Aroyl Group Research Articles

Cyclocondensation of β-(aryl/heteroaryl)methylaminoenones with thionyl chloride: a facile general approach for the synthesis of 2,4-bis(het)aryl-5(het)aroylthiazoles

An efficient, regioselective route to 2,4-bis(het)aryl-5(het)aroylthiazoles has been developed by cyclocondensation of thionyl chloride with novel β-(het)arylmethylaminoenones which are readily accessible by the reaction of (het)arylmethylamines with 1,3-bis(het)arylmonothio-1,3-diketones. The method allows entry to 2,4,5-trisubstituted thiazoles, with full control for the introduction of either a (het)aryl group at 2,4 positions or a (het)aroyl group at 5 position of the thiazole ring.

Iodine/Water‐Mediated Oxidation of o‐Alkynylaroyl Compounds and Application of the Products of Oxidation in the Synthesis of Nitrogen Heterocycles

AbstractA facile iodine/water‐mediated oxidation of the triple bond of o‐alkynylaroyl compounds to furnish tricarbonyl compounds is reported. The reaction proceeds through the formation of isochromenol intermediates by the assistance of the neighbouring aroyl group. The product tricarbonyl compounds are versatile synthetic precursors that, upon treatment with mono‐ and diamines, hydrazines and amino alcohols, afford various heterocyclic scaffolds such as isoindolinones, phthalazines, benzimidazoisoquinolinones, quinoxalines and benzimidazole‐quinoxaline hybrid compounds. Mechanistic aspects of the formation of the above heterocycles are discussed. Finally, a short synthetic route to the isoindolinone natural product, aristolactam BII is reported.

{2,7-Dimethoxy-8-[4-(propan-2-yloxy)benzoyl]naphthalen-1-yl}[4-(propan-2-yloxy)phenyl]methanone

The title compound, C32H32O6, crystallized with two independent molecules in the asymmetric unit. Each molecule has essentially the same feature of non-coplanar aromatic rings whereby the two 4-isopropoxybenzoyl groups are twisted in a perpendicular manner to the naphthalene ring and oriented in the same direction (syn-orientation). The benzene rings of the aroyl groups make dihedral angles of 16.13 (7) and 25.31 (7)° in the two molecules. These benzene rings make dihedral angles of 88.38 (8) and 75.32 (7)° with the naphthalene ring system in one molecule, and 89.71 (7) and 82.11 (7)° in the other. In the crystal, mol­ecules are linked via C—H⋯O hydrogen bonds, forming a three-dimensional network. In one independent molecule, the 2-propyl groups of both isoprop­oxy groups are disordered over two positions with site occupancies of 0.512 (3) and 0.488 (3).

Two methods for generation of aroyl(quinoxalin-2-yl)ketene

By heating a solution of 3-(4-chlorobenzoyl)-4-(4chlorophenyl)pyrrolo[1,2-a]quinoxaline-1,2-dione (I) [1] in boiling anhydrous 1,2,4-trimethylbenzene (pseudocumene, 169–170°C) or a solution of 5-(4-chlorophenyl)-4-[3-(4-chlorophenyl)quinoxalin-2yl]furan-2,3-dione (II) in boiling anhydrous p-xylene (138–139°C) we obtained 4-(4-chlorobenzoyl)-5-(4chlorophenyl)-2-[3-(4-chlorophenyl)quinoxalin-2-yl]1-oxo-1H-pyrido[1,2-a]quinoxalin-3-yl 4-chlorobenzoate (III) in almost quantitative yield. Compound III is formed as a result of thermal decarbonylation of pyrroloquinoxalinedione I or furandione II, with generation of aroyl(quinoxalinyl)ketene IV which undergoes dimerization via [4 + 2]-cycloaddition involving imidoylketene fragment of one molecule IV and ketene C=C bond of the other and subsequent [1,3]-acylotropic migration of the aroyl group. The different decarbonylation temperatures of compounds I and II indicate different thermal stabilities of the dioxopyrrole and dioxofuran rings. The spectral parameters of compound III were very similar to those of model 4-benzoyl-5-phenyl-2-(3phenylquinoxalin-2-yl)-1-oxo-1H-pyrido[1,2-a]quinoxalin-3-yl benzoate whose structure was determined

2,7-Dimeth-oxy-8-(4-propyl-benzo-yl)naphthalen-1-yl](4-propyl-phen-yl)methanone.

In the title compound, C32H32O4, the 4-propyl­benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti­parallel, and their benzene rings make a dihedral angle of 8.64 (10)°. The dihedral angles between the naphthalene ring system and the benzene rings are 69.37 (8) and 69.45 (8)°. In the crystal, C—H⋯O inter­actions link adjacent mol­ecules via their aroyl groups.

Chemospecific and Regioselective Ethereal Methyl-Oxygen Bond Cleavage Behavior of Aroylated Dimethoxynaphthalenes by Combined Action of AlCl<sub>3</sub> and Aroyl Group

AlCl3-mediated cleavage of ethereal methyl–oxygen bond in aroylated 2,7-dimethoxynaphthalene compounds proceeds chemospecifically and regioselectively. The ethereal bond at the β(2)-position of 1-monoaroylated 2,7-dimethoxynaphthalene is cleaved readily and predominantly against the β(7)-position, whereas scission of β-ethereal bonds of 1,8-diaroylated 2,7-dimethoxynaphthalene hardly undergoes like the non-aroylated mother frame compound of 2,7-dimethoxynaphthalene.

(5-Benzoyl-3,6-dimethoxynaphthalen-2-yl)(phenyl)methanone

The asymmetric unit of the title compound, C26H20O4, contains two independent conformers. The aromatic rings of the aroyl groups are twisted with respect to the naphthalene ring systems to form dihedral angles of 66.58 (6) and 66.45 (6)° in one conformer, and 75.00 (7) and 81.17 (6)° in the other conformer. The crystal packing is stabilized by weak inter­molecular C—H⋯O hydrogen bonds and by C—H⋯π inter­actions.

(4-Chlorophenyl)(2,7-dimethoxy-8-nitronaphthalen-1-yl)methanone

In the title compound, C19H14ClNO5, the aroyl group is attached to the naphthalene ring system with a non-coplanar configuration. The dihedral angle between naphthalene ring system and benzene ring is 70.62 (6)°. The nitro group is oriented in parallel with the adjacent carbonyl plane. The torsion angle of the carbonyl group and naphthalene ring is 54.68 (19)° (C—C—C—O), and that of nitro group and naphthalene ring is 54.26 (18)° (O—N—C—C). In the crystal, π–π inter­actions between naphthalene systems [centroid–centroid distances = 3.5633 (9), 3,5634 (9), and 3.9758(9) Å], C—H⋯O hydrogen bonds, inter­molecular N—O⋯Cl inter­actions [2.9937 (12) Å] and C—H⋯π contacts are observed.

1,8-Bis(4-aminobenzoyl)-2,7-dimethoxynaphthalene

The title compound {systematic name: [8-(4-aminobenzoyl)-2,7-dimethoxynaphthalen-1-yl](4-aminophenyl)methanone}, C26H22O4N2, possesses crystallographically imposed twofold symmetry, with two C atoms lying on the rotation axis. In the crystal, the mol­ecules inter­act through inter­molecular N—H⋯O hydrogen bonds between the amino and meth­oxy groups on the naphthalene ring systems and N—H⋯π inter­actions between the amino groups and the naphthalene rings. Furthermore, weak C—H⋯O hydrogen bonds and π–π stacking inter­actions between the benzene rings are observed. The centroid–centroid and inter­planar distances between the benzene rings of the aroyl group and the naphthalene ring systems of adjacent mol­ecules are 3.6954 (8) and 3.2375 (5) Å, respectively. The dihedral angle between the mean planes of the benzene ring and the naphthalene ring system is 83.59 (5)°. The benzene ring and the carbonyl group in the benzoyl unit are almost coplanar [C—C—C—O torsion angle = 175.91 (10)°].

(2,7-Dimethoxynaphthalen-1-yl)(phenyl)methanone

The asymmetric unit of the title compound, C19H16O3, contains three independent conformers. Each of the three conformers has essentially the same feature of non-coplanar aromatic rings whereby the aroyl group at the 1-position of the naphthalene ring is twisted in a perpendicular manner to the naphthalene ring. The dihedral angles between the benzene ring planes and the naphthalene ring systems are 75.34 (7), 86.47 (7) and 76.55 (6)° in the three conformers. The crystal structure is stabilized by inter­molecular C—H⋯O hydrogen bonds.

(2,7-Dimethoxynaphthalene-1,8-diyl)bis(4-fluorobenzoyl)dimethanone

The title compound, C26H18F2O4, is a naphthalene derivative in which the two aroyl groups at the 1- and 8-positions (peri positions) are anti to each other. There is an appreciable difference in the dihedral angles between the naphthalene ring system and the two benzene rings [66.88 (7)° and 88.09 (6)°]. In the crystal, weak C—H⋯O inter­actions involving one of the carbonyl groups and an aromatic C—H group ortho to the F atom seem to stabilize the packing of the mol­ecules.

Intramolecular Cooperativity in the Reaction of Diacyl Phosphates with Serine β-Lactamases

Asymmetric diaroyl phosphates (ArCOOPO(2)(-)OCOAr', where Ar = Ph, Ar' = 4-biphenyl, 2-benzothiophenyl and 2-benzofuranyl) have been prepared, evaluated as serine (classes A, C, and D) beta-lactamase inhibitors, and compared with respect to the latter with their symmetric parents, where Ar = Ar'. The asymmetric compounds, in general, were found to react with the beta-lactamases in two modes, corresponding to different orientations with respect to the active site, whereby either of the two aroyl groups may acylate the enzyme to form two different inert acyl-enzymes, E-COAr and E-COAr' . In all cases, the asymmetric compounds, in one orientation, react more rapidly with the enzymes tested than one symmetrical parent but not both. From comparisons of activation free energy differences, it was found that the changes in free energy on changing from one aryl group to another, in either the acyl group or the leaving group, were not additive, i.e., that the effect of changing one aroyl group to another depended on the leaving group and vice versa. Thus, intramolecular cooperativity between the aroyl groups must exist, arising either from direct interaction between them or from protein-mediated interaction or from a combination of both. Such cooperativity brings fresh opportunities and challenges to the search for novel beta-lactamase inhibitors.

Synthesis and evaluation of pyrido[1,2- a]pyrimidines as inhibitors of nitric oxide synthases

A series of new 3-aroylpyrido[1,2- a]pyrimidines were synthesized from aryl methyl ketones in a simple two-step procedure and evaluated as nitric oxide synthases (NOS) inhibitors. In order to perform a structure–activity relationship study, different aroyl groups were introduced in 3-position and methyl groups were introduced at different positions of the pyrimidine heterocycle. Compounds with a biphenyloyl, benzyloxybenzoyl or naphthoyl group displayed the highest inhibitory effects which were further increased by introduction of a methyl group in position 8 of the pyrido[1,2- a]pyrimidine moiety. Some of the compounds exhibited promising inhibitory effects with selectivity toward the purified inducible NOS (iNOS) and were also active against iNOS expressed in stimulated RAW 264.7 cells.

Reaction of 3-(polyfluoroacyl)chromones with hydrazines: new regioselective synthesis of RF-containing pyrazoles

Reactions of 3-(polyfluoroacyl)chromones with hydrazine, methyl-and phenylhydrazines proceed by the mechanism of nucleophilic 1,4-addition with subsequent pyrone ring opening and heterocyclization at the polyfluoroacyl group to 4-(2-hydroxyaroyl)-3-polyfluoro-alkylpyrazoles or at the aroyl group to 4-polyfluoroalkyl-2,4-dihydrochromeno[4,3-c]pyrazol-4-ols. Regiochemistry of the products was established based on the data of 2D-experiments HSQC, HMBC, and NOESY and X-ray diffraction study.

Five-membered 2,3-dioxo heterocycles: LXII. Reaction of 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with N,N′-dihydroxycyclohexane-1,2-diamine. Unusual rearrangement in the spiro[quinoxaline-2,2′-pyrrole] system

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with N,N′-dihydroxycyclohexane-1,2-diamine to give 3-aroyl-1′,4,4′-trihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrole-2,2′-quinoxaline]-3′,5(1H,4′H)-diones which underwent rearrangement into 1′-aroyloxy-4,4′-dihydroxy-1-(2-hydroxyphenyl)-4a′,5′,6′,7′,8′,8a′-hexahydro-1′H-spiro[pyrrolidine-2,2′-quinoxaline]3′,4,5(4′H)-triones via [1,4]-migration of the aroyl group. The product structure was proved by X-ray analysis.

Development of C-C Bond Formation and Asymmetric Reactions Catalyzed by <i>N</i>-Heterocyclic Carbenes

N-Heterocyclic carbenes have been studied for their ability to catalyze C-C bond formations and asymmetric reactions. The fluoro groups of fluorobenzenes are nucleophilically substituted with aroyl groups derived from aromatic aldehydes due to the catalytic action of imidazolidenyl carbenes to afford ketones. N-Heterocyclic carbenes mediate the addition of trimethylsilyl cyanide to aldehydes to yield cyanohydrin trimethylsilyl ethers. The use of chiral imidazolidenyl carbenes derived from (R,R)-1,3-bis[(1-naphthyl)ethyl]imidazolium chloride led to enantioselective cyanosilylation. C2-symmetric imidazolidenyl carbenes catalyze the asymmetric acylation of racemic secondary alcohols.

Interactions of aroyl-and heteroaroyltrifluoroacetones with thiobenzoylhydrazine

The interaction of aroyl(heteroaroyl)trifluoroacetones with thiobenzoylhydrazine may occur at both carbonyl groups. Reaction at the trifluoroacetyl group is facilitated by terminal substituents in the 1,3-dicarbonyl part, which leads can effectively conjugate with the adjacent carbonyl group. The products of condensation at the trifluoroacetyl group are 2-[2-aryl(heteroaroyl)-2-oxoethyl]-5-phenyl-2-trifluoromethyl-2,3-dihydro-1,3,4-thiadiazoles, while condensation at the aroyl(heteroaroyl)group gave 3-aryl(heteroaryl)-5-hydroxy-1-thiobenzoyl-5-trifluoromethyl-4,5-dihydro-1H-pyrazoles, which are not prone to tautomeric transformations in solution.

N-Heterocyclic Carbene-Catalyzed Nucleophilic Aroylation of Fluorobenzenes

In N-heterocyclic carbene (NHCs) catalyzed nucleophilic substitution of fluorobenzenes, fluoro groups are replaced by aroyl groups, which are derived from aromatic aldehydes. 1,3,4,5-Tetramethylimidazol-2-ylidene is found to be an efficient catalyst. The catalyst loading can be reduced to 1 mol % without a significant decrease in the product yields. Polysubstituted benzophenones are synthesized from fluorobenzenes and benzaldehydes by the NHC-catalyzed aroylation.

含窒素複素環式カルベン化学の新展開：有機触媒としての利用

N-heterocyclic carbenes have been studied for their abilities to catalyze C-C bond formation/cleavage and asymmetric reactions. N-heterocyclic carbenes generated from imidazolium, benzimidazolium, triazolium, pyrido[1, 2-c]imidazolium, pyrido[2, 1-c]triazolium, and dipyrido[1, 2-c : 2'1'-e]imidazolium iodide were found to be effective catalysts in benzoin condensation. The acidity of the azolium salts at the C2-hydrogen of the imidazolium or the triazolium moieties relates to the base effect on the reaction. These carbenes can also be employed in retro-benzoin condensation, which is a new method of synthesizing ketones by C-C bond cleavage of α-substituted benzoins. Chloro and fluoro groups of haloarenes are nucleophilically substituted by aroyl groups originated from aromatic aldehydes by catalytic action of imidazolidenyl and triazolidenyl carbenes to afford ketones. N-heterocyclic carbenes mediate the addition of trimethylsilylcyanide to aldehydes to yield cyanohydrin trimethylsilyl ethers. The use of chiral imidazolidenyl carbene derived from (R, R)-1, 3-bis[(1-naphthyl)ethyl] imidazolium chloride led to enantioseletive cyanosilylation. C2-symmetric imidazolidenyl carbenes catalyze asymmetric acylation of racemic secondary alcohols.

Geometric isomerism in the series of fluoroalkyl-containing 1,2,3-trione 2-arylhydrazones

According to the 1H, 13C, and 19F NMR data, fluoroalkyl-containing 1,2,3-trione 2-arylhydrazones in CDCl3 exist exclusively, while in (CD3)2CO preferentially, as isomers in which the acyl or aroyl group is involved in intramolecular hydrogen bond. The isomer structure was assigned on the basis of the chemical shifts of the carbonyl carbon atoms and fluorine atoms and carbon-fluorine spin-spin coupling constants J C-F. X-Ray diffraction data showed that 1,2,3-trione 2-arylhydrazones in crystal have the same structure as in CDCl3 solution. Quantum-chemical calculations were performed to rationalize predominant formation of 1,2,3-trione 2-arylhydrazone isomers with a free polyfluoroacyl group.