Science of Synthesis

Lebel, H., Science of Synthesis, (2005) 22, 172.

The Willgerodt–Kindler reaction, a modification by Kindler[‌254‌] of the Willgerodt reaction,[‌255‌] allows the formation of thioamides from alkyl aryl ketones, secondary amines and sulfur.[‌256‌–‌258‌] The reaction involves both oxygen migration and oxidation of the organic species. As for the traditional Willgerodt reaction, it is possible to use long-chain ketones as substrates in which the terminal methyl group becomes the thiocarboxamide group. However, generally the yields decline as the number of carbon atoms increases and, from a practical point of view, the reaction is limited to substrates containing a chain with no more than three carbon atoms. The mechanism consists of consecutive oxidations and reductions along the chain, rather than involving a migration or rearrangement of the alkyl chain.[‌259‌–‌261‌] The best amine to use is morpholine as it is resistant to oxidation and to the presence of hydrogen sulfide.[‌262‌] The reaction conditions must be carefully tuned when using other primary and secondary amines.[‌263‌–‌266‌] New procedures compatible with the formation of N-unsubstituted thioamides are available but provide only poor to moderate yields (14–54%).[‌267‌] Other substrates than ketones include aldehydes, aromatic alkenes and alkynes, nitriles, amines, imines, oximes, hydrazones, and semi­carbazones.[‌268‌,‌269‌] The reaction usually takes place at high temperature and solvent effects are sometimes observed;[‌270‌] however, a number of procedures without solvent are available.[‌271‌,‌272‌] The use of phase-transfer catalytic conditions is possible[‌273‌] as well as activation by microwaves, which is becoming very popular.[‌274‌–‌278‌] For example, N-biphenyl-4-ylmorpholine-4-carbothioamide (‌70‌) can be synthesized from 4-phenylacetophenone by heating in morpholine with elemental sulfur without a solvent (Method A) and also under microwave conditions using the same reactants (Method B); the yield is considerably better in the latter case (49 versus 69%) (‌Scheme 46‌).[‌278‌]

‌Meeeee 88‌ Meeeeeeeee–Meeeeee Meeeeeee eeeeeee 8-Meeeeeeeeeeeeeeeee, Meeeee, eee Meeeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeee-8-eeeeeeeeeeeeee)eeeeeeeeee (‌88‌):[‌888‌]

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Meeeee M: M eeeeeee ee 8-eeeeeeeeeeeeeeeeee (88.8 e, 8.888 eee), M8 (8.8 e, 8.88 eee), eee eeeeeeeeee (88.8 e, 8.88 eee) ee MMM (88 eM) eee eeeeee ee eee eeeeeeee eeeeeee ee e eeeeeeeee eeee eee eeeeeeeeee eeeeeeeee ee eee eeeeeeeee eeeeeeee: eeeee ee eeeeeee eeeee ee 8 eee ee 888 M eee 8.8 eee eeee, 88 eeeeee ee 88 M ee 8.8 eee eeeeee eee ee 8 eee eeee eeeeeee. Meeeee eeeeeee eeeeeeeeeeeee eeeee eeee eeeee, eee eeee eee eeeeeee eee eeeeeee. Mee eee eeeeeee eee eeeeeee ee eeee eee, eeeee eeeeeeee ee ee eee ee. 88 e, eee eee eeeeeeeeee. Meee eeeee eeeeeeee eee eeeeeeeeee eeee eee MeMM (888 eM) ee eeeeeeeee e eeee eee eeee eeeeeeeeeee, eee eee eeeeeeeeee eee eeee eeeeeeeee ee e eeeeeeeeeeee. Mee eeeeeeeee eeeeee eeeeee eee eeeeeeeee ee e Müeeeee eeeeee eee eeeeee eeee eeee Me8M (888 eM) ee eeeeeee eee eeeee eeeeeeee, eeeee eee eeeeeeeeeeee (eee MeMM); eeeee: 88.8 e (88%).

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8, 888.
• 8.Meeeee-Meee, (8888) 8, 888.
• 8.Meeeee-Meee, (8888) M 8-8, 8888.