N-(2-Pyridyl)amides of 2,4-Dioxobutyric Acids in Reactions with Diazoalkanes

N-(2-Pyridyl)amides of 4-R-2-alkoxy-4-arylcrotonic acids and 3-alkoxy-3-aroylmethyl-2-oxo-2,3-dihydroimidazo[1,2-a]pyridines have been synthesized by the interaction of N-(2-pyridyl)amides of 4-aryl-2,4-dioxobutyric acids with diazoalkanes. The structure and mechanism of formation of the products are discussed.     

An Abnormal Reaction of N-(2,4-dinitrophenyl)-L-proline with Thionyl Chloride

N-(2,4-Dinitrophenyl)-4-amino-n-butyl aldehyde 3 was obtained with high yield of 80% when N-(2,4-dinitrophenyl)-L-proline 1 reacted with SOCl2 at room temperature,However,the anticipated product N-(2,4-dinitrophenyl)-Tetrahydropyrrolyl-2-(4-methylthiophenyl)ketone 2 did not be produced.The mechanism was discussed in this article.     

A Convenient Synthesis of 4-(2-Furyl)-2-substituted Thiazoles Utilising [Hydroxy(tosyloxy)iodo]benzene

A facile synthesis of 4-(2-furyl)-2-substituted thiazoles by hypervalent iodine oxidation of 2-acetylfuran (1) using [hydroxy(tosy-loxy)iodo]benzene, followed by treatment of the reaction mixture with appropriate thioureas/thioamides is described.     

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.     

Boron chelate complexes with 4-[N-(R-pyrid-2-yl)carbamoyl]-3-amino-2-cyanobuten-2-ic acid esters (codimers of N-(R-pyrid-2-yl)amides and the ethyl ester of cyanoacetic acid)

Mono- and binuclear boron chelates have been synthesized by the action of butylthiodibutylborane on the ethyl esters of 4-[N-(R-pyrid-2-yl)carbamoyl]-3-amino-2-cyanobuten-2-ic acids (codimers of N-(R-pyrid-2-yl) amides and the ethyl ester of cyanoacetic acid). Complexes of this type can exist in solution in the form of two tautomers: acetamide acid derivatives or the corresponding ketene N,O-acetals.N. D. Zelinski Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 9, pp. 2162–2170, September, 1992.     

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).     

Synthesis and anti-inflammatory activities of some N-[pyridyl(phenyl)carbonylamino]-tert-butyl/phenyl-1,2,3,6- tetrahydropyridines

Nucleophilic attack of tert-butyl/phenylpyridines 3 on 1-chloro-2,4-dinitrobenzene 4 results in the formation of tert-butyl/phenyl substituted 2,4-dinitrophenylpyridinium chlorides 5. Benzoyl hydrazide and pyridyl acid hydrazides 6 were reacted with the pyridinium chlorides 5 furnishing the 2,4-dinitroanilino derivatives 7, which were subsequently hydrolyzed with water: p-dioxane to yield N-[pyridyl(phenyl)carbonylimino]-tert-butyl/phenylpyridinium ylides 8. The title compounds 9, N-[pyridyl(phenyl)carbonylamino]-tert-butyl/phenyl-1,2,3,6- tetrahydropyridines, were obtained by sodium borohydride reduction of the pyridinium ylides 8. The anti-inflammatory activities of compounds 9a-p were determined using the carrageenan-soaked sponge model of inflammation in Sprague Dawley rats. All compounds tested showed moderate to good anti-inflammatory effects compared to indomethacin. Compounds 9b, 9c and 9p were the most active analogs of the group in this model.     

Thionation using fluorous Lawesson's reagent

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).     

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.     

Unprecedented 1,4-stannatropy: effective generation of azomethine ylides as nitrile ylide equivalents from N-(stannylmethyl)thioamides

Generation and cycloaddition of less- or non-stabilized azomethine ylides, or nitrile ylide equivalents, via unprecedented 1,4-stannatropy of N-(tributylstannylmethyl)thioamides were achieved. The reactions with dipolarophiles, such as electron-deficient alkenes and alkynes, afforded corresponding pyrrolidine and pyrrole derivatives effectively.     

Enantioswitchable catalysts for the asymmetric transfer hydrogenation of aryl alkyl ketones

A subtle change in the ligand structure, replacing the carbonyl oxygen with sulfur in simple alpha-amino acid amides, resulted in a dramatic activity and selectivity improvement in the rhodium- or ruthenium-catalyzed reduction of ketones under hydrogen transfer conditions. In addition, in most cases, a switch of the product's absolute configuration was observed on going from amides to the corresponding thioamides. Under optimized conditions, we obtained the secondary alcohol products in high yield and enantioselectivity (up to 97% ee) using only 0.25 mol % catalyst loading. [structure: see text]     

Di-μ-hydroxy-bis(N,N,N′,N′-tetramethylenediamine)-copper(II) chloride [Cu(OH)·TMEDA]2Cl2: an efficient, practical catalyst for benzylation and allylation of amides

An efficient protocol for the benzylation or allylation of amides using the corresponding benzyl or allyl chlorides as electrophiles under basic conditions with commercially available 5 mol % of [Cu(OH)TMEDA]₂Cl₂ as catalyst was developed. Under these conditions, unprotected amino acids were benzylated without any racemization.     

3-[N-(4-甲基苯基)氨基羰基]-5-[4-(4-甲酸基苯甲氧基)苯亚甲基]-2,4-噻唑烷二酮的合成

以对甲苯胺和对甲基苯甲酸甲酯为起始原料,经NBS溴化、亲核取代、酸水解和Knoevenagel缩合等6步反应合成了抗细菌生物膜化合物—3-[N-(4-甲基苯基)氨基羰基]-5-[4-(4-甲酸基苯甲氧基)苯亚甲基]-2,4-噻唑烷二酮,总收率57.3％,其结构经1H NMR,ESI-MS和元素分析确证.     

"Codimers" of N-(pyrid-2-yl) amides and ethyl cyanoacetate

Potential chelating-forming ligands and reagents for heterocyclization — ethyl esters of 4-[N-(R-pyrid-2-yl)carbamoyl]-3-amino-2-cyanobuten-2-oic acids ["codimers" of cyanoacetic acid ethyl ester (EECA) and the corresponding (pyrid-2-yl) amides of this same acid) — were synthesized in two ways: by condensation of 2-dialkylborylamidopyridines (picolines) with EECA (via chelate compounds of boron) and by the reaction of EECA dimer with 2-aminopyridines (picolines).N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 2, pp. 371–376, February, 1992.     

The electrochemical fluorination of N-(ω-chloroalkyl)pipecolines and N-(ω-chloroalkyl)hexamethyleneimines

Electrochemical fluorinations of six kinds of N-(ω-chloroalkyl)pipecolines [N-(2-chloroethyl)-2-, N-(3-chloropropyl)-2-, N-(2-chloroethyl)-3-, N-(3-chloropropyl)-3-, N-(2-chloroethyl)4- and N-(3-chloropropyl)-4-pipecolines] and two kinds of N-(ω- chloroalkyl)-substituted hexamethyleneimines [N-(2-chloroethyl)- and N-(3-chloropropyl)hexamethyleneimines] were conducted. From these starting materials, corresponding chlorine-retained fully fluorinated amines together with ring isomerized products were formed in yields of 7.6～14.8% from the former and 5.4～5.5% from the latter, respectively. New chloropolyfluoroamines obtained in the present investigation have been isolated and characterized by spectroscopic (infrared, ¹⁹F nmr and mass) and elemental analysis.     

Thionation of N‐(ω‐Halogenoalkyl)‐Substituted Amides with Lawesson's Reagent: Facile Synthesis of 4,5‐Dihydro‐1,3‐thiazoles and 5,6‐Dihydro‐4H‐1,3‐thiazines

The thionation and cyclization of N‐(ω‐halogenoalkyl)‐substituted amides (and related compounds) with Lawesson's reagent (LR=2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide) has been investigated. Treatment of the amides 1 with LR gave the corresponding thioamides 2 in moderate to good yields (Table). The latter, upon treatment with base, afforded, either in a separate step or in a one‐pot procedure, the cyclized title compounds, i.e., the 4,5‐dihydro‐1,3‐thiazoles 3 or the corresponding 5‐6‐dihydro‐4H‐thiazines 4 via dehydrohalogenation.     

New facile synthesis of N-sulfinylamine derivatives using N,N′-sulfinylbisimidazole and N-(chlorosulfinyl)imidazole

Treatment of amine derivatives such as amines, sulfonamides, and amides with N,N′-sulfinylbisimidazole $\text{1}$ and N-(chlorosulfinyl)imidazole $\text{2}$$\text{in situ}$ respectively gives the corresponding N-sulfinylamine derivatives ($\text{3}$); the latter reaction using N-(chlorosulfinyl)imidazole $\text{2}$ yields $\text{3}$ in almost quantitative yields at 20°C under mild conditions.     

Efficient and beta-Stereoselective Synthesis of 4(5)-(beta-D-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles(1)

A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.     

First dynamic kinetic resolution of selenium-containing chiral amines catalyzed by palladium (Pd/BaSO4) and Candida antartica lipase (CAL-B)

An efficient method for chemoenzymatic dynamic kinetic resolution of selenium-containing chiral amines (organoselenium-1-phenylethanamines) has been developed, leading to the corresponding amides in excellent enantioselectivities and high isolated yields. This one-pot procedure employs two different types of catalysts: Pd on barium sulphate (Pd/BaSO₄) as racemization catalyst and lipase (CAL-B) as the resolution catalyst.     

Synthesis and cyclizations of N-(2,3-, 3,4- and 3,5-dimethylphenyl)-beta-alanines

A series of 1-aryl substituted dihydro-, 5-methyl-dihydro- and 6-methyl-dihydro-2,4(1H,3H)pyrimidinediones and their 2-thio analogues were obtained by reaction of the corresponding beta-alanines or alpha-methyl- and beta-methyl-beta-alanines with urea or potassium thiocyanate. The reaction of N-(2,3- and 3,5-dimethylphenyl)-alpha-methyl-beta-alanines with ethyl acetoacetate gave 1-(2,3- or 3,5-dimethylphenyl)-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)pyridones. The combined spectral data obtained by (1)H-, (13)C-,(1)H/(13)C (HETCOR) NMR and IR provided useful information about the structure of the products synthesized in this work.