Preparation of 3-(trimethylsilanyl)propynoic acid N - (hydroxyalkyl)amides

New 3-(trimethylsilanyl)propynoic acid N -(hydroxyalkyl)amides were synthesized by the reaction of silyl-protected aminoalcohols with 3-(trimethylsilanyl)propynoyl chloride in high yields. The reaction of unprotected ethanolamine with 3-(trimethylsilanyl)propynoyl chloride caused N,O-bisacylation and the formation of 2-[3-(trimethylsilanyl)propynoyl)aminoethyl 3-(trimethyl-silanyl)propynoate.


Introduction
Amides of propynoic acid feature a variety of pharmacological profiles; [1][2][3][4][5][6][7][8] they have been used for the synthesis of rapamycin, 9 an immunosuppressant, and they serve as building blocks in organic chemistry, in particular, for the formation of heterocyclic systems which may be of special interest as biologically active compounds.
Silicon-substituted propynoic acid amides have received little attention.3-(Trimethylsilanyl)propynoic acid N-benzylamide has been prepared from lithiated 2-propynoic acid amide and chlorotrimethylsilane; its reaction with arylisocyanates in the presence of triethylamine has been reported to afford Z-trimethylsilydenehydantoin. 10 Previously, we have described the synthesis of 3-(trimethylsilanyl)propynoic acid N,Ndialkylamides, 11,12 their fragmentation under electron impact 2 and the determination of their basicity by an IR method. 13Furthermore, the reaction of trimethylsilanyl-and tert-butylpropynoic acid N,N-dialkylamides with triethylgermyllithium leads to the corresponding triethylpropynoyl-germanes in high yields. 14he goal of this investigation is the synthesis of new amides of 3-(trimethylsilanyl)propynoic acid containing an N-hydroxyalkyl group by the reaction of 3-(trimethylsilanyl)propynoyl chloride 4)] and 1,3-diamino-2-propanol 5.The target amides may be of interest as biologically active compounds and as the starting material, for example, for the synthesis of acetylenic oxazolines.

Results and Discussion
The investigation of the reaction of 3-(trimethylsilanyl)propynoyl chloride (1) with ethanolamine (2) revealed the influence of the reaction conditions: (1) The ratio of reactants employed, (2) the order and rate at which the reactants were mixed, (3) the nature of the base used and its impact on the type of products formed.

Scheme 1
Employing ethanolamine as reactant and base (i.e.carrying out the reaction of 1 and 2 at the ratio 1:2) in CHCl 3 or Et 2 O afforded a mixture of products: amidoester 6, 3-(trimethylsilanyl)propynoic acid N-(2-hydroxyethyl)amide (7), and propynoic acid N-(2-hydroxyethyl)amide (8) (Scheme 2).The reaction mixture was analyzed by IR and 1 H NMR spectra with reference to the spectra of the individual products (vide infra).Amide 8, which is presumed to be formed upon heterolysis of the Si-C sp bond in amide 7, was isolated after column chromatography on Al 2 O 3 .

Scheme 2
Carrying out the reaction by adding ethanolamine (2) to 3-(trimethylsilanyl)propynoyl chloride (1) favors the formation of amide 6.However, fast addition of 3-(trimethylsilanyl)propynoyl chloride (1) to ethanolamine (2) or inverting the order of mixing the reactants, i.e. adding 2 to a solution of 1 gave rise to a mixture of 6 and 8. Obviously, these conditions (probably due to the excess of base and presence of traces of water in ethanolamine) induce the heterolysis of Si-C sp bond of the presumed precursor of 8, the hydroxyalkyamide 7.
Low solubility of ethanolamine in organic solvents complicates the synthesis of amide 7 substantially.

Scheme 4
The 1 H NMR spectra of amides 6 and 7 display two sets of spectra with different intensities indicating the presence of the two rotational isomer (E and Z) due to hindered amide rotation. 16he

Experimental Section
General Procedures.IR Spectra of products 6-11 (KBr pellets or liquid films) were recorded on a Specord 75 IR instrument. 1 H, 13 C, and 29 Si NMR spectra of DMSO-d 6 and CDCl 3 solutions were recorded on a Bruker DPX-400 spectrometer, with (Me 3 Si) 2 O or cyclohexane as internal standards.1,4-Dinitroethylenediamine (EDNA) was used as a solution in THF (0.005 M).

3
Scheme 3 1 H NMR spectrum of 11 displays six NCH 2 group signals, three NH signals and three Me 3 Si group signals.This reflects the presence of three amide rotamers (EE, EZ, and ZZ) and was confirmed by a shift of the signal positions upon heating to 60 °C in CDCl 3. Heating a DMSO-d 6 solution of 11 to 120 °C brought about coalescence of the multiple signals.Furthermore, the diastereotopic protons of the NCH 2 groups give rise to an additional splitting pattern.In conclusion, it has been shown that O-silyl protected aminoalcohols are required (with one exception) to accomplish the selective N-acylation with 3-(trimethylsilanyl)propynoyl chloride furnishing 3-(trimethylsilanyl)propynoic acid N-(hydroxyalkyl)amides.