935-66-0

The invention relates to an alpha, beta-deuterated amine compound, a deuterated drug and a reduction deuteration method of a nitrile organic matter for synthesizing the alpha, beta-deuterated amine compound. The method is characterized by comprising the f

A simple and efficient system for the hydration and α-deuteration of nitriles to form amides, α-deuterated nitriles, and α-deuterated amides catalyzed by a single pincer complex of the earth-abundant manganese capable of metal-ligand cooperation is reported. The reaction is selective and tolerates a wide range of functional groups, giving the corresponding amides in moderate to good yields. Changing the solvent from tert-butanol to toluene and using D2O results in formation of α-deuterated nitriles in high selectivity. Moreover, α-deuterated amides can be obtained in one step directly from nitriles and D2O in THF. Preliminary mechanistic studies suggest the transformations contributing toward activation of the nitriles via a metal-ligand cooperative pathway, generating the manganese ketimido and enamido pincer complexes as the key intermediates for further transformations.

4-Methoxy-3-(trimethylphosphonio)phenolate was obtained from a regioselective addition of PMe3 to p-quinone monoacetal. This compound undergoes hydrogen isotope exchange with D2O or CD3CN, and is capable of catalyzing H/D exchange of CD3CN with substrates bearing weakly acidic hydrogens. It exhibits similar reactivity to phosphorus ylides for olefinations of aldehydes. A possible tautomerization between the phosphonium phenolate zwitterion and phosphonium ylide is proposed for the first time to rationalize the unique reactivity.

Intermolecular photoreactions of tetracyanobenzene (TCNB) with benzyl cyanide (BzCN), benzyl alcohol (BzOH) and various others were investigated in the solid state (cocrystal) and in solution. The new solid-state photocoupling reaction found for the cocrystal TCNB·BzCN, giving a stilbene derivative followed by the solution isomerization into an isoindole derivative, is a very limited reaction. On the other hand, its solution photocondensation to give products of the diphenylmethane type occurred quite generally, probably under acidic conditions. (C) 2000 Elsevier Science Ltd.

Several ring-substituted tert-butyl phenylperacetates (YC6H4CH2CO3But) and their deuterated versions (YC6H4CD2CO3But) were prepared (Y: p-OCH3, p-CH3, p-H, and p-NO2). Thermolyses at 80°C in CDCl3 showed excellent first-order kinetics. The rates have been measured as kYH × 104 and kYD × 104 s-1: 11.9 and 9.20 (p-OCH3), 2.64 and 2.22 (p-CH3), 1.06 and 0.93 (p-H), 0.164 and 0.156 (p-NO2). Hammett correlations were derived to yield ρYH+ = -1.17 and ρYD+ = -1.12. However, better Hammett plots were obtained with three points (p-OCH3, p-CH3, and p-H) showing ρYH+ = -1.35 and ρYD+ = -1.28. SDKIE was calculated as 1.293 (p-OCH3), 1.189 (p-CH3), 1.140 (p-H), and 1.051 (p-NO2), showing substantial substituent effects. Values of kYH/kYD for p-NO2 showed little temperature dependence. Hammett correlations and SDKIE were derived from the same kinetic entity that is the bond cleavage.

The secondary α deuterium and heavy atom kinetic isotope effects found for two different S(N)2 reactions suggest that the magnitude of secondary α deuterium kinetic isotope effects can be determined by the length of only the shorter (stronger) reacting bond in an unsymmetrical S(N)2 transition state rather than by the usual nucleophile-leaving group distance. Although this means the interpretation of these isotope effects is more complex than has been recognized, the results suggest that they can be used to determine whether an S(N)2 transition state is symmetrical or unsymmetrical.

The chemistry and energetics of the initial C-H bond cleavage step in dopamine β-monooxygenase (DβM, E.C. 1.14.17.1) catalysis has been explored using 1-(2-aminoethyl)-1,4-cyclohexadiene (CHDEA) as a probe. DβM has been previously shown (Wimalasena, K.; May, S. W. J. Am. Chem. Soc. 1989, 111, 2729) to catalyze the aromatization of CHDEA to phenylethylamme (PEA). We now report that the side chain hydroxylated product, 2-amino-1-(1,4-cyclohexadiene)ethanol (CHDEA-OH), is also a direct product of the DβM/CHDEA reaction. The PEA:CHDEA-OH product ratio is 2.7 at pH 5.2 and 37 °C for the DβM/CHDEA reaction. The side chain deuterated analog, 1-(2-amino-1,1-dideuterioethyl)-1,4-cylohexadiene, undergoes aromatization almost exclusively. The ring deutefated analog, 1-(2-aminoethyl)-3,3,6,6-tetradeuterio-1,4-cyclohexadiene, favors side chain hydroxylation 2.6 times over aromatization. The hexadeuterio derivative, 1-(2-amino-1,1-dideuterioethyl)-3,3,6,6-tetradeuterio-1,4-cyclohexadiene (CHDEA-d6), prefers aromatization 3.9 times. The apparent kinetic isotope effects of CHDEA-d6 are small, 1.8 for kcat and 1.3 for kcat/Km, suggesting that the initial C-H bond cleavage is only partly rate limiting in the CHDEA/DβM reaction analogous to the normal DβM hydroxylation reaction. The intrinsic isotope effects for the exocyclic and ring methylene hydrogens are estimated to be 9.9 and 7.0, respectively. The alteration of the product ratiodue to deuterium substitution suggests that activation energies of the initial C-H bond cleavage steps for the two pathways are similar. In contrast to the high thermodynamic driving force for the ring methylene hydrogen abstraction, the similar activation energies must be a consequence of the proximity and/or the relative orientation of the corresponding hydrogens of the enzyme-bound CHDEA with respect to the activated copper oxygen species.

Photolysis of 3-benzyl-3-chlorodiazirine and its deuterated homologues 3-chloro-3-(phenyldideuteriomethyl)diazirine and 3-chloro-3-((pentadeuteriophenyl)methyl)diazirine has been investigated by means of IR and UV-vis spectroscopy in argon and xenon matri

-

-