Oxidative reactions under neutral conditions

The reaction of 3-amino-1,2,4-triazine 1-oxide 1 with methyl iodide in the presence of sodium bicarbonate leads to the methylation of the amino group to afford 3-methylamino-l,2,4-tiiazine 1-oxide 123. This iV-oxide 123, under neutral conditions in the presence of Mel, undergoes methyl group migration to the N(2) atom of the 1,2,4-triazine ring, yielding 3-imino-2-methyl-1,2,4-triazine 1-oxide 124. The same product 124 was obtained by direct methylation of compound 1 under neutral conditions (84TL1677). 

The epoxidation of unsaturated materials is the most commonly used reaction of dioxiranes. The reaction, whether carried out in situ or using the solution method, gives high yields of epoxides, usually in rapid reactions. The isolated dioxirane method is particularly useful in cases where oxidation products are sensitive to the acidic conditions of the most commonly used epoxidation reagents or the basic conditions of the in situ method. Use of the isolated dioxirane permits reaction under neutral conditions so that labile epoxides are conveniently prepared. When the desired epoxide is sensitive to moisture, the dioxirane solution can be dried with molecular sieves for use in such epoxidations. The epoxidation of water-insoluble alkenes with the in situ method requires the use of a phase-transfer catalyst, but the reaction still proceeds in high yields. Dioxiranes, in situ generated... 

Among all the pyridine derivatives, 2-amino-3,5-dicyano-6-sulfanyl pyridines are even more interesting because of their potential therapeutic applications. In synthetic chemistry, the cyclocondensation of aldehydes, malononitrile, and thiols is the most straightforward pathway. In general, this transformation can be realized under basic conditions. The bases reported included EtsN, DABCO, piperidine, morpholine, thiomorpholine, pyrrolidine, N,N-DIPEA, pyridine, 2,4,6-collidine, DMAP, aniline, iV-methylaniline, A,A-dimethylaniline and N,N-diethylaniline. Reactions under neutral conditions have been explored as well. In these cases, Cul nanoparticles [75], ZnCl2 [76], and nanocrystalline magnesium oxide [77] have been applied as the catalysts. 

Allylic acetates are widely used. The oxidative addition of allylic acetates to Pd(0) is reversible, and their reaction must be carried out in the presence of bases. An important improvement in 7r-allylpalladium chemistry has been achieved by the introduction of allylic carbonates. Carbonates are highly reactive. More importantly, their reactions can be carried out under neutral con-ditions[13,14]. Also reactions of allylic carbamates[14], allyl aryl ethers[6,15], and vinyl epoxides[16,17] proceed under neutral conditions without addition of bases. 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

The structure of the product of the Reimer-Tiemann reaction of 1,2,3-trimethylindole (24) has been confirmed as 3-dichloromethyl-1,3-dimethyl-2-methyleneindoline (25) by spectroscopy and oxidation to the iV -methyloxindole when the dichlorocarbene was generated under neutral conditions a ring-expanded product, 3-chloro-1,4-dimethyl-2-methylene-1,2-dihydroquinoline (26) could be isolated and oxidized to the corresponding a-quinolone. These reactions presumably proceed by mechanisms similar to those discussed for 2,3-di-... 

Z-Acetonitrolic acid rapidly loses N02 to form unstable acetonitrile oxide, which could be detected by monitoring its subsequent reactions (86). Arylnitrolic acids 12 (X = />-Cl. m-N02, o-N02) exist in the -configuration and undergo slow loss of N02 to give nitrile oxides. Subsequently it was shown (87) that nitrolic acids are converted to nitrile oxides in practically quantitative yields under neutral conditions (heating in THF). 

A study of the reactions of halogeno-phosphines with ketone derivatives has been extended to (44), which forms a heterocycle (45a) with dichloro(phenyl)phosphine38 under neutral conditions. The analogous oxide (45b) has already been isolated from... 

Efficient cleavage of A.A-dimethylhydrazones to yield the parent ketones (>90%) is effected under neutral conditions with tetra-n-butylammonium persulphate [40], The procedure is particularly useful for compounds with acid-sensitive substituents, e.g. vinyl or ketal groups. Similarly, reaction times for the oxidative cleavage of semicarbazones with sodium nitrite or nitrate/trimethylsilyl chloride are reduced by the addition of benzyltriethylammonium chloride [41]. 

These are relatively rare reactions for RuO - as with primary alcohols, further oxidation to carboxylic acids normally occurs. Examples are given in Table 3.3. Generally, under neutral conditions, aldehydes are formed but under acidic or alkaline conditions carboxylic acids are the main oxidation products. 

Selectivity for each product formation may also be controlled by an effective catalyst system. After the discovery of the reaction by Heck, Stille applied the reaction to organic synthesis, as he observed the preferential formation of [3-methoxy esters under neutral conditions and 1,2-diesters in the presence of a base. As Bianchini reported in 2001, selective formation of a,/3-unsaturated ester product is established by an addition of protic acid such as y)-TsOH in bis-phosphine/Pd-catalyzed oxidative alkoxycarbonylation. ... 

Several alkyne-linked bis-2H-indazoles have been synthesized by the double cycliza-tion of butadiyne-linked (167) phenyltriazenes or phenyldiazenes, in turn obtained by Cu(OAc)2-mediated homocoupling of ethynylphenyltriazenes (Scheme 46).144 The reactions proceed rapidly under neutral conditions with mild heating, affording the heterocycles in excellent yields. By using Pd as catalyst under oxidative conditions, bis-2//-indazoles (170) were obtained directly from ethyne-linked phenyltriazenes (169). DFT calculations revealed for these reactions low barriers to cyclization that... 

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