Amides 3a Research Articles

Photochemical Cleavage and Release of Para-Substituted Phenols from α-Keto Amides

In aqueous media alpha-keto amides 4-YC6H4OCH2COCON(R)CH(R')CH3 (5a, R = Et, R' = H; 5b, R = iPr, R' = Me) with para-substituted phenolic substituents (Y = CN, CF3, H) undergo photocleavage and release of 4-YC6H4OH with formation of 5-methyleneoxazolidin-4-ones 7a,b. For both 5a,b quantum yields range from 0.2 to 0.3. The proposed mechanism involves transfer of hydrogen from an N-alkyl group to the keto oxygen to produce zwitterionic intermediates 8a-c that eliminate the para-substituted phenolate leaving groups. The resultant imminium ions H2C=C(OH)CON+(R)=C(R')CH3 9a,b cyclize intramolecularly to give 7a,b. The quantum yields for photoelimination decrease in CH3CN, CH2Cl2, or C6H6 due to competing cyclization of 8a,b to give oxazolidin-4-one products which retain the leaving group 4-YC6H4O- (Y = H, CN). A greater tendency to undergo cyclization in nonaqueous media is observed for the N,N-diethyl amides 5a than the N,N-diisopropyl amides 5b. With para electron releasing groups Y = CH3 and OCH3 quantum yields for photoelimination significantly decrease and 1,3-photorearrangment of the phenolic group is observed. The 1,3-rearrangement involves excited state ArO-C bond homolysis to give para-substituted phenoxyl radicals, which can be observed directly in laser flash photolysis experiments.

Synthesis and biological activity of 4-thiazolidinones, thiosemicarbazides derived from diflunisal hydrazide

Two novel series of 4-thiazolidinone derivatives, namely 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylic acid [2-(5-nitro-2-furyl/substituted phenyl)-4-thiazolidinone-3-yl]amides ( 5a–g) and 2-(2′,4′-difluoro-4-hydroxybiphenyl-3-carbonylhydrazono)-3-alkyl/aryl-4-thiazolidinones ( 6a–e) together with 5-(2′,4′-difluoro-4-hydroxybiphenyl-5-yl)-2-cyclohexylamino-1,3,4-oxadiazole ( 7a) have been synthesized as title compounds. 1-(2′,4′-Difluoro-4-hydroxybiphenyl-3-carbonyl)-4-alkyl/arylthiosemicarbazides ( 4a–g) were also obtained and used as intermediate to give the title compounds. All synthesized compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, antiviral and antimicrobial activities against various virus, bacteria and fungi strains.

Bu3SnH‐Mediated 5‐Exo Selective Radical Cyclization of N‐Vinyl‐α,β‐unsaturated Amides Leading to γ‐Lactams.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Synthesis of (4E )-N -(4-chlorophenyl)-5-substituted-2-diazo-3-oxopent-4-enoic Acid Amides

The (4E)-N-(4-chlorophenyl)-5-(3-chlorophenyl)-2-diazo-3-oxopent-4-enoic acid amides 5a˜j were synthesized with N-(4-chlorophenyl)-2-diazo-3-oxobutyramide 4 from p-chloroaniline and various arylaldehydes. The yielded products 5a˜j were investigated with NMR, MS, IR, and X-ray crystallographic techniques.

Preparation and photophysical properties of benzimidazole-based gels

Two kinds of benzimidazole-based compounds, pyridinium salts ( 1a– 3b) and amides ( 4a, 4b), which consist of long alkyl chains and benzimidazole moiety, were designed as blue colour fluorescent gelators. The pyridinium salts 1a– 3b were synthesized using the simple and economical microwave-assisted method. The gelation ability of 1a– 2b in a variety of organic solvents was higher than that of 3a– 4b. The SEM of the gels showed fibrous, spherical and filmlike morphologies depending on the gelators and the solvents. Red shift of fluorescence spectra and blue shift of absorption spectra from solution to gel state was observed in the organic solvent tested. The fluorescence intensity of the gel and the solution state increased with the increase of the solvent polarity. The fluorescence quantum yields of the gels were found to be considerably lower by one or two orders of magnitude than those of the solutions.

Bu 3SnH-mediated 5-exo selective radical cyclization of N-vinyl-α,β-unsaturated amides leading to γ-lactams

Treatment of N-vinyl-α,β-unsaturated amides 1a– h with Bu 3SnH and a catalytic amount of AIBN in boiling benzene caused 5-exo cyclization of allylic O-stannyl ketyl radicals generated by addition of Bu 3Sn· on the amide-oxygen atoms to provide γ-lactams 2a– h after acidic workup. When enamide 1d was treated with Bu 3SnH in the presence of AIBN followed by aldehydes 3a– d , sequential radical cyclization and aldol reactions occurred to afford anti-adducts 4a– d and syn-adducts 5a, b .

The synthesis of substituted bipiperidine amide compounds as CCR3 ligands: Antagonists versus agonists

Structure–activity relationship study of bipiperidine amide 1 has identified the reverse bipiperidine amide 4a as a CC chemokine-3 (CCR3) receptor antagonist. Optimization of the structure–activity relationship of compound 4a has resulted in the identification of a CCR3 antagonist 4i as well as a CCR3 agonist 13.

The First Cu(I)‐Mediated Nucleophilic Trifluoromethylation Reactions Using (Trifluoromethyl)trimethylsilane in Ionic Liquids.

The new ionic liquids (5a–8a) were used as reaction media for nucleophilic trifluoromethylation reactions of trifluoromethyl(trimethyl)silane with (1) aryl, allyl, benzyl, and alkyl halides in Cu(I)-mediated C–C bond formation reactions, and (2) carbonyl functionalities catalyzed with Ph3P or CsF. In addition, conversion of benzyl bromide as a model compound to benzyl fluoride was examined in 6a using CsF as the fluorinating reagent. The morpholinium-based ionic liquid (6a) stood out as an efficient solvent system comparable to organic solvents and superior to the other new ionic liquids prepared in this work as well as to [bmim]+[PF6]−. Neat reactions of N-methyloxazolidine (1), N-methylmorpholine (2), N-methylimidazole (3) or N-methyltriazole (4) with 2-(2-ethoxyethoxy)ethyl bromide (BrCH2CH2OCH2CH2OCH2CH3, 9) or 2-bromoethyl methyl ether (BrCH2CH2OCH3, 10) at 75 or 105 °C gave the N-(2-ethoxyethoxy)ethyl- or N-methoxyethyl-substituted oxazolidinium, morpholinium, imidazolium and triazolium quaternary bromides (1a–4a, 1b–4b) which were metathesized with LiN(SO2CF3)2 to form the respective room-temperature liquid bis(trifluoromethanesulfonyl)amides 5a–8a and 5b–8b in high yields with transition or melting points 310 °C as determined by thermogravimetric analyses (TGA). Densities range between 1.29 and 1.53 g cm−3 at 25 °C.

Synthesis, luminescence and electrochromism of aromatic poly(amine–amide)s with pendent triphenylamine moieties

A new triphenylamine-containing aromatic dicarboxylic acid monomer, N,N-bis(4-carboxyphenyl)-N′,N′-diphenyl-1,4-phenylenediamine (2), was synthesized from the amination reaction between 4-aminotriphenylamine and 4-fluorobenzonitrile and subsequent alkaline hydrolysis of the dinitrile intermediate. A series of novel aromatic poly(amine–amide)s with triphenylamine units in the main chain and as the pendent group were prepared from the newly synthesized dicarboxylic acid and various aromatic diamines. These poly(amine–amide)s were amorphous and readily soluble in many organic solvents. All the polymers could be solution-cast into flexible films with good mechanical properties. They had excellent levels of thermal stability associated with high glass-transition temperatures (226–261 °C). These polymers exhibited strong UV–vis absorption bands at 350–365 nm in NMP solution. Their photoluminescence spectra showed maximum bands around 512–543 nm in the green region. The hole-transporting and electrochromic properties are examined by electrochemical and spectroelectrochemical methods. Cyclic voltammograms of the poly(amine–amide) 5a prepared from the dicarboxylic acid monomer 2 with a structurally similar diamine monomer N,N-bis(4-aminophenyl)-N′,N′-diphenyl-1,4-phenylenediamine (4a) exhibited four reversible oxidation redox couples in acetonitrile solution at E1/2 = 0.60, 0.80, 0.97 and 1.13 V, respectively. All the poly(amine–amide)s exhibited excellent reversibility of electrochromic characteristics by continuous five cyclic scans between 0.0 to 1.30 V, with a color change from the original pale yellowish neutral form to the green and then to blue oxidized forms.

A novel route to imidoylbenzotriazoles and their application for the synthesis of enaminones.

Reactions of secondary amides 2a-i with 1-chloro-1H-benzotriazole and triphenylphosphine give imidoylbenzotriazoles 3a-i. The treatment of 3a,b,e,g with silyl enol ethers 5a,b in the presence of potassium tert-butoxide provides a new general approach to enaminoketones 6a-h.

5-Cyanoamino-4-imidazolecarboxamide and Nitrosative Guanine Deamination: Experimental Evidence for Pyrimidine Ring-Opening during Deamination

5-Cyanoamino-4-imidazolecarboxamide 4a (R = CH2-O-CH2-CH2-OH) has been synthesized, purified, and fully characterized by MS, MS/MS, HRMS, IR spectroscopy, and by 1H and 13C NMR spectroscopy. It is shown that cyclization of 4a yields the guanine 6a and the isoguanine 12a. Our findings provide experimental evidence in support of our hypothesis that the formation of oxanine and xanthine in nitrosative guanine deamination may proceed via pyrimidine ring-opened intermediates. The observed formation of 6a from the amide 4a (XH2 = NH2) shows that, in analogy, oxanine can be formed from 3 (XH = OH). The formation of 12a from 4a reveals for the first time the possibility that oxanine might be formed by a second pathway that involves electrocyclic reaction of 3. Finally, the new chemistry suggests the possibility for a new dG-to-dG cross-link.

Study on the stevioside analogues of steviolbioside, steviol, and isosteviol 19-alkyl amide dimers: synthesis and cytotoxic and antibacterial activity.

A new group of steviolbioside amide dimers 2a-g, derivatives 2h-i and their related steviol and isosteviol amide dimers 3a and 4a were prepared by reacting aliphatic alkylamine and alkyldiamines with PyBOP and DIEA. The synthesized compounds had cytotoxic effects on cancer and human embryonic lung cells. Compounds 3a, 4a, 2b and 2h were cytotoxic to cancer cells and to a lesser extent to human embryo lung cells. Compounds 2f, 2g and 4 of this series had favorable antibacterial effects, and were superior to penicillin G at inhibiting growth of Bacillus subtilis (BCRC 10029). The cytotoxicity and antibacterial effects may depend on the dimerization and derivative moieties in relation to the respective aglycons.

Microwave assisted N-chlorination of secondary amides

Acyclic (1a–c), and cyclic (4a–f) secondary amides are N-chlorinated by N-chlorobenzotriazole under 15–20 minutes of microwave heating to give the corresponding N-chloro secondary amides (3a–c, 5a–f) in yields of 50-80%.

Alternating poly(ester amide)s from succinic anhydride and α,ω‐amino alcohols: synthesis and thermal characterization

AbstractAlternating poly(ester amide)s 6a–e from succinic anhydride and α,ω‐amino alcohols H2N—(CH2)x—OH (x = 2–6) 2a–e were obtained in two steps: α‐carboxyl‐ω‐hydroxy amides 3a–e were prepared from the starting materials in a highly selective reaction, followed by a polycondensation reaction. 1H and 13C NMR analyses of the poly(ester amide)s clearly reveal the alternating microstructure. The poly(ester amide)s with homologous α,ω‐amino alcohols H2N—(CH2)x—OH (x = 2–6) are semi‐crystalline materials, their melting points show the odd/even effect observed for [n]‐polyamides and [n]‐polyurethanes. Heating the poly(ester amide)s 6a–e yields the corresponding N‐(hydroxyalkyl) imides 4a–e with no trace of cyclic ester amides. Theoretical calculations revealed that the cyclic ester amides 5a–e are clearly richer in energy than the isomeric N‐(hydroxyalkyl) imides. These results show that cyclic ester amides can not be prepared from N‐(hydroxyalkyl) imides by ring‐enlargement reactions. Copyright © 2003 Society of Chemical Industry

One‐Pot Synthesis of N‐Aryl‐5‐aryl‐2‐furoyl Amides via Reaction of 5‐Aryl‐2‐furoic Acid with Arylamines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Resolution of 1-Aryl-1,2,3,4-Tetrahydroisoquinolines via Crystallization ofO-Acetylmandelic Amides

(R)-O-Acetylmandelic acid is an efficient chiral auxiliary for the resolution of racemic 1-aryl-1,2,3,4-tetrahydroisoquinolines 2 and 3 via crystallization of the corresponding diastereomeric amides 5 and 7. Acidic hydrolysis of (R,S)-O-acetylmandelylanilide 7b afforded optically pure (>99% ee) (S)-1-(2-aminophenyl)-1,2,3,4-tetrahydroisoquinoline (3b). Removal of the chiral auxiliary attached to the tetrahydroisoquinoline nitrogen (amide 5a) afforded partially racemized amine 2 both under hydrolytic and reductive cleavage conditions. Brønsted acid catalyzes migration of the chiral auxiliary from the isoquinoline nitrogen to aniline (6a → 7a).

A novel L-neopentylglycine derivative as auxiliary for copper-catalyzed asymmetric Michael reactions.

L-Neopentylglycine diethylamide (4a). was prepared from the new unnatural amino acid L-neopentylglycine (1). The utilization of amide 4a as a chiral auxiliary in the copper(II)-catalyzed asymmetric Michael reaction was investigated in comparison with L-valine diethylamide (4b). Cyclic beta-oxocarboxylates 7 react with 4a and 4b to give the respective enaminoesters 8, which were converted with methyl vinyl ketone (9) in the presence of 10 mol% Cu(OAc)(2). H2O at room temperature in acetone to yield the optically active Michael addition products (R)-10a, b with high selectivity independent of the starting enamine. In the case of the seven-membered beta-oxocarboxylate 7c, however, the valine-derived enamine 8f led to higher enantioselectivity for product 10c. Despite the bulkiness of the neopentyl group, the isopropyl group with an alpha-branch has a better stereoinducing effect.

Synthesis and anti-inflammatory activity of phthalimide derivatives, designed as new thalidomide analogues

This paper describes the synthesis and anti-inflammatory activity of new N-phenyl-phthalimide sulfonamides ( 3a– e) and the isosters N-phenyl-phthalimide amides ( 4a– e), designed as hybrids of thalidomide ( 1) and aryl sulfonamide phosphodiesterase inhibitor ( 2). In these series, compound 3e (LASSBio 468), having a sulfonyl-thiomorpholine moiety, showed potent inhibitory activity on LPS-induced neutrophil recruitment with ED 50=2.5 mg kg −1, which was correlated with its inhibitory effect on TNF-α level.

N,N-Dilithioarylamines as New Building Blocks in Amide Chemistry; the Structure of a Carbanion-Stabilized [C2N5Li10]2− Cluster

2-Biphenylamine reacts with (dimethylamino)trimethylstannane in a 2:1 molar ratio, undergoing transamination to the distannylamine 1a. The extremely air and moisture sensitive (2-biphenyl)-N,N-dilithium amide 2a is obtained by the stannazane cleavage reaction of 1a with nBuLi in MeOtBu. Compound 2a is the first example of a highly reactive, doubly metallated amine that can be used as a precursor in inorganic synthesis under fairly mild conditions. For example, both lithium atoms can be substituted by boryl or silyl groups, which cannot be introduced using other routes. Amide 2a crystallizes as a cluster containing five RNLi2 units, and is unexpectedly stabilized by two methanide anions. When the methanide ions are included, the lattice of the central C2N4Li8 unit represents a section of the antiisomorphic lattice of the CaF2-type. DFT (B3LYP) calculations and population analysis (NBO) have been carried out to get further insights into the thermodynamics of several dilithioamines (RNLi2)n (R = H, CH3, Ph; n = 1−6). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Benzene fused monocyclic enediynyl amides: synthesis, reactivity and DNA-Cleavage activity in comparison to the corresponding sulfonamides

Monocyclic enediynyl amides 2a–2c have been synthesized via the corresponding free amine 5. Kinetic studies in chloroform revealed the reactivity of these amides towards Bergman cyclization to be less than that of the corresponding sulfonamides. However, differential scanning calorimetry (DSC) measurements in the solid state and DNA-cleavage studies in aqueous buffer showed higher reactivity for the amides than the sulphonamides.