Chemical properties of N-Benzoylimines of quinazoline,quinoxaline, and phthalazine

Reactions of 1-benzoylimino-4-phenylquinazolinium (I), 1-benzoylimino-3-phenylquinox-alinium (II), and 3-benzoylimino-1-phenylphthalazinium betaines (III) with nucleophiles (hydroxide and cyanide ions) and 1,3-dipolarophiles (acetylenic esters and maleimides) were investigated. Heating I in aqueous alkali gave 3-phenylindazole, while similar treatment of II and III resulted in the formation of 1-benzoylamino-2-oxo-3-phenylquinoxaline and 2-benzoylamino-1-oxo-4-phenylphthalazine, respectively. Reaction of II and III with cyanide ion afforded 2-cyano-3-phenylquinoxaline and 1-cyano-4-phenylphthalazine in high yields, respectively. 1,3-Dipolar cycloaddition reactions of I and III with dimethyl acetylenedicarboxylate and ethyl propiolate afforded primary 1:1 cycloadducts, while the reaction of II with dimethyl acetylenedicarboxylate gave a product which is formed by ring opening of a primary adduct. The reaction of I-III with N-methyl and N-phenylmaleimides afforded the corresponding primary 1:1 cycloadducts in high yields, whose stereochemical assignment was made on the basis of nmr spectroscopy.     

Synthesis of benzazepines and their rearrangement to quinolines and pyrrolo(2,3-b) quinolines

BECKMANN or SCHMIDT rearrangement of ethyl trans-4-oxo-1-phenyl-2-tetralincarboxylate ( 2 ) affords ethyl trans-2,3,4,5-tetrahydro-2-oxo-5-phenyl-1H-benzo [b] azepine-4-carboxylate ( 4 ). Mild treatment of trans-2,3,4,5-tetrahydro-1-methyl-2-oxo-5-phenyl-1 H-benzo-[b] azepine-4-carboxylic acid ( 7 ) with thionyl chloride and pyridine in dimethylformamide and subsequent reaction with an amine yields the corresponding benzazepine-4-carboxamide. If he it is applied during the preparation of the acid chloride, rearrangement occurs yielding cis and trans derivatives of hydrocarbostyril. 2,3,4,5-Tetrahydro-1,4-methano-1-methyl-5-phenyl-1 H-benzo-[b] azepinium chloride ( 25 ) reacts with primary or secondary amines to cis-tetrahydroquinoline derivatives. When heated above its melting point, trans-4,5-dihydro-2-methylamino-5-phenyl-3H-benzo-[b] azepine-4-carboxylic acid ( 29 ) rearranges with elimination of water to a mixture of cis-and trans-2,3,3a,4-tetrahydro-1-methyl-2-oxo-4-phenyl-1H-pyrrolo [2,3-b] quinoline ( 32 and 31 ). The reduction of 31 was investigated. The mechanisms of the rearrangements are discussed.     

Reaction of sulfene and dichloroketene with open-chain N,N-disubstituted α-aminomethyleneketones. Synthesis of N,N-disubstituted 4-amino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides and of 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones

Cycloaddition of sulfene to N,N-disubstituted 3-amino-2-methyl-1-phenyl-2-propen-1-ones (I) and 3-amino-1,2-diphenyl-2-propen-1-ones (II) occurred in good to moderate yield only in the case of aliphatic N-substitution to give 4-dialkylamino-3,4-dihydro-(5-methyl-6-phenyl)(5,6-diphenyl)-1,2-oxathiin 2,2-dioxides. Polar 1,4-cycloaddition of dichloroketene to I and II occurred only in the former case, giving in good to moderate yield N,N-disubstituted 4-amino-3,3-dichloro-3,4-dihydro-5-methyl-6-phenyl-2H-pyran-2-ones which were dehydrochlorinated with DBN to N,N-disubstituted 4-amino-3-chloro-5-methyl-6-phenyl-2H-pyran-2-ones. In the reaction of 2-methyl-1-phenyl-3-diphenylamino-2-propen-1-one with dichloroketene, a product was isolated which was proven by uv, ir, nmr and chemical evidence to be the dipolar ion VI, the supposed intermediate of the polar 1,4-cycloaddition of dichloroketene to N,N-disubstituted enaminones.     

Reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone derivatives and the properties of the obtained products

N′-(4-Oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides and N′-(3-methyl-4-oxo-1,4-dihydronaphthalen-1-ylidene)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides were synthesized by reactions of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 1,4-naphthoquinone or 2-methyl-1,4-naphthoquinone. The alkylated analogues of the above products were obtained using ethyl iodide. The interaction of 5-oxo-1-phenylpyrrolidine-3-carbohydrazides with 2,3-dichloro-1,4-naphthoquinone was followed by formation of N′-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-1-phenyl-5-oxopyrrolidine-3-carbohydrazides. All these compounds were characterized using ¹H, ¹³C NMR, IR and mass spectra. Some of the new compounds were tested for the antimicrobial and antifungal activity.     

Mass spectrometry of 4N-pyrimidinyl amino acids

The electron impact mass spectra of N-(1H-2-oxo-4-pyrimidinyl) amino acids are discussed. It was established that thermal elimination of water took place prior to mass fragmentation of all these compounds with the formation of bicyclic structures. The fragmentation of bicyclic ions led to 1H-2-oxo-pyrimidinyl species.     

Competing processes in condensation of 3,3-bis(methylthio)-2-cyano-<Emphasis Type="Italic">N</Emphasis>-arylacrylamides with cyanoacetanilides

Reaction of cyanoacetanilides with 3,3-bis(methylthio)-2-cyano-N-arylacrylamides proceeds to form isomeric N,1-diaryl-1,6-dihydropyridine-3-carboxamides. A single crystal consisting of 2-amino-4-methylthio-N-(2-methoxyphenyl)-6-oxo-1-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide and 2-amino-4-methylthio-1-(2-methoxyphenyl)-6-oxo-N-phenyl-5-cyano-1,6-dihydropyridine-3-carboxamide was studied by XRD.     

Stabilization of even-electron ions by cyclization of substituents on 3N- and 4N-nitrogens in 4N-substituted cytosines

Electron impact mass spectra of 4N-substituted derivatives of cytosine are reported. The strong influence of 4N-substituents on the mode of mass fragmentation occurring upon electron impact ionization was proved. The presence of α-carbon in the 4N-substituent extends the possibilities of fragmentation via rearrangement leading to formation of even-electron bicyclic ions containing quaternary 3N-nitrogen. When β-carbon was present in the 4N-substituent, the decomposition based on elimination of alkenes was detected as well as the rearrangement leading to formation of bicyclic even-electron ions containing quaternary 3N- or 4N-nitrogen.     

Beiträge zum Studium einiger Heterocyclen. XLIV—Massenspektrometrische Untersuchungen einiger 2-(p-X-Phenyl)-5-Y-4-acetylthiazole

The fragmentation under eletron impact of some new 2-phenyl-4-acetyl-thiazoles has been studied. The compounds investigaed exhibit molecular ion peaks. Substituents in the para position of the bensene ring do not influence the fragmentation patterns but only the relative abundances of the molecular ion and some fragment ions. However, by introdicing CI and Br in position 5 of the thiazole some signifiecant differences appear (‘ortho effect’). A rearrangement also occurs involving a 5-membered cyclic transition state. Intense doubly charged ions are obseved a fact which is attributed to the presence of two easily ionizable centres.     

N-hetaryl-2-cyanoacetamides in the synthesis of substituted (E)-N-hetaryl-2-cyanoacrylamides, (E)-N-alkyl-N-hetaryl-2-cyanoacrylamides, and 6-amino-2-oxo-4-phenyl-1-(pyridin-2-yl)-1,2-dihydropyridine-3,5-dicarbonitriles

Knoevenagel condensation of N-hetaryl-substituted cyanoacetamides with aldehydes gave the corresponding (E)-N-hetaryl-2-cyanoacrylamides which were converted into (E)-N-alkyl-N-hetaryl-2-cyanoacrylamides and 6-amino-2-oxo-4-phenyl-1-(pyridin-2-yl)-1,2-dihydropyridine-3,5-dicarbonitriles. The structure of (E)-N-(pyridin-2-yl)-2-cyano-3-phenylprop-2-enamide was determined by X-ray analysis. Original Russian Text ? I.V. Dyachenko, V.D. Dyachenko, E.B. Rusanov, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 1, pp. 81–86.     

A new pyrimidine-derived ligand,N-pyrimidine oxalamic acid,and its Cu(II), Co(II), Mn(II), Ni(II), Zn(II), Cd(II), and Pd(II) complexes: synthesis,characterization, electrochemical properties,and biological activity

A new heterocyclic compound N-(5-benzoyl-2-oxo-4-phenyl-2H-pyrimidin-1-yl)-oxalamic acid has been synthesized from N-amino pyrimidine-2-one and oxalylchloride. Bis-chelate complexes of the ligand were prepared from acetate/chloride salts of Cu(II), Co(II), Mn(II), Ni(II), Zn(II), Cd(II), and Pd(II) in methanol. The structures of the ligand and its metal complexes were characterized by microanalyses, IR, AAS, NMR, API-ES, UV-Vis spectroscopy, magnetic susceptibility, and thermogravimetric analyses. An octahedral geometry has been suggested for all the complexes, except for Pd(II) complex, in which the metal center is square planar. Each ligand binds using C(2)=O, HN, and carboxylate. The cyclic voltammograms of the ligand and the complexes are also discussed. The new synthesized compounds were evaluated for antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi using the microdilution procedure. The Cu(II) complex displayed selective and effective antibacterial activity against one Gram-positive spore-forming bacterium (Bacillus cereus ATCC 7064), two Gram-positive bacteria (Staphylococcus aureus ATCC 6538 and S. aureus ATCC 25923) at 40–80 µg mL^?1, but poor activity against Candida species. The Cu(II) complex might be a new antibacterial agent against Gram-positive bacteria.     

The elimination of metal(I) hydride in the mass spectra of some metal(II) compounds

Metal(I) hydrides are eliminated as neutral species in the electron impact ionization mass spectra of copper(II) and palladium(II) complexes of ethylene-N,N′-3-benzoylprop-2-en-2-amine. Deuterium labelling shows that the hydrogen atom of the metal(I) hydride is derived predominantly from the ethylene bridge both for ion source reactions and for metastable ion transitions. Evidence supporting the proposed rationalization for elimination of metal(I) hydride is provided by the observation of an analogous reaction in the mass spectrum of (ethylene-N,N′-salicylaldiminato)copper(II). The mass spectrum of ethylene-d₄-N,N′-3-benzoylprop-2-en-2-amine shows an unusual rearrangement to give [C₇H₅D₂]⁺ ions involving a formal phenyl-to-methylene transfer.     

Synthesis,characterization, cyclic voltammetry,and antimicrobial properties of N-(5-benzoyl-2-oxo-4-phenyl-2H-pyrimidine-1-yl)-malonamic acid and its metal complexes

A new heterocyclic compound, N-(5-benzoyl-2-oxo-4-phenyl-2H-pyrimidin-1-yl)-malonamic acid, was synthesized from N-aminopyrimidine-2-one and malonyldichloride. Bis-chelate complexes of the ligand were prepared from acetate/chloride salts of Cu(II), Co(II), Ni(II), Mn(II), Zn(II), Cd(II), Fe(III), Cr(III), and Ru(III) in methanol. The structures of the ligand and its metal complexes were characterized by microanalyses, IR, NMR, API-ES, UV-Vis spectroscopy, magnetic susceptibility, and conductometric analyses. Octahedral geometry was suggested for all the complexes, in which the metal center coordinates to ONO donors of the ligand. Each ligand binds the metal using C=O, HN, and carboxylate. The cyclic voltammograms of the ligand and the complexes were also discussed. The compounds were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacteria, and fungi using microdilution procedure. The antimicrobial studies showed that Cu(II), Fe(III), and Ru(III) complexes exhibited good antibacterial activity against Gram-positive bacteria with minimum inhibitory concentrations between 20 and 80 µg mL^?1. However, the ligand and the complexes possess weak efficacy against Gram-negative bacterium and Candida strains. As a result, we suggest that these complexes containing pyrimidine might be a new group of antibacterial agents against Gram-positive bacteria.     

Transition Metal Complexes of an Antipyrine Derivative

The stepwise formation constants of N-antipyrinyl-N′-3-phenyl-2-propenoyl-thiourea (I) complexes with metal ions of the first transition series, Cu(II), Ni(II), Co(II), Mn(II) and Zn(II) have been determined in 70% (V/V) ethanol-water medium. The formation constants for the chelates follow the Irving-Williams series: Zn(II)<Cu(II)>Ni(II)>Co(II)>Mn(II) The effect of ionic radius and electronegativity on the chelate formation are discussed. Complexes of Cu(II) and Ni(II) have been synthesised and characterised by elemental analysis, electrolytic conductance, IR spectra and magnetic susceptibility measurements. The ligand forms bis-complexes with Cu(II) and Ni(II). The binding sites are oxygen and sulphur atoms.     

Reaction of 6-chloro-2-[1-methyl-2-(N-methylthiocarbamoyl)]-hydrazinoquinoxaline 4-oxide with dimethyl acetylenedicarboxylate

The reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 4a with methyl or phenyl isothiocyanate gave 6-chloro-2-[1-methyl-2-(N-methylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 7a or 6-chloro-2-[1-methyl-2-(N-phenylthiocarbamoyl)hydrazino]quinoxaline 4-oxide 7b , respectively, whose reaction with dimethyl acetylenedicarboxylate afforded 6-chloro-2-[N-methyl-N-(5-methoxycarbonylmethylene-3-methyl-4-oxo-2-thioxoimidazolidin-1-yl)]aminoquinoxaline 4-oxide 8a or 6-chloro-2-[N-methyl-N-(5-methoxycarbonylmethylene-4-oxo-3-phenyl-2-thioxoimidazolidin-1-yl)]aminoquinoxaline 4-oxide 8b , respectively.     

Synthesis and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

Modification of biologically active amides and amines with fluorine-containing heterocycles 2*. N-(2-Thienyl)imines on the base of methyl trifluoropyruvate in cyclocondensation with 1,3-N,N-binucleophiles

An approach to the modification of the biologically active compounds, substituted 2-aminothiophenes, with fluorine-containing five-membered heterocycles is proposed. The reaction of 2-aminothiophenes with methyl trifluoropyruvate yields the corresponding N-(2-thienyl)imines, their subsequent cyclocondensation with 1,3-N,N-binucleophiles (2-aminothiazoline and benzamidines) furnished 5-oxo-6-trifluoromethyl-2,3,5,6-tetrahydroimidazothiazoles and 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1H-imidazoles.     

Mass-spectrometric study of physiologically active β-thiosemicarbazones of N-alkylisatins

The molecular ions of isatin (I) and N-methyl- (II) and N-ethylisatin (III) -thiosemicarbazones undergo fragmentation via many pathways with the elimination of NH₃, H₂S, CO, CH₂N₂, CHN₃, CH₂N₂S, CH₂NS, and CHNS particles; this is due to primary localization of the charge on the heteroatoms of the thiosemicarbazone residue. A previously unknown rearrangement, which consists in migration of an HS group to the -carhon atom of the heteroring with subsequent ejection of a CHN₃ fragment. The [M — CO]⁺ ions undergo fragmentation with the elimination of CH₂N₂S; in the case of II and III fragmentation is preceded by detachment of a hydrogen atom (II) or a methyl group (III) from the substituent attached to the ring nitrogen atom. The [M — CO, -H, -CH₂NS]⁺ (II) and [M — CO, -CH₃, -CH₂N₂S]⁺ (III) ions undergo fragmentation with the ejection of HCN in two ways through both the ring nitrogen atom and the thiosemicarbazone residue. Schemes for the principal pathways of fragmentation and rearrangements are presented. The compositions of the ions were confirmed by the high-resolution mass spectra and the mass spectra of the N-deuteroalkyl derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 1979.     

1,4-Benzodiazepines III . Cyclization paths of hexaminium salts of 2-chioroacetamido-5-ehlorobenzophenone and its N-methyl derivative

This study reports the isolation and characterization of hexaminium salts of 2-chloroacetamido-5-chlorobenzophenone (I) and of 2-(N-methyl)chloroacetamido-5-chlorobenzophenone (II). The 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (VI) and 7-chloro-1,3-dihydro-1-meth-yI-5-phenyl-2H-1,4-benzodiazepin-2-one (VII), respectively are of pharmacodynamic importance. Based on chromatographic separation of some intermediates, and on spectrophotometric monitoring of cyclizations I → VI and II → VII, respectively, two different pathways for these reactions have been proposed. Since the slowest step in the reaction sequence II → VII follows the quasi first order rate law, intramolecular nucleophilic attack of the benzophenone carbonyl group on the hexamine moiety proved to be decisive for the cyclization (scheme II). However, cyclization I → VI seems to incorporate quite different solvolytic pathways in addition to one corresponding to the sequence II → VII. Isolated 4-imidazolidinone intermediates N,N' -methylene-bis[3-{2 -benzoyl-4-chIoro)phenyI]-4-imidazolidinone(III), and 3-(2 -benzoyl-4′-chlorophenyI)-4-imidazolidinone hydrochloride (IV) recyclize into the 1,4-benzodiazepine VI. The optimal reaction conditions have been found to be between pH 6-7.     

Preparation of N-aryl-2,4-diaminopentanes by the ring opening reaction of 1-aryl-3,4,5,6-tetrahydro-2-(1H)pyrimidinones

1-Aryl-3,4,5,6-tetrahydro-2-(1H)pyrimidinones (I) underwent reductive ring opening reaction with lithium aluminum hydride to afford N-aryl-2,4-diaminopentanes (II) in good yields. On the other hand, 3,4,5,6-tetrahydro-3,4,6-trimethyl-1-phenyl-2-(1H)-pyrimidinone (V) gave only cyclic diamine, 3,4,6-trimethyl-1-phenylhexahydropyrimidine (VI), in 60% yield.     

PHOSPHORYL TO CARBONYL MIGRATION OF AMINO GROUPS IN MIXED ANHYDRIDES. REACTIVITY AND CRYSTAL STRUCTURE OF N-METHYL-2-BENZOYLOXY-2-OXO-1,3,2-OXAZAPHOSPHORINANE

Abstract

Cyclic mixed anhydride, N-methyl-2-benzoyloxy-2-oxo-1,3,2-oxazaphosphorinane (1a) has been synthesised and the rate of its fragmentation involving nitrogen migration from phosphorus to carbonyl carbon has been measured. (1a) was found to be ca. 60 times less reactive than the non-cyclic, O-methyl-N,N-dimethyl analogue. The crystal and molecular structure of (1a) has been determined using x-ray diffraction. Pna2₁, a=22.229(6), b=7.597(2), c=7.210(2) Å; V=1217.6(6) ų. Final R=3.08% for 1037 reflections with I(rel) > 2[sgrave]I(rel) and 157 parameters. The observed conformation of the molecule of (1a) is very different from that required for the fragmentation to occur; in order to achieve the geometry postulated for the transition state significant rotations about the P[sbnd]O and O[sbnd]C bonds would be necessary and steric hindrance by the 4,6-axial hydrogens would be expected.