TMSCl as a Rate-Accelerating Additive in Acylations of Amines with 5-(α-Amino-α′-hydroxy)methylene Meldrum Acids

Abstract

Aspects are presented of the acylation of amines, alcohols, and thiols with 5-(α-amino-α′-hydroxy)methylene Meldrum acids. We placed special emphasis on the acylation reaction of secondary amines with 5-(α-amino-α′-hydroxy)methylene Meldrum acids, which, because of their basicity, caused problems concerning salt formation with a Meldrum acid derivative. We found that secondary amines, which react at the slowest rate and give a poor yield with 5-(α-amino-α′-hydroxy)methylene Meldrum's acid, react quickly and with high yields with the same reagent in the presence 1 to 3 equivalents of TMSCl. Acylation with this derivative of Meldrum acid was optimized for such factors as reaction temperature, solvent polarity, and acidity of the environment. We have prepared a wide range of nonsymmetrical malononic acid diamids, esters, and thioesters of malonamic acid.

GRAPHICAL ABSTRACT

Keywords:

• Acylation
• amides
• decarboxylation
• enols
• ketens

ACKNOWLEDGMENT

This scientific work was financed from Funds for Science in 2010–2011 as Research Project NN204 088338.

Notes

^a Equimolar amount of reagent.

^b 2,5 eq of TFA was added.

^c Reaction mixture was saturated with HCl.

^d Excess of 1a was used.

Solvents A = DCM; B = benzene; C = dioxane, D = toluene, E = ethylbenzene.

Note. Solvents D, toluene; E, ethylbenzene; F, acetonitrile.