Search

Chlorination of o-cresol, m-cresol, and m-xylenol using sulfuryl chloride in the presence of a range of poly(alkylene sulfide)s and a Lewis acid (aluminum or ferric chloride) has been studied. The sulfur containing catalysts used led to the production of para-chlorophenols in high yields and higher para/ortho ratios than for reactions in the absence of such poly(alkylene sulfide)s. The effectiveness of the polymers was found to be dependent on the length of the spacer groups between the sulfur atoms. For example, polymers with shorter spacers provided high yields of 4-chloro-o-cresol (ca. 97%), while polymers with at least one longer spacer provided high yields of both 4-chloro-m-cresol (up to 94.6%) and 4-chloro-m-xylenol (up to 97.6%).

C30H25FN10S⋅C3H7NO, triclinic, P1̄ (no. 2), a = 10.9189(6) Å, b = 12.3898(7) Å, c = 13.9206(7) Å, α = 199.412(4)°, β = 110.024(5)°, γ = 105.904(5)°, V = 1631.17(17) Å3, Z = 2, R gt(F) = 0.0536, wR ref(F 2) = 0.1471, T = 296 K.

C25H17BrFN3S, triclinic, P1̄ (no. 2), a = 11.2926(6) Å, b = 11.5832(4) Å, c = 16.9974(9) Å, α = 109.211(4)°, β = 90.211(4)°, γ = 95.290(4))°, V = 2089.21(18) Å3, Z = 4, R gt(F) = 0.0580, wR ref(F 2) = 0.1797, T = 296 K.

Various poly(alkylene sulfide)s have been synthesized and used as catalysts to enhance the para-regioselectivity in chlorination of phenol and 2-chlorophenol using freshly distilled sulfuryl chloride in the presence of AlCl3 as an activator. Poly(alkylene sulfide)s having alternating spacers, one having three methylene groups and the second having three, six or nine methylene groups were the most para-regioselective catalysts in chlorination of both phenol and 2-chlorophenol. For example, chlorination of phenol and 2-chlorophenol in the presence of optimal examples of such poly(alkylene sulfide)s gave 4-chlorophenol and 2,4-dichlorophenol as the major products in 94.8 and 95.4% yields, respectively, compared with 75.4 and 55.0% yields in the absence of catalysts. In addition, double chlorination of phenol in the presence of poly(alkylene sulfide)s gave 2,4-dichlrophenol in up to 97.1% yield compared with only 58.6% in the absence of catalysts.

The complete molecule of the title compound, C16H12Cl4N2O4, is generated by a crystallographic centre of symmetry. In the crystal, N—H...O hydrogen bonds link the molecules into [010] chains featuring R 2 2(10) loops. The chains are cross-linked by short Cl...N contacts [3.224 (2) Å].

The complete mol-ecule of the title compound, C

The title compound, C

The mol-ecule of the title compound, C

C28H20FN3O2S, triclinic, P1̄ (no. 2), a = 9.1325(7) Å, b = 11.5184(9) Å, c = 11.6535(9) Å, α = 74.682(7)°, β = 84.253(6)°, γ = 76.720(6)°, V = 1149.68(15) Å3, Z = 2, R gt(F) = 0.0574, wR ref(F 2) = 0.1438, T = 296(2) K.

C28H23F2N3OS, monoclinic, I2/a (no. 15), a = 20.3481(8) Å, b = 10.2647(4) Å, c = 23.6975(11) Å, β = 105.317(5)°, V = 4773.8(4) Å3, Z = 8, R gt(F) = 0.0489, wR ref(F 2) = 0.1543, T = 296(2) K.

C23H16ClN5O, monoclinic, P21/c (no. 14), a = 10.0503(6) Å, b = 17.5265(9) Å, c = 22.8763(16) Å, β = 91.554(6)°, V = 4028.1(4) Å3, Z = 8, R gt(F) = 0.0748, wR ref(F 2) = 0.2274, T = 296(2) K.

C18H17N5O2, monoclinic, P21/n (no. 14), a = 20.3702(7) Å, b = 7.3482(2) Å, c = 23.2504(10) Å, β = 106.507(4)°, V = 3336.8(2) Å3, Z = 8, R gt(F) = 0.0571, wR ref(F 2) = 0.1507, T = 296(2) K.

The molecule of the title compound, C26H17ClFN3OS, comprises benzofuranyl (A), thiazolyl (B), pyrazolyl (C), chlorophenyl (D) and fluorophenyl (E) ring systems. Rings A–D are almost coplanar, as indicated by the twist angles between the ring pairs A/B, B/C and C/D of 7.6 (1), 4.7 (1) and 6.9 (2)°, respectively. Ring E is twisted by 73.2 (1)° from the plane through ring C. In the crystal, pairwise C—H...F interactions link the molecules into inversion dimers. Aromatic π–π interactions are also observed between rings A and E and between rings B and C for neighbouring pairs of molecules related by inversion symmetry. Taken together, the weak interactions generate [010] chains.

The title molecule, C22H21FN8O, comprises fluorophenyl (A), methyltriazolyl (B), methyltriazolyl (C) and tolyl (D) rings. The twist angles between the planes through neighbouring ring pairs A/B, B/C and C/D are 45.0 (1), 9.4 (1) and 43.2 (1)°, respectively. Intermolecular π–π interactions between rings A and C and between B and D propagate the structure in the [010] direction and weak C—H...O interactions also occur.

The asymmetric unit of the title compound, C20H17N5O, consists of two independent molecules. The molecules comprise tolyl (A), triazolyl (B), pyrazolecarbaldehydyl (C) and phenyl (D) groups. The angles between the planes through neighouring rings A/B, B/C and C/D are 39.1 (1), 6.0 (1) and 12.6 (1)°, respectively, for the first molecule and 46.0 (1), 4.6 (1) and 8.5 (2)°, respectively, for the second. In the crystal, the two independent molecules form dimers linked by four C—H...O hydrogen bonds with each O atom accepting two such links.

The title compound, C27H17ClFN3O2S, comprises chromonyl (A), thiazolyl (B), pyrazolyl (C), chlorophenyl (D) and fluorophenyl (E) rings with twist angles between the planes of adjacent rings pairs A/B, B/C, C/D and C/E of 14.1 (1), 18.2 (2), 1.3 (1) and 4.9 (1)°, respectively. The crystal structure is characterized by a range of intermolecular interactions including C—H...F, C—H...Cl and C—H...O contacts. Aromatic π–π stacking between chromonyl groups and chlorophenyl groups [centroid–centroid separations = 3.7170 (16) and 4.017 (2) Å, respectively] lead to columns of molecules propagating parallel to the [100] direction.

The title compound, C23H17ClFN5OS, comprises fluorophenyl (A), furanyl (B), pyrazolyl (C), methylthiazoyl (D) and chlorophenyl (E) rings. The B–C–D–E linked ring system is close to planar with the dihedral angles B/C, C/D and D/E being 7.6 (1), 3.4 (1) and 8.4 (1)°, respectively. The fluorophenyl group is almost perpendicular to the pyrazoyl ring, as indicated by an A/C twist angle of 79.4 (1)°. In the crystal, inversion dimers linked by pairs of C—H...S contacts are observed.

C23H17F2N5OS, monoclinic, P21/c (no. 14), a = 5.2272(4) Å, b = 26.7398(15) Å, c = 15.2645(10) Å, β = 97.726(7)°, V = 2114.2(2) Å3, Z = 4, R gt(F) = 0.0547, wR ref(F 2) = 0.1371, T = 296(2) K.

In the title solvate, C28H20ClN7O2S·C3H7NO, the main molecule consists of chlorophenyl (A), thiadiazolyl (B), pyrazolyl (C), phenyl (D) and indolyl (E) rings, with twist angles between neighbouring rings A/B, B/C, C/D and D/E of 32.6 (1), 14.8 (1), 60.8 (1) and 20.1 (1)°, respectively. The dimethylformamide solvent molecule accepts an N—H...O hydrogen bond from the indole group. In the extended structure, molecules related by 21 screw axes are stacked in the [001] direction to form columns linked by weak C—H...O interactions.

In the title hydrate, C17H18N6O·H2O, the twist angles between the least-squares planes of the pyrolyl/methyltriazolyl/tolyl groups are 11.4 (2) and 7.9 (1)°, respectively. In the crystal, centrosymmetric tetramers (two organic molecules and two water molecules) are linked by N—H...O and O—H...O hydrogen bonds. Weak aromatic π–π stacking interactions between the triazolyl rings [centroid–centroid separation = 3.6422 (10) Å] link the tetramers.

The asymmetric unit of the title compound, C17H13N5O, comprises four independent molecules (A–D). The respective interplanar angles between the phenyl/oxadiazole/methyltriazole/phenyl rings for the four independent molecules are A 8.8 (2), 13.0 (2), 22.5 (2)°; B 6.3 (2), 8.9 (2), 29.0 (1)°; C 4.0 (2), 10.0 (2), 24.5 (2)°; D 3.5 (2), 10.1 (2), 27.2 (2)°. In the crystal, molecules form two separate stacks parallel to the b-axis direction: one consists of A and D molecules, and the other of B and C molecules. Aromatic π–π stacking is observed within each stack, with the shortest centroid–centroid separation being 3.552 (2) Å.

The asymmetric unit of the title compound, C37H28BrClN8S, comprises one molecule. The molecule consists of two ring systems joined by a C—C bond between the dihydropyrazolyl and pyrazolyl rings of the two extended ring systems. The angles between adjacent ring planes of the tolyl–triazolyl–pyrazolyl–phenyl ring system are 48.2 (1), 12.3 (2) and 22.2 (2)°, respectively, with angles of 19.7 (1), 5.6 (2) and 0.9 (2)° between the rings of the chlorophenyl–thiazolyl–dihydropyrazolyl–bromophenyl set. The pyrazolyl and dihydropyrazolyl rings are inclined at 68.3 (1)° to one another. In the crystal, C—H...Cl interactions form chains of molecules parallel to theb-axis direction.

The asymmetric unit of the title compound, C20H18N8O2, comprises one complete molecule and a half molecule completed by crystallographic twofold symmetry leading toZ= 12. The dihedral angles between the planes of the linked phenyl and methyltriazolyl groups are 69.48 (5) and 44.85 (9)° for the first molecule and 42.88 (9)° for the second. The conformations of the diformyl hydrazyl groups of the molecules are similar as indicated by C—N—N—C torsion angles of −83.4 (2) and −86.4 (3)°. In the crystal, neighbouring molecules are linked by pairs of N—H...O hydrogen bonds to form independent columns propagating parallel to thec-axis direction.

C9H11ClN2S, monoclinic, Pc (no. 7), a = 14.8440(4) Å, b = 7.2002(2) Å, c = 10.0920(2) Å, β = 99.733(2)°, V = 1063.10(5) Å3, Z = 4, R gt(F) = 0.0399, wR ref(F 2) = 0.1099, T = 296(2) K.

In the title compound, C27H20BrN5O, the dihedral angle between the heterocyclic rings is 10.2 (2)°. The phenyl ring bound to the triazole ring is disordered over two orientations in a 0.808 (4):0.192 (4) ratio. In the crystal, C—H...O interactions form chains along [010]. π–π interactions are observed between the phenyl–pyrazolyl unit and the phenylene group of a neighbouring molecule.

In the title compound, C19H27F3N2OS2, the dihedral angle between the benzene ring and dithiocarbamate group is 67.00 (9)° and a weak intramolecular N—H...S interaction generates anS(7) ring. Thetert-butyl group is disordered over two orientations in a 0.628 (14):0.372 (14) ratio. In the crystal, inversion dimers linked by pairs of weak C—H...O interactions generateR22(20) loops and the aromatic rings of neighbouring pairs of molecules are involved in very weak π–π stacking interactions [centroid–centroid separation = 4.0042 (13) Å].

In the title molecule, C8H7BrClNO2, the bromochlorophenyl ring is inclined to the methylcarbamate unit by 32.73 (7)°. In the crystal, N—H...O hydrogen bonds form chains of molecules parallel to [100].

In the title compound, C15H16N4O3S, the dihedral angle between the aromatic rings is 15.90 (19)°. The molecule features two intramolecular N—H...O hydrogen bonds, which both close S(6) rings. In the crystal, weak C—H...O interactions link the molecules into [010] chains.

C13H11N3O2, triclinic, P1̄ (no. 2), a = 7.889(2) Å, b = 9.367(3) Å, c = 9.630(3) Å, α = 64.82(3)°, β = 106.507(4)°, γ = 84.57(2), V = 585.1(3) Å3, Z = 2, R gt(F) = 0.0550, wR ref(F 2) = 0.1455, T = 293(2) K.

The chemistry of thioxoquinazolines has considerable values and has gained an increased interest in both synthetic and biological fields. Therefore, the methods of syntheses and modification of such ring systems remain the focus of various researchers. Indeed, some of the reactions have been applied successfully for the production of various valuable compounds and has also led to a ring system modifications. The present review discusses the synthetic methods, reactions, and biological activities of such compounds which have been reported recently.

Traditional Friedel-Crafts acylation reactions of aromatics suffer from low regio-selectivity towards para- or more linear isomers and usually require stoichiometric quantities of Lewis acids, which are hydrolysed to produce toxic waste during aqueous work-up. Zeolites can catalyse and enhance the selectivity in Friedel-Crafts acylation reactions of simple aromatics and heterocycles. For example, high regioselectivity was achieved in acylation of aromatic ethers, aromatic hydrocarbons and heterocycles over zeolites. This brief review highlights the importance of zeolites to enhance the regioselectivity in Friedel-Crafts acylation reactions.

The molecule of the title compound, C10H11N3O, is planar, including the ethyl group, as indicated by the N—C—C—C torsion angle of 1.5 (2)°. In the crystal, inversion-related molecules are stacked along theaaxis. Molecules are oriented head-to-tail and display π–π interactions with a centroid-to-centroid distance of 3.6664 (8) Å. N—H...O hydrogen bonds between molecules generate a `step' structure through formation of anR22(10) ring.

In the title molecule, C13H10N2S, the dihedral angle between the planes through the non-H atoms of the methylbenzene and thiazolopyridine groups is 36.61 (5)°. In the crystal, the thiazolopyridine groups of inversion-related molecules overlap, with a minimum ring-centroid separation of 3.6721 (9) Å. Furthermore, the methylbenzene groups from neighbouring molecules interact edge-to-face at an angle of 71.66 (5)°. In addition, weak C—H... N hydrogen bonds form chains exending along [100].

Directed lithiation of substituted pyridines containing a directing metalating group (DMG) with a lithium reagent in anhydrous solvent at low temperature gives the corresponding lithium intermediates in-situ, which on reactions with electrophiles produce the corresponding substituted derivatives. The method is simple, general, convenient and often high yielding.

C9H11BrN2S, orthorhombic, P212121 (no. 19), a = 7.5187(3) Å, b = 8.0634(3) Å, c = 17.5320(6) Å, V = 1062.90(7) Å3, Z = 4, R gt(F) = 0.0216, wR ref(F 2) = 0.0536, T = 296(2) K.

C28H19N5O2, monoclinic, Cc (no. 9), a = 13.9896(9) Å, b = 21.9561(14) Å, c = 7.1643(5) Å, β = 91.782(6)°, V = 2199.5(3) Å3, Z = 4, R gt(F) = 0.0632, wR ref(F 2) = 0.1727, T = 150(2) K.

C11H14N2O2, orthorhombic, P212121 (no. 19), a = 7.3227(3) Å, b = 10.9955(4) Å, c = 26.3709(9) Å, V = 2123.30(14) Å3, Z = 8, R gt (F) = 0.0372, wR ref (F 2) = 0.0907, T = 150 K.

In the title compound, C20H21N3O2·H2O (EQR·H2O), the quinazoline ring system forms dihedral angles of 53.1 (1) and 85.6 (1)° with the phenyl ring and the amide link, respectively. In the crystal, O—H...O hydrogen bonds link two EQR and two water molecules into a centrosymmetricR44(18) ring motif. N—H...O hydrogen bonds further link these hydrogen-bonded fragments into columns extending in [010].

In the title compound, C11H16N2O, the dihedral angle between the mean plane of the 4-methypyridine group and the plane of the amide link is 16.7 (1)°, and there is a short intramolecular C—H...O contact. Hydrogen bonding (N—H...O) between amide groups forms chains parallel to thebaxis. Pairs of methylpyridine groups from molecules in adjacent chains are parallel but there is minimal π–π interaction.

In the title molecule, C11H13N3O, the propyl group is almost perpendicular to the quinazolin-4(3H)-one mean plane, making a dihedral angle of 88.98 (9)°. In the crystal, molecules related by an inversion centre are pairedviaπ–π overlap, indicated by the short distances of 3.616 (5) and 3.619 (5) Å between the centroids of the aromatic rings of neighbouring molecules. Intermolecular N—H...N and N—H...O hydrogen bonds formR66(30) rings andC(5) chains, respectively, generating a three-dimensional network. Weak C—H...O interactions are also observed.

Lithiation of ureas (I) and (VI) followed by quenching with various electrophiles, such as aldehydes (II), ketones (IV) and alkyl halides (VII) affords the corresponding 3-substituted isoindolin-1-ones (III), (V), and (VIII), respectively, in good yields.

Treatment of substrates (I) according to A) allows the efficient synthesis of derivatives which are functionalized at the ortho side chain.

Trifluoroacetic anhydride-induced dehydration of substituted 2-(pivaloylaminomethyl)phenyl- and 2-(dimethylaminocarbonylmethyl)phenylmethanols gives the corresponding isoindolines in excellent yields when there are aryl substituents at the methanol carbon atom.

Lithiation of various N'-benzyl-N,N-dimethylureas with t-BuLi (3.3 mole equivalents) in anhydrous THF at 0 degrees C followed by reactions with various electrophiles afforded the corresponding 3-substituted isoindolin-1-ones in high yields.

Directed lithiation of substituted pyridines containing a directing metalating group (DMG) with a lithium reagent in anhydrous solvent at low temperature gives the corresponding lithium intermediates in-situ, which on reactions with electrophiles produce the corresponding substituted derivatives. The method is simple, general, convenient and often high yielding.

In the title compound, C22H28N2, the dihedral angle between the planes of the phenyl ring and the dihydroquinazoline ring system (r.m.s. deviation = 0.030 Å) is 24.95 (7)° and bothn-butane chains assume all-transconformations. In the crystal, N—H...N hydrogen bonds link the molecules intoC(4) chains propagating in the [001] direction.

Trifluoroacetic anhydride-induced dehydration of substituted 2-(pivaloylaminomethyl)phenyl- and 2-(dimethylaminocarbonylmethyl)phenylmethanols gives the corresponding isoindolines in excellent yields when there are aryl substituents at the methanol carbon atom.