Aryl derivatives formylation

Hydroxy group of rru -7,9u-H-7-(prepared from 7-formyl-2-(2-pyrimidyl)perhydropyrido[l,2-u]pyrazine by the treatment with MeOCH2P(Ph)3Cl in the presence of -Pr2NH in THF at 0°C, than with BuLi at room temperature (99MIP6). 

Functional biaryl derivatives are important industrial chemicals. They are used as monomers for the production of high performance and other polymers, as well as dyes, pharmaceuticals and agrochemical intermediates. We have developed an improved method for the dehalogeno-dimerization of aryl bromides to yield biaryl derivatives under mild conditions (temperature < 100°C, atmospheric pressure) using a common base, a 5 % Pd/C catalyst (0.1 - 10 % w/w, based on the starting material) in an aqueous medium and formyl hydrazine as the reducing agent. Several examples of biaryl derivatives are discussed. 

Pyrazolo[4,3-e][l,2,4]triazine derivatives have been prepared from oximes of 5-aryl- and 5-formyl-l,2,4-triazines <06MI191 >. Novel pyrazolo[5,1 -c][ 1,2,4]triazines incorporating an Af-(2-oxoethyl)phthalimide moiety have been reported <06JCR(S)6>. 

Other electrophilic substitution reactions on aromatic and heteroaromatic systems are summarized in Scheme 6.143. Friedel-Crafts alkylation of N,N-dimethyl-aniline with squaric acid dichloride was accomplished by heating the two components in dichloromethane at 120 °C in the absence of a Lewis acid catalyst to provide a 23% yield of the 2-aryl-l-chlorocydobut-l-ene-3,4-dione product (Scheme 6.143 a) [281]. Hydrolysis of the monochloride provided a 2-aryl-l-hydroxycyclobut-l-ene-3,4-dione, an inhibitor of protein tyrosine phosphatases [281], Formylation of 4-chloro-3-nitrophenol with hexamethylenetetramine and trifluoroacetic acid (TFA) at 115 °C for 5 h furnished the corresponding benzaldehyde in 43% yield, which was further manipulated into a benzofuran derivative (Scheme 6.143b) [282]. 4-Chloro-5-bromo-pyrazolopyrimidine is an important intermediate in the synthesis of pyrazolopyrimi-dine derivatives showing activity against multiple kinase subfamilies (see also Scheme 6.20) and can be rapidly prepared from 4-chloropyrazolopyrimidine and N-bromosuccinimide (NBS) by microwave irradiation in acetonitrile (Scheme... 

Under favourable circumstances, the initially formed /V-ylid reacts further through C-N cleavage. Thus, in the presence of a strong nucleophile, such as a phenoxide anion, the quaternary dichloromethylammonium cation forms an ion-pair with the phenoxide anion (Scheme 7.27), which decomposes to yield the alkyl aryl ether and the /V-formyl derivative of the secondary amine [22, 23]. Although no sound rationale is available, the reaction appears to be favoured by the presence of bulky groups at the 4-position of the aryl ring. In the absence of the bulky substituents, the Reimer-Tiemann reaction products are formed, either through the breakdown of the ion-pair, or by the more direct attack of dichlorocarbene upon the phenoxide anion [22,23],... 

The transformation of lithio derivatives of dibenzothiophene into alkyl, alkenyl, hydroxyalkyl, formyl, acetyl, carboxylic acid, alkyl and arylsilyl, boronic acid, aryl and carbinol derivatives of dibenzothiophene is dealt with in the appropriate sections. In addition, the four mono-tritio derivatives of dibenzothiophene have been prepared from the corresponding lithio derivatives via hydrolysis with tritiated water (Section III, 0,2). ... 

Another entry into the preparation of 3-arylpyrroles starts with the reaction of the 3-iodopyrrole derivative shown in 6.28. with hexabutyl-distannane in the presence of a palladium catalyst. The formed intermediate was reacted, in the presence of a similar catalyst system, with different aryl iodides to give the desired products in good to excellent yield38 It is worth mentioning that the presence of a formyl group in the 2-position of he pyrrole had no adverse effect on the efficiency of the couplings. 

Numerous derivatives of (1) have been thus prepared, notably 2,3-dimethyl (or dialkyl)benzofurans Bz-substituted by alkyl radicals,36,213-218 methoxyl groups,101,219-221 halogen atoms,217,222-224 aryl groups,225 acetyl groups,215,218,226 formyl groups,222,226 and carboxyl groups.226,227 The method is especially valuable in the case of formyl derivatives, which are difficult to obtain otherwise. 

The use of iodoacetic acid as an aryl radical trapping agent has confirmed the intermediacy of aryl radicals in some hydrodediazoniation reactions, whether these are initiated or not.4 Spontaneous hydrodediazoniation of aryldiazonium fluoroborates occurs in warm dimethylformamide (DMF). Detailed study5 of the conversion of the 4-nitro derivative into nitrobenzene indicates a homolytic mechanism in which H-atom abstraction occurs from both sites in DMF with a formyl methyl preference of 3.5 1.0. High yields of mixed perfluorinated biaryls may be obtained by the catalytic dediazoniation of pentafluorobenzenediazonium ions in acetonitrile containing aromatic substrates and small amounts of iodide salts. The catalytic role of iodide and the isomeric product distributions indicate that arylation proceeds through the pentafluorophenyl radical in an efficient homolytic chain process.6... 

Recently, the synthesis of 5-aryl-2-oxopyrrole derivative 210 as synthon for the highly substituted pyrrole 211 as starting compound for fused heterocycle 212 was published [56], Diethyl 6-bcnzyl-5-phenyl-6//-thieno[2,3-/ ]pyrrolc-2,4-dicarboxylatc 212 was prepared from ethyl l-benzyl-5-chloro-4-formyl-2-phcnyl-l //-pyrrolc-3-carboxylate 211 and ethyl 2-sulfanylacetate in refluxing ethanol (Scheme 41). 

Furan[10] and its 2-formyl derivative (Eq. 5) [11] are arylated at 2- and 5-posi-tions, respectively. Arylation of 3-ethoxycarbonylfuran and its thiophene analogue occurs selectively at the 2-position in toluene, whereas the 5-position is attacked preferentially in NMP (Eq. 6) [12], It has been proposed that paths b and a, respectively, predominantly participate in the former and latter reactions. 

Aryl-4-chloromethylselenazoles (72) are hydrolyzed to alcohols (73). Manganese dioxide oxidation of (73) affords 4-formyl derivatives (74) which by condensation with ethyl azidoacetate give azidocrylates (75). Thermal cyclization of compounds (75) give pyrrolo[3,2-d]selenazoles (76 Scheme 27) (79JHC1563). 

The N-alkylation of amides followed by hydrolysis furnishes a good route for making secondary amines. The formyl, acetyl, and aryl-sulfonyl " derivatives of amines are best suited for alkylation (method 358). Hydrolysis is accomplished by refluxing concentrated hydrochloric acid alone or in acetic acid. N-Alkyl-formamides prepared by the addition of olefins to nitriles (method 355) are hydrolyzed with aqueous alkali. Similar hydrolytic procedures... 

Another reaction of the lithiated l,3-dithiole-2-thione 103 with aryl carboxaldehydes, followed by acidic quenching of the resulting oxyanions, afforded bisalcohol products 109. In the presence of perchloric acid, a 1,4-aryl shift was observed to furnish new formylated derivatives 112 and 113. Phenyl and 2-methoxyphenyl diols gave dihydrofurans 110 and 111, respectively (Scheme 7) <2001CC369>. 

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