The synthesis and transition temperatures of some 4'-alkyl- and 4'-alkoxy-4-cyano-3-fluorobiphenyls

The preparation of 4'-alkyl- and 4'-alkoxy-4-cyano-3-fluorobiphenyls by four different procedures is described and discussed; the best method involves palladium(0)-catalysed coupling of arylboronic acids and 4-bromo-(or 4-iodo-)-2-fluorobenzonitrile. The effects on transition temperatures of fluoro substitution ortho to the terminal cyano group in biphenyls are compared with the effects in other terminal cyano compounds and in mesogens without a terminal cyano group. The effect of the ortho fluoro substituent in 4-cyanobiphenyls is particularly large and is probably due to the severe disruption of antiparallel correlations; the depressions of the smectic A and nematic phase stabilities are similar which suggests that, as for compounds with alkyl or alkoxy terminal groups, the fluoro substituent at the 3-position has a tendency to enhance smectic character, but this is offset by the molecular broadening it causes.     

Synthesis of Magnesium Octa-4,5-phenoxyphthalocyanine and Sulfo- and Alkylsulfamoyl Derivatives on Its Basis

By the reaction of nucleophilic substitution of bromine atom and the nitro group of 4-bromo-5- nitrophthalonitrile 4,5-diphenoxyphthalonitrile was obtained and on its basis new derivatives of octa-4,5- phenoxyphthalocyanine were synthesized soluble in water- and organic solvents. The spectral properties and thermodestruction of the products were investigated.     

Nucleophilic substitution in 4-bromo-5-nitrophthalodinitrile: XI. Preparation,properties, and prediction of mesomorphism in mixed-substituted phthalocyanines containing aryloxy and benzotriazole fragments

Stepwise nucleophilic substitution of bromine and nitro group in 4-bromo-5-nitrophthalodinitrile has led to a series of phthalonitriles containing benzotriazole and aryloxy fragments; basing on them, the mixed-substituted phthalocyanines have been prepared. The spectral properties of products have been studied. According to simulation of columnar mesomorphism only one of the products is not capable of mesomorphism characteristic of discotic mesogens; the result has been confirmed with the experiment.     

Dipyrido[1,2-a;3′,4′-d]imidazole systems

Novel tricyclic dipyridoimidazole derivatives can be readily synthesised in one pot processes from various highly fluorinated pyridine systems such as pentafluoropyridine and relatively nucleophilic 2-aminopyridine derivatives. Further nucleophilic aromatic substitution reactions of the novel tricyclic scaffolds allow the regioselective synthesis of various nitrogen, oxygen, carbon and sulfur-functionalised dipyridoimidazole products.     

Unusual regioselective reaction of 2,6-dichloro-4-methylnicotinonitrile with malononitrile dimer

Russian Chemical Bulletin - The reaction of 2,6-dichloro-4-methylnicotinonitrile with malononitrile dimer in the presence of triethylamine leads to regioselective nucleophilic substitution of the...     

ortho-Mercuration of ferrocenylimines

The mercuration of a series of aryliminomethylferrocenes occurred predominantly in an ortho-position of the substituted ferrocenyl ring to yield 2-mercurated ferrocenylimines. The regiospecificity of this reaction suggests that the mercury is directed into the ortho-position by coordination of the mercury to imino nitrogen with subsequent electrophilic substitution. The chromatographic and spectral properties of the 2-mercurated products show the presence of an intramolecular N → Hg coordination via the five-membered ring in these molecules, which was further confirmed by the single-crystal structure analysis of 2-chloromercuro-1-[(4-methoxyphenylimino)methyl]ferrocene.     

Aziridine carboxylate from D-glucose: synthesis of polyhydroxylated piperidine, pyrrolidine alkaloids and study of their glycosidase inhibition

The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through conjugate addition of benzylamine and in situ intramolecular nucleophilic expulsion of bromine. The regioselective aziridine ring-opening, using water as a nucleophile, resulted in the alpha-hydroxy-beta-aminoester 6, which was exploited in the synthesis of six and five membered azasugars 1b/1c and 2b/2c, respectively. The glycosidase inhibitory activity of the title compounds was evaluated.     

手性螺-环丙烷化合物中手性辅基的区域性转换反应的研究

通过串联的不对称双Michael加成/分子内亲取代反应,一举得到了具有四个新手性中心的螺环/环丙烯类化合物(4).4在丙酮-5%HCl溶液中50℃下发生区域选择性单水解转换反应,得到螺[1-溴-4-羟基-5-氧杂-6-氧代双环[3.3.0]已-2,3'-(4'-亲核氧基-5'-孟氧基丁内酯)](5),化学产率53%～69%,光学纯度d.e≥98%.4在甲醇/TsOH催化下,实现了区域选择性单醇解转换反应,得到螺[1-溴-4-甲氧基-5-氧杂-6-氧代双环[3.1.0]已烷-2,3'-(4'-亲核氧基-5'-孟氧基丁内酯)](6),化学产率50%～78%,光学纯度d.e.≥98%.经元素分析,[α]D^20,UV,IR,1^HNMR,13^CNMR,MS以及X射线四圆衍射测定,确认了它们的化学结构。     

Nitropyrazoles 22. On reactivity of 3,5-dinitro-4-(phenylsulfonyl)pyrazole and its N-methyl derivative

3,5-Dinitro-4-(phenylsulfonyl)pyrazole (5) obtained by oxidation of 3,5-dinitro-4-(phenylthio)pyrazole with 30% H₂O₂ in AcOH was involved into nucleophilic substitution reaction with thiophenol, which proceeded with substitution of the phenylsulfonyl group at position 4. N-Methyl-3,5-dinitro-4-(phenylsulfonyl)pyrazole obtained by methylation of 5 with dimethyl sulfate was involved into nucleophilic substitution reaction with thiophenol, p-bromophenol, and morpholine with the regioselective substitution of the nitro group at position 5 to form 5-R-3-nitro-4-(phenylsulfonyl)pyrazoles.     

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of S_N2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl₂, triggers a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.     

Nitropyrazoles

N-Substituted 3,4-dinitropyrazoles, 1,5-dimethyl-3,4-dinitropyrazole and 1-methoxy-methyl-5-methyl-3,4-dinitropyrazole, undergo nucleophilic substitution when reacted with S-, O-, and N-nucleophiles. The substitution occurs regioselectively at the 3-position, affording products in good yields. Anions of N-unsubstituted 3,4-dinitropyrazoles, 1H-3(5)-methyl-4,5(3)-dinitropyrazole and 1H-4,5(3)-dinitropyrazole, also react in water with S-nucleophiles with regioselective substitution of the nitro groups in the position 3(5).     

Effect of molecular oxygen on the kinetics and mechanism of the reaction of 2-bromo-1-ethylpyridinium bromide with triethylamine in acetonitrile

The nucleophilic aromatic substitution of bromine into 2-bromo-1-ethylpyridinium bromide (I) in its reaction with triethylamine (II) is accompanied by subsequent oxidation of the intermediates by molecular oxygen dissolved in acetonitrile. The following reaction products were identified: 1-ethyl-2-pyridone, triethylamine N-oxide, and the hydrobromide salt of triethylamine. The reaction kinetics was studied with reagents ratios     

由4-甲氧基-2-溴代丁烯内酯合成螺环-环丙烷类化合物的研究

以4-甲氧基-2-溴代丁烯内酯为合成子,在温和条件下与不同的亲核试剂通过串联的双Michael加成及分子内的亲核取代反应,得到螺环-环丙烷类化合物8a～8d.通过元素分析,IR,¹HNMR,¹³CNMR和MS对化合物进行了结构表征,其中化合物8d经单晶X射线衍射测定,确定了其立体化学结构.     

Synthesis of functionalized pyridazin-3(2H)-ones via selective bromine-magnesium exchange and lactam directed ortho C-H magnesiation

Selective bromine-magnesium exchange on 2-benzyl-5-bromo-4-methoxypyridazin-3(2H)-one could be achieved when MesMgBr was used as reagent. With more nucleophilic RMgCl species (R = Bu, i-Pr, Ph) both nucleophilic addition-elimination at C-4 and bromine-magnesium exchange at C-5 occurred. In 2-benzyl-5-bromopyridazin-3(2H)-one, which does not contain a substituent at C-4, addition could not be suppressed. Less nucleophilic Mg amides (TMPMgCl·LiCl) allowed regioselective C-H magnesiation at the C-4 position in such substrates, as exemplified for 2-benzyl-5-chloro- and 2-benzyl-6-chloropyridazin-3(2H)-one. Quenching of the magnesiated pyridazinones with electrophiles gives access to a variety of hitherto unknown pyridazin-3(2H)-one derivatives.     

Nucleophilic Substitution in 4-Bromo-5-nitrophthalodinitrile: V. Synthesis of 5-Nitro-4-(4-R-phenoxy)phthalodinitriles and Phthalocyanines Derived from Them

A series of aryloxy-substituted phthalodinitriles were prepared by nucleophilic aromatic substitution of bromine in 4-bromo-5-nitrophthalodinitrile, and the corresponding phthalocyanines were synthesized. The physicochemical properties of phthalocyanines depend on the substituent in the aryl moiety.     

Activation of chlorine and fluorine by a phenylazo group towards nucleophilic aromatic substitution. Regioselective preparation of polysubstituted anilines

A phenylazo group was used for selective activation of ortho fluorine and chlorine atoms towards nucleophilic aromatic substitution with the propanethiolate anion. This enabled a regioselective synthesis of three substituted 4-alkoxyanilines. The regioselectivity of substitution was confirmed by comparison of experimental NMR chemical shifts with empirically predicted values. The observed reactivity of the substrates is discussed in the context of the substituent effect.     

An efficient synthesis of 5-bromo-2-methoxy-6-methylaminopyridine-3carboxylic acid

An efficient synthesis of 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid (1), a carboxylic acid moiety of a potent dopamine D2 and D3 and serotonin-3 (5-HT3) receptors antagonist, (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1 ,4-diazepin-6-yl)-2-methoxy-6-methylaminopyridine-3-carboxamide, is described. Reaction of methyl 2,6-difluoropyridine-3-carboxylate (12) with methylamine in EtOH at -25 degrees C gave a mixture of methyl 2-fluoro-6-methylaminopyridine-3-carboxylate (13) and the regioisomer 14 in a ratio of 57 : 43. On the other hand, reaction of 12 and methyl 2,6-dichloropyridine-3-carboxylate (16) with sodium methoxide in tetrahydrofuran (THF) and CH2Cl2 provided the 2-methoxypyridine-3-carboxylic esters 20 and 23, respectively, as main products. Similar reaction of 16 in N,N-dimethylformamide (DMF) and MeOH proved to be highly regioselective for the 6-position. A much greater regioselectivity for substitution at the 6-position (>97%) was observed when 16 was treated with 4-methylbenzenethiolate anion in DMF (quantitative yield). After methoxylation of methyl 2-chloro-6-(4-methylbenzenethio)pyridine-3-carboxylate (25b) and successive oxidation of the 6-benzenethio moiety, nucleophilic substitution of the sulfoxide derivative 28 with methylamine gave the 6-methylamino derivative 8. Finally, bromination of 8 and alkaline hydrolysis produced the desired product 1 in an overall yield of 67%.     

Nucleophilic Substitution in 4-Bromo-5-nitrophthalodinitrile: IV. 5-Nitro-4-(phenylthio)phthalodinitrile and Octa-substituted Metal Phthalocyanines Based Thereon

5-Nitro-4-(phenylthio)phthalodinitrile was obtained by nucleophilic substitution of the bromine atom in 4-bromo-5-nitrophthalodinitrile. The product was used to prepare copper(II) and cobalt tetra(5-nitro-4-phenylthio)phthalocyanines, and their spectral properties were studied.     

Synthesis of Bioactive Natural Polymethoxyflavones and Their Vinyl Ether Derivatives

Bioactive natural polymethoxyflavones 1-6 and their vinyl ether derivatives 7-15 were synthesized by bromination, aromatic nucleophilic substitution, methylation, benzyl protection, Friedel-Crafts acetylation, aldol condensation, cyclization, DDQ dehydrogenation, regioselective demethylation, debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials. Among them, compounds 7-15 are new compounds. Natural products 2-4 were firstly total synthesized. The syntheses of compounds 1, 5 and 6 were efficiently improved by the new synthetic routes. The structures of all synthetic compounds were confirmed by NMR, IR spectra and MS.     

Nucleophilic substitution of 4-bromo-5-nitrophthalodinitrile: XIII. Synthesis and properties of 4-(1-benzotriazolyl)-5-(4-tritylphenoxy)phthalonitrile and phthalocyanines based thereon

4-(1-Benzotriazolyl)-5-(4-tritylphenoxy)phthalonitrile was synthesized by nucleophilic substitution of bromine and nitro group of 4-bromo-5-nitrophthalonitrile, and on its basis the corresponding octa-substituted phthalocyanines were obtained. Spectral properties of the synthesized compounds were investigated.