Carbon dioxide: A reagent for the protection of nucleophilic centres and the simultaneous activation of alternative locations to electrophilic attack. : Part I. A new synthetic method for the 2-substitution of 1-unsubstituted indoles.

Indole was converted into several 2-substituted derivatives by using carbon dioxide both for $\text{N}$-protection and to give an intermediate carbanion stabilizing group. $\text{t}$-Butyllithium was used as a lithiating agent at the $\text{alpha}$-carbon atom of the indole enamino group. The resulting 2-substituted indole-1-carboxylic acids underwent smooth thermal decarboxylation under mild conditions. Alternatively, with longer reaction times the protecting group is lost during the reaction.     

Synthesis and anticancer activity evaluation of 3-(4-oxo-2-thioxothiazolidin-5-yl)-1H-indole-carboxylic acids derivatives

Abstract

A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano[3,4-b]indole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of 3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.     

10-chloro-19-norcardiosteroids

Substitution of the angular aldehyde by halogen in cardiosteroids in two steps was studied. The first step was oxidation of the aldehyde and production of the cooresponding 19-carboxylic acids; the second, decarboxylation of the 19-carboxylic acids using N-chlorosuccinimide or chloride salts. The 10-chloro-19norcardiosteroids: 10-chloro-19-norstrophanthidine (1), 10-chloro-19-norcymarin (2), 10-chloro-19norconvallatoxin (3), 10-chloro-19-norstrophalloside (4), and 10-chloro-19-norbovoside A (5) were prepared for the first time. The intermediates strophalloside-19-carboxylic acid and bovoside A-19-carboxylic acid were also prepared for the first time and characterized.     

Regioselective C-H functionalization directed by a removable carboxyl group: palladium-catalyzed vinylation at the unusual position of indole and related heteroaromatic rings

The palladium-catalyzed oxidative vinylation of indole-3-carboxylic acids with alkenes effectively proceeds via directed C-H functionalization and decarboxylation to produce the corresponding 2-vinylated indoles. Similarly, pyrrole-, furan-, and thiophenecarboxylic acids also undergo decarboxylative vinylation.     

Carboxylation of indoles and pyrroles with CO2 in the presence of dialkylaluminum halides

The Lewis acid-mediated carboxylation of arenes with CO₂ has been successfully applied to 1-substituted indoles and pyrroles by using dialkylaluminum chlorides instead of aluminum trihalides. Thus, the carboxylation of 1-methylindoles, 1-benzyl-, and 1-phenylpyrroles proceeds regioselectively with the aid of an equimolar amount of Me₂AlCl under CO₂ pressure (3.0 MPa) at room temperature to afford the corresponding indole-3-carboxylic acids and pyrrole-2-carboxylic acids in 61-85% yields, while the same treatment of 1,2,5-trimethylpyrrole affords the 3-carboxylic acid in 52% yield.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3-hydroxy, 3-alkoxy,and 3-alkyl derivatives

Methods for the synthesis of novel 3-hydroxy, 3-alkoxy, and 3-alkyl indole-2-carboxylic acids and esters are described. Dieckmann cyclization of various 2-[(carboxymethyl)amino]benzoic acid diesters yielded 1-unsubstituted-, 1-methyl-, and 1-phenyl-3-hydroxy-1H-indole-2-carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1H-indoles to 1-phenylindoles.     

Coordination of metal ions by indolic acids. Complexes of indole-3-carboxylic,indole-3-acetic,indole-3-β-acrylic,indole-N-acetic and indole-N-methyl-2-carboxylic acids with some divalent metal ions

Complexes of formula M(L)₂·nH₂O [M=Co or Ni; L=indole-3-carboxylic (I3CH), indole-3-acetic (I3AH), indole-N-acetic (INAH), indole-N-methyl-2-carboxylic (INMH) and M=Co or Ni and Cu, L=indole-3-β-acrylic acids (I3βH)] were pepared and characaterized by i.r. and electronic spectroscopy and by susceptibility measurements and e.s.r. at room and low temperature. The cobalt and nickel complexes exhibit a distorted octahedral coordination except the Co(I3C)₂ complex for which a tetrahedral coordination was suggested. The Cu(I3β)₂·H₂O shows e.p.r. features that can be interpreted if the triplet state, S=1, depending on the temperature, is able to migrate through the crystal lattice of carboxylate dimers such as the copper(II) acetate monohydrate.     

Synthesis of phenylacetylene containing 1,2,3-triazole group

Bromination of (E)-1-[4-(2-carboxy-vinyl)phenyl]-[1,2,3]triazole-4-carboxylic acid ethyl ester, which was synthesized in 90% yield by a Huisgen-type [3 + 2]-cycloaddition reaction between 3-(4-azidophenyl) acrylic acid and ethyl propiolate, in CHCl₃ followed by a debrominative decarboxylation reaction with Et₃N in DMF under microwave irradiation condition afforded stereoselective (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in 94% yield. Treatment of (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester with EtONa in DMF afforded 1-(4-ethynylphenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in a yield of 90%.     

Derivatives of 1-aryl-5-methoxyindoles

By fusion with potassium hydroxide, derivatives of 1-aryl-3-ethoxycarbonyl-5-methoxy-2-methylindole are converted into the corresponding indole-3-carboxylic acids. When the indole-3-carboxylic acids are heated to their melting points, they are readily converted into derivatives of 1-arylindoles with unsubstituted -positions. A similar cycle of conversions has been carried out for 3-ethoxycarbonyl-5-methoxy-2-methyl-1-phenylbenzoindole. The reactions of derivatives of 1-aryl-5-methoxy-2-methylindoles with formaldehyde and dimethylamine hydrochloride gives Mannich bases.     

Halogenierte Pentan-4-olid-carbonsäuren

Halogenated pentane-4-olide carboxylic acids. A new synthesis of halogenated pentane-4-olide-4-carboxylic acids starting from α-methylideneglutaronitrile is reported. Different reaction conditions yielded 1,2-dichloro-2,4-butane dicarboxylic acid instead, the decarboxylation of which gave access to 3-chloro-but-3-ene-1-carboxylic acid.     

Silver-catalyzed facile decarboxylation of coumarin-3-carboxylic acids

A simple and highly efficient protocol with mild reaction conditions has been developed that allows the smooth protiodecarboxylation of diversely functionalized coumarin-3-carboxylic acids. In the presence of catalytic amounts of Ag₂CO₃ and acetic acid, even un-activated coumarin-3-carboxylic acids were converted in good to excellent yields and with great preparative ease to the corresponding coumarin derivatives.     

Streamlined access to 2,3-dihydropyrazino[1,2-a]indole-1,4-diones via Ugi reaction followed by microwave-assisted cyclization

An efficient method is developed to construct drug-like 2,3-dihydropyrazino[1,2-a]indole-1,4-diones from 1H-indole-2-carboxylic acids, ethyl pyruvate, isocyanides, and primary amines via a one-pot, two-step procedure involving Ugi reaction and microwave-assisted cyclization.     

PhI(OAc)2/I2-Mediated Decarboxylative C4-Amination of Coumarin-3-Carboxylic Acids via Csp2−H Dehydrogenative C−N Cross-Coupling under Ambient Conditions

An efficient and straightforward protocol for accessing a new series of functionalized 4-aminocoumarins from PIDA/I₂-mediated decarboxylative C₄-amination of coumarin-3-carboxylic acids via direct C_sp2−H dehydrogenative C−N cross-coupling with secondary amines under ambient conditions has been accomplished. The notable advantages of this protocol are the tolerance of diverse functional groups, mild reaction conditions at ambient temperature, moderate to good yields, short reaction times (in minutes), high regioselectivity, gram-scale applicability, and eco-friendliness. This is the first report of decarboxylative C_sp2−H cross-dehydrogenative C−N coupling of coumarin-3-carboxylic acids for synthesizing 4-aminocoumarins.     

Synthesis of novel 1-phenyl-1H-indole-2-carboxylic acids. II. Preparation of 3-dialkylamino, 3-alkylthio, 3-alkylsulfinyl,and 3-alkylsulfonyl derivatives

The synthesis of novel indole-2-carboxylic acids with amino- and sulfur-containing substituents in the indole 3-position is described. An Ullmann reaction with bromobenzene converted 1H-indoles with 3-(acetylamino)- and 3-(diethylamino)-substituents into 1-phenyl-1H-indoles. Reaction of 3-unsubstituted indoles with thionyl chloride provided indole 3-sulfinyl chlorides, which reacted with alkyl and aryl Grignard reagents to form the corresponding sulfoxides. The indole sulfoxides thus obtained were reduced to sulfides or oxidized to sulfones.     

Studies on decarboxylation reactions. Part 5 . Micellar catalysis and mixed solvents effects on the decarboxylation of some N-alkyl- or N-aryl-substituted 5-amino-1,3,4-oxadiazole-2-carboxylic acids

The effect of micelles and mixed solvents on the decarboxylation of some N-alkyl- or N-aryl-substituted 5-amino-1,3,4-oxadiazole-2-carboxylic acids has been studied. The data support the unimolecular decarboxylation mechanism proposed by us. Moreover, they show that mixed solvents and micelles have different effects on reactivity of the amino acids under study.     

Enantioselective catalysis,C. Decarboxylation of malonic acids in the presence of copper(I) compounds — Not a copper(I) catalysis but a base effect

Summary The catalytic decarboxylation of malonic acids, claimed to be catalyzed by copper(I) compounds, has been investigated. Decarboxylation of different malonic acid derivatives (1–5) in acetonitrile was far more effective with Cu₂O than with CuCl. Thus, the decarboxylation is obviously influenced by the basicity of the anion. In the decarboxylation of phenylmalonic acid (3),bis(tricyclohexylphosphane)copper(I) hydrogenphenylmalonate (6) and potassium hydrogenphenylmalonate (7) show nearly identical rate constants. It is concluded that the monoanions of the malonic acid derivatives are the reactive species undergoing decarboxylation. Further experiments are presented which demonstrate that everything that increases the concentration of the monoanions also increases the rate of decarboxylation. In the enantioselective decarboxylation of the monoethyl ester of methylphenylmalonic acid (2), the enantiomeric excess of (S)-(+)-ethyl 2-phenylpropionate could be raised to 34.5%ee using the alkaloid cinchonine.Dedicated to Prof. Dr.J. Müller on the occasion of his 60^th birthday.     

Synthesis of ortho- and para-quinones of the benzindole series

Ethyl esters of -(3-chloro-1,4-naphthoquinon-3-yl)crotonic or cinnamic acids were obtained by the reaction of 2,3-dichloro-1,4-naphthoquinone with ethyl esters of N-substituted -aminocrotonic or -aminocinnamic acids. These esters were converted by alkaline fusion into benz[f]indole-4,9-dione-3-carboxylic acids, and into ethyl esters of benz[g]indole-4,5-dione-3-carboxylic acid by the action of acetic acid.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 66–68, January, 1989.     

Theoretical studies on the mechanism of the thermal decarboxylation and decarbonylation of a number of α-keto-acids

Both processes of decarboxylation and decarbonylation of a number of acids including RCOCO2H,R=H,CH3,CH2F,CF3,CH=CH2,Ph,OH have been studied by semi-empirical MO theory AMI method to verify the reaction mechanism of each process and the effect of different substituents on them.The calculated results are consistent with the experimental reports and can be summed up as follows:(1) The decarboxylation of these acids to form aldehydes and carbon dioxide is concerted and takes place through a 4-membered ring transition state in which a partial negative charge develops on the carbon of the α-carbonyl group,so that the inductive effect of some substituents is favourable for this process.(2) Their decarbonylation into carboxylic acids and carbon monoxide however is the attack of the OH on the carbon of the alkyl portion of the acid,forming a 3-membered ring transition state.(3) The activation energy of decarbonylation is lower than that of decarboxylation,since oxygen is more nucleophilic than hydrogen and als     

Three-component condensation of 3-aminothiophene-2-carboxylic acid derivatives with aldehydes and Meldrum’s acid

A convenient method was developed for the synthesis of the previously unknown substituted 6,7-dihydro-4H-thieno[3,2-b]pyridin-5-ones based on the three-component condensation of 3-aminothiophenes, Meldrum’s acid, and aromatic aldehydes. 3-Aminothiophenes are easily formed in situ by decarboxylation of 3-aminothiophene-2-carboxylic acids in an acidic medium. Sodium salts of the latter acids were prepared by alkaline hydrolysis of the corresponding available esters.     

A new synthesis of some indolecarboxylic acids

1-Substituted isatins are transformed into indole derivatives by means of ethyl chloroacetate. In fact, under the conditions of the Darzens reaction they give two glycidic ester isomers 4 and 5 which, by hydrolysis in alkaline medium, undergo a transposition to indole-2,3-dicarboxylic acids 2 together with minor amounts of indole-3-carboxylic acids 3 . From isatin itself, 2,3-dicarboxyindole-1-acetic acid ( 6 ) was obtained.