Thiocarbamoylation of amine-containing compounds

The reaction of 3-amino-4-methylbenzoic acid with tetramethylthiuram disulfide in DMF afforded 3-N,N-dimethylthioureido-4-methylbenzoic acid. Thermolysis or treatment of the latter with acidic reagents resulted in elimination of dimethylamine to form 3-isothiocyanato-4-methylbenzoic acid whose reaction with hydrazine yielded substituted thiosemicarbazide. The reactions of the latter with aldehydes and ketones gave thiosemicabazones, and its reaction with tetramethylthiuram disulfide afforded 3-(2-mercapto-1,3,4-thiadiazol-5-ylamino)-4-methylbenzoic acid. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 743–746, April, 1999.     

Amine-carbon disulfide promoted synthesis of novel benzo[e][1,3]thiazepin-5(1H)-one derivatives

In this paper, a simple method is introduced for the synthesis of novel 4-substituted-3-thioxo-3,4-dihydrobenzo[e][1,3]thiazepin-5(1H)-one derivatives. The synthesis is based on a two-step reaction of 2-methylbenzoic acid, an amine, and carbon disulfide. In the first step, 2-methylbenzoic acid reacts with sulfuric acid in ethanol, followed by the reaction with N-bromosuccinimide to produce ethyl 2-(bromomethyl)benzoate. Amine and carbon disulfide react in a separate flask in basic medium to give carbamodithioate salt. Carbamodithioate and ethyl 2-(bromomethyl)benzoate react together in dimethylformamide to produce the desired 4-substituted-3-thioxo-3,4-dihydrobenzo[e][1,3]thiazepin-5(1H)-one derivatives. The method is simple and fast and is applicable to a wide variety of substrates and gives the desired products in high isolated yields.     

铕-邻菲罗啉-甲基苯甲酸二、三元配合物的NMR研究

本文报道了希土铕（Ｅｕ＾３＋）与甲基苯甲酸（包括邻位ｏ－ＭＢＡ，间位ｍ－ＭＢＡ，对位ｐ－ＭＢＡ）及邻菲罗啉（ｐｈｅｎ）形成的二元和三元固体配合物的制备，对它们进行了元素分析，确定该配合物的组成为：二元：Ｅｕ（ＣＨ３Ｃ６Ｈ５ＣＯＯ）３，三元：Ｅｕ（ｐｈｅｎ）（ＣＨ３Ｃ６Ｈ５ＣＯＯ）３。对上述配合物的结构作了核磁共振氢谱（＾ＨＮＭＲ）和碳谱（＾１３ＣＮＭＲ）的研究，并用红外光谱（ＩＲ）作了进一步确定。     

(N-Isocyanimino)triphenylphosphorane-Mediated,One-Pot,Efficient Synthesis of Sterically Congested 1,1,1-Trifluoro-2-(5-aryl-1,3,4-oxadiazol-2-yl)-2-propanol Derivatives via Intramolecular Aza-Wittig Reaction

Reactions of (N-isocyanimino)triphenylphosphorane with 1,1,1-trifluoroacetone in the presence of aromatic (or heteroaromatic) carboxylic acids (3-methylbenzoic acid, 1-naphthalenecarboxylic acid, 2-naphthalenecarboxylic acid, 2-furancarboxylic acid, and 2-thiophenecarboxylic acid) proceed smoothly at room temperature and in neutral conditions to afford sterically congested 1,1,1-trifluoro-2-(5-aryl-1,3,4-oxadiazol-2-yl)-2-propanol derivatives in high yields. The reaction proceeds smoothly and cleanly under mild conditions, and no side reactions were observed.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Identification and quantification of polar naphthalene derivatives in contaminated groundwater of a former gas plant site by liquid chromatography-electrospray ionization tandem mass spectrometry

A liquid chromatography (LC) method followed by electrospray ionization (ESI) and tandem mass spectrometry (MS-MS) was developed for the quantification of acidic naphthalene derivatives in the concentration range 0.1 to 100 microg/l without excessive sample preparation. For optimal sensitivity the LC-MS-MS measurements were performed recording mass fragmentation by collision induced dissociation in the multiple reaction mode. The collision energy was optimized for every analyte. The matrix effects of the sample were investigated by spiking standards of 1-naphthoic acid with humic acid (HA) and with calcium chloride. While HA decreased the signal intensity an increase was observed in the presence of calcium chloride. For the investigated groundwater samples of a tar oil contaminated site a complete separation of the analytes from the sample matrix by reversed-phase separation could be obtained. The absence of matrix effects on quantification results was confirmed by comparison of results based on external calibration with those based on standard addition of the analytes to a groundwater sample. In four groundwater samples of the contaminated site naphthalene derivatives like 1-naphthoic acid, 2-naphthoic acid, 1-naphthylacetic acid, 2-naphthylacetic acid, 1-hydroxy-2-naphthoic acid, 2-hydroxy-3-naphthoic acid, and naphthyl-2-methylenesuccinic acid have been detected.     

P2O5-Hexamethyldisiloxane (HMDS): An Efficient System to Induce the Three-Component Reaction of Enolic Systems,Aromatic Aldehydes,and Acetonitrile

Three-component reaction of an enolizable compound, such as acetophenone, methyl acetoacetate, 4-hydroxycoumarin, 2-naphthol, or 3-hydroxy-2-naphthoic acid; an aromatic aldehyde, and acetonitrile induced by phosphorus pentoxide and hexamethyldisiloxane leads to 2-acetylamino ketones, methyl 3-(acetylamino aryl methyl)-3-oxobutanoates, 3-(acetylamino aryl methyl)-4-hydroxycoumarins, 1-(acetylamino aryl methyl)-2-naphthols, or 4-(acetylamino aryl methyl)-3-hydroxy-2-naphthoic acids in excellent yields.     

Amidobenzoate and carboxylate bonding of 2-amino-3-methylbenzoic acid in an oxorhenium(v) complex

The complex [ReO(Hamb)(H₂amb)(PPh₃)] (1) was prepared by the reaction of cis-[ReO₂I(PPh₃)₂] with two equivalents of 2-amino-3-methylbenzoic acid (H₃amb) in toluene under reflux conditions. Crystallographic data show that 1 contains the coordinated amidobenzoate chelate (Hamb) and symmetrically chelating carboxylate ion (H₂amb) in a pseudo-octahedral geometry.     

A thermodynamic study of the complexation reaction of beryllium(II), magnesium(II) and calcium(II) with 3-hydroxy-2-naphtoic acid

The thermodynamic stability constants and thermodynamic parameters for the complexation reaction of Be²⁺, Mg²⁺ and Ca²⁺ with 3-hydroxy-2-naphthoic acid have been determined pH metrically in a 70% v/v dioxane-water medium in the presence of potassium nitrate. The study showed the formation 1:1 and 1:2 complexes of Be²⁺, Mg²⁺ and 1:1 complex of Ca²⁺ with 3-hydroxy-2-naphthoic acid. The order of overall stability is Be²⁺>Mg²⁺>Ca²⁺.     

The Preparation of Substituted 1(2H)-Isoquinolinones from Dilithiated 2-Methyl-N-arylbenzamides, 2-Methyl-N-(arylmethyl)-benzamides,or 2-Methylbenzoic Acid, 2,2-Dimethylhydrazide

2-Methyl-N-arylbenzamides (N-aryl-ortho-toluamides), 2-methyl-N-(arylmethyl)-benzamides (substituted benzyl, N-benzyl-ortho-toluamides), or 2-methylbenzoic acid, 2,2-dimethylhydrazide (ortho-toluic acid, N,N-dimethylhydrazide), were dilithiated with excess lithium diisopropylamide, and the resulting polyanion-type intermediates were condensed with aromatic esters followed by acid cyclization to the 3-substituted-1(2H)-isoquinolinones (isocarbostyrils).     

Fluorescence of zirconium-naphthalene complexes: effect of ortho-naphthalene substitution

The effect of the position of substituents on the formation of metal-naphthalene complexes has been investigated. Two positional isomers, 1-hydroxy-2-naphthoic acid (1H2NA) and 3-hydroxy-2-naphthoic acid (3H2NA), have been chosen. A comparative study of the luminescence behaviour of the two isomers in the presence of Zr(IV) has been performed. Interesting results were obtained. While 1-hydroxy-2-naphthoic acid is quenched in the presence of Zr(IV), 3-hydroxy-2-naphthoic acid produced high-fluorescence enhancement. Several pH studies were performed between pH 2.5 and 5.0 and the stoichiometries of the complexes were also established at the different pH values tested, by use of the Benesi-Hildebrand method. In addition, the formation constants have been calculated. Finally, quenching and lifetime studies were performed in an attempt to establish the type of quenching (static or dynamic) that is produced when a complex is formed between 1-hydroxy-2-naphthoic acid and zirconium metal ion.     

Synthesis of 4-oxo-1,3-benz- and naphthoxazinium salts from o-hydroxyarylamides

The acid-catalyzed acylation of primary and secondary o-hydroxyarylamides, the probable reaction scheme, and the possibility of the formation of 4-oxo-1,3-arenooxazinium salts and analogs in the reaction of amides of salicylic, coumaric, and 1-hydroxy- and 3-hydroxynaphthoic acids and their N-alkyl(aryl)derivatives with excess amounts of aliphatic acid anhydrides and 70% perchloric acid, as well as by the acid cyclization of O- and N-mono- and diacyl derivatives of these amides, are examined. Twelve previously unknown 2-alkyl- and 2-styryl-4-oxo-1,3-naphth[3,2-e]-and -[1,2-e]oxazinium perchlorates were synthesized. N-Methyl- and N-benzylamides of 8-acetoxy-1-naphthoic acid are formed instead of the expected peri-cyclic analogs of oxazinium salts in the reaction of 8-hydroxy-1-naphthoic acid anilides with acetic anhydride and perchloric acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1611–1616, December, 1979.Original article submitted May 31, 1978; revision submitted April 2, 1979.     

Acid–Base Behavior in Supercritical Water: β-Naphthoic Acid–Ammonia Equilibrium

Equilibrium constants for the reaction of -naphthoic acid and ammonia, K _BHA, were measured with UV-vis spectroscopy in water from 25°C to 400°C. At high density K _BHA decreases with temperature, the normal behavior for an exothermic reaction of a stronger acid and base to a weaker acid and base. At low density, the reaction becomes endothermic as the solvation of the ionic products becomes weaker. These data were combined with literature results for the dissociation of water and ammonia to determine equilibrium constants for the dissociation of -naphthoic acid and the reaction of -naphthoic acid and OH^- Whereas the density (and dielectric constant) of water have only a modest effect on the isocoulombic reaction of -naphthoic acid and OH^-, they have a large effect on all of the other reactions which are ionogenic.     

钝化萘衍生物的磺化反应研究

研究了带吸电子取代基的一系列钝化萘衍生物与SO~3进行的磺化反应, 用^1H NMR分析反应混合物的组成.1-萘磺酸以71:20:9的比例产生1,5-, 1,6-和1,7-萘二磺酸, 进一步磺化得到1,3,5-, 1,3,6-萘三磺酸和1,3,5,7-萘四磺酸. 1-萘甲醛的单硫化得到比例为55:9:6:30的5-, 6-,7-和8-磺酸取代物. 1-苯甲酮萘则以83:11:6的比例得到5-,6-,和7-磺酸取代物. 1-硝基萘仅得到5位磺化产物. 1-萘甲酸和1-萘甲酸甲酯得到5位和8位取代产物. 所有的2位取代萘衍生物均先得到5和8位取代产物. 提出了生成SO~3络合物及迫位磺化的历程.     

Lewis acid-assisted oxidative cross-coupling of 2-naphthol derivatives with copper catalysts

The oxidative coupling reactions between 2-naphthol and 3-hydroxy-2-naphthoic acid derivatives using a copper catalyst under an O₂ atmosphere in the presence of a catalytic amount of the Lewis acid, such as Yb(OTf)₃, were carried out. A highly cross-coupling selective or specific reaction effectively proceeded to give a C₁ symmetrical BINOL derivative.     

Large-Scale Synthesis of 4-Methyl-2-(2H-1,2,3-triazol-2-yl)benzoic Acid – A Key Fragment of Single Orexin Receptor Antagonist ACT-539313 – through Cu2O-Catalyzed,Ligand-Free Ullmann–Goldberg Coupling

A vastly improved 2nd generation process for the large scale manufacturing of 4-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid ( 1 ) through an Ullmann–Goldberg coupling from 2-bromo-4-methylbenzoic acid and 1H-1,2,3-triazole has been developed. The new process features several key process improvements compared to the original process: 1) MeCN was found as new reaction solvent, replacing the previously used undesired 1,4-dioxane, 2) the CuI/DMCHDA catalyst system was successfully replaced by inexpensive Cu₂O in the absence of any ligand, 3) the amounts of 1H-1,2,3-triazole and K₂CO₃ were both drastically decreased compared to the original route, 4) the potassium salt of the desired N²-isomer directly crystallized from the reaction mixture and was isolated by filtration. The more soluble, undesired N¹-isomer potassium salt was purged into the mother liquor. 5) After dissolution of the N²-isomer potassium salt in H₂O and acidification with aq. HCl, the free carboxylic acid 1 crystallized as a white, crystalline solid in 61 % yield (200 g scale) and excellent HPLC purity (99.8 % a/a).     

The Metal-Ammonia Reduction of 1-Naphthoic Acid

The reduction of aromatic compounds with alkali metals in liquid anhydrous ammonia (Birch Reduction and its modifications) has developed as an effective method for the synthesis of 1,4-cyclohexadiene derivatives, and has been the subject of several reviews.^1,2 In many cases, particularly with polynuclear compounds,² the reaction is complicated by subsequent isomerizations, and/or the reduction of initial products which are often themselves subject to reduction under the reaction conditions. Recently, we have shown that inverse quenching techniques can provide a substantial improvement in this reduction reaction by minimizing the effect of excess metal during the quenching process.³ Application of these methods to 1-naphthoic acid 1 have not only provided an excellent synthesis of 1,4-dihydro-1-naphthoic acid, but we believe will furnish a much improved general technique f o r the reduction of polynuclear aromatic carboxylic acids.     

The Reaction of the cis-ReO2 + Core with 2-Amino-3-Methylbenzoic Acid

The reaction of a twofold molar excess of 2-amino-3-methylbenzoic acid (H₃amb) with cis-[ReO₂I(PPh₃)₂] in ethanol led to the isolation and characterization of the six-coordinate [Re(amb)(OEt)I(PPh₃)₂] (1). The X-ray crystal structure of 1 illustrates that the trianionic ligand amb acts as a bidentate chelate via the doubly deprotonated amino nitrogen, which is present in 1 as an imide, and the deprotonated acetoxy oxygen. The Re=N bond length is 1.751(3)?Å, and the Re=N–C angle [143.6(3)°] deviates considerably from linearity.     

Thermodynamic study of the sublimation of six aminomethylbenzoic acids

The Knudsen mass-loss effusion technique was used to measure the vapour pressures at different temperatures of the following substituted benzoic acids: 2-amino-3-methylbenzoic acid at T between 343.16 K and 357.17 K; 2-amino-5-methylbenzoic acid at T between 345.15 K and 361.16 K; 2-amino-6-methylbenzoic acid at T between 339.17 K and 355.15 K; 3-amino-2-methylbenzoic acid at T between 367.16 K and 381.22 K; 3-amino-4-methylbenzoic acid at T between 363.18 K and 377.16 K; and 4-amino-3-methylbenzoic acid at T between 367.17 K and 383.14 K. The standard, p⁰ =  10⁵Pa, molar enthalpies, entropies, and Gibbs energies of sublimation at T =  298.15 K were derived from the temperature dependence of the vapour pressure using estimated values for the heat capacity differences between the gas and the crystal phases of the studied compounds.     

N.m.r. studies on aromatic compounds. I—13C n.m.r. spectra of some mono- and disulpho-substituted hydroxycarboxylic acids

Carbon-13 n.m.r. spectra of 3-hydroxy-4-sulpho-2-naphthoic, 3-hydroxy-5-sulpho-2-naphthoic, 3-hydroxy-7-sulpho-2-naphthoic, 5-sulphosalicylic, 3-hydroxy-5,7-disulpho-2-naphthoic, 1-hydroxy-4,7-disulpho-2-naphthoic, and 3,5-disulphosalicylic acids were recorded with and without proton noise-decoupling. Analyses of the spectra were carried out for all compounds except 3-hydroxy-5-sulpho-2-naphthoic acid which dimerized. The fine splitting caused by long-range coupling was used in identifying the lines of the ¹³C n.m.r. spectra.     

“一锅法”合成2-氨基-N,3-二甲基-5-卤代苯甲酰胺

报道了从3-甲基-2-氨基苯甲酸出发一锅三步合成2-氨基-N,3-二甲基-5-卤代苯甲酰胺的方法.3-甲基-2-氨基苯甲酸(1)与固体光气反应生成中间体8-甲基-2H-3,1-苯并噁嗪-2,4(1H)-二酮(2),化合物2与甲胺水溶液发生胺解反应生成2-氨基-N,3-二甲基苯甲酰胺(3),3再与氯代丁二酰亚胺(NCS)、溴代丁二酰亚胺(NBS)或碘代丁二酰亚胺(NIS)发生芳香亲电取代反应生成目标产物2-氨基-N,3-二甲基-5-卤代苯甲酰胺(4～6).整个反应过程不需分离中间产品,最终产物经减压浓缩除去有机溶剂后,直接从水中析出针状晶体,总收率达到87%～94%,较文献报道的分步法收率提高30%以上.该方法工艺操作简单、反应条件温和、反应时间短、收率高,是一条环境友好的绿色合成路线.