Dl‐3.5.3′.5′‐Tetramethyl‐Thyronin

Abstract

dl-3.5.3′.5′-Tetramethyl-thyronin (II) wird, ausgehend von 2.6-Dimethylanilin, in 10 Stufen mit einer Gesamtausbeute von 5% d. Th. dargestellt. Seine Eigenschaften werden mit denen von dl-Thyronin, dl-Thyroxin, dl-3.5.3′.5′-Tetranitro-thyronin und entsprechend substituierten Thio-thyroninen verglichen

Electrophilic substitution in highly substituted diphenyl ethers

“…The number of protons is determined by dividing the total area under each of the peaks by the area corresponding to a single proton. -Hydroxy-3,5,2',6'-tetramethyldiphenyl Ether (1) and Its Methyl Ether ( 2) 4.86 (1) °The positions of the peaks are given in units. The number of protons, accurate to within ±5% of the whole numbers; are in parentheses.…”

“…Due to resonance forms such as 18, the bonds connecting the aryl rings via the ether oxygen in unhindered diphenyl ethers will have some double bond character. The effect of twisting such a single bond in a conjugated system away from coplanarity by steric forces may affect the spectrum in any of three ways: (1) no change in wavelength of the maximum but a decrease in the absorption intensity, caused by relatively small twists, (2) absorption maximum shifts to shorter wavelengths in addition to decreased absorption intensity, caused by larger twists than the first effect, (3) spectrum is similar to the sufn of the spectra of the component parts of the molecule on either side of the twisted bond; this effect occurs when the twist is large enough to almost completely eliminate interaction between the two portions of the molecule.18 Studies reported by Burawoy and Chamberlain,14 Dahlgard (13) L. L. Ingraham, "Steric Effects in Organic Chemistry," M. Newman, Ed., Wiley, New York, N. Y., 1956, 484.…”

“…Electrophilic substitution products of 4-hydroxy-3,5,2',6'-tetramethyldiphenyl ether (1) and its methyl ether (2) have been used as intermediates for the preparation of tetramethyl analogs of thyroxine. In this connection, Bruice, Kharasch, and Winzler in 1954 reported that nitration of 2 in acetic anhydride resulted in 4 '-nitro-4-methoxy-3,5,2', 6 '-tetramethyldiphenyl ether (3).…”

“…4 Later, Bielig and Lützel reported that bromination and chloromethylation experiments with 2 resulted in the derivatives 5 and 6 which are substituted in the 4' position of the phenoxy ring. 5 The product obtained by chloromethylation was converted to an amino acid derivative of 1 which was reported to be 7, the structural analog of thyroxine in which all of the iodines have been replaced with methyl groups. This product has since been used in several biological studies designed to determine the effect of methyl relative to that of other substituents on the thyroxine nucleus.6 More recently, Van Heyningen has brominated 1 in acetic acid and reported the 4'-bromo derivative 8.7 8This product was converted by metal exchange and carbonation to a carboxylic acid.…”

“…ture 9, has also been used in biological studies. 3 In none of the above cases did the authors offer structural proofs (1) This work was presented in part at the 142nd National Meeting of the American Chemical Society in Atlantic City, N. J., Sept 1962. (2) General Electric Space Sciences Laboratory, Valley Forge, Pa.…”