A new method for the synthesis of N-substituted (4-oxo-4,5,6,7-tetrahydroindol-3-yl)acetic acids

A new method for the synthesis of N-substituted 2-(4-oxo-4,5,6,7-tetrahydroindol-3-yl)acetic acids was developed. Alkylation of cyclic 1,3-diketones with 3,5,5,5-tetrachloropentan-2-one affords 1,4-diketones, which undergo cyclization with different primary amines into N-substituted 3-(2,2,2-trichloroethyl)-4,5,6,7-tetrahydroindol-4-ones. Acid hydrolysis of the latter gives the corresponding indol-3-ylacetic acids. The structures of the compounds obtained were confirmed by ¹H and ¹³C NMR data.     

Aniline-terephthalaldehyde resin p-toluenesulfonate (ATRT) as a highly efficient and reusable catalyst for alcoholysis,hydrolysis, and acetolysis of epoxides

Alcoholysis, hydrolysis, and acetolysis of epoxides were carried out in the presence of a catalytic amount of aniline-terephthalaldehyde resin p-toluenesulfonate (ATRT) to give the corresponding β-substituted alcohols in good yields. Alcoholysis and hydrolysis of epoxides catalyzed by ATRT proceeded faster than those by pyridinium p-toluenesulfonate (PPTS).     

Synthesis of N-(3- and 4-substituted phenyl)-O-isobutyl thionocarbamates from O-isobutyl xanthate and amines using a nano-platinum multi-walled carbon nanotube catalyst

Abstract  

Twelve N-(3- and 4-substituted phenyl)-O-isobutyl thionocarbamates, eight of which are novel, were synthesized from O-isobutyl xanthate and 3- and 4-substituted anilines in the presence of a nano-platinum aminophenyl modified multi-walled carbon nanotube catalyst. The nano-Pt catalyst was prepared on a carbon nanotube support modified by diazotization, nitro group reduction, and subsequent microwave-assisted nano-Pt precipitation. The catalyst was characterized by Fourier transform infrared (FT-IR) spectroscopy, elemental analysis, thermogravimetric analysis, and transmission electron microscopy. The nano-platinum/modified carbon nanotube catalyst was compared with a commercial Pt/active carbon catalyst in terms of product purity and yield. The results obtained by the use of the catalysts were additionally compared with those obtained by reaction of sodium isobutyl xanthogenacetate and 3- and 4-substituted anilines. Full structure characterization of the synthesized N-(substituted phenyl)-O-isobutyl thionocarbamates was achieved using FT-IR, ¹H and ¹³C NMR, and mass spectrometric methods, and their purity was proved by elemental analysis and gas chromatography. The new catalytic method offers advantages over the commercial method, such as higher yields and no product purification is required, thus conforming to the principles of ecologically friendly syntheses.     

超声法合成新型3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物

去甲去氢斑蝥素与取代芳胺反应得到了一系列N-取代苯基去甲去氢斑蝥酰亚胺, 再与5-氯/苯氧基-4-(α-氯-α-肟基甲基)-3-甲基-1-苯基吡唑甲酰基氯代肟发生1,3-偶极环加成反应生成一系列未见报道的3-(5-氯/苯氧基-3-甲基-1-苯基-4-吡唑基)异噁唑N-取代苯基去甲去氢斑蝥酰亚胺衍生物. 所合成化合物经元素分析, IR, ¹H NMR, ¹H-¹HCOSY, NOESY确证结构.     

Synthesis of aryl- and heteryl-containing gem-acylnitrocyclohexenes

Reactions of 2-aryl(heteryl)-1-acetyl(benzoyl)-1-nitroethenes with 2,3-dimethyl-1,3-butadiene led to the formation of products of [4+2]-cycloaddition, 1-acyl-6-aryl(heteryl)-3,4-dimethyl-1-nitro-3-cyclohexenes. Their structure was proved by IR and ¹H NMR spectroscopy.     

The Isotopomeric (Z)- and (E)-2,3-Dimethyl(1,1,1,4,4,4-2H6)but-2-enes: Mechanistic Probes for Stereospecific Epoxidation

By unambiguous methods, (Z)- and (E)-2, 3-dimethyl(1, 1, 1, 4, 4, 4-²H₆)but-2-enes ( 3 ) were synthesized and transformed to the epoxides 4 with 3-chloroperbenzoic acids. Both the isotopomeric olefins and the epoxides are detected separately by ¹H-NMR at 400 MHz. Epoxidation of (Z)- 3 with [Rh^ICl(PPh₃)₃]/cumene hydroperoxide resulted in a 1: 1 mixture of (Z)- and (E)- 4 , while reaction of (Z)- 3 with [Fe^III(tpp)]Cl/PhIO gave only (Z)- 4 (tpp = tetraphenylporphyrin).     

1H- und 13C-NMR-Untersuchungen zur Struktur N-substituierter Tetrazole—Die Strukturen des N-Methoxycarbonyl-, N-Acetyl- und N-(Tri-n-butylstannyl)-tetrazols sowie Substituenteneffekte auf δ13C und 1J(CH)

The ¹H and ¹³C NMR spectra of several isomeric N-substituted tetrazoles have been investigated. ¹³C NMR is shown to be more useful for distinguishing between structural isomers of N-substituted tetrazoles except for those carrying electropositive substituents like SnBu₃. Correlations of δC-5 (inverse) and ¹J(C-5,H) with s?₁ found for 1-substituted tetrazole allowed the identification of the N SnBu₃ derivative as 1-(tri-n-butylstannyl)tetrazole. The phenyl carbon chemical shift difference ΔC′ = δC-3′-δC-2′ is insignificant for structure elucidation and conformational studies of N-substituted 5-phenyltetrazoles; ΔH′ from ¹H NMR spectra seems to be more useful.     

Configurational assignments of oximes derived from 5-formyl and 5-acyl-1,2,4-triazines

The configuration of (3-substituted)-1,2,4-triazin-5-ylcarbaldoximes and (3-substituted)alkyl-1,2,4-triazin-5-ylketoximes was determined by means of ¹H-nmr, ¹³C-nmr, ¹⁵N-nmr and homonuclear NOE-difference spec-troscopy. Oximes resulting from reaction of 1,2,4-triazines with nitroalkanes were found to be either pure E-isomers or E/Z-mixtures with the amount of E-isomer greatly predominating. Detailed ¹³C-nmr data of the oximes investigated are presented.     

Asymmetric Hydrolytic Kinetic Resolution with Recyclable Macrocyclic CoIII–Salen Complexes: A Practical Strategy in the Preparation of (R)‐Mexiletine and (S)‐Propranolol

A chiral cobalt(III) complex ( 1 e ) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R‐(?)‐1,2‐diaminocyclohexane with trigol bis‐aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1 e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47 % with respect to the epoxides, 53 % with respect to the diols) and high enantioselectivity (ee>99 % for the epoxides, up to 96 % for the diols) were achieved in 2.5–16 h. The Co^III macrocyclic salen complex ( 1 e ) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)‐mexiletine and (S)‐propranolol.     

Synthesis and spectral properties of 2-methylthio-3H-4-(para-substituted-phenyl)-7-[(o-, and p-substituted)-phenylthio]-1,5-benzodiazepines

A series of twelve new 2-methylthio-3H-4-(p-substituted phenyl)-7-[(o-, and p-substituted)phenylthio]-1,5-benzodiazepines, which have potentially useful pharmacological properties, has been synthesized by condensing the 3,3-dimercapto-1-(para-substituted-phenyl)-2-propen-1-one with 3,4-diamino phenyl-R-phenylthio ethers, and subsequently the 1H-1,5-benzodiazepine-2-thiones obtained were treated with sodium hydride and methyl iodide. The structure of all products was corroborated by ir, ¹H-nmr, ¹³C-nmr and ms.     

Studies on organophosphorus compounds: XV. A new method for the synthesis of α-amino-substituted benzylphosphonic acids

A new synthetic method for the preparation of α-amino-substituted benzylphosphonic acids with moderate to good yields was developed by the following sequence of reactions. Diethyl phosphoramide was reacted with substituted benzaldehyde and triphenyl phosphite in the presence of catalytic amount of BF₃·Et₂O. Diphenyl α-(N-phosphorylamino)-substituted benzylphosphonates ( 1 ) thus obtained was then treated with hydrogen bromide in acetic acid to remove selectively the amino-protecting group with the formation of diphenyl α-amino-substituted benzylphosphonates ( 2 ), a key intermediate in phosphorus peptide synthesis, which was then successively hydrolyzed with hydrobromic acid to give corresponding hydrobromide of α-amino-substituted benzylphosphonates with excellent yields. The free aminophosphonic acid ( 3 ) was obatined from the latter by treatment with propylene oxide. ³¹P NMR studies demonstrated that a linear relationship exists in plotting δ versus δ constants of nuclear substituent in 1 series. The p-substituted compounds give, as a rule, higher value in ³¹P NMR spectra than those from meta- and ortho-substituents.     

Determination of epoxides by high-performance liquid chromatography following derivatization with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-diethyldithiocarbamate

A reversed-phase, high-performance liquid chromatography (RP-HPLC) method that allows quantitation of low levels of epoxides has been described. The method involved derivatization of epoxides using 100- to 1,000-fold excess N,N-diethyldithiocarbamate (DTC) at 60 °C for 20 min at neutral pH. The unreacted DTC was then decomposed to CS₂ and diethyl amine by acidification of the reaction mixture to pH 2 using orthophosphoric acid. The first two steps could be performed in the same reaction vessel by sequential addition of reagents. In the final step, an aliquot (20 μL) of the derivatized sample was analyzed for the presence of stable esters of DTC by RP-HPLC using a Supelcosil LC-18-S (150 × 4.6-mm) column and a mobile phase consisting of 40% (v/v) acetonitrile in water at a flow of 1 mL min⁻¹. Using UV detection at 278 nm, the epoxides gave linear responses in the concentration range of 0.25 to 50 μM. The method is robust, and as low as 5 pmol of the analyte could be successfully detected and quantified with recoveries of ≥94%. Following a minimal pretreatment such as ultrafiltration (molecular weight cutoff 5,000 Da), the method is suitable for analysis of epoxides in complex physiological fluids (e.g., fetal bovine serum). The method has been rigorously evaluated and adapted in our laboratory for routine analysis and determination of stability of epoxides of 1,3-butadiene and other alkenes added to cell cultures.     

1H and 13C NMR spectra of cyclic trimers,tetramers and pentamers derived from p-substituted phenylacetylenes

The ¹H and ¹³C spectra of p-substituted 1,3,5-triarylbenzenes, 7- and p-substituted 1,3,9-triaryl-9-methyl-fluorenes and 2-, 10- and p-substituted 6,12,13a-triaryl-12-methylbenzo(6,7)cycloheptadieno[1,2,3-jk]fluorenes have been examined. p-Substituents were methoxy, methyl and fluorine groups. The ¹H spectra were recorded at 300 MHz and permitted assignments for the aromatic protons by selective proton decouplings. Partial assignment of the carbon atoms in the ¹³C spectra was also possible.     

Gas-phase Meerwein reaction of epoxides with protonated acetonitrile generated by atmospheric pressure ionizations

Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) as well as atmospheric pressure photoionization (APPI). Ethylnitrilium ion ( CH₃ - C o \mathop N⁺ HCH_3 - C \equiv \mathop N\limits^ + H and its canonical form CH₃ - \mathop C⁺ = NHCH_3 - \mathop C\limits^ + = NH) is shown to efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction proceeds by the initial formation of an oxonium ion followed by three-to-five-membered ring expansion via an intramolecular nucleophilic attack to yield the Meerwein reaction products. The density functional theory (DFT) calculations at the B3LYP/6-311 + G(d,p) level show that the gas-phase Meerwein reaction is thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein reaction products yields the net oxygen-by-nitrogen replacement of epoxides with a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers a novel and fast LC-MS approach for the direct analysis of epoxides that might be of genotoxic concern during drug development. Understanding and utilizing this unique gas-phase ion/molecule reaction, the sensitivity and selectivity for quantitation of epoxides can be enhanced.     

Synthesis of 3-aminomethyl-substituted pyrazoles and isoxazoles

A series of new 3-(aminomethyl)pyrazoles and 3-(aminomethyl)isoxazoles was synthesized along a route involving the formation as key intermediates of esters of 5-substituted 1H-pyrazole-3-carboxylic and 1H-isoxazole-3-carboxylic acids. All compounds obtained were characterized by physicochemical constants, IR, ¹H, ¹³C NMR, and mass spectra.     

N-(取代对三氟甲基苯基)-N'-(1,3,5-三取代)吡唑-4-羰基硫脲的合成与生物活性

为了寻找高效低毒的农药, 从3-甲基-1-取代苯基-5-吡唑酮出发, 经过几步反应得到5-氯-3-甲基-1-取代苯基-4-吡唑羰基异硫氰酸酯. 5-氯-3-甲基-1-取代苯基-4-吡唑羰基异硫氰酸酯分别与对三氟甲基苯胺和2,6-二氯-4-三氟甲基苯胺反应得到10个未见文献报道的N-(取代对三氟甲基苯基)-N'-(1,3,5-三取代)吡唑-4-羰基硫脲类化合物, 其结构经元素分析, IR, ¹H NMR确证. 初步生物活性测试结果表明部分化合物有一定的杀菌活性.     

Theoretical study of homogeneous electron self-exchange in polar aromatic molecules: the role of the reactant structure

The solvent reorganization energies λ₀ of the electron self-exchange reaction between neutral molecules (nitrobenzene, its five para-substituted derivatives and benzonitrile) and the corresponding radical anions are discussed in terms of the Kirkwood approach combined with a semi-empirical calculation of the reactant structure (AM1 and intermediate neglect of differential overlap (INDO) methods). The theoretical values of λ₀ are compared with the experimental reorganization energies λ calculated from the Marcus equation and the homogeneous rate constants k_ex. It is found that the values of λ₀ obtained using the INDO method are approximately equal to the experimental λ, whereas the AM1 method gives poor results for para-substituted nitrobenzenes. The linear correlation of log k_ex with a_N² where a_N is a nitrogen coupling constant, established for para-substituted nitrobenzenes is interpreted. A simple criterion for slow electron transfer of an arbitrary flat polar arene is formulated in terms of the reactant structure and the model of the “specifying group” suggested earlier by some of the authors.     

A Theoretical Study on the Tautomerism of C-Carboxylic and Methoxycarbonyl Substituted Azoles

DFT calculations (B3LYP/6-31+G^**) have been carried out on 106 tautomers and conformers of NH-azoles bearing CO₂H and CO₂CH₃ groups. The following azoles systems have been studied: 2-substituted pyrroles, 2-substituted indoles, 2-substituted imidazoles, 2-substituted benzimidazoles, 4(5)-substituted imidazoles, 3(5)-substituted pyrazoles, 3-substituted indazoles (1H and 2H), 3,4(5)-substituted-1,2,3(5)-triazoles, 2,3(5)-substituted-1,2(3),4-triazoles, 4(5)-1,2,3,4(5)-tetrazoles. In the case of pyrazole, 3,5-disubstituted derivatives have also been computed, including four dimers.Dedicated to our friend Professor Vladimir I. Minkin on his 70th anniversary.     

Synthesis and structural studies of mono- and bis-n 5-cyclopentadienyl)hafnium(IV) derivatives of heterocyclic thioketones

Summary The reactions of dichlorobis(n ⁵-cyclopentadienyl)hafnium(IV) with four different classes of heterocyclic thioketoneviz., 3-substituted-4-amino-S-triazole-5-thiol, 1-substituted-2-thiohydantoin, 5-substituted 1, 3, 4-oxadiazole-2-thione and 1-substituted tetrazoline-5-thione were studied in anhydrous tetrahydrofuran in the presence of base. The reaction products were characterized on the basis of elemental analyses, electrical conductance, magnetic susceptibility and spectral (electronic, infrared and¹H n.m.r.) data.     

Structure of 2(5)-alkyl-4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones,cyclocondensation products of benzil with aliphatic ketones

The reaction of benzil with methyl alkyl ketones gave three isomeric cyclopentenone derivatives, 2-substituted and cis- and trans-5-substituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones. cis- and trans-2,5-Disubstituted 4-hydroxy-3,4-diphenylcyclopent-2-en-1-ones were formed in analogous reaction of benzil with dialkyl ketones. The structure of the products was confirmed by ¹H NMR spectroscopy and molecularmechanics calculations.