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A tandem regioselective one-pot synthesis of 3-amino-[1,2,4]-triazoles has been achieved from 1,3-disubstituted thioureas using molecular iodine. In this one-pot strategy, the intermediate carbodiimide generated in situ from thiourea upon reaction with HCONHNH2 gives diaryl/alkylhydrazinecarboximidamide or acylureidrazone, which then undergoes an intramolecular cyclodehydration to afford the corresponding 3-amino-[1,2,4]-triazole. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas correlate well with the pKas of the parent amines attached, in which the amine having higher pKa goes to the ring nitrogen while the other nitrogen remains flanked as an exocyclic nitrogen of the triazole core. This method is milder and environmentally sustainable giving good to excellent yields of the desired products.

Ortho-fluoro and -chloro substrates (I) undergo intramolecular arylthiolation via in situ generated halothioureas in the presence of CuO nanoparticles.

Copper(II) as the catalyst in a cross dehydrogenative coupling (CDC) reaction has been demonstrated for the synthesis of benzylic esters using aldehydes and alkylbenzenes as coupling partners.

Thiosemicarbazides (I) and (III), generated in situ from dithiocarbamate salts and formic hydrazide and benzhydrazide, are converted into oxadiazoles (II) and (IV) by cyclodesulfurization with molecular iodine.

A direct access to symmetrical and unsymmetrical 2,5-disubstituted [1,3,4]-oxadiazoles has been accomplished through an imine C–H functionalization of N-arylidenearoylhydrazide using a catalytic quantity of Cu(OTf)2. This is the first example of amidic oxygen functioning as a nucleophile in a Cu-catalyzed oxidative coupling of an imine C–H bond. These reactions can be performed in air atmosphere and moisture making it exceptionally practical for application in organic synthesis.

A one-pot, tandem process has been developed for the synthesis of a library of tetrazoles from aryl isothiocyanates. Condensation of aryl isothiocyanates with ammonia, and aryl amines (R-NH2) provided mono, 1,3-disubstituted symmetrical and unsymmetrical thioureas, which on desulfurization with molecular iodine (I2) led to formation of the corresponding heterocumulene (cyanamides or carbodiimides). The in situ generated heterocumulene on subsequent treatment with sodium azide at room temperature gave corresponding tetrazoles. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas was found to be correlated with the basicities (pKa's) of the parent amines attached to the thiourea. Aryl-sec-alkyl unsymmetrical thioureas gave thioamido guanidino products rather than the 5-aminotetrazoles produced by HgCl2 mediation of the reaction. Bis-thioureas derived from aryl isothiocyanates and hydrazine gave thiadiazoles exclusively.

In the present study, three divergent reaction paths emerged when o-haloanilides were subjected to CuO nanoparticles in water. o-Halo (I, Br) phenylbenzamides in the presence of CuO nanoparticles and Cs2CO3 in water at 100 °C provided o-hydroxyphenyl benzamides as the major product. However, a complete change in selectivity was observed in the presence of an organic base/ligand (TMEDA), giving 2-arylbenzoxazole as the exclusive product. The above selectivities were not clearly distinct when the corresponding alkylamides were treated either in the presence or absence of the ligand. A number of o-halophenyl alkylamides provided either exclusively o-dehalogenated products or a mixture of o-dehalogenated and o-hydroxylated products, but none gave 2-alkylbenzoxazoles. In addition to the above selectivities, the use of an environmentally friendly solvent (water) and base, and the recyclability of the catalyst make this procedure a benign alternative to the existing methods for the synthesis of these molecules, viz. o-hydroxybenzamides and o-arylbenzoxazoles.

An “on-water” one-pot process has been engineered for the preparation of 2-aminobenzothiazole from ortho-halo (–F, –Cl, –Br and –I) substituted unsymmetrical thioureas. For ortho –I and –Br substrates the reactions afford 2-aminobenzothiazoles under metal free condition promoted by base. However, the relatively inert ortho –Cl and –F substrates undergo intramolecular arylthiolation only in the presence of CuO nanoparticles yielding 2-aminobenzothiazoles. This methodology provides easy access to aminobenzothiazoles utilising even the ortho –Cl and –F substrates. The catalyst is recyclable several times without loss of substantial activity. Other remarkable features include the wide range of functional group tolerance, absence of chromatographic purification (for ortho –I and –Br substrates) and providing moderate to excellent yield of the products under mild conditions, thus rendering the methodology as a highly eco-friendly alternative to the existing methods.

A one-pot synthesis of 3-amino-1,3,4-oxadiazoles has been achieved from the corresponding dithiocarbamate salt, employing the thiophilic property of molecular iodine. The precursor thiosemicarbazides could be derived in situ which underwent an intramolecular cyclodesulfurization in the presence of iodine to afford 3-amino-1,3,4-oxadiazoles exclusively. Apart from being milder and environmentally sustainable, this method involves a simple, reliable approach to give good to excellent yields of the desired products and is compatible with a wide range of functional groups.

A one-pot, tandem process has been developed for the synthesis of a library of tetrazoles from aryl isothiocyanates. Condensation of aryl isothiocyanates with ammonia, and aryl amines (R-NH(2)) provided mono, 1,3-disubstituted symmetrical and unsymmetrical thioureas, which on desulfurization with molecular iodine (I(2)) led to formation of the corresponding heterocumulene (cyanamides or carbodiimides). The in situ generated heterocumulene on subsequent treatment with sodium azide at room temperature gave corresponding tetrazoles. The product regioselectivity for unsymmetrical 1,3-disubstituted thioureas was found to be correlated with the basicities (pK(a)'s) of the parent amines attached to the thiourea. Aryl-sec-alkyl unsymmetrical thioureas gave thioamido guanidino products rather than the 5-aminotetrazoles produced by HgCl(2) mediation of the reaction. Bis-thioureas derived from aryl isothiocyanates and hydrazine gave thiadiazoles exclusively.