Francisco Sánchez-Viesca

Theoretical Study of Intramolecular, CHX (X = N, O, Cl), Hydrogen Bonds in Thiazole Derivatives†

CH [Formula: see text] X (X = N, O, or Cl) hydrogen bonds formed intramolecularly in 2-methyl-4-(2-chloro-4,5-dimethoxyphenyl)thiazole (Ia), 2-amino-4-(2-chloro-4,5-dimethoxy phenyl)thiazole (Ib), 2-amino-4-(2,4,5-trimethoxyphenyl)thiazole (Ic), and 2-methyl-4-(2,4,5-trimethoxyphenyl)thiazole (Id) were studied by means of all-electron calculations performed with the B3LYP/6-311++G(d,p) method. Computed ground states, in the gas phase, show the presence of a single H-bond, CH [Formula: see text] Cl, in each Ia and Ib moiety, and two H-bonds, CH [Formula: see text] N and CH [Formula: see text] O, for each Ic and Id molecule. H [Formula: see text] Cl, H [Formula: see text] N, and H [Formula: see text] O distances are shorter than the sum of the X and H van der Waals radii. H-bond energies of ≅2.0 kcal/mol were estimated for Ia and Ib and ≅4.0 kcal/mol for Ic and Id. These results agree with those of the theory of atoms in molecules, since bond critical points were found for these H [Formula: see text] X bonds. Finally, the chemical shifts in the (1)H NMR were calculated by the GIAO method; in Ia and Ib they are merely due to the different topological positions of the H atoms. But in Ic and Id the shifts of H [Formula: see text] N and H [Formula: see text] O have signatures of H-bond formations.

Flat versus twisted rotamers of 2,4-­disubstituted thiazoles: the effect of intermolecular hydrogen bonds

In the title compounds, 2-amino-4-(2-chloro-4,5-dimethoxyphenyl)-1,3-thiazole, C(11)H(11)ClN(2)O(2)S, (I), and 4-(2-chloro-4,5-dimethoxyphenyl)-2-methyl-1,3-thiazole, C(12)H(12)ClNO(2)S, (II), the dihedral angles between the thiazole moiety and the chloroaryl group are 51.61 (10) and 8.44 (14), respectively. This difference is a consequence of intermolecular hydrogen bonds forcing the stabilization of a twisted rotamer in (I). Substitution of the amino function by a methyl group precludes these contacts, giving a flat rotamer in (II).

4-(4-bromophenyl)-2-methyl-1,3-thiazole.

In the structure of the title compound, C(10)H(8)BrNS, the dihedral angles between the planes of the thiazole and aryl rings, viz. 4.2 (6) and 7.5 (6) degrees for the two independent molecules, are consistent with insignificant molecular perturbation by the weak intermolecular contacts. The molecules are close to being related by a non-crystallographic inversion centre, with C-H.pi and pi-pi intermolecular interactions observed.

On the Baeyer-Emmerling Synthesis of Indigo

The first indigo synthesis is of interest since at that time the structure of indigo was unknown. So, there was not target molecule but a blurred target: synthesize a blue dye that by oxidation gives isatin. Thus, this synthesis stands between chemical insight and good luck. An unexpected fact was the formation of an unwanted coloured compound (indigo red) besides of indigo blue. However, the undesired compound resulted later to be beneficial according to Chinese medicine and now is used in Cancer Treatment. We update this synthesis providing formulas, systematic nomenclature and reaction mechanisms which are absent in the original communications. Critical comments are also given.

An Autogenic Electromeric Effect as Inductor of an Abnormal Polarization in Pyridine N-Oxide

Nitration of pyridine N-oxide gives 4-nitropyridine N-oxide. This is an abnormal nitrone reactivity involving an electronic back-donation. However, the textbooks treat this result in a very brief way, without any insight. Which are the experimental antecedents of this reaction? What theory was proposed to explain them? What reactivity is overturned by these proposals? How theory and practice can come to agree on this subject? All these questions will be treated and answered in this communication.

Efecto electromérico autógeno en el N-óxido de piridina y su nitración

Linton found out that the dipole moment of pyridine N-oxide is appreciably smaller than the expected theoretical value. Thus, he postulated the contribution of three ‘excited structures’, with a negative electric charge at the 2-, 4- and 6-position. However, a typical electrophilic substitution such as nitration, afforded only the 4-nitro derivative. This discrepancy between theory and experiment prompted us to study the pyridine N-oxide physical properties, since its reactivity is derived from them. Besides, these negative charged rings require an unexpected polarization and a reaction mechanism must be provided. We propose intermolecular induced polarization as a viable path. We uncovered that only one of the three structures before mentioned is supported by the observed reactivity and by 13C nuclear magnetic resonance data. On rejecting 2 of the Linton’s ‘excited structures’, we have explained the regioselectivity found in pyridine N-oxide nitration.

Impedimento eléctrico y otros factores en la nitración de la 2-aminopiridina

The different isomer yields observed in many aromatic electrophilic substitution reactions can be explained by steric hindrance. However, this is not the case when there are drastic differences in the reaction yields of the isomeric products obtained. This is generally due to the presence of other factors, for instance, electric rejection between two positive charges in the reaction stage. Thus, a very important point to bear in mind is electric hindrance, a new theoretical concept. We have taken as an example 2-aminopyridine nitration. We provide an extended theory on this subject, which is in accordance with the observed regiochemistry and with the reaction yields of the isomeric products obtained. Dipole moments were also taken into account. We discuss too the 2-nitraminopyridine rearrangement in acidic medium. The theoretical discussion is also in agreement with reported trans-nitration experimental results. Our proposals were also contrasted with the findings from thermolysis and photolysis carried out with 2- nitraminopyridine.