Cyclisations par l'intermédiaire de fonctions phénylthioet phénoxy-carbamyle. I. Diphényl-1,2-alcoyl-5-dioxo-3,6-hexahydro-triazines-1,2,4

The N-(p-nitrophenoxy-carbonyl) and N-(phenylthio-carbonyl) derivatives of α-amino-acyl-hydrazides cyclize in presence of diazomethane, yielding hexahydro-1, 2, 4-triazines with simultaneous formation of p-nitro-anisole or thio-anisole respectively. The molecules with a phenoxycarbonyl function such as N-(phenoxycarbonyl)-glycyl-(N, N′-diphenylhydrazide) give the corresponding ring products and anisole only in solvents with high dielectric constant (e.g. nitromethane). The phenylthio-carbonyl derivatives give the same ring products in presence of lead acetate by the intervention of HO^?. The p-nitrophenoxycarbonyl derivatives give rise to the same cyclisations in the presence of pyridine by the intermediate of carbamyle-pyridinium ion acting as electrophile. These different types of intramolecular reactions are illustrated by the formation of 1, 2-diphenyl-5-alcoyl-3, 6-dioxo-1, 2, 4-hexahydro-triazines.     

Research on heterocyclic compounds. XIII. Synthesis of 4,5-dihydro-5-oxo-3-isoxazoleacetic acid and related compounds

Some new 4,5-dihydro-5-oxoisoxazole derivatives were synthesized as part of a study to prepare potential antiinflammatory agents. The reaction of the diethyl ester of 3-oxopentanedioic acid with hydroxylamine afforded the 3-hydroxyimino derivative, which was then cyclized to the title compound. This reacted with diazomethane to give a couple of isomeric methyl derivatives, namely methyl 2,5-dihydro-2-methyl-5-oxo-3-isoxazoleacetate and methyl 5-methoxy-3-isoxazoleacetate. Reaction of these compounds with ammonia gave the corresponding acetamides. All compounds were characterized by elemental analysis, uv, ir, and ¹H-nmr spectra.     

Synthesis of Substituted Methyl Pyridazine-4-carboxylates via Cycloaddition of Diazomethane to 2,3-Disubstituted 2-Cyclopropenecarboxylic Acids

A three-step procedure has been developed for the synthesis of 3,5-disubstituted methyl pyridazine-4-carboxylates from accessible 2,3-disubstituted 2-cyclopropenecarboxylates. In the first step, cyclopropene derivatives react with diazomethane to give adducts having 2,3-diazabicyclo[3.1.1]hex-2-ene structure. The regio- and stereoselectivity of the cycloaddition has been determined. The second step is isomerization of the bicyclic adducts into 1,4-dihydropyridazine derivatives by the action of sodium methoxide. Finally, oxidation with potassium permanganate yields the target pyridazine-4-carboxylates.     

Additionen und cycloadditionen an hexafluoracetonazin [1]

Nucleophiles (alcohols, thiols, and amines) react with hexafluoroacetone azine to give 1:1 adducts, which are ascribed a hydrazone structure on basis of the spectroscopic data. From the reaction of hexafluoroacetone azine and diazomethane 1.1′-bicycloamines are obtained. I.r., ¹H-n.m.r., ¹⁹F-n.m.r. and mass spectral data of the new compounds are discussed.     

Synthesis of 3-hydroxy-6-oxo[1,2,4]triazin-1-yl alaninamides, a new class of cyclic dipeptidyl ureas

Cyclohexyl or benzyl isocyanide, benzoyl-, or 4-methoxybenzoylformic acid and semicarbazones underwent Ugi reactions in methanol for 3 days to give the Ugi adducts, which were then stirred with sodium ethoxide in ethanol for 12 h to give 3-hydroxy-6-oxo[1,2,4]triazin-1-yl alaninamides. The X-ray diffraction structure of the first example showed the tautomer having the proton in the O2 atom that was fixed in the crystal by packing in dimers with a H-bond distance of 1.9 A. Selected [1,2,4]triazines were treated with diazomethane for 12 h to get the O-methyl derivatives. Both hydroxy and O-methyl derivatives obtained by this method constitute a new class of pseudopeptidic [1,2,4]triazines composed of two different amino acids, arylglycine and alanine derivatives, in which the N-terminal arylglycine and the peptidic amide nitrogen atoms are bonded through a urea moiety.     

Chemistry of sym-tetracyanoethane. 2. Condensation with carbonyl compounds

The reaction of tetracyanoethane with carbonyl compounds proceeds via the scheme of aldol addition with subsequent cyclization of the resulting adducts to give 5-amino-2,3-dihydrofuran derivatives, the structures of which were confirmed by the ¹³C NMR and mass spectra.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1605–1610, December, 1982.     

Nucleosides. Part LXI. A Simple Procedure for the Monomethylation of Protected and Unprotected Ribonucleosides in the 2′-O- and 3′-O-Position Using Diazomethane and the Catalyst Stannous Chloride

Intensive studies on the diazomethane methylation of the common ribonucleosides uridine, cytidine, adenosine, and guanosine and its derivatives were performed to obtain preferentially the 2′-O-methyl isomers. Methylation of 5′-O-(monomethoxytrityl)-N²-(4-nitrophenyl)ethoxycarbonyl-O⁶-[2-(4-nitrophenyl)ethyl]-guanosine ( 1 ) with diazomethane resulted in an almost quantitative yield of the 2′- and 3′-O-methyl isomers which could be separated by simple silica-gel flash chromatography (Scheme 1). Adenosine, cytidine, and uridine were methylated with diazomethane with and without protection of the 5′ -O-position by a mono- or dimethoxytrityl group and the aglycone moiety of adenosine and cytidine by the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group (Schemes 2–4). Attempts to increase the formation of the 2′-O-methyl isomer as much as possible were based upon various solvents, temperatures, catalysts, and concentration of the catalysts during the methylation reaction.     

Reactions of 6-Alkoxy(alkylthio)carbonylamino-4-hydroxy-2H-pyran-2-ones with Some Electrophilic Reagents

Alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones readily react with electrophiles to give substitution products at C³. Hard electrophilic reagents replace hydrogen both in position 3 and in position 5 of the pyran ring. Methylation of 6-alkoxy(alkylthio)-4-hydroxy-2H-pyran-2-ones with diazomethane leads to formation of O- and N-methyl derivatives.     

Pyrrolo[1,2-d]triazines-1,2,4 III. Etude de la dioxo-1,4 tetrahydro-1,2,3,4 pyrrolo[1,2-d]triazine-1,2,4

1,4-Dioxo-1,2,3,4-tetrahydro-l,2,4-pyrrolo[l,2-～-1,2,4-triazine (1) was synthesized either by cyclising the N-carbethoxyhydrazide of pyrrole-2-carboxylic acid (2) or by alkaline rearrangement of 2-(2-pyrrolyl>5-oxadi- azolone (3). The methylation reactions of the dilactam 1 were achieved with dimethyl sulfate or diazomethane and afforded mixtures of U-methylated and N-methylated derivatives which were isolated by gas chromatography and the structures of which were assigned using ir and ¹H nmr spectra.     

Activation of SO2 by N/Si+ and N/B Frustrated Lewis Pairs: Experimental and Theoretical Comparison with CO2 Activation

The guanidine 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and the substituted derivatives [TBD–SiR₂]⁺ and TBD–BR₂ reacted with SO₂ to give different FLP–SO₂ adducts. Molecular structures, elucidated by X-ray diffraction, showed some structural similarities with the analogous CO₂ adducts. Thermodynamic stabilities were both experimentally evidenced and computed through DFT calculations. The underlying parameters governing the relative stabilities of the different SO₂ and CO₂ adducts were discussed from a theoretical standpoint, with a focus on the influence of the Lewis acidic moiety.     

A new synthesis of ring-fused alkylidenecyclobutanes by ring-enlargement reaction of bicyclo[n.1.0]alkylidene derivatives

Bicyclo[n.1.0]alkylidene derivatives (ring-fused alkylidenecyclopropanes) reacted with diazomethane to give spiro-pyrazolines regioselectively. Thermal decomposition of spiro-pyrazolines resulted in ring-enlargement and afforded ring-fused alkylidenecyclobutanes (bicyclo[n.2.0]alkylidene derivatives) in high yields.     

Unconventional nucleotide analogues: Reaction of carbenes with uracil and uridine derivatives

Carbenes 2a-d (:CCl₂, :CBr₂, :CFC1, :CHCOOC₂H₅) add to the 5,6-double bond of uracil derivatives la-e to give adducts in modest to good yields The unsymmetrically substituted carbenes :CFC1 2c and CHCOOC₂H₅, 2d lead, as expected, to the formation of mixtures of endo and exo-isomers 3c-n which were separated and identified via their ¹H NMR spectra. Reaction of 2d with pyrimidine derivatives 5a,b resulted in products which can be rationalized in terms of addition at either the 5,6 or the 3,4 double bond. Addition of carbenes 2a-c to uridine derivatives gave diastereomeric adducts 12-16 which were isolated and identified. The two diastereomeric series, referred to as A and B, have been correlated and assigned the configurations 5S, 6S and 5R, 6R, respectively, on the basis of X-ray structure analysis of 12B The adducts of 2a,c and the uridine derivatives 11a,b have been deprotected to give 7,7-dihalocyclothymidines.     

A novel 2-C reactivity studies of 1-aroyl-1,2-dihydro-3H-naphtho[2,1-b]pyran-3-ones

The 2-C, methylene group of 1-aroyl-1,2-dihydro-3H-naphtho[2,1-b]pyran-3-ones (2) have been showed to possess a superior reactivity towards many of organic reagents. The naphthopyrones (2) condensed with aromatic aldehydes to give the 2-arylidine derivatives (3). Bromination of 2 gave 1,2-dibromo (4) or 5-bromo (5) derivatives depending on the reaction conditions. The base catalyzed addition or cycloaddition of naphthopyrones (2) to 4-methoxy benzalacetophenone gave the expected Michael adduct (6) or the cyclic adducts (7–9) depending on the type of catalytic base and reaction conditions. Structures of the products have been established by elemental analyses, IR and ¹H NMR spectroscopic methods.     

Pyrrole studies—XXIV: The reactions of 1-methyl-2-vinylpyrrole and 1-phenyl-2-vinylpyrrole with dimethyl acetylenedicarboxylate

The reaction of dimethyl acetylenedicarboxylate with 1-methyl-2-vinylpyrrole is temperature dependent. At 80° the predominant reaction is the [4π + 2π] cycloaddition to give dimethyl 1-methyl-6,7-dihydroindole-4, 5-dicarboxylate, whereas at room temperature Michael addition of the acetylenic ester at the 5-position of the pyrrole ring to give fumaric and maleic ester derivatives also occurs. Unequivocal assignment of the configurations of the Michael adducts have been made on the basis of their ³J_CO,h coupling constants. 1-Phenyl-2-vinylpyrrole reacts with dimethyl acetylenedicarboxylate to give only the [4π + 2π] cycloadduct at room temperature and at elevated temperatures.     

Synthesis of Pyrazolines Based on Levoglucosenone

The 1,3-dipolar cycloaddition of diazomethane to levoglucosenone was found to occur regio- and stereoselectively to form optically active 9,11-dioxa-4,5-diazatricyclo[6.2.1.0^2,6]undec-4-en-7-one. Levoglucosenone was found to react with methyldiazoacetate to give the 2:1 adduct.     

Cycloaddition of diazomethane to unsymmetrical carbodiimides and mass spectroscopy study of 1,5-disubstituted 1,2,3-Triazoles

By the reaction of unsymmetrically substituted carbodiimides with diazomethane the corresponding 1,2,3-triazoles have been obtained. The structure of the adducts was elucidated by IR, UV,¹H-NMR and high resolution mass spectrometry.

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Cycloaddition von Diazomethan an unsymmetrische Carbodiimide und massenspektroskopische Studien an 1,5-disubstituierten 1,2,3-Triazolen

Zusammenfassung Die Struktur der aus unsymmetrischen Carbodiimiden und Diazomethan gebildeten 1,2,3-Triazolen wurde durch IR-,UV-,¹H-NMR- und Massenspektrometrie aufgeklärt.

     

The reaction of perfluoroalkanesulfonyl halides VII. Preparation and reactions of trifluoromethanesulfonyl bromide

The reaction between sodium trifluoromethanesulfinate, which was prepared from trifluoromethyl bromide, with bromine in aqueous solution resulted in the formation of trifluoromethanesulfonyl bromide (CF₂SO₂Br). CF₃SO₁Br reacted with alkenes and alkyne to give the corresponding adducts with the loss of SO₂ in good yields, and with compounds containing active hydrogen to give brominated derivatives. A radical reaction mechanism was proposed and confirmed by EPR study.     

[2+4] Cycloaddition of η6-(styrene)chromium tricarbonyl and conjugated dienes

Cycloaddition of η⁶-(styrene)chromium tricarbonyl to hexa-2,4-diene or cyclopentadiene afford the Diels-Alder adducts with retention of the Cr(CO)₃ group, whereas cyclohexa-1,3-diene undergoes aromatization to give η⁶-(benzene)chromium tricarbonyl. The counter synthesis of these (arene)chromium tricarbonyl derivatives from uncoordinated adducts of the Diels-Alder reaction and chromium hexacarbonyl was carried out.     

Chemistry of sulfonyl isocyanates and sulfonyl isothiocyanates. X. Possible routes to substituted imidazolidinethiones and hexahydropyrimidinethiones

4-Toluenesulfonyl isocyanate (I) reacted with 2-aminoethanol and 3-amino-l-propanol to give 2:1 isocyanate/amino alcohol addition products. 1-Amino-2-propanol and I gave 1:1 and 2:1 adducts while 2-amino-2-methyl-l-propanol afforded only a 1:1 adduct. 4-Toluenesulfonyl isothio-cyanate (III) gave 1:1 adducts with 2-aminoethanol, l-amino-2-propanol and 3-amino-l-propanol, the first two of which were cyclized by concentrated sulfuric acid to 1-(4-toluenesulfonyl)-imidazoline-2-thiones and the third to 1-(4-toluenesulfonyl)hexahydropyrimidine-2-thione. A 1:2 adduct was obtained from III and 2-amino-2-methyl-l-propanol. Amino acids reacted with I and with 4-chlorobenzenesulfonyl isocyanate (II) to give N-(arylsulfonyl)-N¹-(carboxylic acid)-ureas. N-(4-Toluenesulfonyl)-N¹-(acetic acid)-urea (XVI) was converted to the methyl ester (XIX) by concentrated sulfuric acid and methanol and to water-soluble unrecoverable products by sulfuric acid alone. Glycine and III gave N-(4-toluenesulfonyl)-N¹-(acetic acid)-thiourea (XX) which was converted to the methyl ester (XXII) by concentrated sulfuric acid/methanol and to the cyclic 1-(4-toluenesulfonyl)imidazolin-5-one-2-thione (XXI) by sulfuric acid alone.     

Action d'organolithiens sur la méthyl-2 quinoxaline. Etude de la réactivité des adduits

The action of organolithium reagents such as phenyllithium or n-bulyllithium on 2-methylquinoxaline gave lithiation of the methyl group which upon reaction with electtropholesphiles produce side chain alkenyl derivatives. On the other hand organolithium reagents react with the quinoxaline azomethine bond to give I-lithio-2-alkyl)or ary-1)-3 methylquinoxalines which can be further loithiated on the methyl group to give 2-alkyl(or aryl)-3-alkenylquinoxaline derivatives. The adducts can be condensed with clectrophiles such as benzonitrile or methlyl benzoate but only methyl benzoate leads to N condensed derivatives. Furthermore substituted 1,2,3,4-terahydroqinoxalines are available via the above lithio intermediates.