Hydroxy compounds, conversion into

Both aromatic and aliphatic fluoroformates 7 can be readily prepared from phenols or alcohols and carbonyl difluoride and treated with sulfur tetrafluoride without isolation. Hydrogen fluoride evolved in the reaction of hydroxy compounds with carbonyl di fluoride serves as a catalyst for the consecutive reaction with sulfur tetrafluoride.15<)-162 This provides a general, convenient, direct synthesis of aryl and alkyl trifluoromethyl ethers 5 from phenols and alcohols. When the intermediate fluoroformate 7 is isolated prior to treatment with sulfur tetrafluoride, at least one mole equivalent of hydrogen fluoride is necessary to promote the fluorination reaction. 159 163 Representative examples of the conversion of hydroxy compounds 6 into trifluoromethyl ethers 5 via intermediate fluoroformates 7 are given (for other examples 7 -> 5, see Houben-Weyl, Vol. E4, pp 628. 629). 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

The compounds are obtained by coupling diazotized 1-aminoanthraquinone onto 2-hydroxy-3-naphthoic acid, followed by separation, drying, and conversion into the azo dye acid chloride. Condensation with amines (structure 81) is achieved in an aprotic organic solvent. 

The instability of the 3-hydroxymethylindoles over a wide pH range results in the lack of success in acetylation of the hydroxy compound and also in the failure to hydrolyze the acetoxymethylindole without conversion into the bis(3-indolyl)methane (79HC(25-3)l). In contrast with the 3-isomer, 2-hydroxymethylindoles are stable to bases, but are polymerized by acids (79HC(25-3)l). Similarly, it is possible to convert 3-hydroxymethylpyrroles into their acetates and methyl ethers under basic conditions, and reaction with isocyanates yields the expected urethanes (79JMC977). Under acidic conditions, however, they produce the bis(3-pyrrolyl)methanes (B-77MI30504). 

The effect of other substituents on the products of alkaline hydrolysis is well illustrated in the conversion of 4-chloromethylcoumarin (293) to the benzofuran-3-acetic acid (294) in high yield (79CHE815), of 4-hydroxy-6-phenacylpyran-2-one (259) into the benzophenone (295) (70T5255) and of 5-amino-3-methylisocoumarin (297) (formed from the nitro compound 296) into the indole (298) <76JCS(P1)1073, 81CPB249). 

In general, the method of enzymatic cyanohydrin synthesis promises to be of considerable value in asymmetric synthesis because of the synthetic potential offered by the rich chemistry of enantiomerically pure cyanohydrins, including their stereoselective conversion into other classes of compounds such as a-hydroxy carboxylic acids or respective esters, w c-diols, / -aminoalcohols, aziridins, a-azido(amino/fluoro)nitriles, and acyloins [501, 516]. 

However, various attempts to introduce stereospecifically the a-hydroxyl group at the desired position of the double bond by hydroboration were unsuccessful. Eventually hydration of the double bond was accomplished by mercuration-reduction protocol, which although occurring both with high regio and stereoselectivity furnished only the p hydroxy compound 339. The conversion of the latter with formaldehyde into ( )-epielwesine (335) constituted in a formal sense, the synthesis of ( )-elwesine (320) as well, since Sanchez et al 88 had shown that the inversion of the hydroxyl group in 335 could be accomplished with diethylazodicarboxylate, triphenylphosphine and formic acid. 

Ozonolysis has also been demonstrated to play a role in the production of another important intermediate in (3-lactam synthesis, hydroxyl-cepham sulfoxide esters 92.84 Ozonolysis plays a role in the conversion of a methylene group in compound 93 into the required hydroxy group in compound 92 (Scheme 11.25). 

Aminoindoxazenes, which are stable towards acids and bases, can be diazotized in acetic acid Lindemann and Ciss e46,70 reported the conversion of 3-amino-5-nitro- and 3-amino-5-acetamido-indoxazenes into the corresponding 3-hydroxy compounds (indoxazenones), via the diazonium salts. Attempts to prepare 3-hydroxyindoxazene and its 6-chloro derivative by the same route were unsuccessful.46 The structures of these 3-hydroxy compounds would seem doubtful since Boshagen reports a much higher melting point for 3-hydroxy-5-nitro-indoxazene (223.5,46 85-88°,70). 

The conversion of silyl ethers into fluorides may serve as an indirect method for the conversion of hydroxy compounds into fluorides, but in some cases the silyl ethers are not formed from the corresponding alcohols and then a step is saved by direct conversion into the fluorides. Two classes of fluorinating reagents have been used so far to transform silyl ethers into fluorides these are nuoro-A -phosphanes, which were used first, and fluoro-/, -suIfanes. 

Other Reactions.—Reaction of the 17-oxo-steroids (66) and (67) with LDA-EtCN gave the 20-cyano-17/3-hydroxy-compounds (68) and (69) which were dehydrated with SOCl2 pyridine to the 20-cyano-A ° -compounds (70) and (71) respectively/ " Conversion of the 20-cyano-A ° -compound (70) into the 22-aldehyde (72) demonstrated the potential utility of this approach to the... 

The conversion of hydroxy-N-heterocycles into the corresponding alkoxy derivatives by alkylation with alkyl halides or diazo compounds... 

---