Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 9. peculiarities of the reaction of 5(4)-aminoimidazole-4(5)-carboxhydrazide with nitrous acid and of 5-diazoimidazole-4-carboxazide with amines

The reaction of 5(4)-aminoimidazole-4(5)-carboxhydrazide with nitrous acid was investigated. A mixture of four compounds, viz., 5-diazoimidazole-4-carboxazide, 5-diazoimidazole-4-carboxylic acid, 5(4)-aminoimidazole-4(5)-carboxazide, and 2-azahypoxanthine, is formed under all of the investigated conditions, 5(4)-Azidoimidazole-4(5)-carboxamide derivatives were obtained in the reaction of diazoimidazole-carboxazide with various amines in protic and aprotic solvents. 5-N-(Piperidyl)-azoimidazole-4-carboxazide was isolated only in the reaction with piperidine in an aqueous medium.See [1] for Communication 8.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1536–1540, November, 1980.     

Computational Analysis of the Oxygen Addition at the C4a Site of Reduced Flavin in the Bacterial Luciferase Bioluminescence Reaction

The energetic characteristics of selected reaction steps in the bacterial luciferase-catalyzed luminescence reaction were examined by computation using the MNDO-PM3 method. Specifically, a three-step model was proposed to account for the reaction between oxygen and reduced riboflavin 5'-phosphate (1,5H2-FMN) to generate first the 5-hydroFMN-4a-peroxide (5H-FMN-4aOO-) and then the 5-hydro-4a-hydroperoxyFMN (5H-FMN-4aOOH) intermediates. Lysine (Lys-H+) and aspartate (Asp-) were chosen as representative catalytic residues involved in the protonation and deprotonation processes. Results show that deprotonation at the N1 site of 1,5H2-FMN by a basic amino acid residue at the luciferase active site would efficiently accelerate the reaction rate of O2 addition to form 5H-FMN-4aOO-. The most favored site of oxygen attack is at the flavin C4a. With the aid of a catalytic acid group, the 5H-FMN-4aOO- so formed tends to undergo a spontaneous protonation reaction to yield the 5H-FMN-4aOOH.     

脂蛋白脂酶激活剂艾溴利平类似物的合成

合成了两个新型的艾溴利平类似物——N-2 -硝基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰肼(5,总收率28.1％)和N-2-四氮唑基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(7,总收率30.5％).以对氯甲基苯甲酸为原料,经酯化、水解和酰氯反应制得中间体4-[(膦酸二乙酯基)甲基]苯甲酰氯(4);4与2-硝基-4-氯苯肼盐酸盐反应合成了5.4先与2-氨基-5-氯苯腈反应制得N-2-氰基-4-氯苯基-4-[(膦酸二乙酯基)甲基]苯甲酰胺(6);6再与叠氮化钠反应合成了7.其结构经1 H NMR和IR表征.     

Preparation of 1-Trifluoroethyl-4-methoxy-5-chloropyridazin-6-one: Methyl Shift of 4-Methoxy-5-chloropyridazin-6-one

N1-Trifluoroethyl-4-methoxy-5-chloro-3-pyridazone (4) was synthesized by the substitution reaction of 4methoxy-5-chloro-3-pyridazone (1) with trifluoroethyl trifluoromethanesulfonate (A) at basic condition. In the most of reaction conditions, N1-methyl-4-methoxy-5-chloro-3-pyridazone (2) was obtained as a major by-product, which means that the methyl group in the 4-methoxy shifted to N-1 position inter-molecularly aided by A or trifluoroethyl methanesulfonate (B). We obtained N1-methyl-4-trifluoro-ethoxy-5-chloro-3-pyridazone (3) in the reaction of 1 with B at higher temperature in different solvents with different yield (Table 1 ), which mechanism was shown in Figure 1. When we tried to synthesize 4 in the reaction of 1 with trifluoroethyl toluenesulfonate under basic condition, 6 was obtained (Figure 2). All the detailed mechanisms are undergoing investigated.     

Successive electron transfer reaction of the lithium salt of 5-methyl-5,10-dihydrophenazine anion with 4-nitrophenethyl bromide via 4-nitrostyrene

The reaction of lithium salt of 5-methyl-5,10-dihydrophenazine anion with 4-nitrophenethyl bromide in 1,2-dimethoxyethane gave unexpected compounds, 1,2-bis[5-(10-methyl-5,10-dihydrophenazinyl)]-1-(4-nitrophenyl)ethane and 1,4-bis(4-nitrophenyl)-1,4-bis[5-(10-methyl-5,10-dihydrophenazinyl)]butane, while the reaction in dimethyl sulfoxide brought about the formation of 5-methyl-10-(4-nitrophenethyl)-5,10-dihydrophenazine. The successive electron transfer mechanism is proposed for the former reaction via 4-nitrostyrene.     

Catalytic transformation of methane over in-loaded ZSM-5 zeolite in the presence of ethene

Methane is shown to react with ethene over In-loaded ZSM-5 to higher hydrocarbons such as propene and toluene at around 673 K. Such methane conversion is not catalyzed by proton-exchanged ZSM-5 (H-ZSM-5) under the same conditions, only C2H4 being converted to higher hydrocarbons. By using 13C-labeled methane (13CH4) as a reactant, the reaction paths for the formation of propene, benzene and toluene were examined. 13C-labeled propene (13CC2H6) is formed by the reaction of 13CH4 with C2H4. The lack of 13C-labeled benzene revealed that propene is not transformed to benzene, which instead originates entirely from C2H4. The 13C atom is inserted both into the methyl group and benzene ring in the toluene formed. This indicates that toluene is formed by two reaction paths; the reaction of 13CC2H6 with butenes formed by the dimerization of C2H4 and the reaction of benzene with 13CH4. The existence of the latter path was proved by the direct reaction of 13CH4 with benzene. The reaction of methane with benzene was also carried out in a continuous flow system over In-loaded ZSM-5. The reaction afforded 7.6% and 0.9% yields of toluene and xylenes, respectively, at 623 K.     

新型取代苯乙醇葡萄糖氧苷的合成及其抗缺氧活性

以取代苯甲醛为原料,经Wittig反应、水解反应和NaBH₄还原反应制得5个取代苯乙醇衍生物（4a~4e）;以4a~4e和其他芳乙醇（4f~4r）为原料,依次与全乙酰化溴代葡萄糖经Koenigs-Knorr偶联和MeONa/MeOH脱除乙酰保护基,合成了18个取代苯乙醇葡萄糖氧苷类似物（5a~5r,其中5b~5r为新化合物）,其结构经¹H NMR和HR-MS（ESI）表征。采用MTT法研究了5a~5r对缺氧损伤的内皮细胞（EA.hy926）代谢活力的影响。结果表明：5e, 5g, 5m, 5p, 5q和5r对EA.hy926的保护作用优于红景天苷。     

Reaction of α,α-dimethyl-γ-(1-phe nyl-3-methyl-4-pyrazolyl)- β , γ-butenolide with primary amines and ammonia

The conditions for the formation of amides of 4-keto acids, 2-oxo-5-hydroxypyrrolidlnes, 2-oxo-2,3-dihydropyrroles, or 2-oxo-5-aminotetrahydrofurans by reaction of a Δβ,γ-butenolide with primary amines were determined. The reaction with primary aliphatic amines — benzylamine and methylamine — in ethanol gives 2-oxo-5-hydroxypyrrolidines, while reaction with benzylamine in benzene gives the amide of a 4-keto acid. 2-Oxo-5-anilinotetrahydrofuran is formed in the reaction with aniline.     

Reaction of 5-Substituted 4-(Trufluoroacetyl)furan-2,3-diones with Schiff Bases

In reaction of trifluormethyl-containing 1,3-diketones with oxalyl chloride 5-substituted 4-(trifluoracetyl)furan-2,3-diones were synthesized, reaction of which with azomethines resulted in 4-substituted 5-hydroxy-5-(trifluormethyl)dihydrofuran-2,3-diones.     

氯雷他定的合成

以N-甲基-4-哌啶酮和8-氯-10,11-二氢-4-氮杂-5H-二苯并[a,d]-5-环庚酮为原料,经McMurry反应得到8-氯-6,11-二氢-11-(1-甲基-4-哌啶烯基)-5H-苯并[5,6]庚环[1,2-b]吡啶,收率为83.9%,最后与氯甲酸乙酯反应得到氯雷他定,总收率为35.7%。对McMurry反应过程中产生的副产物3、4进行了分离、表征。     

吗啉基修饰的新型香豆素Fe~(3+)荧光探针化合物的合成及其性能

间苯二酚与乙酰乙酸乙酯经亲核取代反应制得7-羟基-4-甲基香豆素(1);1与碘甲烷在乙醚中反应制得7-甲氧基-4-甲基香豆素(2);2与N-溴代丁二酰亚胺在四氯化碳中经2步反应制得3-溴-4(溴甲基)-7-甲氧基香豆素(4);4在四氢呋喃溶剂中与吗啉反应合成了一种新型的基于香豆素的荧光探针化合物——3-溴-7-甲氧基-4-(吗啉代)-2H-吡喃-2-酮(5),其结构经~1H NMR,~(13)C NMR和MS表征。光学性能和金属离子识别性能研究结果表明:5的激发波长为340.15 nm,发射波长为408.35 nm;5对Fe~(3+)有良好的识别作用,在1.0×10-5mol·L~(-1)~9.0×10~(-5)mol·L~(-1)可定量检测Fe~(3+)含量。     

Selective Functionalisation of 5-Methylcytosine by Organic Photoredox Catalysis

The epigenetic modification 5-methylcytosine plays a vital role in development, cell specific gene expression and disease states. The selective chemical modification of the 5-methylcytosine methyl group is challenging. Currently, no such chemistry exists. Direct functionalisation of 5-methylcytosine would improve the detection and study of this epigenetic feature. We report a xanthone-photosensitised process that introduces a 4-pyridine modification at a C(sp³)−H bond in the methyl group of 5-methylcytosine. We propose a reaction mechanism for this type of reaction based on density functional calculations and apply transition state analysis to rationalise differences in observed reaction efficiencies between cyanopyridine derivatives. The reaction is initiated by single electron oxidation of 5-methylcytosine followed by deprotonation to generate the methyl group radical. Cross coupling of the methyl radical with 4-cyanopyridine installs a 4-pyridine label at 5-methylcytosine. We demonstrate use of the pyridination reaction to enrich 5-methylcytosine-containing ribonucleic acid.     

Reactions of 1-methyl-derivatives of 2-oxo-1,2,3,4-tetrahydropyrimidine with phosphorus pentachloride and phosphorus oxychloride

In the reaction of 4-phenyl- and 4,6-diphenyl-1-methyl-2-oxo-5-ethoxycarbonyl-1,2,3,4-tetrahydropyrimidines with phosphorus pentachloride, oxidation and dealkylation takes place in addition to chlorination and as a result one obtained 4-phenyl- and 4,6-diphenyl-1-methyl-5-ethoxycarbonyl-2-pyrimidones and also 4-phenyl-, (4,6-diphenyl)-5-ethoxycarbonyl-2-chloropyrimidines. 1,6-Dimethyl-2-oxo-4-phenyl-5-ethoxycarbonyl-1,2,3,4-tetrahydropyrimidine in the same reaction gives 1-methyl-2-oxo-4-phenyl-5-ethoxycarbonyl 6-dichloromethyl-1,2,3,4-tetrahydropyrimidine, together with 6-chloromethylene- and 6-dichloromethylene-1-methyl-2-oxo-4-phenyl-5-chloro-5-ethoxycarbonylhexahydropyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 668–671, May, 1987.     

Versatile synthesis of 3,5-disubstituted 2-fluoropyridines and 2-pyridones

5-bromo-2-fluoro-3-pyridylboronic acid (3) was prepared in high yield by ortho-lithiation of 5-bromo-2-fluoropyridine (1), followed by reaction with trimethylborate. Suzuki reaction of 3 with a range of aryl iodides gave 3-monosubstituted 5-bromo-2-fluoropyridines 4 in excellent yields. A second Suzuki reaction utilizing the bromo constituent of 4 with aryl and heteroaryl boronic acids provided 3,5-disubstituted 2-fluoropyridines 5, which in turn could be converted to the corresponding 2-pyridones 6.     

Synthesis of 5-alkynyl-2,2,6-trimethyl-1,3-dioxin-4-ones and 1,4-disubstituted-1,2,3-triazoles

Herein we report an approach to the formation of 5-alkynyl-1,3-dioxin-4-ones using Suzuki-Miyaura cross-coupling reaction of potassium alkynyltrifluoroborate salts with 2,2,6-trimethyl-5-iodo-1,3-dioxin-4-one. The resulting 5-ethynyltrimethylsilyl-1,3-dioxin-4-ones obtained through the Sonogashira reaction were further reacted in a Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition to form functionalized 1,4-disubstituted-1,2,3-triazoles in good yields, using mild conditions and ultrasonic radiation to expedite the reaction.     

The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution

Ethyl 4-methyl-2-oxo-7-phenylthio-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylate and/or ethyl 6-methyl-2-oxo-4-(phenylthiomethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate were obtained in the reaction of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with PhSNa or PhSK with or without PhSH, depending on the reagent ratio, reaction time, or temperature, as a result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity-nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)₂/CH₂(COOEt)₂.     

Reaction of 2-(5-aminopyrazol-1-yl)quinoxaline 4-oxides with dimethyl acetylenedicarboxylate

The reaction of 6-chloro-2-hydrazinoquinoxaline 4-oxide 6 with ethyl 2-(ethoxymethylene)-2-cyanoacetate or (1-ethoxyethylidene)malononitrile gave 2-(5-amino-4-ethoxycarbonylpyrazol-1-yl)-6-chloroquinoxaline 4-oxide 7a or 2-(5-amino-4-cyano-3-methylpyrazol-1-yl)-6-chloroquinoxaline 4-oxide 7b , respectively. The reaction of compound 7a or 7b with dimethyl acetylenedicarboxylate resulted in the 1,3-dipolar cycloaddition reaction and then ring transformation to afford 4-(5-amino-4-ethoxycarbonylpyrazol-1-yl)-8-chloro-1,2,3-trismethoxycarbonylpyrrolo[1,2-α]quinoxaline 8a or 4-(5-amino-4-cyano-3-methylpyrazol-1-yl)-8-chloro-1,2,3-trismethoxycarbonylpyrrolo[1,2-α]quinoxaline 8b , respectively.     

Acetals of lactams and acid amides. 40. Synthesis and hydrolytic cleavage of one-ring and two-ring derivatives of 4-pyrimidinone

The reaction of 1-benzyl-5-cyano-6-dimethylaminomethylene-1, 6-dihydro-4-pyrimidinone with acid leads to 5-benzyl-1,2,7,8-tetrahydropyrido[4,3-d]pyrimidine-1,8-dione, whereas the reaction with ammonia leads to a mixture of 3-cyano-4-benzylamino-2-pyridone and 1-amino-5-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. Heating of the latter in aqueous ethylene glycol is accompanied by recyclization to give 4-benzylamino-5,6-dihydropyrido[2,3-d]pyrimidin-5-one. The reaction of 1-benzyl-4-ditnethylaminomethylene-5-cyano-1,6-dihydro-6-pyrimidinone with ammonia leads to 1-amino-7-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. The rate constants for cleavage of the pyrimidine ring in a number of 4-pyrimidinone derivatives were measured.See [1] for communication 39.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 532–537, April, 1984.     

Ambident anion chemistry: The reaction of sterically-hindered phenolate anions with 1H-pyrrole-2,5-diones

The reaction of N-phenylmaleimide, 4a , with sodium 2,6-di-t-butylphenolate, 5a , in dimethylsulfoxide (DMSO) resulted a complex oligomeric mixture. The dimer 8 was isolated from the reaction of the N-alkyl-maleimide 4b with 5a in DMSO. The reaction of 4a with 5a in tetrahydrofuran (THF), which is an aprotic solvent that is known to promote ion pairing, resulted in the isolation of a low yield of 6a . The reaction of 4a with 5a in the hydrogen-bonding solvent t-butyl alcohol gave 6a in slightly higher yield. The N-alkylpyrrolidine-2,5-diones 6c-f were obtained by the reaction of the maleimides 4c-e with the corresponding sodium phenolate 5a-b in t-butyl alcohol reaction medium. The isolated yield of product increased with the size of the N-alkyl substituent of the maleimide. Surprisingly, the reaction of the 2,6-dimethylphenolate 5c with 4d led to the isolation of the dimer 10 with the formation of a quaternary carbon atom. The yield of 6a was observed to counterion dependent, increasing in the order Na⁺ < Li⁺ < MgBr⁺ in t-butyl alcohol. The bismaleimides 12 and 14 were obtained by the reaction of either 11 or 13 with 5d in THF.     

富马酸奈拉西坦的合成工艺改进

报道了一种合成富马酸奈拉西坦(7)的新工艺。以衣康酸二甲酯和苄胺为起始原料,经Michael加成和分子内环合反应制得1-苄基-5-氧代吡咯烷-3-羧酸甲酯(3); 3经NaBH₄还原得1-苄基-4-羟甲基-吡咯烷-2-酮(4); 4经甲磺酰化反应得1-苄基-5-氧代吡咯烷-3-羧酸甲磺酸酯(5); 5经氨解得奈拉西坦(6); 6与富马酸经成盐反应合成7,总收率78.4%,其结构经¹H NMR确证。