Cyano benzenes, synthesis

Scheme 2 Synthesis of 4-cyano-benzene-boronic acid...

Synthesis of 4-cyano-benzene-boronic acid 4. A vacuum isolated triple jacket reactor was charged with THF (76.5 g), triisopropylborate (49.8 g, 265 mmol), and toluene (88 g), and the mixture was cooled to —70°C. A solution of 4-bromo-benzonitrile 2 (40 g, 220 mmol) in toluene (210 g) was added within 20 min and a fine suspension is formed. BuLi (15% in hexane, 131 g, 308 mmol) was added dropwise within 4 h keeping the reaction temperature below —70°C. Hydrochloric... 

Synthesis of 5-(4-cyano-phenyl)-indole 1. A double jacket reactor was charged with 5-bromo-indole 3 (50 g, 250 mmol), 4-cyano-benzene-boronic acid 4 (38.7 g, 263 mmol), and isopropanol (393 g). The reactor was purged with nitrogen. Pd(PTol3)2Cl2 (0.2 g, 0.25 mmol) was added, and the reaction mixture was heated to reflux. Sodium carbonate solutimi (2 M, 250 ml, 500 mmol) was dosed within 2 h. The reaction was stirred for additional 90 min at reflux. The isopropanol was distilled off until the temperature of the distillation residue reached lOO C. The reaction mixture was cooled to room temperature and was extracted with dichloromethane (1,000 ml). The organic phase was extracted with water (250 ml) and was filtered slowly through a bed of silica (40 g) and charcoal (4 g). The filter bed was washed with dichloromethane (100 ml). To the combined dichloromethane phases, toluene (500 ml) was added and dichloromethane was distilled of until the distillation residue reached a temperature of 110°C. The product solution was cooled to 95°C and was seeded. The suspension was cooled slowly (l°C/min) to room temperature. The product is filtered, washed with toluene (50 ml), and dried at 60°C. 5-(4-cyano-phenyl)-indole 1 was obtained as colorless crystals (42.6 g, 188 mmol, 75%). 

The reaction of 3/3-acetoxy-5a-cholest-8(14)-en-7-one with EtjAlCN was the key reaction in a synthesis of cholestanes containing an oxygenated 14a-substi-tuent. Cholest-4-en-3-one reacted smoothly with KCN-acetone cyanohydrin in benzene or acetonitrile containing 18-crown-6 to give the epimeric 5-cyano-cholestan-3-ones. An 11 -hydroxy-group increased the proportion of a-epox-ide produced in the reaction of 3-oxo-A -steroids with H202-0H . A 9a-fluorine substituent also influenced the stereochemistry of the reaction products and a... 

Highly substituted pyridinium salts of type 1 are easily accessible by Hantzsch-type synthesis. They are valuable products in that they can often be transformed easily into otherwise difficultly accessible, highly substituted benzenes or pyridines by base-catalysed rearrangement. For example, treatment of the salt 2 with ethanolic sodium hydroxide at room temperature for one hour gives 2,4-diacetyl-lV,5-dimethylaniline 3 in 85% yield, while 3-acetyl-5-cyano-6-methyl-2-methylamino-4-phenylpyridine 5 is obtained in 88% yield from the salt 4 under the same conditions. 

For the synthesis of 4, 2-cyanobenzyl chloride is first treated with triethyl phosphite to give 2- cyano-(l-diethylphosphonomethyl)benzene [23973-65-1], which reacts with terephthalaldehyde in the presence of sodium methoxide to yield l,4-bis(2-cyanostyiyl)benzene (4) [13001-39-3] [28]... 

The reactions of vinyl(tri-n-butyl)stannanes with the appropriate [cyano(sulfonyloxy)-iodo]benzenes in dichloromethane constitute a facile stereoselective approach to / ,/ -disubstituted vinyl(phenyl)iodonium tosylates and triflates (equation 168)130,131. Although this method has not yet been used for the preparation of a,/ -disubstituted and a,/ ,/ -trisub-stituted analogs, it has been applied to the synthesis of ethenyl(phenyl)iodonium triflate131. The efficiency of this approach may be contrasted with the early work on chlorostannanes and chloroiodanes. 

Difluorobenzonitrile and 2-aminophenol were used [47] in a synthesis of cyanophenoxazines 64 (Scheme 25). After displacement of the fluorine atom activated by the cyano-group, rearrangement and cycli-zation were carried out. Analogous reaction sequences involving catechol, 2-aminothiophenol and benzene-1,2-dithiol have also been studied. 

Simple benzannelation of benzene leads to naphthalene. Related to our synthesis, a great number of benzene derivatives with an acidified methylene group that are ready for condensation with (7), e.g., desoxybenzoin (activated by carbonyl), benzyl-phenylsulphones (activated by sulphonyl), esters of phenylacetic acids, and best-suited, the phenylacetonitriles (activated by cyano) can easily be transformed to arylaminobutadienes 54) and cyclized to naphthalenes (56) ... 

Typically, in the Knoevenagel polycondensation, a terephthalic aldehyde is condensed with a bis-(cyanomethyl)-benzene compound. Since two monomers are used, PPVs with a strictly alternating structure can be synthesized. The Knoevenagel polycondensation allows the convenient synthesis of compounds in that the backbone double bond is substituted. PPV modified with cyano groups show a high EL activity. The synthesis is shown in Figure 3.8. In a quite similar way, PPV can be formed by the Wittig... 

This reaction was initially reported by Reissert in 1905 and extended by Grosheintz and Fischer in 1941 It is the synthesis of aldehyde involving the formation of 1 -acyl-2-cyano-1,2-dihydroquinoline derivatives from acyl chlorides, quinoline, and potassium cyanide and the subsequent hydrolysis of said dihydroquinoline derivatives under acidic conditions to produce quinaldic acid and aldehydes. The original procedure occurs smoothly for aroyl or cinnamoyl chloride in liquid SO2 but not in benzonitrile, ether, dioxane, acetone, or CHCb. However, the modification from Grosheintz and Fischer using hydrogen cyanide and 2 eq. quinoline in absolute benzene is also adaptable for aliphatic acid chlorides. This is one of the methods that converts acyl chlorides into aldehydes and is found to be superior to the normal Rosenmund Reduction. For example, o-nitrobenzoyl chloride has been converted into o-nitrobenzaldehyde in 60% yield by the current reaction, whereas the Rosenmund Reduction is not suitable for such conversion. Therefore, this reaction is referred to as the Grosheintz-Fischer-Reissert aldehyde synthesis or Reissert aldehyde synthesis. ... 

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