Regioselective copper-catalyzed amination of bromobenzoic acids using aliphatic and aromatic amines

A chemo- and regioselective copper-catalyzed cross-coupling procedure for amination of 2-bromobenzoic acids is described. The method eliminates the need for acid protection and produces N-aryl and N-alkyl anthranilic acid derivatives in up to 99% yield. N-(1-Pyrene)anthranilic acid has been employed in metal ion-selective fluorosensing. Titration experiments showed that this pyrene-derived amino acid forms an equimolar complex with Hg(II) in water resulting in selective fluorescence quenching even in the presence of other metal ions such as Zn(II) and Cd(II).     

Microwave-assisted chemoselective copper-catalyzed amination of o-chloro and o-bromobenzoic acids using aromatic amines under solvent free conditions

Copper-catalyzed synthesis of N-aryl anthranilic acid derivatives using effective amination of 2-chloro and 2-bromobenzoic acid under microwave irradiation is reported.Some of the advantages of this method are high chemoselectivity,short reaction times,ease of work up procedure and elimination of the need for acid protection.     

CuI-catalyzed coupling reaction of beta-amino acids or esters with aryl halides at temperature lower than that employed in the normal Ullmann reaction. Facile synthesis of SB-214857

[reaction: see text] The CuI-catalyzed coupling reaction of aryl halides with beta-amino acids or beta-amino esters is completed at 100 degrees C in 48 h, which indicates that the structure of the beta-amino acid has an accelerating effect for the Ullmann-type aryl amination reaction. This coupling reaction can be used to prepare enantiopure N-aryl beta-amino acids. An efficient synthetic route to SB214857, a potent GPIIb/IIIa receptor antagonist, is developed using this method.     

Amination of aromatic olefins with anilines: a new domino synthesis of quinolines

A new catalytic amination of aromatic olefins with anilines is presented. In a domino reaction, substituted quinoline derivatives are obtained in the presence of cationic rhodium complexes, such as [Rh(cod)2]BF4, and PPh3. Ethylbenzene is formed as a by-product in this new oxidative reaction. The first transition metal catalyzed anti-Markovnikov hydroamination of styrene with anilines occurs as a side reaction. Mechanistic investigations strongly support the regioselective oxidative amination of styrene as the key reaction step.     

First direct reductive amination of mucochloric acid: a simple and efficient method for preparing highly functionalized alpha,beta-unsaturated gamma-butyrolactams

[reaction: see text] The first direct reductive amination of mucochloric acid (1) has been accomplished. Reaction of 1 with various alkyl, aryl, and benzylamines, followed by reduction in the same pot, provides an efficient method of obtaining N-benzyl-3,4-dichloro-1,5-dihydro-pyrrol-2-one and N-aryl (or alkyl)-3,4-dichloro-1,5-dihydro-pyrrol-2-ones.     

2-(Trimethylsilyl)ethanesulfonyl amide as a new ammonia equivalent for palladium-catalyzed amination of aryl halides

2-(Trimethylsilyl)ethanesulfonyl amide (SES-NH₂) is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that anilines and anilines with sensitive functional groups can be readily prepared.     

Efficient indoles and anilines syntheses employing tert-butyl sulfinamide as ammonia surrogate

tert-Butyl sulfinamide is an ammonia equivalent for the palladium-catalyzed amination of aryl bromides and aryl chlorides. Using these amine derivatives, it has been observed that indoles and anilines with sensitive functional groups can be readily prepared. This surrogate has also been used for the synthesis of indoles from 2-halophenols using palladium catalyzed cross coupling reaction as the key step.     

Metal-free intermolecular oxidative C-N bond formation via tandem C-H and N-H bond functionalization

The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both a N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.     

Pd-catalyzed intermolecular C-H amination with alkylamines

C-H amination of N-aryl benzamides with O-benzoyl hydroxylamines has been achieved with either Pd(II) or Pd(0) catalysts. Furthermore, we demonstrate that secondary amines can be directly used with benzoyl peroxide in a one-pot procedure that proceeds via the in situ generation of the appropriate O-benzoyl hydroxylamines. This catalytic reaction provides a new disconnection for the convergent synthesis of tertiary and secondary arylalkyl amines starting from benzoic acids.     

Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solvent-free conditions and their anti-fungal activity

A rapid one-pot solvent-free procedure has been developed for the synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones by neat three-component cyclocondensation of anthranilic acid, phenyl acetyl chloride and substituted anilines under microwave irradiation. The experimental methodology and microwave conditions described here are well established, allowing significant rate enhancement and good yields compared to conventional reaction conditions. The reaction is generalized for O, M & P substituted anilines to give quinazolin-4(3H)-ones. Synthesized compounds have been screened for their antifungal activity.     

Synthesis of N-(fluoro phenyl) maleamic acids and N-(fluoro phenyl) maleimides

A series of seven N-(fluoro phenyl) maleamic acids and their N-(fluoro phenyl) maleimides were prepared by the reaction of fluoro phenyl amines ( o-, m-, and p-fluoro, 2.4-, 2.5-difluoro, 2.3.5.6-tetrafluoro and 2.3.4.5.6.-pentafluoro anilines) with maleic anhydride according to substantial modifications made to the reaction conditions used by Searle for the preparation of normal N-aryl maleimides.     

Enol esters: versatile substrates for Mannich-type multicomponent reactions

The interaction of cyclic enol esters with diversely substituted anilines and ethyl glyoxalate yields, under Sc(OTf)3 catalysis, disubstituted N-aryl lactams in a multicomponent reaction. The protocol allows access to the trans stereoisomers after an epimerization of the initial mixture in which the cis isomers predominate. Vinyl acetate yields quinoline derivatives, whereas isopropenyl acetate leads to the corresponding Mannich adducts.     

Green chemical multi-component one-pot synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones under solvent-free conditions and their anti-fungal activity

A rapid one-pot solvent-free procedure has been developed for the synthesis of fluorinated 2,3-disubstituted quinazolin-4(3H)-ones by neat three-component cyclocondensation of anthranilic acid, phenyl acetyl chloride and substituted anilines under microwave irradiation. The experimental methodology and microwave conditions described here are well established, allowing significant rate enhancement and good yields compared to conventional reaction conditions. The reaction is generalized for o-, m- and p-substituted anilines with electron-donating and -withdrawing groups to give quinazolin-4(3H)-ones. Synthesized compounds have been screened for their anti-fungal activity.     

Synthesis and Tautomeric Structure of 7-Arylhydrazono-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines

Two synthetic approaches were developed for the title compounds 8a-g via coupling of diazotized anilines with 7-acetyl-6-methyl-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine 7 , and reaction of N-aryl 2-oxopropanehydrazonoyl chlorides 9 with 4-amino-3-mercapto-5-phenyl-1,2,4-triazole 1 . The tautomeric structures of 8 were elucidated by their spectral analyses and correlation of their acid dissociation constants with Hammett equation.     

Practical approach to 2-thioxo-2,3-dihydroquinazolin-4(1H)-one via dithiocarbamate–anthranilic acid reaction

A practical and straightforward protocol has been developed for the preparation of 2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives from dithiocarbamate chemistry. The method involves the reaction of anthranilic acid derivatives (2-aminobenzoic acid, 2-aminobenzamide and isatoic anhydride) with various dithiocarbamate derivatives using ethanol as solvent. The main advantages of this protocol include practical simplicity, good to high yields, and ease of product isolation, purification and cheapness of the solvent.     

Regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles via copper-catalyzed cyclizations of 2-haloarylcarbonylic compounds

[reaction: see text] A general method for the one-step regioselective synthesis of 1-alkyl- or 1-aryl-1H-indazoles from ortho-halogenated alkanoylphenones, benzophenones, and arylcarboxylic acids, via copper-catalyzed amination, was developed by using 0.2% mol of CuO in the presence of K(2)CO(3). The reaction involves amination followed by intramolecular dehydration. Different functionalized alkyl aryl ketones, diaryl ketones, and benzoic acid derivatives were efficiently coupled with several hydrazines. Ligands commonly employed as catalysts for intermolecular amination were shown to be ineffective for this cyclization.     

Reactions of N-hydroxysuccinimide esters of anthranilic acids with anions of beta-keto esters. A new route to 4-oxo-3-quinolinecarboxylic acid derivatives

A new approach for the synthesis of 4-oxo-3-quinolinecarboxylic acid derivatives is described. This methodology involves the C-acylation of the anions of appropriate beta-keto esters with novel N-hydroxysuccinimide esters of anthranilic acids. The intermediate C-acylation products 3 are spontaneously cyclized to afford 3-ethoxycarbonyl-4-oxoquinoline derivatives 4. The introduction of a variety of substituents at positions 1 and 2 of the quinoline ring is feasible with the selection of suitable anthranilic acids and beta-keto esters. The structure of the obtained 2-substituted 3-ethoxycarbonyl-4-oxoquinolines was confirmed by IR and NMR spectral data.     

Synthesis of poly(benzoxazinone)s by direct polycondensation of dicarboxylic acids with bis(anthranilic acid)s

A convenient method for the synthesis of poly(benzoxazinone)s of high molecular weights has been developed. These polymers were prepared readily by direct polycondensation of aromatic dicarboxylic acids containing phenyl ether structures with bis(anthranilic acid)s using phosphorus pentoxide/methanesulfonic acid (PPMA) as a condensing agent and solvent. Polycondensations proceeded smoothly and were completed within several hours at 140°C to produce poly(benzoxazinone)s with inherent viscosities up to 2.6 dL/g. The synthesis of 2-substituted benzoxazinones by the reaction of aromatic carboxylic acids or dicarboxylic acid with anthranilic acid in PPMA was studied in detail to demonstrate the feasibility of the reaction for polymer formation. The thermogravimetry of the aromatic poly(benzoxazinone)s showed 10% weight loss in air and nitrogen around at 440 and 460°C, respectively.     

Regioselective and enantiospecific rhodium-catalyzed allylic amination with N-(arylsulfonyl)anilines

[reaction: see text]. The regioselective and enantiospecific rhodium-catalyzed allylic amination of secondary allylic carbonates 1 with N-(arylsulfonyl)anilines provides a convenient process for the construction of arylamines 2. This method, in conjunction with ring-closing metathesis and radical cyclization reactions, allows the direct construction of biologically relevant pharmacophores as exemplified by the construction of dihydroquinoline and dihydrobenzo[b]indoline derivatives.     

Efficient [5 + 1]-strategy for the assembly of 1,8-naphthyridin-4(1H)-ones by domino amination/conjugate addition reactions of 1-(2-chloropyridin-3-yl)prop-2-yn-1-ones with amines

A facile synthetic approach for the synthesis of 1,8-naphthyridine-4(1H)-one derivatives via a catalyst free and Pd-supported tandem amination sequence is developed and described. In a case of aliphatic amines reaction proceeds in a catalyst free mode, however anilines demand Pd-supported reaction conditions.