Synthesis of 6,7-dimethoxy-1-[(halophenoxy)-methyl]-1,2,3,4-tetrahydroisoquinolines

Some 6,7-dimethoxy-1-[(halophenoxy)methyl]-1,2,3,4-tetrahydroisoquinolines were synthesized from N-[2-(3,4-dimethoxyphenyl)ethyl]-2-chloroacetamide via three steps in good yield.     

Synthesis of 1,2-di-(4-pyridyl)ethylenediamine and related compounds

Hydrolysis of N,N'-diacyl-1,2-di(4-pyridyl)ethylenediamines 1 in aqueous sulfuric acid gave the corresponding imidazolines 3. 1,2-Di-(4-pyridyl)ethylenediamine 2 was prepared in 61 % yield by treating N,N'-di-t-butyl-oxycarbonyl-1,2-di(4-pyridyl)ethylenediamine 4 with trifluoroacetic acid or in 94% yield by the hydrolysis under basic conditions of N,N'-diphthaloylglycyl-1,2-di(4-pyridy)ethylenediamine 13.     

A New Convenient Approach to Preparation of 5 or 6 or 7-Nitro-1,2,3,4-Tetrahydrisoquinolines and 2-Alkylsulfonyl-5 or 6 or 7-Nitro-1,2,3,4-Tetrahydroisoquinolines

N-alkylsulfonyl-p or m or o -nitrophenylethylamines were treated with (HCHO)n in 60% H₂SO₄/HOAc to give N-alkylsulfonyl-5 or 6 or 7-nitro-1,2,3,4-tetrahydroisoquinolines, then hydrolyzed with 40% HBr to give 5 or 6 or 7-nitro-1,2,3,4-tetrahydroisoquinolines     

1-Phenyl-6,7-disubstituted-aminopropyl)-1,2,3,4-tetrahydroisoquinolines as possible antituberculer agents

The Condensation of 3,4-disubstituted phenylethylamine and benzaldehyde furnished l-phenyl-6,7-disubstituted-1,2,3,4-tetrahydroisoquinolines l. which on reaction with 1,3-dibromopropane gave l-phenyl-6,7-disubstituted-2-(3-bromoprophyl)-1,2,3,4-tetrahydroisoquinolines 2. The reaction of 2 with different secondary amines resulted in the synthesis of 3. The compounds 3 were screened for their in vitro antituberculer activity against Mycobacterium smegmatis, and some of them have been found to be total inhibitors of M. Smegmatis     

Mannich and eschweiler-clarke reaction of 1-benzyl-1,2,3,4-tetrahydroisoquinolines. Studies on the syntheses of heterocyclic compounds. Part CCCXVIII

Modified Mannich reactions of a number of 1-benzyl-1,2,3,4-tetrahydroisoquinolines (Ia-Ie) were attempted to afford the corresponding protoberberine derivatives (IIa-IIe) in good yield. Treatment of both If and Ig with formalin under a variety of Mannich or Eschweiler-Clarke conditions did not give the expected protoberberine derivatives IIf and IIg, but afforded the N-methyl derivatives (VIIa) and (VIIb), respectively.     

Synthesis of N,N'-bis(1,2,3,4-Tetrahydroisoquinolinyl) Dicarboxamides by an Intramolecular α-Diamidoalkylation Reaction

Synthesis of N,N'-bis(1,2,3,4-tetrahydroisoquinolinyl) dicarboxamides from N,N'-dicarboxamides 1 of 2-phenylethylamines and aldehydes 2 by application of α-diamidoalkylation reaction is described.     

The reactions of some pyranylideneiminium salts with amines. Part 1

The iminium salt, N,N-dimethyl-N-[2-(2,6-diphenyl-4H-pyran-4-ylidene)ethylidene]iminium perolilorate ( 1 ), reacts with secondary amines, such as piperidine, by exchanging the dimethyl-amino function for a piperidine. Primary amines react with 1 to give 1-alkyl-2-phenyl-4-phenacylidene-1,4-dihydropyridines. The bisiminium salt, N,N,N',N' -tetramethyI-N,N'-[2-(2,6-diphenyl-4H-pyran-4-ylidene)-1,3-propanediylidene]bis(iminium perchlorate) ( 2 ), reacts with ammonia to give 3,6-diphenylcopyrine and with primary amines to give the corresponding N,N' -dialkyl quaternary copyrines. The salt 2 reacts with secondary amines with exchange of the dimethylamino groups of 2 by the secondary arnine and addition of the amine at the 2-position of the pyran ring.     

Anionic polymerization of 9‐vinylanthracene with the alkyllithium/amine system

The anionic polymerization of 9‐vinylanthracene (VAN) with the alkyllithium (RLi)/amine system was examined to explore new initiator systems that could polymerize VAN at moderate temperatures in hydrocarbon solvents. Important factors in the anionic polymerization of VAN were found to be the high nucleophilicity of the RLi/amine and poly(9‐vinylanthracenyl)lithium (PVANLi)/amine systems, the low steric hindrance of the amine molecule, and good solubility of PVANLi during the polymerization. The t‐butyllithium (t‐BuLi)/N,N,N',N'‐tetramethylethylenediamine (TMEDA) (1.00/1.25) system achieved the highest PVAN yield in toluene at room temperature (ca. 25°C), although the limitations of yield and the number average molecular weight (M_n) were around 90 wt% and 2000, respectively. The results obtained from spectrum analyses suggested that the anionically polymerized PVAN would be considered a favorable polymer for the preparation of new luminescent materials. Copyright © 2009 John Wiley & Sons, Ltd.     

Facile Synthesis and Bioactivity of Novel N,N′‐disubstituted‐1,2,3,4‐tetrahydroquinoxalines

A series of novel N ,N'‐disubstituted‐1,2,3,4‐tetrahydroquinoxalines were designed and synthesized by cyclization and acylation. The structures of all the novel compounds were confirmed by IR, ¹H NMR, ¹³C NMR, and high‐resolution mass spectrometry. The configuration of 4d was determined by X‐ray diffraction. The preliminary biological tests showed that all the products could protect maize against the injury caused by acetochlor to some extent.     

钯和四齿膦配体催化剂应用于Heck反应的研究

设计合成了以联萘二胺为骨架的四齿膦配体N,N,N',N'-四(二苯基膦甲基)-(1,1'-联萘)-2,2'-二胺,并将其与钯组成的催化体系用于苯乙烯和芳卤的Heck反应,该催化体系对各种卤代芳烃都表现出了很高的催化活性.对活化底物对溴苯腈,即使底物与催化剂的物质的量比达到10 000,反应20 h几乎能达到定量转化;该催化体系对活性更低的杂环底物也取得了良好的催化效果.     

PREPARATION OF 1,7-DISUBSTITUTED-1,2,3,4-TETRAHYDROISOQUINOLINES

ABSTRACT

A simple procedure for the preparation of 1,7-disubstituted-1,2,3,4-tetrahydroisoquinolines from 3,4-dihydroisoquinoline (2) is presented. This strategy overcomes the limitation of cyclisation approaches which generally require electron rich ring systems. A variety of 1-substituents has been incorporated using the appropriate organometallic or activated methylene nucleophile to prepare both electron rich (7a–f) and electron deficient 1,7-disubstituted-1,2,3,4-tetrahydroisoquinolines (16, 17).     

Synthese einiger 8-substituierter 2-Methyl-1,2,3,4-tetrahydroisochinoline

Synthesis of Some 8-Substituted 2-Methyl-1,2,3,4-tetrahydroisoquinolines A general route to 8-substituted tetrahydroisoquinolines is exemplified by the preparation of the 2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ol ( 11 ), the -8-carbaldehyde oxime ( 12 ) and the -8-carbonitrile ( 13 ). It involves the conversion of isoquinoline ( 1 ) by partially modified Steps 1, 2, 3, and 5 (see the Scheme) into the 5-bromo-8-nitro derivative 5 , reduction of the latter to the 8-amino derivative 8 and replacement of the NH₂-group with an appropriate substituent by a Sandmeyer-like reaction. The selective reductions of the N-containing ring in 6 (Steps 5, 6, and 8) and of the NO₂-group in 5 (Steps 4 and 7) were also studied.     

A convenient preparation of 4,8-dimethoxy-3-substituted-2(1H)-quinolones by an electrophilic reaction through base-induced deprotonation and its synthetic application for the synthesis of new alkaloids, 3,4,8-trimethoxy-2(1H)-quinolone and 3-formyl-4,7,8-trimethoxy-2(1H)-quinolone(glycocitridine)

Some 4,8-dimethoxy-3-substituted-2(1H)-quinolones were prepared by electrophilic reaction of 4,8-dimethoxy-2(1H)-quinolone with electrophiles in the presence of n-butyllithium-N,N,N',N'-tetramethylethyl-enediamine in fairly good yields. This present method was successfully applied for the synthesis of two new alkaloids bearing the 4,8-dimethoxy-2(1H)-quinolone skeleton.     

Synthesis and polymerization of novel formamidinium salts: A new pathway to polyamides derived from aromatic diamines

A new polycondensation pathway has been developed for the preparation of polyamides at high temperatures. p-Phenylenediamine was converted to N,N-p-phenylene bis(N′,N′-dimethylformamidine) (I), which formed 1–1 and 2–1 salts with terephthalic and adipic acids, respectively: Dicarboxylate salts were polymerizable by heating in bulk or suspension. Low-molecular-weight poly(p-phenyleneterephthalamide) was obtained from N,N-p-phenylene bis(N',N'-dimethylformamidinium) terephthalate above 225°C. The low degree of polymerization was due to terephthalic acid sublimation as well as to the well-known intractability of poly(p-phenyleneterephthalamide). High-viscosity poly(p-phenyleneadipamide) was obtained from N,N-p-phenylene bis(N′,N′-dimethylformamidinum hydrogen adipate) above 200°C. Both salts liberated dimethylformamide (DMF) during polymerization. The adipate salt also released 1 mole of adipic acid during the high-temperature vacuum stage of polymerization. A polycondensation mechanism was proposed for each salt, based on thermal gravimetric analysis (TGA-MS) and infrared (IR) analyses. The hydrolysis of N,N-p-phenylene bis(N',N'-dimethylformamidine), N,N-p-phenylene bis(N',N'-dimethylformamidinium chloride), and the two dicarboxylate salts of (I) was monitored by nuclear magnetic resonance (NMR) at room temperature. The dihydrochloride salt was most resistant to hydrolysis (k_H 6.9 × 10^?9 sec^?1; relative rate 1.0) followed by (I) 7.1, terephthalate salt, 14.9, and adipate salt, 27.2. Both dicarboxylate salts possessed sufficient hydrolytic stability for use as polycondensation monomers     

Efficient One‐Pot Synthesis of Quinazoline and Benzopyrano[2,3‐d]pyrimidine Derivatives Catalyzed by N‐Bromosulfonamides

N,N,N',N'‐tetrabromobenzene‐1,3‐disulfonamide and poly(N ,N ’‐dibromo‐N‐ethyl‐benzene‐1,3‐disulfonamide) were used as efficient catalysts for one‐pot synthesis of new quinazoline derivatives from various aldehydes, 2‐amino‐benzophenone, and ammonium acetate in good to excellent yields and new benzopyrano[2,3‐d ]pyrimidine derivatives from salicylic aldehydes, various cyclic amines, and malononitrile in good to high yields.     

Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives

A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer.     

Investigation of the preparation of pyrimidine isocyanates

Uracil-5-yl isocyanate and 1,3-dimethyluracil-5-yl isocyanate were prepared from the corresponding new carboazides. 1,3-Dimethyluracil-5-ylmethyl isocyanate obtained from the chloro compound and silver cyanate, was polymerized with an anionic initiator to the cyclic trimer. Attempts to isolate uracil-6-yl isocyanate, 1,3-dimethyluracil-6-yl isocyanate, pyrimidinyl-4-isocyanate, and 2,6-dichloropyrimidinyl-4-isocyanate were unsuccessful. Ethyl carbamate derivatives were made from all new azides and isocyanates. Other new pyrimidine derivatives included N,N'-bis(pyrimidine-4-carbonyl)hydrazine, N,N'-bis(1,3-dimethyluracil-5-yl)urea, N,N'-bis(1,3-dimethyluracil-6-yl)urea and N,N'-bis(2,5,6-trichloro-4-pyrimidinyl)oxamide.     

Proton-ionizable crown compounds. 20. The synthesis of polyazatriazolo-, polyazabistriazolo- and bispyridono-crown ligands containing lipophilic hydrocarbon substituents

Four new macrocyclic polyaza-crown compounds containing a triazole subcyclic group and two to five lipophilic hydrocarbon substituents have been prepared from the appropriate polyamine and N-THP-protected 2,5-triazoledimethyl dichloride. N,N,N',N'-Tetrabenzyltetraazabistriazolo-18-crown-6 was prepared from N,N'-dibenzylethylenediamine and N-THP-protected 2,5-triazoledimethyl dichloride. Biscyclohexano-bispyridono-18-crown-6 was prepared from trans- 1,2-cyclohexanediol and THP-protected 4-hydroxy-2,6-pyridinedimethyl ditosylate.     

Studies on Debenzylation and Photolysis of 1-Benzyl- and 1-(β-Phenethyl)-1,2,3,4-tetrahydroisoquinolines

Debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines 1 , 6 , 7 with hydrochloric acid and ethanol gave the corresponding phenolic isoquinolines 2 , 8 , 9 and tetrahydroprotoberberines 4 , 12 , 13 . Compounds 2 , 8 , 9 on photolysis also gave, besides the expected noraporphines 3 , 10 , 11 , the tetrahydroprotoberberines 4 , 12 , 13 [1–4] (Schemes 1 and 2). 6-Benzyloxy-1-(5-benzyloxy-2-bromo-benzyl)-1,2,3,4-tetrahydroisoquinoline (27a) containing no methoxy or methylenedioxy groups either in ring A or C does not give protoberberine during debenzylation; but 28 , the debenzylation product of 27a , on photolysis gives both the noraporphine 29 and the tetrahydroprotoberberine 30 (Scheme 6), proving that during debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines containing additional methoxy or methylenedioxy groups, the necessary formaldehyde comes from the latter groups. During photolysis both the methoxy groups (methylenedioxy groups) and the C(3) atom of the tetrahydroisoquinoline moiety provide the formaldehyde. Veratrole under debenzylation and photolytic conditions and tetrahydroisoquinoline under the latter condition also give rise to formaldehyde (Schemes 8 and 10). The novel bromohomoprotoberberine 43 along with 42 was formed during debenzylation of the 1-phenethyl-1,2,3,4-tetrahydroisoquinoline 41 . Photolysis of 42 yielded the novel nor-homoaporphine 44 , in addition to 43 ; the latter was debrominated to give the homoberbine 45 .     

A facile synthesis of benzo[b]thiophene derivatives

Lithiation of S-(2-methylphenyl) N,N,N',N'-tetramethylphosphorodiamidothioate with sec-BuLi at -105° gave the corresponding benzylic anion which was acylated with various aromatic esters to give various deoxybenzoin derivatives in moderate to high yields. Acidic treatment of these products in refluxing formic acid gave 2-arylbenzo[b]thiophene derivatives. 2-Methylbenzo[b]thiophene and benzo[b]thiophen-2(3H)-one were also prepared using the similar procedure.