Margarita Tlahuextl

Chlorination reactions of ephedrines revisited. Stereochemistry and functional groups effect on the reaction mechanisms

The stereochemistry of the chlorination reactions with SOCl2 of free ephedrine and pseudoephedrine and their hydrochlorides, oxamides and sulfonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (S N2 mechanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (S Ni mechanism). Chlorination reactions in all threo isomers and derivatives hydrochlorides, oxamides or sulfonamides gave the same ratio of erythro (40%) and threo isomers (60%) (SN1 mechanism). Treatment of the isomeric mixture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydrochloride in DMSO with HCl changes the isomeric ratio, increasing the erythro isomer content (65%). Using the erythro ethanolamines it is possible to arrive stereoselectively at the erythro chloroamines if the compound is previously tosylated or converted to the amide, or to the threo chloroamines if the compound is directly chlorinated with SOCl2.

1 H, 13C, 15N, 2D and variable temperature NMR study of the role of hydrogen bonding in the structure and conformation of oxamide derivatives

The structure and conformation of N,N′-bis[(2-hydroxy)phenyl]oxamide (1); N,N′-bis[(2-methoxy)-phenyl]oxamide (2); N,N′-bis(phenyl)oxamide (3); N,N′-bis[(1R,2S)-(–)-norephedrine]oxamide (4); N,N′-bis[(1R,2R)-(–)-norpseudoephedrine]oxamide (5); N-[(2-hydroxy)phenyl]methylamide (6); N-[(2-methoxy)phenyl]methylamide (7); N-phenylmethylamide (8); N-[(–)-norephedrine]-methylamide (9) and N-[(–)-norpseudoephedrine]methylamide (10) were unambiguously established by 1H, 13C, 15N, 2D and variable temperature NMR spectroscopy. A careful NMR investigation of the conformational behaviour in these systems was relevant. It has been found that the dicarbonylic group in compounds 1–5 has a trans geometry, stabilized by intramolecular hydrogen bonding and that they possess a C2 axis. Compounds 1 and 2 are planar and compounds 1, 2, 4 and 5 present the amidic proton coordinated by two oxygen atoms.

Addition reactions of protonic reagents to optically active 2-phenyl-1,3,2-oxazaborolines

Abstract The addition reactions of water and methanol to (4R,5S)-4-methyl-2,5-diphenyl-1,3,2-oxazaboroline 1 (derived from (+)-norephedrine), (4R,5S)-(+)-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaboroline 2 (derived from (+)-ephedrine) and to (4R,5R)-(+)-3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaboroline 3 (derived from (+)-pseudoephedrine) were studied. The reactions gave the corresponding (N–B)-phenyl(2-aminoethoxy)boronic acids (4–6) or methyl esters (7–9). In 4 and 7 the boron atom is a stereogenic center, therefore two diasteromeric derivatives are expected. In compounds 5, 6, 8 and 9 both nitrogen and boron atoms are stereogenic centers and four diasteromers are possible. The structures of the addition products have been established by 1H-, 11B- and 13C-NMR, and that of compound 6 by X-ray diffraction analysis. The reactions with methanol gave only one isomer (7–9). The reaction of 1 with water afforded both boron epimers (50/50 ratio). The reaction of 2 with water observed at −50° showed both B-epimers in 80/20 ratio, whereas the same reaction with 3 gave only one isomer. In all cases the main isomer has the N-methyl trans to the C-methyl group and the B-phenyl cis to the N-methyl group. The X-ray diffraction molecular structure of compound 6 [(4R,5R)-(+)-3,4-dimethyl-2,5-diphenyl-2-hydroxy-1,3,2-oxazaborolidine], confirmed the structure assignment made from the NMR data. Addition reactions to 1,3,2-oxazaborolines are an efficient method to introduce stereoselectively functional groups to boron atom in order to obtain new boron heterocycles.

Three-center intramolecular hydrogen bonding in oxamide derivatives. NMR and X-ray diffraction study

This contribution describes the synthesis and structural investigation of the symmetric and non-symmetric oxamides N,N′-bis(2-hydroxyphenyl)oxamide 1, N,N′-bis(5-tert-butyl-2-hydroxyphenyl)oxamide 2, N,N′-bis(3,5-dimethyl-2-hydroxyphenyl)oxamide 3, N,N′-bis(2-hydroxybenzyl)oxamide 4, N,N′-diphenethyloxamide 5, N-(2-hydroxyphenyl)-N′-(2-methoxyphenyl)oxamide 6, N-(2-hydroxyphenyl)-N′-phenethyloxamide 7, (1S,2R)-(–)-N-(2-hydroxyphenylcarbamoylcarbonyl)norephedrine 8, (1R,2S)-(–)-N-(2-hydroxyphenylcarbamoylcarbonyl) 9, ethyl N-(2-hydroxyphenyl)oxalamate 10 and ethyl N-(2-methoxyphenyl)oxalamate 11. The structures were established by 1H, 13C, 15N and variable temperature NMR spectroscopy. Compounds 1–4 and 6–11 are stabilized by intramolecular three-center hydrogen bonding between the amide proton and two oxygen atoms. The 1H NMR Δδ/ΔT value of the amide proton correlates with the 15N NMR chemical shift. The X-ray diffraction molecular structures of 1 and 11 showed a planar conformation with trans configuration in the solid state, corresponding to the preferred conformation found in solution.

Intramolecular hypervalent CO⋯S interactions in a series of 1,3-benzothiazole derivatives

Seven compounds derived from 2-(4-chlorophenoxy)-2-methylpropionic acid and 2-aminobenzothiazole, 2-amino-6-methylbenzothiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-ethoxybenzothiazole, 2-amino-6-chlorobenzothiazole, 2-amino-6-nitrobenzothiazole, and 2-amino-6-(methylsulfonyl) benzothiazole have been prepared and structurally characterized. This set of 1,3-benzothiazole derivatives (1–7) has been studied by means of elemental analysis, mass spectrometry, IR, NMR (1H, 13C) spectroscopy, and single-crystal X-ray diffraction analysis. This work focuses on the description of the hypervalent contacts (CO⋯S, S⋯S), hydrogen bonds Y–H⋯X (Y = O, N, C; X = O, N, Cl, π) and van der Waals contacts (Cl⋯π, S⋯π, H⋯H) that are found to be the driving forces for the supramolecular arrangements present in the crystal structures.

Do spiroarsoranes exhibit polytopal equilibrium in solution

The spiroarsoranes 5-phenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane (6), (3R,8R)-3,8-dimethyl-5-phenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane (7), (2S,7S)-2,7-dimethyl-5-phenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane (8), and (3S,8S)-3,8-dimethyl-(2R,7R)-2,5,7-triphenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane (9) were prepared by reaction of phenylarsonic acid and the correspondig amino alcohol. The presence of polytopal Delta left arrow over right arrow Lambda equilibrium in 6-9 was demonstrated by HPLC and NMR studies. NBO computations at the MP2/6-31+G(2d,2p) level indicate that methyl substitution in C2 or C3 of the oxazarsolane ring determines the predominance of Delta or Lambda stereoisomers. GIAO B3LYP/6-311++G(2d,2p) computations were used to assign experimental (1)H and (13)C NMR spectra.

Syntheses and structural studies of hexa- and pentacoordinated Zn complexes derived from 2-(aminomethyl)benzimidazole and water

AbstractThe complexes trans-bis[2-(aminomethyl)-1H-benzimidazole-κ2N′,N″]diaquazinc(II) dichloride dihydrate 1 and trans-bis[2-(aminomethyl)-1H-benzimidazole-κ2N′,N″]aquazinc(II) dichloride dihydrate 2 were synthesized selectively by the promotion of O–H···Cl hydrogen bond interactions. The hexacoordinated complex 1 was synthesized at pH 4.5. The dilution of 1 in deionized water produced the pentacoordinated complex 2. NMR and vibrational spectroscopies corroborated the presence of these compounds. Moreover, mass spectrometry and thermogravimetric (TGA) studies demonstrated that chloride ions and crystallization water molecules are essential for the stabilization of 1 but not for complex 2. X-ray diffraction crystallography studies indicated that the presence of two water molecules bonded to the Zn atom elongated all of the coordination bonds. The incidence of a network of hydrogen bond interactions compensates for the unstable hexacoordination. Natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) studies of the crystal structures of 1 and 2 were used to explain the nature of the coordination bonds and the complexes’ stability .

Synthesis and structure of Zn(II) and Cu(II) complexes derived from 2-(aminomethyl)benzimidazole and glycine.

Reactions of 2-(aminomethyl)benzimidazole di-hydrochloride (1·2HCl) and glycine with 3Zn(OH)2·2ZnCO3 or Cu(OAc)2·H2O led to the synthesis of the quaternary coordination complexes 2 and 3. X-ray diffraction showed that these complexes are composed of 2a = [Zn(L)Cl(L′)] and 2b = [Zn(L)(H2O)2(L′)], and of 3a = [Cu(L)(H2O)0.25Cl(L′)] and 3b = [Cu(L)(H2O)1.5(L′)], respectively, where L = 2-(aminomethyl)benzimidazole and L′ = glycinate. Zn(II) in 2a has an intermediate geometry between a square-pyramid and a trigonal bipyramid structure. However, the geometry about the metal ion of units 2b, 3a, and 3b is distorted octahedral. Moreover, the supramolecular structures for 2 and 3 were assembled through N–H⋯O and O–H⋯Cl hydrogen bonds. In these complexes, H2O and N–H groups serve as proton donors, whereas chloride and C=O groups serve as proton acceptors. Also π–π stacking interactions between aromatic rings contribute to the stabilization of the supramolecular structure of 2 and 3. The Zn and Cu complexes were studied by infrared and Raman spectroscopy, which indicated that 2 and 3 have similar molecular structures in the solid state. Ultrasound activation at the end of the reaction was necessary to yield 2. Graphical Abstract