A methodology to generate 2-thio- and 2-oxoimidazoles through an addition-cyclization-isomerization reaction of propargylcyanamides with thiol and alcohol nucleophiles is described. In general, the reaction sequence allows for the rapid formation of highly substituted 2-thio- and 2-oxoimidazoles in good to excellent yields.

General Experimental Methods Materials 4,4-Dimethylpentanoic acid was synthesized by Françoise Gregoire. Sample preparation NMR samples of 3-(trimethylsilyl)-propionic acid in water, dimethyl sulfoxide, methanol, ethanol, isopropyl alcohol, tert-butyl alcohol, tetrahydrofuran, and toluene were prepared with constant concentrations of 0.05 M. The acid was prepared by dissolving equivalents of sodium 3-(trimethylsilyl)-propionate and sodium bisulfate in water and ethanol. To ensure completion of the reaction, the mixture was evaporated to dryness under reduced pressure to remove the water and ethanol. The resulting sodium sulfate was filtered after dissolution in the dissolved deuterated solvent. The anion was prepared by dissolving sodium 3-(trimethylsilyl)propionate and 1.0 equiv. of tetrabutylammonium bromide in ethanol and evaporated to dryness under reduced pressure. The resulting mixture was taken up in each deuterated solvent and filtered from the residual sodium bromide. Spectral acquisition 1 H NMR spectra were acquired for all solvent samples at ambient temperature with either a 300 MHz or 600 MHz NMR spectrometer with signal lock on the deuterated solvent. The 1 H NMR peaks were referenced to known chemical-shift positions of the alcohols and/or TMS. Determination of for the trimethylsilyl, carboxyl, and carboxylate substituent One drop of ethyltrimethylsilane was added to 0.75 mL each of the target solvents, water, dimethyl sulfoxide, methanol, isopropyl alcohol, and tert-butyl alcohol. The 1 H NMR spectra of each sample were taken on a 300 MHz spectrometer. The resulting A 2 B 3 spectra were analyzed with gNMR to obtain the S3 vicinal coupling constant for use in determining for the trimethylsilyl substituent in the solvents of interest. 6 The value for the trimethylsilyl substituent in each target solvents was-0.37 indicating that the substituent was less electronegative than hydrogen with a reported value of-0.18. 6 The same procedure for propionic acid afforded a value for the carboxyl group independent of solvent of 0.39, which is the value reported by Altona. 6 For determination of for the carboxylate substituent, tetrabutylammonium propionate was prepared by mixing propionic acid with sodium hydroxide solution until the pH was neutral. One equiv. of tetrabutylammonium bromide dissolved in ethanol was then added and the mixture evaporated to dryness under reduced pressure to remove the ethanol. One drop of liquid was added to 0.75 ml of the deuterated solvents, water, dimethyl sulfoxide, methanol, tert-butyl alcohol, tetrahydrofuran, and toluene. The resulting mixture was filtered from the residual sodium bromide. The 1 H NMR spectra at 300 MHz for the ethyl vicinal coupling constant, converted to values for the carboxylate substituent, had more variation than for the unassociated acid being 0.44 in water, 0.43 in dimethyl sulfoxide, 0.35 in methanol, 0.35 in tert-butyl alcohol, 0.41 in tetrahydrofuran, and 0.27 in toluene. The value of 0.29 for the carboxylate group in water is reported by Altona...

The conformational equilibrium of 3-(dimethylazinoyl)propanoic acid (DMAPA, azinoyl ) N + (O -) has a weak pH-dependence in D 2 O, with a slight preference for trans in alkaline solutions. The acid ionization constants of the protonated amine oxide and carboxylic functional groups as determined by NMR spectroscopy were 7.9 × 10 -4 and 6.3 × 10 -6 , respectively. The corresponding value of K 1 /K 2 of 1.3 × 10 2 is not deemed large enough to provide experimental NMR evidence for a significant degree of intramolecular hydrogen bonding in D 2 O. Conformational preferences of DMAPA are mostly close to statistical (gauche/trans ) 2/1) in other protic solvents, e.g., alcohols. However, the un-ionized form of DMAPA appears to be strongly intramolecularly hydrogen-bonded and gauche in aprotic solvents.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.