Acid-sensitive substrates

CH3CH(Cl)OEt, PhNMc2, CH2CI2, 0°, 10-60 min. These conditions are effective for extremely acid-sensitive substrates or where conditions 1 and 2 fail. 

The introduction of the BDT group proceeds under these rather neutral conditions, and this may prove advantageous for acid-sensitive substrates. The BDT group can also be reduced with Raney nickel to a methyl group or with Bu3SnH to a 2-[(methylthio)phenylthio]methyl ether (MTPM ether)... 

The TBDMS ester can be converted directly to an acid chloride [DMF, (COCl)2, It, CH2CI2] and then converted to another ester, with different properties, by standard means. This procedure avoids the generation of HCl during the acid chloride formation and is thus suitable for acid-sensitive substrates. ... 

HgCl2, CaCO, MeCN, H2O. The calcium carbonate is used as an acid scavenger for acid-sensitive substrates. 

BZOSO2CF3, —78°, CH2CI2, few min. With acid-sensitive substrates, pyridine is used as a cosolvent. This reagent also reacts with ketals, epoxides, and aldehydes. ... 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

When carbon tetrabromide is used, the alkyl bromide is formed. Providing moisture is excluded from the reaction mixture (HX is formed otherwise), the reaction conditions are completely neutral, affording a convenient preparation of the halides of acid-sensitive substrates (for example, sugars). 

The acid catalyzed hydration of olefins is frequently attended by decomposition or rearrangement of the acid-sensitive substrate. A simple and mild procedure for the Markovnikov hydration of double bonds has recently been devised by Brown and co-workers 13). This reaction, which appears to be remarkably free of rearrangements, initially involves the addition of mercuric acetate to the double bond to give the 1,2-... 

Sulfones. This oxidant is useful for selective oxidation of sulfides to sulfones (10,328). Oxidations of acid-sensitive substrates should be buffered with Na2C03. 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Nitronium tetrafluoroborate is a very efficient reagent for the D-nitration of alcohols and glycols containing both primary and secondary hydroxy functionality (Equation 3.7). Yields of nitrate ester are high and frequently quantitative. 0-Nitration with nitronium salts produces a strong acid and so an acid-binding agent should be present for acid sensitive substrates. 

Nitrogen dioxide in the presence of ozone has been used for aromatic nitrations." Such conditions are useful for the nitration of reactive and acid sensitive substrates. Lewis acids have been used in ozone-mediated nitrations with nitrogen dioxide." ... 

The key feature of Br0nsted acid catalysis is often the choice of a catalyst with the appropriate acidity for particular substrate classes. Whereas less reactive substrates require stronger Brpnsted acids than the widely used phosphoric acids for activation, acid-sensitive substrates tend to decompose under strongly acidic conditions. Thus, weaker Brpnsted acid catalysts may prove beneficial. 

Scheme 6.18 Product range of the tetrahydropyranylation of acid-sensitive substrates catalyzed by thiourea 9.

It should be kept in mind that on conducting electrooxidation in general, EGA generation does occur in an anode compartment or in a proximity of an anode surface in parallel to the desired oxidation of substrates. So a proper choice of electrolytes and solvents is essential for the successful treatment of any acid-sensitive substrates and products. 

This procedure is characterized by the easy isolation of a high-purity product in excellent yield. The reaction illustrates a general method6 for the conversion of aryl methyl ethers to the corresponding phenols, and has proved to be of special advantage with acid-sensitive substrates.6 7... 

Jones oxidation is very easy to carry out, because of the absence of need to keep anhydrous conditions. Furthermore, it is very cheap. It is the oxidation of choice for robust substrates on a big scale. It is neither suitable for very acid sensitive substrates, nor for the preparation of many aldehydes. 

The decomposition of acid-sensitive substrates during Swern oxidations can also be explained by the presence of adventitious hydrogen chloride. This can be avoided by the use of freshly distilled oxalyl chloride and carefully dried DMSO.174... 

The same reaction can also be carried out with dimethyl sulfoxide and hydrochloric acid in dioxane at 25°. The actual reagent is presumed to be chlorodimethylsulfonium ion. The method is not suitable for acid-sensitive substrates. 

Oxidations with alkyl hydroperoxides are carried out at close to neutral conditions as possible, which makes them particularly useful towards the derivatization of acid-sensitive substrates. 

Improved selectivity may be obtained with acid-sensitive substrates due to avoidance of accumulation of hydrogen halide, and in the case of iodination the reverse reaction can be suppressed. 

The highly efficient Michael addition of acid sensitive substrates such as pyrrole and indoles to stmcturally diverse electron-deficient olefins in aqueous media at room temperature using aluminium dodecyl sulfate trihydrate, [A1(DS)3]-3H20, as a new Lewis acid surfactant catalyst affords 2-substituted pyrroles 442-445 (Scheme 95) and... 

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