A study of the Willgerodt–Kindler reaction to obtain thioamides and α-ketothioamides under solvent-less conditions (original) (raw)
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Tetrahedron, 2019
A simple method for the synthesis of thioamide derivatives in DMSO at room temperature and at 120 C has been developed. Total 27 compounds were prepared under both conditions via a one-pot, three component reaction between substituted aromatic aldehydes, elemental sulfur powder, and cyclic secondary amines. By optimizing the mole ratio of sulfur powder and amines, we have successfully carried out Willgerodt-Kindler reaction of aromatic aldehydes at room temperature. At 120 C, it is catalyst free reaction with lower reaction time whereas at room temperature, due to the additional amine molecule, Willgerodt-Kindler reaction of aromatic aldehydes is successfully carried out at room temperature. On gram-scale, the reaction is successfully attempted under both conditions with good yields.
International Journal of Biological and Chemical Sciences, 2014
Montmorillonite K-10 was used in the acid catalysis of the Willgerodt-Kindler's reaction (WK) under microwave heating for synthesis of thiobenzamides. Yields of 67% and 43% for the synthesis of morpholin-4yl (phenyl) methanethione (1) and [4-(dimethylamino) phenyl] (morpholin-4-yl) methanethione (2) respectively, showed that the mixture (aldehyde, sulfur, morpholine and K-10) is quite suitable for this reaction. This enables to deduct that the conditions of acid catalysis with the K-10 are favourable to the WK's reaction of carbonyl compounds. Furthermore, yields of 81% and 74% respectively for the synthesis of thioamides 1 and 2 in basic catalysis with 4-methylmorpholine allows to confirm that this reaction is more advantageous in basic catalysis. The structures of thioamides synthesized were characterized and confirmed by spectroscopy Infrared (IR), nuclear magnetic resonance (1 H and 13 C NMR) and mass spectrometry (MS).
Convenient synthesis ofn-methylpyrrolidine-2-thione and some thioamides
Korean Journal of Chemical Engineering, 2003
The synthesis of thioamides and thiolactams, which are used as important organic intermediates, has attracted great attention. However, expensive reagents, severe reaction conditions and low yields of the target products made conventional methods inconvenient and economically infeasible. To overcome these disadvantages, we investigated a new process for synthesizing thioamides and thiolactams. We examined thermal reactions of CS 2 with Nmethyl-2-pyrrolidinone, formylamide, acetamide and N,N-dimethylformylamide, respectively. The results show that under optimum conditions N-methylpyrrolidine-2-thione and the corresponding thioamides can be obtained in good to excellent yields by the above thionation reactions.
ChemistrySelect, 2016
An efficient protocol was developed for the Friedel Crafts type thioarylation for the synthesis of aromatic/heteroaromaticthioamide derivatives from aryl isothiocyanates and electron rich aromatic/heteroaromatic molecules by employing the Lewis acid AlCl 3 and the less hazardous solvent cyclohex-ane at 708C. The developed protocol offers advantages over the previous methods such as use of stoichiometric amount of reactants/reagent, less toxic solvent, shorter reaction time and higher yields.
Organic Chemistry: Current Research, 2017
The Willgerodt-Kindler (WK) reaction of is one of most synthesis methods used to access the thioamides. The known to thioamides have made this reaction more attractive in catalytic synthesis methods. Heterogeneous catalysis acid with the montmorillonite K-10 applied to this reaction under activation microwave for the synthesis of phenyl (morpholino) methanethiones derivatives shows that the mixture (aldehyde, sulfur, morpholine and K-10) is not only appropriate, but optimizes the reaction. This solid catalyst was easily separated from the reaction mixture and was recycled at least twice (02) without any loss of activity. Operational simplicity, short reaction times, excellent yields and benign environmental conditions are other advantages of this protocol, thus respecting the principles of green chemistry. Among the thioamides synthesized, 4-(morpholine-4-carbonothioyl)benzoic acid (h) is a novel molecule which to our knowledge has never before been synthesized. We obtained it with a yield of 68%. In summary, we can be concluded that the heterogeneous catalysis acid conditions with the montmorillonite K-10 favourable to the Willgerodt-Kindler reaction for carbonyl compounds. The structures of thioamides synthesized were characterized and confirmed by highresolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) 1D and 2D (COSY, HSQC, HMBC).
The reductive alkylation of thioamides by Grignard reagents in the presence of Ti(OiPr)4 is the subject of a study involving 20 different substrates. The influence of various parameters has been evaluated, showing notably that the yields of this moderately efficient process can be improved in several cases by applying a slow addition of the Grignard reagent. The results presented in this contribution also provide new insight into the reactivity of the proposed key intermediates, namely, a metalated iminium species and, ultimately, an α-metalated amine. Interestingly, by control of the temperature and the amount of Grignard reagent engaged, the reaction can be directed toward the selective formation of the former titanium intermediate complex. This represents an extension of the original method, allowing the synthesis of various previously inaccessible substituted amines by subsequent addition of a nucleophilic reagent. This role can be played not only by organomagnesium compounds but also by alkyllithium reagents, alkyltitanium(IV) complexes, and lithium aluminum hydride. The properties of the α-metalated amine final intermediate have also been explored, demonstrating that this complex is a poor nucleophile but can act as a radical precursor, which is especially evidenced when the resulting radical species are stabilized. Overall, this chemistry thus proves unexpectedly rich and can plausibly lay the basis for the development of new applications in the future.
Kinetics of Thiazole Formation Using α-Halo Ketones and Thioamides
Oriental Journal Of Chemistry
The current approach involves the kinetic investigation of Thiobenzamide (TB) and cyclohexanone thiosemicarbazone (CTSC) in solution with 3-chloroacetylacetone(3-CAA). The study revealed a second-order rate constant with respect to both reactants, thioamide and an α-halo carbonyl compound. The energy of activation (Ea) was found to be Ea 48.8176 kJ/mol/K for thiobenzamide and 33.08692157 kJ/mol/K for Cyclohexanone thiosemicarbazone. The salt effect study showed the formation of ionic species during the reaction. The reactions were studied with respect to changes in dielectric constant using solvent systems like water-ethanol and water-isopropanol.