Discovery of a New Polymorph of 5-Methoxy-1H-Indole-2-Carboxylic Acid: Characterization by X-ray Diffraction, Infrared Spectroscopy, and DFT Calculations.

This study presents a new 5-methoxy-1H-indole-2-carboxylic acid (MI2CA) polymorph investigated by single-crystal X-ray diffraction, infrared spectroscopy, and density functional theory (ωB97X-D) calculations employing two basis sets (6-31++G(d,p) and aug-cc-pVTZ). The compound crystallizes in the monoclinic system, space group P21/c (a = 4.0305(2) Å, b = 13.0346(6) Å, c = 17.2042(9) Å, ß = 91.871(5)°, Z = 4). In the crystalline structure, the formation of cyclic dimers via double hydrogen bonds O-H⋯O between MI2CA molecules was observed. Interactions between the NH groups of the indole rings and the adjacent methoxy groups, as well as C-H⋯O contacts, significantly influence the spatial arrangement of molecules. The results from DFT calculations, including dimeric and trimeric structures, agree well with the experimental structural and spectroscopic data. Analysis of the infrared spectra confirms the conclusions drawn from X-ray diffraction studies and reveals differences between the IR spectra of the newly obtained polymorph and that reported earlier in the literature. This comprehensive study sheds some light on the MI2CA polymorphism and is important for a potential pharmacological applications of this compound.

Tricyclic Quaternary Ammonium Salts Derived from Cinchona Alkaloids.

Tricyclic systems with quaternary bridgehead nitrogen atoms are rare but an interesting class of compounds. Chiral quinuclidine derivative salts with fused five and six-membered rings (X-ray) were obtained via modification of Cinchona alkaloids. The ease of ring formation was dependent on its size, while even mild activation sufficed to close the five membered ring. On the other hand the systems with fused benzene and a six-membered ring formed atropisomers separated by a barrier of ca. 15 kcal/mol, whose interconversion was studied by DFT and NMR.

Monoimine derived from trans-1,2-diaminocyclohexane and ethyl glyoxylate: an intermediate in aza-Diels-Alder and Mannich reactions.

Novel enantiopure policyclic nitrogen heterocycles have been obtained in the diastereoselective aza-Diels-Alder or Mannich reaction of dienes with imine formed in situ from ethyl glyoxylate and (1R,2R)-diaminocyclohexane.

The role of free space in photochemical reactions in crystals at high pressure - the case of 9-methylanthracene.

The influence of pressure on the course of [4+4] photodimerization in crystals of 9-methylanthracene is presented. The studies were performed at 0.1 and 0.4 GPa. As a result of the reaction at high pressure, crystals of the pure product were obtained, which allowed for monitoring of the reaction until its completion. The initial increase in the unit-cell volume caused by the reaction under ambient conditions was reduced at high pressure due to the decrease in the void volume. Despite the smaller size of the void volume at high pressure, dimer molecules formed during the reaction changed the orientation of the monomer molecules in the crystal structure. The size of the voids above the terminal rings of the monomers correlates with the position of the terminal rings in the dimer. The reaction rate increased at high pressure, indicating that the decrease in the distance between adjacent monomers caused by pressure dominates over the decrease in the void volume. This distance is statistically constant as the reaction progresses, contrary to the reaction at ambient pressure.

Structural reasons for the formation of multicomponent products and the influence of high pressure.

(S)-(-)-1-Phenylethanaminium 4-(2,4,6-triisopropylbenzoyl)benzoate (S-PEATPBB) undergoes a photochemical reaction in its crystalline form upon UV irradiation and forms three different products: the first product is the result of a Yang cyclization with the participation of the δ-H atom of o-isopropyl (product D) and the second and third products are obtained via a Norrish-Yang reaction with the involvement of the γ-H atom of 2-isopropyl (product P) and 6-isopropyl (product Z). These products are formed in different proportions (D > P >> Z). The path and kinetics of the reaction were monitored step-by-step using crystallographic methods, both under ambient and high-pressure conditions. The reactivity of S-PEATPBB depends strongly on the geometry of the reaction centre and the volume of the reaction cavity. Due to the geometrical preferences making the cyclization reaction easier to proceed, product D dominates over the other products, while the formation of product Z becomes difficult or almost impossible at high pressure. The reaction proceeds with an increase of the unit-cell volume, which, suppressed by high pressure, results in a significant decrease of the reaction rate. The crystal lattice of S-PEATPBB shows high elasticity. The quality of the partially reacted crystal remains the same after decompression from 0.75 GPa to 0.1 MPa.

Monitoring structural transformations in crystals. 13. On photocyclization in 2,3,4,5,6-pentamethylbenzophenone, 1,3-diphenylbutan-1-one and 2,4,6-triisopropyl-4'-methoxybenzophenone.

The geometrical parameters governing the potential for the photocyclization reaction occurring in crystals of 2,3,4,5,6-pentamethylbenzophenone, C(18)H(20)O, (I), 1,3-diphenylbutan-1-one, C(16)H(16)O, (II), and 2,4,6-triisopropyl-4'-methoxybenzophenone, C(23)H(30)O(2), (IV), have been evaluated. Compound (IV) undergoes photocyclization but (I) and (II) do not, despite the fact that their geometrical parameters appear equally favourable for reaction. The structure of the partially reacted crystal of the photoactive compound, i.e. 2,4,6-triisopropyl-4'-methoxybenzophenone-3,5-diisopropyl-7-(4-methoxyphenyl)-8,8-dimethylbicyclo[4.2.0]octa-1,3,5-trien-7-ol (9/1), 0.90C(23)H(30)O(2).0.10C(23)H(30)O(2), (III), was also determined, providing structural evidence for the reactivity of the compound. It has been found that the carbonyl group of the photoactive compound reacts with one of the two o-isopropyl groups. The study has shown that the intramolecular geometrical parameters are not the only factors influencing the reactivity of compounds in crystals.

2-Oxo-2-phenyl-N-[(R)-1-phenylethyl]acetamide and N,N-dimethyl-2-(1-naphthyl)-2-oxoacetamide: possibility of Yang photocyclization in a crystal.

The crystal structures of 2-oxo-2-phenyl-N-[(R)-1-phenylethyl]acetamide, C16H15NO2, (I), and N,N-dimethyl-2-(1-naphthyl)-2-oxoacetamide, C14H13NO2, (II), were determined in an attempt to understand the reason for the lack of Yang photocyclization in their respective crystals. In the case of (I), the long distance between the O atom of the carbonyl group and the gamma-H atom, and between the C atom of the carbonyl group and the gamma-C atom, preclude Yang photocyclization. For (II), the deviation of the gamma-H atom from the plane of the carbonyl group and interactions between the naphthalene rings are regarded as possible reasons for the chemical inertia. The two independent molecules of (I) differ in their conformation. N-H...O hydrogen bonds link molecules of (I) into chains extended along the b axis.

rac-3-Benzoyl-2-methylpropionic acid and its organic salts: possibilities of Yang photocyclization in crystals.

The analysis of the crystal structures of rac-3-benzoyl-2-methylpropionic acid, C(11)H(12)O(3), (I), morpholinium rac-3-benzoyl-2-methylpropionate monohydrate, C(4)H(10)NO(+).C(11)H(11)O(3)(-).H(2)O, (II), pyridinium [hydrogen bis(rac-3-benzoyl-2-methylpropionate)], C(5)H(6)N(+).(H(+).2C(11)H(11)O(3)(-)), (III), and pyrrolidinium rac-3-benzoyl-2-methylpropionate rac-3-benzoyl-2-methylpropionic acid, C(4)H(10)N(+).C(11)H(11)O(3)(-).C(11)H(12)O(3), (IV), has enabled us to predict and understand the behaviour of these compounds in Yang photocyclization. Molecules containing the Ar-CO-C-C-CH fragment can undergo Yang photocyclization in solvents but they can be photoinert in the crystalline state. In the case of the compounds studied here, the long distances between the O atom of the carbonyl group and the gamma-H atom, and between the C atom of the carbonyl group and the gamma-C atom preclude Yang photocyclization in the crystals. Molecules of (I) are deprotonated in a different manner depending on the kind of organic base used. In the crystal structure of (III), strong centrosymmetric O...H...O hydrogen bonds are observed.

Monitoring photo-induced transformations in crystals of 2,6-difluorocinnamic acid under ambient conditions.

Several conditions need to be fulfilled for a photochemical reaction to proceed in crystals. Some of these conditions, for example, geometrical conditions, depend on the particular type of photochemical reaction, but the rest are common for all reactions. The mutual directionality of two neighbouring molecules determines the kind of product obtained. The influence of temperature on the probability of a photochemical reaction occurring varies for different types of photochemical reaction and different compounds. High pressure imposed on crystals also has a big influence on the free space and the reaction cavity. The wavelength of the applied UV light is another factor which can initiate a reaction and sometimes determine the structure of a product. It is possible, to a certain degree, to control the packing of molecules in stacks by using fluoro substituents on benzene rings. The crystal and molecular structure of 2,6-difluorocinnamic acid [systematic name: 3-(2,6-difluorophenyl)prop-2-enoic acid], C9H6F2O2, (I), was determined and analysed in terms of a photochemical [2 + 2] dimerization. The molecules are arranged in stacks along the a axis and the values of the intermolecular geometrical parameters indicate that they may undergo this photochemical reaction. The reaction was carried out in situ and the changes of the unit-cell parameters during crystal irradiation by a UV beam were monitored. The values of the unit-cell parameters change in a different manner, viz. cell length a after an initial increase starts to decrease, b after a decrease starts to increase, c increases and the unit-cell volume V after a certain increase starts to decrease. The structure of a partially reacted crystal, i.e. containing both the reactant and the product, namely 2,6-difluorocinnamic acid-3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid (0.858/0.071), 0.858C9H6F2O2·0.071C18H12F4O4, obtained in situ, is also presented. The powder of compound (I) was irradiated with UV light and afterwards crystallized [as 3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid toluene hemisolvate, C18H12F4O4·0.5C7H8] in a space group different from that of the crystal containing the in-situ dimer.

The crystal and molecular structure of sodium 4-(2,4,6-triisopropylbenzoyl)benzoate in terms of the photochemical behaviour of the anion.

Contrary to the known 4-(2,4,6-triisopropylbenzoyl)benzoate salts, di-µ-aqua-bis[tetraaquasodium(I)] bis[4-(2,4,6-triisopropylbenzoyl)benzoate] dihydrate, [Na2(H2O)10](C23H27O3)2·2H2O, (1), does not undergo a photochemical Norrish-Yang reaction in the crystalline state. In order to explain this photochemical inactivity, the intermolecular interactions were analyzed by means of the Hirshfeld surface and intramolecular geometrical parameters describing the possibility of a Norrish-Yang reaction were calculated. The reasons for the behaviour of the title salt are similar crystalline environments for both the o-isopropyl groups in the anion, resulting in similar geometrical parameters and orientations, and that these interaction distances differ significantly from those found in salts where the photochemical reaction occurs.

Monitoring structural transformations in crystals. 11. Yang photocyclizations--one type of reaction, but diversity of structural changes.

Structural changes proceeding in a crystal during the Yang photocyclization of the salt 6,6-diethyl-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate with (1S)-1-(4-methylphenyl)ethylamine were monitored by means of X-ray structure analysis. The course of the photoreaction was evaluated on the basis of the geometrical parameters for the pure reactant crystal. Variations in the cell constants, the product content, the geometry of the reaction centre, the orientation of molecular fragments and the geometry of hydrogen bonds were described and analyzed. It was found that the cell volume increased until 56% product content and decreased thereafter. The distance between the directly reacting C atoms was constant, approximately 3.0 A, until approximately 75% reaction progress. Analysis of the distance between atoms that would participate in the formation of the second (unobserved) enantiomorph excluded the formation of such an isomer. Molecular fragments varied their orientation during the photoreaction, and the largest change was observed for the carboxylate group despite its participation in strong hydrogen bonds. The geometry of the hydrogen bonds changed during the photoreaction. The largest change was 0.17 A for the D...A distance and 13 degrees for the D-H...A angle. A comparison of the intra- and intermolecular parameters for the studied salt with data for other compounds undergoing the Yang photocyclization in crystals revealed a diversity of structural changes brought about by this type of photochemical reaction.