Phenyl formate, formylation

Phenol is not formylated with HC02Me / HF / BF3. On the contrary phenyl formate 22 gives by Fries rearrangment /t-hydroxybenzaldehyde 22 (Fig. 9). 

Osotriazoles of diketones previously had been described by von Pech-mann 2 0) who obtained them by the oxidation of the corresponding di-hydrazones. The corresponding osotriazoles of the sugars are formed directly by the action of copper sulfate. The formation of the phenyl-D-glucoso-triazole (II) from glucose phenylosazone (I) is illustrated. Its structure is demonstrated by oxidation with periodic acid to the 2-phenyl-4-formyl-osotriazole (III) which is identical with the product obtained previously by von Pechmann from mono-0-acetyldinitrosoacetone phenylhydrazone (IV). 

Nitrobenzene was used as solvent in an investigation as it is frequently used in Friedel-Crafts reactions and facilitates the solubility of aluminum chloride. However, nitrobenzene may inhibit the formylation reaction as the polar NO2 group competes with CO in the protonation reaction (CHO ), resulting in low or no reactivity. Another possible reason for the apparent unreactivity of phenol under these conditions was proposed by Olah ° and involves the formation of phenyl formate (0-formylation of phenol). These compounds decarbonylate easily, instead of undergoing acid catalysed Fries rearrangement to the aldehyde [Eq (2.13)]. 

The formation of pyrazoles from reactions of suitably substituted 2-arylazirines and molybdenum hexacarbonyl has been discussed earlier in this section (see Schemes 89, 90)47 an analogous procedure depicting the transformation of 2-formyl-3-phenyl-2H-azirine into 3-phenylisoxazole is illustrated in Scheme 109.47... 

Bode and co-workers further extended redox esterification to include carbon-carbon bond breaking of formyl-cyclopropanes [113]. Both esters and thioesters are formed in high yield and good enantioselectivities (Scheme 31). The M-mesityl substituted triazolium salt 191 proved to be the most efficient pre-catalyst providing complete suppression of the benzoin reaction. Electron-deficient substituents, such as phenyl ketone, readily provide ester formation. 

Similarly l-phenyl-3-methyl-4-formyl-5-chloropyrazole reacts with thioglycollic acid in the presence of alkali to yield a mercaptopyrazole derivative that could be cyclized to thieno[2,3-c]pyrazole in the presence of alkali (69KGS760, 69ZOR1498). Similar to this is the reported formation, via 311, of 312 from 310 and mercaptoacetanilide (73ZOR2416). 

Interposition of a methylene group between the phenyl ring and the heterocycle leads to the benzyldiami nopyrimidines, a class of compounds notable for their antibacterial activity. Condensation of hydrocinnamate 54 with ethyl formate leads to the hydroxymethylene derivative 55. In this case, too, the heterocyclic ring is formed by reaction with guanidine. This sequence probably involves initial addition-elimination to the formyl carbon to form 56 cyclization in this case involves simple amide formation. Tautomerization then affords the hydroxy derivative 57. This is converted to tetroxoprim (58) by first replacing the hydro) l by chlorine and then- displacement of halogen with ammonia. 

An unusual reaction leading to the formation of 4-thioxopyrazolo[3,4-d]-pyrimidines has been reported. 1-Substituted 4-cyano-5-aminopyrazoles (103, R = H) react with phenyl isothiocyanate in dimethylformamide (DMF) saturated with hydrogen chloride to yield 1-substituted 4(5//)-pyrazolo[3,4-d]-pyrimidinethione (110). A proposed reaction sequence involved an initial nucleophilic addition of phenyl isothiocyanate to the protonated o-amino-nitrile to give an o-aminothioamide (108), followed by formylation by the dimethylformamide-hydrogen chloride mixture affording 109, which then cyclizes to the final product 110 (70MI1). 

The cited160,161 formation of polychloropyrans 120 -> 121 and 120 - 122 may be regarded as proceeding via 2-phenyl-3,4,5-trichloro- or 3,4,5-tri-chloropyrylium chlorides, which are attacked by a chloride ion. The transformation of pyrylium salts 219 to 4-formyl-4//-pyrans 220 with hippuric acid, acetic anhydride, and sodium acetate2651 is discussed in Section IV,J. 

The various methods for introducing a formyl group (—COH) into a phenolic nucleus are discussed in Section 6.10.1, p. 990. The formation of phenolic ketones (e.g. HO-C6H4-COR) by the standard Friedel-Crafts acylation procedure (i.e. the reaction of a phenol with an acid chloride in the presence of aluminium chloride) does not always give acceptable yields except in the case of polyhydroxyphenols (p. 1006). The preferred method is to convert the phenol into the phenyl ester and to subject this to rearrangement (the Fries reaction) in the presence of aluminium chloride. 

The features of the electronic structure of aryl-substituted pyrazolines influence their chemical properties. For example, in the case of 3-substituted 7V-phenyl-pyrazolines 100 reactions of formylation, acylation, nitration, sulfonation, azocoupling and other electrophilic processes involve the para position of the 7V-phenyl ring, with formation of compounds 101 [103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113]. On the other hand, some electrophilic reactions, including nitration, bromination, chlorination, formylation and azocoupling, for 3-unsubstituted pyrazolines 102 occur at position 3, yielding heterocycles 103 and in some cases as a mixture with 104 [108, 114, 115] (Scheme 2.26). This fact provides evidence for orbital control of these reactions. 

Reaction of the (1 / ),(—)- or (KV),(+)-tricarbony l(2-su Instituted benzaldehyde)chromium complexes 181 with the dianion of /-butylmethanesulfonamide affords, after decomplexation and intramolecular cyclization, the enantiomeri-cally pure 3-(2-phenyl-substituted)/ -sultam derivatives 182. The reaction of the dianion on the pro-stereogenic formyl group is key to the diastereoselective formation of the new stereogenic center, and it is controlled by means of... 

Acetylphenyl butyl tellurium is formylated at the acetyl-methyl group by methyl formate and sodium in diethyl ether. The formyl compound is converted to butyl 2-(diazoacetyl)-phenyl tellurium upon treatment with 4-methylbenzenesulfonyl azide1. The diazoacetyl group is converted to the dibromoacetyl group by bromine in diethyl ether1. 

Besides formyl compounds, 2-acetyl,92 2-benzoyl,93 and 2-ethox-alyl94-96 cyclohexanones have been cyclized with hydroxylamine, to give 3-methyl-, 3-phenyl-, and 3-ethoxycarbonyl-4,5,6,7-tetrahydro-indoxazenes, respectively. In some cases the simultaneous formation... 

A convenient and inexpensive method to transform electron rich aromatic aldehydes to phenols," or a,p-unsaturated aldehydes to vinyl formates, utilizes 30% hydrogen peroxide catdyzed by bis(n-nitro-phenyl) diselenide. A two-step formylation/MCPBA oxidation procedure (Scheme 25) was utilized by Kishi and coworkers in the 100 g scale conversion of 2,6-dimethoxytoluene to the mitomycin precursor (76). An organic peroxy acid was not required for the conversion of 9-formyl-6-methylellipticine (77) to... 

The preparation and reactions of the azine, phenylhydrazone, and phenyl-semicarbazone of 4-amino-5-formyl-2-methyltriazole proceeded normally. One acetal has been prepared as follows. 4-Amino-3-benzyl-5-formyltriazole and boron trifluoride (as diethyl ether complex), stirred in methanol, gave 4-amino-3-benzyl-5-dimethoxymethyltriazole (20°C, 6 hr, 53%) and a dimeric by-product, 4-amino-3-benzyl-5-(3-benzyl-5-dimethoxytriazol-4-ylimino-methyl)triazole [73JCS(P1)2037]. The amino group in 4-aminotriazole-5-carbaldehydes lends itself readily to the formation of amidines and imidates (Section III,B,1), but it resists acylation. 

N-Substituted acetanilides (69), the original substrates studied by Vilsmeier (see Scheme 1), are highly reactive compounds for quinoline formation. Thus, quinolinium salts (70) derive from the action of phosgene,55 while 2-quino-lones (71) are readily formed by Vilsmeier formylation of the same sub-strates." b 7 The formylation of IV-phenylacetanilides (69 R1 = Ph) was initially misinterpreted,58 but has now been shown to be a highly efficient route to l-phenyl-2-quinolones.57... 

As in the formation of pyrimidinoquinolines in Section II,B,2 (p. 229), 5-phenyl-thiouracils can be formylated and preferably separately cyclized... 

Photoformylation (the photo-Riemer-Tiemann reaction) of phenols (phenol, 2-methyl, 3-methyl, 4-methyl, 4-chloro, 4-bromo, 4-nitro and 4-phenyl phenol) has also been studied by irradiation in chloroform with KOH and pyridine. The yields reported are variable but formylation is reported only to occur in the 2-position ° °. This process involves the addition to phenol of radicals produced from chloroform. An electron transfer mechanism (transfer from excited state phenol to chloroform) is thought to be involved. The radical ion pair eliminates HCl and combination affords the products 232-234 (Scheme 26). The principal product is the ether and this undergoes partial conversion to the formate. The other products formed in low yield are the aldehydes . In another application of the photo-Riemer-Tiemann reaction, this time in cyclodextrin, the phenols can be converted into 4-hydroxybenzaldehydes with high selectivity . ... 

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