Synthesis of novel antibacterial and antifungal dithiocarbamate-containing piperazine derivatives via re-engineering multicomponent approach.

A metal-free multicomponent synthetic route for the diverse preparation of dithiocarbamate-containing piperazine derivatives was developed through the C-N bond cleavage of DABCO ring. This multicomponent re-engineering approach proceeds via the reaction of amines, CS2 and DABCO salts in one pot. Various DABCO salts and secondary amines are tolerated well in this protocol to afford a broad spectrum of dithiocarbamate-containing piperazines in good to high yields. Then, the selected compounds have been deployed against some critical types of bacteria and fungi. A certain number of synthesized compounds revealed not only appropriate antibacterial activity as investigated by disc fusion and minimum inhibitory concentration methods against bacteria (Gram-positive and Gram-negative), but also depicted good to excellent antifungal activity.

DABCO bond cleavage for the synthesis of piperazine derivatives.

The applications of DABCO (1,4-diazabicyclo[2.2.2]octane) in the synthesis of piperazine derivatives including biologically active compounds via C-N bond cleavage are investigated in this review. Different reagents such as alkyl halides, aryl(heteroary) halides, carboxylic acids, diaryliodonium salts, tosyl halides, activated alkynes, benzynes etc. were applied for the preparation of the corresponding quaternary ammonium salts of DABCO, which are very good electrophiles for various nucleophiles such as phenols, thiophenols, thiols, alcohols, aliphatic and aromatic amines, sulfinates, phthalimide, indoles, NaN3, triazole and terazoles, NaCN, enols and enolates, halides, carboxylic acid salts etc. Besides preactivated DABCO salts, the in situ activation of DABCO in multicomponent reactions is also an efficient tactic in synthetic organic chemistry for the diversity oriented synthesis of drug-like piperazine derivatives.

Ensembling three multicomponent reactions for the synthesis of a novel category of pseudo-peptides containing dithiocarbamate and N,X-heterocylic groups.

Consecutive multicomponent reactions have been applied for the synthesis of novel pseudo-peptides bearing dithiocarbamate and N,X-heterocyclic groups (X = S, O) in only one structure. The first multicomponent reaction includes the synthesis of dithiocarbamates using an amine or amino acid, CS2 and an electrophile. The second MCR is synthesis of Asinger imines using 2-chloroisobutyraldehyde, NaXH (X = S, O), ketone and ammonia. The final MCR is Ugi reaction to afford the corresponding three-dimensional pseudo-peptides. Various Asinger imines, carboxylic acids and isocyanides were applied in this protocol to provide diversities of pseudo-peptides in high to excellent yields.

Transition-Metal-Free Coupling Reaction of Dithiocarbamates with Indoles: C-S Bond Formation.

A one-pot three-component route for the direct introduction of dithiocarbamates into indoles using a C-H sulfenylation strategy mediated by molecular iodine is disclosed. Various indole derivatives including 1-methylindole, 2-methylindole, 3-methylindole, and 5-substituted indoles were applied successfully in this protocol to afford diverse indole-dithiocarbamates containing the dithiocarbamate group on the position two or three in good to high yields. The reactions do not require transition metals or disulfiram but use an environmentally benign solvent and simple commercially available starting materials.

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni's reagent.

A one-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates by the reaction of secondary amines, carbon disulfide and Togni's reagent is described. The reactions proceed in moderate to good yields. A similar reaction using a primary aliphatic amine afforded the corresponding isothiocyanate in high yield. A variable temperature NMR study revealed a rotational barrier of 14.6, 18.8, and 15.9 kcal/mol for the C-N bond in the dithiocarbamate moiety of piperidine, pyrrolidine, and diethylamine adducts, respectively. In addition, the calculated barriers of rotation are in reasonable agreement with the experiments.