Synthesis of 1-substituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones

1,2-Disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones are prepared for the first time through an activated Pictet-Spengler reaction of the corresponding imines of 2-(1,4-dimethoxynaphth-2-yl)ethylamine in the presence of an acyl chloride and AlCl(3) followed by an oxidation with silver(II) oxide in nitric acid. Depending on the reaction conditions the N-trichloroacetyl protecting group could be cleaved off, converted to an N-methoxycarbonyl group or transformed to an N-(2-oxoacetamide) moiety. The synthesized 1,2-disubstituted 1,2,3,4-tetrahydrobenz[g]isoquinoline-5,10-diones constitute a new class of quinones, which has not been reported yet.     

N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的合成

报道了N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的简便合成方法. 分别以4-氨基苯甲酸乙酯和4-氨基苯甲酰基-L-谷氨酸二乙酯为起始物, 经甲基化、烯丙基化、溴羟基化、环氧化、开环、脱保护等反应首次合成了6个新型5-取代氨基嘧啶类化合物, 并通过¹H NMR, ¹³C NMR 和MS对其化学结构进行了表征. 初步生物活性结果表明, 苯环侧链的L-谷氨酸酯部分是此类化合物抑制人重组二氢叶酸还原酶的必需结构.     

Electrochemical oxidation of 6-hydroxy-1,2,3,4-tetrahydro-β-carboline in aqueous solution

The electrochemical oxidation of 6-hydroxy-1,2,3,4-tetrahydro-β-carboline (1), an alkaloid which occurs naturally in the mammalian brain, has been studied in aqueous solution particularly at physiological pH. The first voltammetric oxidation peak of 1 observed at the pyrolytic graphite electrode generates a radical intermediate which dimerizes to give 5,5′-bi-(6-hydroxy-1,2,3,4-tetrahydro-β-carboline) (3). However, the putative radical intermediate can also be further oxidized (1e) to give a C(5)-centered carbocation which can either dimerize in an ion-substrate reaction to give 3 or be attacked by water to give 5,6-dihydroxy-1,2,3,4-tetrahydro-β-carboline (8) which is rapidly oxidized further to 1,2,3,4-tetrahydro-β-carboline-5,6-dione (9). In the presence of glutathione dione 9 forms the 8-S-glutathionyl conjugate of 8 which is easily oxidized to the 8-S-glutathionyl conjugate of 9. It is suggested that 1 might be an alkaloid which is elevated in the brain as a result of chronic alcoholism, and the roles of the oxidative transformations of this compound in some of the addictive and neurophathological consequences of ethanol consumption are discussed.     

Acetamidine complexes as catalysts for ethylene polymerization

The reaction of (2,6-diisopropyl-phenyl)-acetimidoyl chloride or (2,6-dimethyl-phenyl)-acetimidoyl chloride with 2,6-dimethylaniline in the presence of triethylamine yields a mixture of isomers N′-(2,6-diisopropyl-phenyl)-N-[1-(2,6-diisopropyl-phenylimino)-ethyl]-N-(2,6-dimethyl)-acetamidine (1a) and N-(2,6-diisopropyl-phenyl)-N-[1-(2,6-diisopropyl-phenylimino)-ethyl]-N′-(2,6-dimethyl)-acetamidine (1b), and N,N′-bis-(2,6-dimethyl-phenyl)-N-[1-(2,6-dimethyl-phenylimino)ethyl)]-acetamidine (2), respectively. The addition of isomers (1a + 1b) to nickel (II) dibromide 2-methoxyethyl ether, (NiBr₂[O(C₂H₄OMe)₂]) gives a mixture of new nickel complexes, [NiBr₂{N′-(2,6-diisopropyl-phenyl)-N-[1-(2,6-diisopropyl-phenylimino)-ethyl]-N-(2,6-dimethyl)-acetamidine}] (3a) and [NiBr₂{N-(2,6-diisopropyl-phenyl)-N-[1-(2,6-diisopropyl-phenylimino)-ethyl]-N′-(2,6-dimethyl)-acetamidine}] (3b). Similarly, ligand 2 reacts with nickel (II) dibromide 2-methoxyethyl ether to afford the complex [NiBr₂{N,N´-bis-(2,6-dimethyl-phenyl)-N-[1-(2,6-dimethyl-phenylimino)ethyl)]-acetamidine}] (4). The structures of the ligands and nickel complexes have been determined by single crystal X-ray diffraction.The addition of MAO to these complexes generates catalytically active species for the homopolymerization of ethylene. The polymer products are high molecular weight (80-169 K). At temperatures of up to 60 °C both catalysts are a single site giving a monomodal molecular weight distribution. However, at 70 °C the mixture (3a + 3b) shows a bimodal molecular weight distribution.     

Synthesis of N-(2-carboxy-4-nitroaryl)-β-alanines and their cyclization to quinoline derivatives

N-(2-Carboxy-4-nitroaryl)-β-alanines were obtained by reaction of 2-chloro-5-nitrobenzoic acids with β-alanine. The products were converted to the corresponding 1,2,3,4-tetrahydro-4-oxo-6-nitroquinolines by cyclization.     

Reaction of nitrosobenzene with 1,2,3,4-tetrachloro-5,5-ethylenedioxycyclopentadiene

The reaction of nitrosobenzene with 1,2,3,4-tetrachloro-5,5-ethylenedioxycyclopentadiene gives rise to N-phenyldichloromaleimide 1 and the unsaturated trichloro-hydroxy-ester-lactam 2.     

Photochemical synthesis of 1,2,3,4-tetrahydroisoquinolin-3-ones from N-chloroacetylbenzylamines

When N-chloroacetyl-3-hydroxybenzylamine (37) in aqueous acetonitrile was irradiated, both ortho and para photocyclizations with reference to the OH group occurred to give 7- and 5-hydroxy-3-oxo-1,2,3,4-tetrahydroisoquinolines (52,53). Similarly, 1-methylisoquinoline derivatives (54,55) were synthesized. N-Chloroacetyl-3,5-dihydroxybenzylamine (39) gave a single photoproduct, 5,7-dihydroxy-3-oxo-1,2,3,4-tetrahydroisoquinoline (56). These photocyclizations were smoothly extended to the synthesis of 1-benzyl, 1-(4′-methoxybenzyl)- and 1-(3′,4′,5′-trimethoxybenzyl)-isoquinoline derivatives (58～64).     

Tungstophosphoric acid catalyzed synthesis of N-sulfonyl-1,2,3,4-tetrahydroisoquinoline analogs

An operationally simple and eco-friendly protocol has been developed for the synthesis of N-sulfonyl-1,2,3,4-tetrahydroisoquinolines 3 using the modified Pictet-Spengler reaction of N-sulfonylphenylethylamines 1 and various aldehydes 2 in the presence of tungstophosphoric acid hydrate.     

Super acid-induced Pummerer-type cyclization reaction: improvement in the synthesis of chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines

Improved synthesis of four stereoisomeric chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines (1a, b, ent-1a, b) was achieved via the super acid-induced cyclization of chiral N-[1-methyl-2-(phenylsulfinyl)ethyl]-N-(1-phenylethyl)formamides (4a, b, ent-4a, b) using the Pummerer-type cyclization reaction as a key step. The cyclization leading to the isoquinoline ring proceeded in a quantitative manner when trifluoromethane sulfonic acid (TFSA) was used as the super acid, although Friedel-Crafts-type alkylation of 4-phenylsulfanyl TIQ derivatives (5) with benzene used as the solvent accompanied cyclization to yield the 4-phenyl-TIQs (7). The byproduct (7) was exclusively formed when a large excess amount of TFSA was used.     

Polymerization of norbornene by palladium(II) complexes bearing ethylene-bridged bisindolinyl- or bis(1,2,3,4-tetrahydroquinolinyl) ligands

Novel moisture and air stable, cationic palladium(II) amine complexes (1–4) of the general type [Pd(N∩N)(X)₂](BF₄)₂, [N∩N=1,2-bis(N-indolinyl)ethane (BIE) 1, 3; 1,2-bis(N-1,2,3,4-tetrahydroquinolinyl)ethane (BTQE) 2, 4; X=NCCH₃, H₂O] were found to catalyze the polymerization reaction of bicyclo[2.2.1]hept-2-ene at room temperature. The amorphous polymer products consist of 2,3-linked norbornene units; no indications for ring opened species could be observed. The polymerization activity of the diaqua-complexes 3, 4 is superior compared to their acetonitrile analogues due to a facile activation by a Wacker-type reaction. The cationic Pd(II)-compounds are inactive towards homo- and copolymerization reactions of polar monomers, like acrylates or carbon monoxide. However, addition of methylacrylate resulted in polynorbornene products with increased molecular weight and narrow molecular weight distributions.     

5-phenyl-1,2,3,4-thiatriazole-3-oxide: A new class of heteroaromatic N-oxides

Oxidation of 5-phenyl-1,2,3,4-thiatriazole (1) with peroxytrifluoroacetic acid yields 5-phenyl-1,2,3,4-thiatriazole-3-oxide (2) a representative of a new class of heteroaromatic N-oxides. The structure is based on the mass spectral fragmentation of 2 and the isotope labelled with ¹⁵N at position 2. IR and ESCA measurements are consistent with this assignment. The thermal, photochemical, and chemical properties of the oxide are discussed.     

Convenient synthesis of fluorinated quinoline, 1,2-dihydroquinoline, and 1,2,3,4-tetrahydroquinoline derivatives

A convenient synthetic method for 2-polyfluoroalkylated quinoline systems through the efficient generation of perfluoroalkylated imine from o-vinylanilines with perfluorinated hemiacetals or aldehyde hydrates was developed. In most cases, the major products are 2-polyfluoroalkyl-1,2-dihydroquinoline derivatives 3, which can be converted to either quinolines or 1,2,3,4-tetrahydroquinolines.     

Synthesis and Investigation of 1,2,3,4-Thiatriazol-5-ylcarbamates

Methyl 1,2,3,4-thiatriazol-5-ylcarbamate (2a), ethyl 1,2,3,4-thiatriazol-5-ylcarbamate (2b), 2-butyl 1,2,3,4-thiatriazol-5-ylcarbamate (2c), allyl 1,2,3,4-thiatriazol-5-ylcarbamate (2d), and 3-(1,2,3,4-thiatriazol-5-yl)oxazolidin-2-one (2e) were synthesized with high yields by the reaction of the corresponding carbon(isothiocyanatidic) acid, alkyl esters, and sodium azide in aqueous solution. The compounds were characterized by ¹H, ¹³C, and ¹⁵N NMR, vibrational spectroscopy (IR), and single crystal X-ray diffraction. The thermal stability was investigated by differential scanning calorimetry.     

Base-promoted regioselective synthesis of 1,2,3,4-terahydroquinolines and quinolines from N-boc-3-piperidone

An efficient synthesis of 1,2,3,4-tetrahydroquinolines with donor and acceptor group has been delineated by base mediated ring transformation of 6-aryl-4-substituted-2H-pyran-2-one-3-carbonitriles by N-boc-3-piperidone followed by consecutive deprotection of Boc group under acidic conditions. This reaction involves 2 new bond formations namely C4a-C5 and C8a-C8 in order to create the nucleus. Various donor and acceptor functional groups like aryl, heteroaryl, nitrile, methylsulfanyl and secondary amine were installed in 1,2,3,4-tetrahydroquinolines. We extended our approach to synthesize the fused 1,2,3,4-tetrahydroquinolines by using 2-oxobenzo[h]chromenes as precursor. Further, we synthesized fused and isolated quinolines through aromatization of 1,2,3,4-tetrahydroquinolines by DDQ in excellent yields. Single-crystal X-ray analysis of the Boc protected tetrahydroisoquinoline 6t showed the steric hindrance between N-Boc and aryl group.     

Benzoxadiazocines,benzothiadiazocines and benzotriazocines-IV : Ring closure of 1-(2-[n-(2-chloroethyl and 2-hydroxyethyl)-n-methylamino]phenyl)-3-phenylthioureas. tetrahydroquinoxaline vs.dihydro-3,1,6-benzothiadiazocine and hexahydro-1,3,6-benzotriazocinethione formation

While base induced ring closure of 1-(2-[N-(alkylsulfonyl and arylsulfonyl)-N-(2-chloroethyl)amino]phenyl)-3-phenylthioureas 1 had furnished the corresponding type 2 dihydro-3,1,6-benzothiadiazocine derivatives rather than the isomeric hexahydro-1,3,6-benzotriazocinethiones (3) or tetrahydroquinoxalines (4), base induced ring closure of the related N-(2-chloroethyl)-N-Me derivatives 9a-9c, 10a and lOb furnishes type 14 tetrahydroquinoxalines. 14a is obtained also by treating the N-(2-hydroxyethyl)-N-Me derivative 11 with the triphenylphosphine-diethyl azodicarboxylate (DEAD) reagent. In situ replacement of the chlorine atom of compound 9a by iodine in the absence of base as well as treatment of 1-(2-[N-(2-hydroxyethyl)-N-methylamino]phenyl)-1-methyl-3-phenylthiourea (18) with the triphenyl-phosphine-DEAD reagent furnishes the benzimidazole derivatives 16 and 22, respectively, whose formation may be rationalised by assuming the intermediacy of the dihydro- and tetrahydro-3,1,6-benzothiadiazocine derivatives 12a · HI and 20, respectively, and their subsequent ring contraction.     

Asymmetric synthesis of (1R,2S,3R)-2-acetyl-4-(1,2,3,4-tetrahydroxybutyl)thiazole

Two different methods for preparing the thiazole analogue 3 of the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4- tetrahydroxybutyl)imidazole 1 are reported.     

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide

Alkylation of 1-hydroxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxide 1 and its silver salt 10 with different alkylating agents (diazomethane, diazoacetone, bromoacetone, α-bromoacetophenone, methyl iodide, methyl vinyl ketone) was studied. Alkylation of compound 1 with diazo compounds and salt 10 with halocompounds results predominantly in O-alkylation products, 1-alkoxy-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 5,7-dioxides. The Michael reaction of compound 1 with methyl vinyl ketone involves the triazole nitrogen atom to give 1-(3-oxobutyl)-1H-[1,2,3]triazolo[4,5-e][1,2,3,4]tetrazine 3,4,6-trioxide. The structures of the compounds synthesized were established by ¹H, ¹³C, ¹⁴N NMR spectroscopy and mass spectrometry.     

l-Proline-catalyzed five-component domino reaction leading to multifunctionalized 1,2,3,4-tetrahydropyridines

Multifunctionalized 1,2,3,4-tetrahydropyridines are concisely synthesized in good yields via l-proline-catalyzed or l-proline/FeCl₃-cocatalyzed one-pot multicomponent reactions (MCRs). The MCRs involve a domino hydroamination/prins reaction/Mannich-type reaction/intramolecular dehydration-cyclization process. The molecular structure of 5baa, one of multifunctionalized 1,2,3,4-tetrahydropyridines, was confirmed by single-crystal X-ray diffraction.     

Attempts to prepare aromatic O-acyl-hydroxylamines—I : Dehydrohalogenation of 1-bromo-4-acetoxyimino-1,2,3,4-tetrahydrophenanthrene by tetramethylammonium dimethylphosphate

The dehydrohalogenation of 1-bromo-4-acetoxyimino-1,2,3,4-tetrahydrophenanthrene by tetramethylammonium dimethylphosphate gave a mixture of products. Ten of these were identified and together account for 70% of the total yield. The proposed reaction mechanism implicates the corresponding O-acetyl-hydroxylamine 15 as an intermediate. Attempts to prepare O-esters or O-ethers of aromatic hydroxylamines by dehydrogenation, with quinones, of the corresponding oximino-derivatives of oxo-1,2,3,4-tetrahydro-naphthalene and oxo-1,2,3,4-tetrahydro-phenanthrene were without success.     

The structures and ultraviolet spectra of the bromination products of 6,6-diphenylfulvene

Bromination of 6,6-diphenylfulvene 1 gives trans-trans-trans-1,2,3,4-tetrabromo-1,2,3,4-tetrahydro-6,6-diphenylfulvene 3 via trans-1,2-dibromo-1,2-dihydro-6,6-diphenylfulvene 2. Compound 3 in cyclohexane or carbon tetrachloride is converted by heating or exposure to sunlight to its trans-cis-trans stereoisomer 4. The structures of 3 and 4 have been established by X-ray crystallography. Compound 3 is converted to a third stereoisomer 5 on standing in chloroform or dichloromethane solution. Anomalies in the ultraviolet spectra of 3–5 can be interpreted in terms of an interaction of the π system with the bromine atoms at C(1) and C(4). The formation of addition products from 1 is indicative of its olefinic rather than aromatic character.