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The non-H atoms of the title molecule, C19H16N2O2, are almost coplanar (r.m.s. deviation = 0.019 Å), apart from the phenyl group, which is disordered with two components of almost equal occupancy: the dihedral angle between them is 78.9 (3)°. In the crystal, weak C—H...N hydrogen bonds link the molecules into [001] chains and aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.747 (2) Å] form columns parallel to the c-axis direction.

The title compound, C13H9NO4, is almost planar (r.m.s. deviation = 0.071 Å). In the crystal, weak C—H...O and C—H...N interactions connect the molecules into ribbons propagating parallel to thea-axis direction.

In the title compound, C12H13N3O, thep-tolyl ring is twisted away from the mean plane (r.m.s. deviation = 0.044 Å) of the rest of the molecule by 50.84 (6)°. In the crystal, molecules are linked by C—H...π interactions, forming zigzag chains propagating in theb-axis direction.

C29H23N7O, triclinic, P1̅ (no. 2), a = 8.2785(12) Å, b = 12.1750(18) Å, c = 13.8122(16) Å, α = 114.401(13)°, β = 103.083(11)°, γ = 93.384(12)°, V = 1216.5(3)Å3, Z = 2, R gt(F) = 0.0713, wR ref(F 2) = 0.1880, T = 293(2) K.

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.

C24H23N5O3S, triclinic, P1̅ (no. 2), a = 9.1704(9) Å, b = 10.1253(11) Å, c = 12.2182(14) Å, α = 83.686(10)°, β = 89.542(9)°, γ = 76.982(9)°, V = 1098.5(2) Å3, Z = 2, R gt(F) = 0.0551, wR ref(F 2) = 0.1510, T = 296(2) K.

C20H17N5O, triclinic, P1̅ (no. 2), a = 11.5358(7) Å, b = 13.8746(9) Å, c = 16.3942(10) Å, α = 85.958(5)°, β = 87.407(5)°, γ = 87.619(5)°, V = 2612.8(3)Å3, Z = 6, R gt(F) = 0.0607, wR ref(F 2) = 0.1510, T = 293(2) K.

C23H17ClFN5S2, monoclinic, P21/c (no. 14), a = 20.9691(12) Å, b = 11.5316(6) Å, c = 9.2546(4) Å, β = 95.484(4)°, V = 2227.6(2) Å3, Z = 4, R gt(F) = 0.0468, wR ref(F 2) = 0.1126, T = 296 K.

C28H20FN3OS, triclinic, P1̅ (no. 2), a = 9.5719(5) Å, b = 10.7499(6) Å, c = 10.9238(5) Å, α = 95.470(4)°, β = 102.133(4)°, γ = 97.962(4)°, V = 1079.30(10) Å3, R gt(F) = 0.0482, wR ref(F 2) = 0.1143, T = 150(2) K.

C11H14N2O2, orthorhombic, P212121 (no. 19), a = 7.5411(2) Å, b = 11.5148(2) Å, c = 12.5370(2) Å, V = 1088.64(4) Å3, Z = 4, R gt (F) = 0.0301, wR ref (F 2 ) = 0.0826, T = 296 K.

C13H10N2OS, monoclinic, P21/c (no 14), a = 14.182(3) Å, b = 5.9674(6) Å, c = 26.683(4) Å, β = 101.162(17)°, V = 2215.4(6) Å3, Z = 8, R gt (F) = 0.0634, wR ref (F 2) = 0.1514, T = 150 K.

C10H14N2O, monoclinic, Cc (no. 9), a = 6.8354(9) Å, b = 13.8221(17) Å, c = 10.2905(12) Å, β = 90.625(11)°, V = 972.2(2) Å3, Z = 4, R gt(F) = 0.0526, wR ref(F 2) = 0.1335, T = 296(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.

In the title compound, C12H14N2S, the cyclohexane ring adopts a chair conformation with the exocyclic C—C bond in an equatorial orientation. The mean plane through the cyclohexane ring (all atoms) is twisted from the thiazolopyridine ring system (r.m.s. deviation = 0.013 Å) by 39.57 (6)°. In the crystal, molecules form (100) sheets, although there are no specific directional interactions between them. The crystal stucture was refined as a two-component perfect twin.

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.

In the title compound, C10H14N2O, the pyridine ring is inclined to the mean plane of the amide moiety [N—C(=O)C] by 17.60 (8)°. There is an intramolecular C—H...O hydrogen bond present involving the carbonyl O atom. In the crystal, molecules are linkedviaN—H...N hydrogen bonds, forming chains propagating along [100]. Thetert-butyl group is disordered over two sets of sites with a refined occupancy ratio of 0.758 (12):0.242 (12).

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 molecule, C9H10N2S, one of the methyl groups is almost co-planar with the thiazolopyridine rings with a deviation of 0.311 (3) Å from the least-squares plane of the thiazolopyridine group. In the crystal, weak C—H...N hydrogen-bonding interactions lead to the formation of chains along [011].

The title compound, C10H12N2S, does not contain any strong hydrogen-bond donors but two long C—H...N contacts are observed in the crystal structure, with the most linear interaction linking molecules along [010]. The ellipsoids of thetert-butyl group indicate large librational motion.

In the title compound, C10H10N2S, all non-H atoms are almost coplanar [maximum deviation = 0.103 (1) Å]. In the crystal, N—H...S interactions formR22(8) rings linking pairs of molecules related by inversion. The molecular pairs are stacked along [100]. A herringbone arrangement of pairs in the [010] direction forms layers parallel to (010).

In the title compound, C9H10BrClN2S, the dimethylthiourea group is twisted from the benzene ring plane by 54.38 (6)°. In the crystal, the amino groups are involved in the formation of N—H...S hydrogen bonds, which link the molecules into chains along [010]. Weak C—H...Cl interactions further link these chains into layers parallel to theabplane.

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.

There are two molecules in the asymmetric unit of the title compound, C11H16N2O. The pyridine rings and amide groups overlap almost perfectly (r.m.s. overlay fit = 0.053 Å), but the tertiary butyl groups have different orientations: in one molecule, one of the methyl C atoms issynto the amide O atom [O—C—C—C = −0.8 (3)°] and in the other the equivalent torsion angle is 31.0 (2)°. In the crystal, the two independent molecules are linked by a pair of N—H...N hydrogen bonds in the form of anR22(8) loop to form a dimer. A C—H...O interaction connects the dimers into [100] chains.

Lithiation of N'-benzyl-N,N-dimethylurea and its substituted derivatives with t-BuLi (3.3 equiv) in anhydrous THF at 0 °C followed by reaction with various electrophiles afforded a range of 3-substituted isoindolin-1-ones in high yields.

In the title compound, C17H27N3OS2, the amide group is approximately coplanar with the pyridine ring [dihedral angle = 1.6 (1)°], whereas the dithiocarbamate group is nearly perpendicular to the pyridine ring [dihedral angle = 76.7 (1)°]. In the crystal, pairs of weak C—H...O hydrogen bonds link the molecules into inversion dimers.

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.

In the title compound, C12H7N3O2S, the dihedral angle between the planes of the thiazolopyridine ring system (r.m.s. deviation = 0.005 Å) and the benzene ring is 3.94 (6)°. The nitro group is rotated by 7.6 (2)° from its attached ring. In the crystal, extensive aromatic π–π stacking [shortest centroid–centroid separation = 3.5295 (9) Å] links the molecules into (001) sheets.

Reaction of 3H-quinazoline-4-thione (1) with two mole equivalents of an alkyllithium (t-BuLi, n-BuLi or MeLi) at−78 °C in dry THF gave the corresponding 2-alkyl-1,2-dihydro-3H-quinazoline-4-thione (4, 5 or 6) in high yield. Similarly, reactions of 4-(methylthio)quinazoline (7), 4-(ethylthio)quinazoline (8) and 4-methoxyquinazoline (9) with alkyllithiums (one mole equivalent) gave the corresponding 4-substitued 2-alkyl-1,2-dihydroquinazolines 11–18. On the other hand, blocking position 2 with a phenyl group in 4-(methylthio)-2-phenylquinazoline (20) and 4-methoxy-2-phenylquinazoline (21) resulted in reaction with two mole equivalents of alkyllithiums to give 4,4-dialkyl-2-phenyl-3,4-dihydroquinazolines 22–24.

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.

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.

In the title compound, C10H11F3N2O, the dihedral angle between the dimethylurea and phenyl group planes is 37.49 (7)°. In the crystal, molecules are linked by N—H...O hydrogen bonds, generating chains propagating in the [010] direction. The trifluoromethyl group is disordered over two orientations in a 0.577 (12):0.423 (12) ratio.

Lithiation of N′-(2-methylbenzyl)-N,N-dimethylurea and N-(2-methylbenzyl)pivalamide with two mole equivalents of tert-butyllithium at -78 ˚C takes place on the nitrogen and on the methyl group at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding side-chain-substituted derivatives in high yields. Dehydration of the products obtained from reactions with carbonyl compounds in some cases gives the corresponding tetrahydroisoquinolines in excellent yields, while in other cases dehydration takes place within the substituted side chain to produce the corresponding alkenes in excellent yields.

2-Methyl-4-(methylthio)quinazoline has been lithiated, in the 2-methyl group, with n-BuLi at -78 °C in THF. The lithium reagent thus obtained reacts with a variety of electrophiles (iodomethane, iodoethane, D2O, benzaldehyde, 4-anisaldehyde, hexan-2-one, acetophenone, benzophenone, cyclohexanone) to give modified 2-substituted 4-(methylthio)quinazolines in excellent yields. Similarly, lithiation of 4-methoxy-2-methylquinazoline followed by reactions with various electrophiles gave the corresponding modified 2-substituted 4-methoxyquinazolines in excellent yields. Lithiations of 2-ethyl-4-(methylthio)quinazoline, 4-(methylthio)-2-propylquinazoline, 2-ethyl-4-methoxyquinazoline and 4-methoxy-2-propylquinazoline, followed by reactions with a range of electrophiles, behave in a similar manner to give the corresponding modified 2-substituted derivatives in good yields.

Directed lithiation of N-(2-methoxybenzyl)pivalamide with two mole equivalents of t-BuLi in anhydrous THF at -78 ˚C followed by reactions with various electrophiles gave ring substitution, but ortho to the methoxy group rather than ortho to the pivaloylaminomethyl group, which was unexpected in view of earlier results reported with n-BuLi.

Directed lithiation of various substituted benzylamines takes different courses depending on the substituents at nitrogen and on the aryl ring and/or the nature of the alkyllithiums. Lithiation of N-benzylpivalamide with t-BuLi gives a mixture of ring (2-position) and side-chain lithiated species, but the 2-lithiated isomer can be obtained cleanly via bromine-lithium exchange of N-(2-bromobenzyl)pivalamide. N'-Benzyl-N,N-dimethylurea, N'-(4-substituted benzyl)-N,N-dimethylureas and N-(4-substituted benzyl)pivalamides give 2-lithiated derivatives directly with t-BuLi at -78 °C. By contrast, lithiation of N-(2-methoxybenzyl)pivalamide occurs at the 6-position, ortho- to the methoxy group, while lithiation of N'-(2-methoxybenzyl)-N,N-dimethylurea gives a mixture of 2- and 6-lithiated species. All organolithiums are converted in high yields to their corresponding substitution products on reactions with various electrophiles.