The concept of C-derivatization of amino acids via ß-and -chloro amino acids, obtained by selective free-radical chlorination in strong acid solution, is now extended to the -chlorination of an amino acid and in turn to the first synthesis of the optically active isomers of 3-methylproline. The exceedingly convenient synthesis does not affect the two asymmetric centers of the isoleucines employed as starting material; therefore it delivers the isomeric 3-methylprolines in optically pure form directly, without resolution. Moreover it concurrently establishes the absolute configuration of each of the four isomers. The J¡,¡ proton coupling values of the cis-trans isomers are practically identical.(10) Authors thank Mr. R. H. Redfield of these laboratories for performing several amino acid analyses.(11)
and dried over magnesium sulfate. Evaporation of the solvent in uacuo afforded 2.36 g. of a dark tar.This tar wm dissolved in the minimum amount of chloroform and introduced onto a column of neutral alumina. During elution with chloroform a broad yellow band, and above it a broad rust-colored band, developed on the column. The eluate collected before the yellow band reached the bottom of the column was concentrated in vacuo to give 0.658 g. of brown oil, which crystallized upon standing in the refrigerator. The yellow and rust-colored bands were eluted, and the eluates were concentrated to give brown oils which did not crystallize upon chilling. They were discarded.The brown crystals were placed in a sublimator and heated to 110" (0.025 mm.). The product sublimed as oily white crystals, which weighed 0.268 g. (12%). Since a sample of this sublimate darkened when allowed to stand in the air at room temperature, the remainder was kept refrigerated. A portion of this sublimate wm rinsed with several drops of ether in an attempt to remove the oily material.As soon as the oily sublimate began to crystallize, the sublimation was interrupted and the cold finger was cleaned. Sublimation then was resumed at 80" (0.025 mm.). This fractional sublimation did not effect removal of the oily material. One additional sublimation at 100" (0.025 mm.) gave slightly oily white crystals, m.p. 107-117" with previous softening, which were submitted for analysis.An infrared spectrum of the compound in a potassium bromide pellet had a band at 1638 cm.? (carbonyl absortion).The preparation of 5-carbethoxythieno[3,2-b]pyrrole (IIIb) is accomplished by condensation of 2-methyl-3nitrothiophene (I) with diethyl oxalate followed by stannous chloride reduction of the product, ethyl 3-nitrc-2thienylpyruvate (IIb), in an over-all yield of 4770. A similar procedure gives rise to 2,5-dicarbethoxythieno-[3,2-b]pyrrole (XIY) from 2-methyl-3-nitro-5-carbethoxythiophene (XII) in an over-all yield of 38%. Some typical electrophilic, aromatic reactions are carried out on these two thieno [3,2-b] pyrrole derivatives. Structures of the various substances are proposed on the basis of chemical and spectral data.
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