N-[3-nitro(amino)coumarin-4-yl]anthranilic acid amides. Synthesis of 6,7,8,13-tetrahydro[1]benzopyrano[4,3-b][1,4] benzodiazepine-6,8-dione

The reaction of 3-nitro-4-chlorocoumarin with anthranilic acid was used to synthesize N-(3-nitro-4-coumarinyl)-anthranilic acid, from which, through the acid chloride, we obtained a number of amides, which were reduced to N-(3-amino-4-coumarinyl)anthranilic acid amides The latter are cyclized under the influence of hydrochloric acid to 6,7,8,13-tetrahydro[1]benzopyrano-[4,3-b][1, 4]benzodiazepine-6,8-dione, which was also obtained from N-(3-amino-4-coumarinyl)anthranilic acid by its thermolysis or treatment with hydrochloric acid.See [1] for our preliminary communication.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1208–1212, September, 1989.     

Nonpolymeric hydrogelator derived from N-(4-pyridyl)isonicotinamide

A series of pyridyl amides derived from isonicotinic acid, nicotinic acid, and benzoic acid have been synthesized. Only N-(4-pyridyl)isonicotinamide 1 is found to be an efficient hydrogelator with a minimum gelator concentration of 0.37 wt %. A wide range of concentrations (0.37-20 wt %) could be used to form hydrogels. The other amides, namely, N-(3-pyridyl)isonicotinamide 2, N-(2-pyridyl)isonicotinamide 3, N-(phenyl)isonicotinamide 4, N-(4-pyridyl)nicotinamide 5, N-(3-pyridyl)nicotinamide 6, and N-(4-pyridyl)benzamide 7, did not show any gelation properties. Fourier transform infrared spectroscopy, variable temperature 1H NMR, single-crystal diffraction and X-ray powder diffraction (XRPD), and scanning electron microscopy have been used to characterize the gel. Single-crystal diffraction and XRPD studies indicate that the morph responsible for gel formation is different from that in its bulk solid and xerogel.     

Solvent extraction of technetium(VII) by cyclic amides

The extraction behavior of heptavalent technetium with cyclic amides inn-dodecane from nitric acid solution was studied. The amides investigated are N-(2-ethyl)hexylbutyrolactam(EHBLA). N-(2-ethyl)hexylvalerolactam(EHVLA), N-(2-ethyl)hexyl-caprolactam (EHCLA), N-octylcaprolactam(OCLA), a mixture of 3-octyl-N-(2-ethyl)hexylvalerolactam and 4-octyl-N-(2-ethyl)hexylvalerolactam (3,4,OEHVLA), 2-octyl-N-(2-ethyl)hexylcaprolactam(2OEHCLA), a mixture of 3-octyl-N-(2-ethyl)hexylcaprolactam and 5-octyl-N-(2-ethyl)hexylcaprolactam(3,5,OEHCLA) and that of 3-octyl-N-octylcaprolactam and 5-octyl-N-octylcaprolactam(3,5,OOCLA). From the results of the distribution ratio of Tc(VII) as a function of acid concentration, cyclic amides concentration and HTcO₄ concentration, the effects of both the ring size of cyclic amide and structure of the substituents attached to different positions of the cyclic ring on the extraction behavior of Tc(VII) were discussed. A clear steric hindrance was observed. For applications, 3,4,OEHVLA is proposed as the best extractant for Tc from acidic solution.     

Extended application of a chiral stationary phase based on (+)-(1 8-crown-6)-2,3,11,12-tetracarboxylic acid to the resolution of N-(substituted benzoyl)-alpha-amino acid amides

A chiral stationary phase (CSP 1) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid was applied to the resolution of N-(substituted benzoyl)-alpha-amino acid amides and esters. N-(Substituted benzoyl)-alpha-amino acid amides were well resolved using a mixture of acetic acid-triethylamine-acetonitrile (0.01:0.05:100, v/v/v) as an optimum mobile phase while N-(substituted benzoyl)-alpha-amino acid esters were not resolved at all. In contrast, both N-(substituted benzoyl)-alpha-amino acid amides and esters were not resolved at all or resolved very poorly on another CSP (CSP 2), which lacks the two N-H hydrogens of the amide tethers of CSP 1. Among the substituents on the benzoyl group of analytes, the nitro group was the best for good resolution of analytes on CSP 1. From these results, the two N-H hydrogens of the amide tethers of CSP 1, the carbonyl oxygen of the amide group of analytes, and the nitro group on the benzoyl group of analytes were concluded to play significant roles in chiral recognition. In addition, various N-(3,5-dinitrobenzoyl)leucine amides with different lengths of N-alkylamide chains were resolved on CSP 1 and N-(3,5-dinitrobenzoyl) leucine N-propylamide was found to show the best chiral recognition in terms of the separation (alpha = 1.30) and the resolution factor (Rs= 3.17).     

Azomethine ylides from tin-substituted cyclic carbinol amides: a new route to highly substituted pyrrolizidines

[reaction: see text] Addition of organolithium and organomagnesium reagents to N-(tri-n-butylstannylmethyl)phthalimides yields N-(tri-n-butylstannylmethyl) cyclic carbinol amides, which form azomethine ylides upon treatment with HF.pyridine. This novel route to azomethine ylides allows rapid access to highly functionalized pyrrolizidines (1,2,3,9b-tetrahydropyrrolo[2,1-a]isoindol-5-ones).     

Study of the factors that control the ratio of the products between 5-fluorouracil, uracil, and tetrahydrobenzoxazepine O,O-acetals bearing electron-withdrawing groups on the nitrogen atom

(RS)-1-(2-Nitrobenzenesulfonyl)- and (RS)-1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepines are better substrates than 1-acyl-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 degrees C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1" position, while the attachment of the uracil fragment is through N-3" or N-1" of the cyclic or acyclic products, respectively. The causes that influence the course of the reactions are analyzed and discussed. Examination of the (1)H NMR spectra revealed the presence of a single form for the secondary amine 11 and of two conformers for the tertiary sulfonamides 7a,b, 9a,b, and 10b and for the amides 7d and 13, with the following distribution: 7a, 59/41; 7b, 53/47; 9a, 52/48; 9b, 59/41; 10b, 56/44; 7d, 50/50; 13, 80/20. On increasing the temperature, the (1)H NMR spectrum (DMSO-d(6)) of 7b showed coalescence at 110 degrees C. The torsional barrier determined [DeltaG(c)++ value of 19.0 +/- 0.2 kcal.mol(-1) (79.1 +/- 1.0 kJ.mol(-1))] proved to be the highest ever observed for sulfonamide moieties.     

Sur l'orientation de l'acétylation des nitriles et amides coumariliques Bz-méthoxylés

The acetylation of coumarilic amides and nitriles gave slowly 5-acetylcoumarilamide and a mixture of 5-acetylcoumarilic acid, 4-acety1-2-cyanobenzofuran and 5-acetyl-2-cyanobenzofuran. Using the same conditions, the acetylation of methoxy derivatives of these amides and nitriles gave rapidly and in high yields, the corresponding ortho and para derivative with or without demethylation.     

A convenient protocol for selective cleavage of 2-hydroxy acid amides. Application to semisynthesis of the cyclic heptapeptide aza HUN-7293

A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy acid amides under smooth conditions. Successful application of this methodology to the open-chain transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide 18 with unprotected N-terminus in 70-75% yield. This result demonstrates that the protocol developed even works in the presence of an ester and several methylated and unmethylated amide bonds. Finally, a sequence of ligation of methyl D-dehydroglutaminate (20) to the C-terminus of the saponification product 21, followed by the degradation protocol and ring closure, allowed chemical "point mutation" at the DGCN site affording the aza analogue of HUN-7293 (24) in 15% overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of 2-hydroxy acid amides.     

Comparative Studies on the Amidoalkylating Properties of N-(1-Methoxyalkyl)Amides and 1-(N-Acylamino)Alkyltriphenylphosphonium Salts in the Michaelis–Arbuzov-Like Reaction: A New One-Pot Transformation of N-(1-Methoxyalkyl)Amides into Phosphonic or Phosphinic Analogs of N-Acyl-α-Amino Acids

Abstract

It was demonstrated that N-(1-methoxyalkyl)amides do not react with trimethyl phosphite under neutral or basic conditions. The treatment of N-(1-methoxyalkyl)amides with trialkyl phosphites or dialkyl phosphonites, triphenylphosphonium tetrafluoroborate, and Hünig's base caused immediate formation of the corresponding 1-(N-acylamino)-alkyltriphenylphosphonium tetrafluoroborates, followed by the slow Michaelis–Arbuzov-like reaction of phosphonium salt with phosphites or phosphonites to α-(N-acylamino)-alkanephosphonic or α-(N-acylamino)alkanephosphinic acid esters, respectively. A plausible mechanism of the considered transformations, assuming an equilibrium between N-(1-alkoxyalkyl)amide, triphenylphosphonium tetrafluoroborate, 1-(N-acylamino)alkyltriphenyl-phosphonium salt, N-acylimine, and N-acyliminium salts, is discussed.     

含磺酰胺基和羧苯基的异方酰胺的合成

以3-[邻(或对)羧苯胺基]-4-羟基-3-环丁烯二酮(1a, 1b)为底物,与一些磺胺反应, 成功地制得了14个新的不对称取代的异方酰胺。3a～3f和4a～4f结构上的共同特点是, 有药物作用的磺酰胺和邻(或对)氨基苯甲酸的结构单元, 通过方酸四碳环的桥接作用而共存于同一分子之中。     

The standard enthalpies of formation of crystalline N-(carboxymethyl)aspartic acid and its aqueous solutions

The energy of combustion of N-(carboxymethyl)aspartic acid (CMAA) was determined by bomb calorimetry in oxygen. The standard enthalpies of combustion and formation of crystalline N-(carboxymethyl)aspartic acid were calculated. The heat effects of solution of crystalline CMAA in water and a solution of sodium hydroxide were measured at 298.15 K by direct calorimetry. The standard enthalpies of formation of CMAA and its dissociation products in aqueous solution were determined.     

Reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid <Emphasis Type="Italic">N</Emphasis>-(4-acetylaminosulfonylphenyl)amides with hydrazine hydrate and phenylhydrazine

Reaction of 4-aryl-2-hydroxy-4-oxo-2-butenoic acid N-(4-acetylaminosulfonylphenyl)amides with hydrazine hydrate and phenylhydrazine in acetic acid has afforded N-[4-(acetylaminosulfonyl)phenyl]-5-arylpyrazole-3-carboxamides.     

Derivatives of the N-(pyrid-2-yl)amides of 3-aminocrotonic acid as chelating ligands

New chelating ligands, N-(pyrid-2-yl)amides of 4,4,4-trichloro-3-amino-2-cyanocrotonic acid have been synthesized from N-(pyrid-2-yl)amides of cyanoacetic acid and CCl₃CN. It has been demonstrated that by the action of butylthiodibutylborane they form binuclear boron chelate complexes. Analogous chelates have also been obtained from the N-(pyrid-2-yl)amides of acetoacetic and 4,4,4-trichloro-3-aminocrotonic acids.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 974–979, April, 1992.     

Amidation of Diamantane with Carboxylic Acid Amides and Carbon Tetrachloride in the Presence of Binder-Free Ni-HY Zeolite

Russian Journal of Organic Chemistry - N-(Diamantan-1- and 4-yl) carboxamides were synthesized by reaction of diamantane with carboxylic acid amides in the presence of carbon tetrachloride and...     

Synthesis of 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro- 1,6-naphthyridines by a directed lithiation reaction

N-(tert-butoxycarbonyl)anilines (7), are easily converted in a one pot reaction sequence into the N- (tert-butoxycarbonyl)-1,2,3,4-tetrahydroquinolines (8), by directed ortho lithiation followed by reaction with 1- chloro-3-iodopropane, hence providing a new versatile quinoline ring nucleus synthesis. In an analogous reaction 2-N-(tert-butoxycarbonyl)- and an 2-N-(pivaloylamino) pyridine are converted to 1,2,3,4-tetrahydro-1,6- naphthyridines.     

Phosphoric Anhydride in Organic Synthesis. Migration of the Dihydroxyphosphoryl Group in Amides

Acyclic and cyclic amides are phosphorylated by phosphoric anhydride. The phosphorylated acyclic amides exhibit a pronounced tendency to N-O reversible or irreversible phosporotropy. In cyclic amides it is less specific. For hydrazide of benzoic acid there is determined 1 – 4 reversible phosphorotropy.     

N-苄基酰胺类化合物的合成

分别以3-甲氧基苄胺, （S）-α-苯乙胺, （R）-α-苯乙胺或苄胺为原料,对甲苯磺酸为催化剂,甲苯为溶剂,分别与正戊酸、软脂酸、己二酸和对硝基苯甲酸经酰化反应合成了6个N-苄基酰胺类化合物,收率10.7%～22.3%,其中N-(3-甲氧基苄基)戊酰胺为新化合物,其结构经¹H NMR, IR和元素分析表征。     

Synthesis of 6‐Fluoro‐7‐cyclic Amino‐substituted Dicarboxylic Acid Quinolones and their Antibacterial Activity

Novel 1‐carboxymethyl‐6‐fluoro‐7‐cyclic amino‐substituted‐4‐oxo‐1,4‐dihydroquinolone‐3‐carboxylic acids 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j , 7k , 7l , 7m , 7n were synthesized as a new class of quinolones. Ethyl‐6‐fluoro‐7‐chloro‐1,4‐dihydro‐4‐quinoline‐3‐carboxylic acid was prepared from conventional method and reacted with ethyl bromoacetate to furnish N‐carboxymethyl derivatives. The compounds were screed against various Gram‐positive and Gram‐negative bacterial strains. Antibacterial activity data is validated by molecular docking studies.     

Nitrogen and sulfur containing heterocycles. 50. Synthesis and reactions of 6-oxopyrimido[4,5-b][1,4]thiazine-7-carboxylic acid derivatives

Reaction of 5-amino-6 mercaptopyrimidines with diethyl bromomalonate gave ethyl 6-oxopyrimido-[4,5-b][1,4]thiazine-7-carboxylates, from which there was synthesized a series of derivatives at the carboxyl group (amides, hydrazides, and, from the latter, urethanes). Desulfurization of the 6-oxopyrimidothiazine-7-carboxylic acid esters gave N-(pyrimidin-5-yl)monoamides of ethyl malonate.For communication 49 see [1].Center for Chemistry of Drugs—All-Russian Research Chemical-Pharmaceutical Institute, Moscow 119021, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 822–828, June, 1999.     

Synthesis of N-(Hydroxy)amide- and N-(Hydroxy)thioamide-containing peptides

Methods developed with N-(benzoyloxy)amines and hydroxamic acids were used in the synthesis of N-(hydroxy)amide-containing pseudopeptides. Acylation of N-(benzoyloxy)phenethylamine with the acid chloride of N(alpha)-Fmoc-L-leucine provided a N(alpha)-Fmoc-N-(benzoyloxy)-L-leucinamide in 90% yield. Deprotection of the benzoyl group (using 10 vol % NH(4)OH/MeOH) provided the N(alpha)-Fmoc-N-(hydroxy)-L-leucinamide in 87% yield. In general, the appended Fmoc group allowed for further elaboration of the N-hydroxy-N-(alkyl)amides using classic peptide-coupling methods. A practical synthetic strategy was developed, and racemization issues were addressed using diastereomeric Val-Leu derivatives. In addition, N-(hydroxy)thioamides were generated from the corresponding N-(benzoyloxy)thioamides. N-(Benzoyloxy)thioamides were obtained in moderate yields (53-76%) from the reaction of the corresponding N-(benzoyloxy)amides with Lawesson's reagent (i.e., 2, 4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disu lfide). In summary, this new technology allows for the introduction of either N-hydroxyamide or N-(hydroxy)thioamide linkages into pseudopeptide chains without racemization.