3-Hydroxy-4-alkoxy substitution

Thermal oxidation of unsaturated fats is accompanied by considerable isomerization of double bonds, leading to products containing trans double bonds and conjugated double bond systems. Non-volatile decomposition products are formed by thermal oxidation, hydrolysis and cyclization. A large number of hydroxy, alkoxy-substituted, epoxy and keto compounds are produced by oxidation, free fatty acids and mono- and diacylglycerols by hydrolysis, and cyclic monomers by cyclization of polyunsaturated fatty acids in heated fats. Aldehydo glycerides (also referred to as core aldehydes ) and keto glycerides... 

It will be observed that most syntheses yield pyrylium salts in which positions 2,4, and 6 are substituted. Since according to formulas Ib-lc these positions have a partial positive charge, it can readily be understood why electron-donating substituents (hydroxy, alkoxy, alkyl, or aryl) in these positions stabilize the pyrylium salts. Only three pyrylium salts which do not have substituents in either a-position have been reported and few unsubstituted in y or in one a-position they are less stable toward hydrolysis, and in the case of perchlorates they explode more easily, than 2,4,6-trisubstituted compounds. In fact, the former are secondary, the latter tertiary carbonium ions. This fact also explains why the parent compound (1) was prepared only in 1953. 

Stepanov et a/.143,144 report the ring opening of the monoxide (116) to several 2-oxaadamantane derivatives, where 116 is readily obtained by perbenzoic acid oxidation of 35. Treatment of 116 under various conditions yields different products. Thus, with aqueous acid it yields l-hydroxy-3-hydroxymethyl-2-oxaadamantane (117), with alcohols (R = CH3, C2H5) in acidic or basic media 1-alkoxy-substituted (118), and with hydrochloric acid l-chloro-3-hydroxymethyl-2-oxaadamantane(119). l-Methyl-2-oxaadaman-tane (120) is prepared by LAH reduction of the carbonyl group in 35 to alcohol 121 and subsequent cyclization with acid.140,142... 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

Treatment of a-hydroxy- or a-alkoxy-substituted hexahydro-oxazolo[3,4-r ]pyridin-3-ones with an acid allows for the generation of bicyclic iV-acyliminium ions which can then smoothly react with nucleophiles, usually with high diastereoselectivities (Scheme S3) <2001EJ01267, 1998SL206>. 

Due to the lack of suitable aliphatic starting materials, the synthesis of aromatic forms of monocyclic 1,2,5-thiadiazoles was not accomplished for more than 70 years after the first report of the benzo analogues. General synthetic methodology for monocyclic 1,2,5-thiadiazoles was devized which readily leads to a variety of substituted derivatives, alkyl, aryl, halo, hydroxy, alkoxy, cyano, and amino as well as the parent system. A general model for substrates applicable in these syntheses... 

In each table, substituted azoles are ordered in the following way alkyl, substituted alkyl, aryl, formyl, acetyl, carboxylic acid, alkoxycarbonyl, cyano, amino, azido, diazonium salt, nitroso, nitro, hydroxy, alkoxy, fluoro, chloro, bromo, and iodo. 

Alkyl-substituted pyridines have been complexed with a wide variety of other boron Lewis acids, BH3, B(OH)3, and BX3, where X is a selection of alkyl, aryl, hydroxy, alkoxy, and aryloxy groups <87JCS(P2)77l). 

Other 7- substituents that have been introduced include the dialkylamino, acetamido, hydroxy, alkoxy and alkylthio groups (B-71MI11209). Acylation of the 7-amino group by heterocycles such as cyanuric chloride and its derivatives was inevitable, as was incorporation of a 7-triazole substitution pattern by diazotization of the 7-amino group and o-coupling with 2-naphthylamine followed by triazolization (94). 

Halo, alkoxy, hydroxyaryl, and phenylmercapto derivatives have attained commercial importance. Compared to substitution next to the hydroxy group, substitution next to the amino group leads to brighter dyes and improved affinity. 

Prior to the discovery of a-sulfonation of anthraquinone, nitration was the only useful method for preparing a-substituted anthraquinones. The nitro group of a-nitroanthraquinones can be replaced in a manner similar to the sulfonic acid moiety, e.g., by chlorine atoms and amino, hydroxy, alkoxy, or mercapto groups. Reduction readily yields aminoanthraquinones. Nitration of anthraquinone has gained increasing importance because of environmental considerations, this method offering an economical alternative to a-sulfonation... 

Chloro-l,2-dithiolium cations can be used in the form of crystalline perchlorates.33 These compounds react with hydroxy-substituted and/or alkoxy-substituted aromatic compounds to give 3-aryl-l,2-dithiolium cations (Eq. 11). 

R2 = hydroxy, alkoxy, alkylthio, substituted alkyl, substituted phenyl, o-hydroxyphenyl... 

The ammoxidation of toluenes substituted with electron-donating groups, for example hydroxy- and alkoxy-substituted toluenes is rather less selective. However, under carefully chosen conditions (choice of the catalyst, feed composition, reaction conditions) adequate yields of nitriles can be achieved. Stabihty of the catalyst performances is typically an issue. 

Methanol (CH3OH) resonates at 849.2, and the range for hydroxy-substituted carbons is 8 49-75. Dimethyl ether [(CH3)20] resonates at 8 59.5, and the range for alkoxy-substituted carbons is 8 59-80. The ether range is translated a few ppm to a higher frequency (downfield) from alcohols, because each ether must have one additional 3 effect with respect to the analogous alcohol. 

The specific nature of 1,2,4-triazine /V-oxides discussed in Section II,C is also manifested in the SNH reactions. Treatment of 1,2,4-triazine 2-oxides containing electron-donating groups at C-3 with methanol, ethanol, or isopropanol in the presence of hydrochloric acid results in 6-alkoxy-substituted 1,2,4-triazines 137 (Scheme 77) (77JOC3498). The reaction is proposed to involve the addition of alcohol to C-6 of the hydroxy-1,2,4-triazinium cation 135, followed by elimination of water. The presence of an electron-donating group at C-3 seems also to be important because it contributes considerably to the stabilization of the intermediate cationic species 136 (Scheme 77). 

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