD.

Synthesis of Pyrimidine Fused Quinolines by Ligand-Free Copper-Catalyzed Domino Reactions.

Herein, we report two novel methods for the synthesis of pyrimidine fused quinolines using a one-pot C-C and C-N bond forming strategy from the reaction of 6-aminouracils with 2-bromobenzaldehydes or 2-bromobenzyl bromide derivatives in the presence of 10 mol % CuCl2 without using any ligand. The reaction of 2-bromobenzaldehyde or its derivatives with 6-aminouracils in the presence of K2CO3 as base and a catalytic amount of CuCl2 in DMF medium under microwave heating conditions provides corresponding pyrimidine fused quinoline derivatives in good yields within 30 min. Alternatively, pyrimidine fused quinoline derivatives have been synthesized from the reaction of 2-bromobenzyl bromides with 6-aminouracil derivatives in the presence of molecular oxygen, CuCl2 (10 mol %), and K2CO3 as base in DMF under reflux conditions. Structures of all the products were unambiguously confirmed by spectroscopic techniques and by recording single crystal XRD of 3a.