Efficient Synthesis of Novel Coumarin‐3‐carboxamides (=2‐Oxo‐2H‐1‐benzopyran‐3‐carboxamides) Containing Lipophilic Spacers

The novel coumarin‐3‐carboxamides (=2‐oxo‐2H‐1‐benzopyran‐3‐carboxamides) 5a – 5g containing lipophilic spacers were synthesized through the Ugi‐four‐component reaction (Scheme 1). The reactions of aromatic aldehydes 1 , 4,4′‐oxybis[benzenamine] or 4,4′‐methylenebis[benzenamine] as diamine 2 , coumarin‐3‐carboxylic acid (=2‐oxo‐2H‐benzopyran‐3‐carboxylic acid; 3 ), and alkyl isocyanides 4 lead to the desired substituted coumarin‐3‐carboxamides 5a – 5g at room temperature with high bond‐forming efficiency. These novel coumarin derivatives exhibit brilliant fluorescence at 544 nm in CHCl₃.     

NMR and conformational studies of new 5‐phenylpyrrole‐carboxamide derivatives

The ¹H and ¹³C NMR resonances of 22 5‐(5‐substituted‐2‐nitrophenyl)‐1H‐pyrrole‐2‐carboxamides, 22 5‐(5‐substituted‐2‐aminophenyl)‐1H‐pyrrole‐2‐carboxamides, and 9 5‐phenyl‐1H‐pyrrole‐2‐carboxamides were assigned completely using the concerted application of one‐ and two‐dimensional experiments (DEPT, gs‐HMQC and gs‐HMBC). NOE studies and conformational analysis confirm the preferred conformations of such compounds. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of 5‐methyl‐4‐oxo‐2‐(coumarin‐3‐yl)‐N‐aryl‐3,4‐dihydrothieno[2,3‐d]‐pyrimidine‐6‐carboxamides

Possible approaches to synthesis of 5‐methyl‐4‐oxo‐2‐(coumarin‐3‐yl)‐N‐aryl‐3,4‐dihydrothieno[2,3‐d]pyrimidine‐6‐carboxamides 4 have been discussed. It is shown that the preferable approach is cyclization of 2‐iminocoumarin‐3‐carboxamides 1 , utilizing 5‐amino‐3‐methyl‐N²‐arylthiophene‐2,4‐dicarboxamides 2 as binucleophilic reagents. The proposed procedure allowed us to easily obtain 4 in two stages, using common reagents. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:341–346, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20303     

Microwave‐Assisted Direct Amidation of Ethyl 1‐Phenyl‐5‐hydroxy‐1H‐pyrazole‐4‐carboxylate

Microwave‐assisted treatment of ethyl 5‐hydroxy‐1‐phenyl‐1H‐pyrazole‐4‐carboxylate with excess primary aliphatic amines in 1‐propanol at 140°C and with excess pyrrolidine or piperidine in 2‐methoxyethanol at 180°C produced the corresponding carboxamides in good yields.     

Indole‐N‐Carboxylic Acids and Indole‐N‐Carboxamides in Organic Synthesis

Indoles are ubiquitous structures that are found in natural products and biologically active molecules. The synthesis of indoles and indole‐involved synthetic methodologies in organic chemistry have been receiving considerable attention. Indole‐N‐carboxylic acids and derived indole‐N‐carboxamides are intriguing compounds, which have been widely used in organic synthesis, especially in multicomponent reactions and C?H functionalization of indoles. This Minireview summarizes the advances of reactions involving indole‐N‐carboxylic acids and indole‐N‐carboxamides in organic chemistry, and discusses the synthetic potential and perspective of this field.     

A facile one step synthesis of 1,6 ‐dihydro‐7H‐pyrazolo[4,3‐d]‐pyrimidin‐7‐ones

A general synthetic approach to pyrazolo[4,3‐d]pyrimidines is reported. Aldehydes, arylideneanilines, carboxylic acids and orthoesters are used as one‐carbon units for bridging the two amino functions of 4‐amino‐1‐alkyl‐3‐propylpyrazole‐5‐carboxamides.     

1,6‐ and 1,7‐naphthyridines. IV. Synthesis of hydroxycarboxamide derivatives

A series of 8‐hydroxy‐1,6‐naphthyridin‐5(6H)‐one‐7‐carboxamides 1 and the isomeric 5‐hydroxy‐1,7‐naphthyridin‐8(7H)‐one‐6‐carboxamides 2 were synthesized. N‐Lactam unsubstituted compounds 1a‐c and 2a,b were obtained by alkoxide‐induced rearrangement of the corresponding quinolinimidoacetamides 3 . Compounds 1e,f and 2e,f were synthesized by heterocyclization of the corresponding quinolinamic esters 6 and 7 . Spectroscopic properties (uv, ir, ¹H and ¹³C nmr and ms) were analyzed and the proposed structures confirmed.     

A modified,economical and efficient synthesis of variably substituted pyrazolo[4,3‐d]pyrimidin‐7‐ones

1‐Methyl‐3‐propyl‐1H‐pyrazole‐5‐carboxylic acid ( 3 ) was exclusively brominated at the 4‐position by bromine in the dark. Brominated product 8 was then converted into 1‐methyl‐3‐propyl‐1H‐pyrazole‐5‐car‐boxamide 9 by successive treatment with thionyl chloride and ammonium hydroxide. Carboxamide 9 was treated with various aroyl amides under microwave (MW) irradiation to afford 4‐aroylamino‐1‐methyl‐3‐propyl‐1H‐pyrazole‐5‐carboxamides 10‐22 and 5‐aryl‐1‐methyl‐3‐propyl‐1,6‐dihydro‐1H‐pyrazolo[4,3‐d]pyrimidin‐7‐ones 23‐35. The 1H‐pyrazole‐5‐carboxamides 10‐22 were also converted to pyrimidinones 23‐35 either by conventional heating or by MW irradiation. However, MW irradiation method gives excellent yields in very short time.     

On the Reactions of Furan‐2,3‐diones with Oxindole (=1,3‐Dihydro‐2H‐indol‐2‐one) and Lawesson Reagent. Synthesis of New 1,3‐Dihydro‐2H‐indol‐2‐ones,Bis‐furanones,and Bis‐pyrrolones

Lactone analogues of 3‐substituted oxindoles (=1,3‐dihydro‐2H‐indol‐2‐ones) and nonbenzoid oxa‐analogous isoindigoid or nonbenzoid isoindigoid dyes were prepared by the reactions of furan‐2,3‐diones with oxindole and Lawesson reagent (Schemes 1 and 3), respectively. So, new derivatives of 2‐oxobutanoic acid, bis‐furanone, and bis‐pyrrolone, which are potentially biologically active compounds, were synthesized for the first time.     

Synthesis of Novel Pyrazino[2,1‐a]isoindolediones via Intramolecular Hydroamination of 2,3‐Dihydro‐3‐oxo‐2‐(prop‐2‐yn‐1‐yl)‐1H‐isoindole‐1‐carboxamides

Novel derivatives of pyrazino[2,1‐a]isoindolediones were synthesized through 6‐exo‐dig intramolecular hydroamination of 2,3‐dihydro‐3‐oxo‐2‐(prop‐2‐yn‐1‐yl)‐1H‐isoindole‐1‐carboxamides followed by 1,3‐H shift, in the presence of sodium hydride in DMF at 80°. All products were obtained in good yields (60 – 80%) within short reaction time (40 – 60 min).     

Synthesis of novel 3‐ and 5‐substituted indole‐2‐carboxamides

The preparation of several novel 3,5‐substituted‐indole‐2‐carboxamides is described. A 5‐nitro‐indole‐2‐carboxylate was elaborated to the 3‐benzhydryl ester, N‐substituted ester, and carboxylic acid intermedi ates, followed by conversion to the amide and then reduction of the 5‐nitro group to the amine. Indole‐2‐carboxamides with 3‐benzyl and 3‐phenyl substituents were prepared in four steps from either a 3‐bromo indole ester using the Suzuki reaction or from a 3‐keto substituted indole ester. N‐Alkylation of ethyl indole‐2‐carboxylate, followed by amidation and catalytic addition of 9‐hydroxyxanthene gave a 3‐xanthyl‐indole‐2‐carboxamide analog and a spiropyrrolo indole as a side product.     

Synthesis and biological activity evaluation of differently substituted 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides and ‐carbothioamides

Differently substituted phthalic anhydrides can react either with semicarbazide or thiosemicarbazide to give respectively 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides or 1,4‐dioxo‐3,4‐dihydrophthal‐azine‐2(1H)‐carbothioamides under mild conditions and generally with good yields. These compounds have been tested in order to evaluate their anti‐microbial activity. Furthermore a new synthetic pathway to phtha‐lazino[2,3‐b]phthalazine‐5,7,12,14‐tetraone has been devised.     

Two‐Step Synthesis of Multifunctional γ‐Lactams from γ‐Lactone

We present herein an efficient and rapid method for the synthesis of N,1‐dialkyl‐4‐(2‐hydroxyethyl)‐5‐oxopyrrolidine‐3‐carboxamides based on the conversion of γ‐lactone to γ‐lactam via the conjugate addition of primary amines to an ethyl α‐functionalized acrylate followed by intramolecular cyclization.     

One‐Pot Synthesis of Dispiro[oxindole‐3,3′‐pyrrolidines] by Three‐Component [3+2] Cycloadditions of in situ‐Generated Azomethine Ylides with 3‐Benzylidene‐2,3‐dihydro‐1H‐indol‐2‐ones

An efficient one‐pot, three‐component synthesis of novel dispiro[oxindole‐3,3′‐pyrrolidines] by 1,3‐dipolar cycloaddition of azomethine ylides, in situ generated by reaction of 1,2‐diones with sarcosine and subsequent decarboxylation, with a series of (E)‐3‐benzylidene‐2,3‐dihydro‐1H‐indol‐2‐ones is reported. Molecular complexity is generated in only one synthetic step. All reactions proceed with excellent regioselectivity and in good‐to‐excellent yields. The workup is easy, the reaction times are short, and no catalyst is required.     

New Methods for the Synthesis of 3‐Amino‐6,7‐Dihydro‐5H‐Cyclopenta[c]Pyridine‐4‐Carbonitriles and Cyclopenta[d]Pyrazolo[3,4‐b]Pyridines via a Smiles‐type Rearrangement

By reaction with sodium ethoxide and as a function of their structures, 2‐[(1‐alkyl(aryl)‐4‐cyano‐6,7‐dihydro‐5H‐cyclopenta[c ]pyridin‐3‐yl)oxy]acetamides 11 gave 1‐amino‐5‐alkyl(aryl)‐7,8‐dihydro‐6H‐cyclopenta[d ]furo[2,3‐b ]pyridine‐2‐carboxamides 10 and/or 1‐alkyl(aryl)‐3‐amino‐6,7‐dihydro‐5H‐cyclopenta[c ]pyridine‐4‐carbonitriles 12 .     

Synthesis and Nematocidal Activity of N‐Substituted 3‐Methyl‐1H‐pyrazole‐4‐carboxamide Derivatives Against Meloidogyne incognita

A series of novel pyrazole carboxamides were designed and synthesized through multi‐step reactions from ethyl acetoacetate and triethyl orthoformate, and their structures were characterized by Fourier transform infrared, ¹H‐NMR, ¹³C‐NMR, mass spectrometry, and elemental analysis. The preliminary insecticidal activity showed that some of them possessed good insecticidal activities against Meloidogyne incognita.     

1‐(2′‐Anilinyl)prop‐2‐yn‐1‐ol Rearrangement for Oxindole Synthesis

A synthetic method that relies on NIS (N‐iodosuccinimide)‐mediated cycloisomerization reactions of 1‐(2′‐anilinyl)prop‐2‐yn‐1‐ols to gem‐3‐(diiodomethyl)indolin‐2‐ones and 2‐(iodomethylene)indolin‐3‐ones has been developed. The reactions were shown to be chemoselective, with secondary and tertiary alcoholic substrates exclusively giving the 3‐ and 2‐oxindole products, respectively. In the case of the latter, the transformation features an unprecedented double 1,2‐OH and 1,2‐alkyl migration relay. Density functional theory (DFT) calculations based on proposed iodoaminocyclization species provide insight into this unique divergence in product selectivity.     

Rearrangement of spiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] to pyrrolo[1,2‐a]indole derivatives

Heating of 1′‐(N‐substituted carbamoyl)methylspiro[2H‐1‐benzopyran‐2,2′‐[2H]indoles] with potassium hydroxide in ethanol yields diastereomeric 5a,13‐methano‐6H‐1,3‐benzoxazepino[3,2‐a]indole‐12‐carbox‐amides. Reduction of the latter with sodium borohydride affords 1,2,3,9a‐tetrahydro‐2‐hydroxyaryl‐9H‐pyrrolo[ 1,2‐a] indole‐3 ‐carboxamides.     

Copper‐catalyzed Synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde by Step‐wise and One‐pot Three‐component Huisgen's 1,3‐dipolar Cycloaddition Reaction

An efficient method for the synthesis of N‐alkylated 2‐(4‐substituted‐1H‐1,2,3‐triazol‐1‐yl)‐1H‐indole‐3‐carbaldehyde has been developed starting from oxindole and indole using Huisgen's 1,3‐dipolar cycloaddition reaction of organic azides to alkynes. The effect of catalysts and solvent on these reactions has been investigated. Among all these conditions, while using CuSO₄·5H₂O, DMF was found to be the best system for this reaction. It could also be prepared in a one‐pot three‐component manner by treating equimolar quantities of halides, azides, and alkynes. The Huisgen's 1,3‐dipolar cycloaddition reaction was performed using CuSO₄·5H₂O in DMF with easy work‐up procedure.     

A Simple and Efficient Regioselective and Chemoselective Synthesis of New Substituted 3‐Methyl‐6‐arylpyridazine‐4‐carboxamides and 5‐Oxo‐3‐aryl‐5,6‐dihydropyrido[4,3‐c]pyridazine‐8‐carbaldehydes

A facile, green, and one‐pot approach is described for the regioselective synthesis of new substituted 3‐methyl‐6‐arylpyridazine‐4‐carboxamides in water at room temperature. Subsequent treatment of these products with the Vilsmeier reagent led to chemoselective and regioselective production of new 5‐oxo‐3‐aryl‐5,6‐dihydropyrido[4,3‐c]pyridazine‐8‐carbaldehydes in good to excellent yields.