Weakly basic reaction condition

Hydroxylamines and alkylhydroxylamines possess high nucleophilicity and can react with a variety of primary and secondary alkylating agents. The reactivity of hydroxylamines in the majority of these reactions resembles that of primary and secondary amines. While hydroxylamine and Af-alkylhydroxylamines 1 are ambident nucleophiles, under neutral or weakly basic reaction conditions alkylation proceeds exclusively on nitrogen atom to give products of type 2 (equation 1). Deprotonation of the OH group of hydroxylamines results in O-alkylation products. 

Figure 7.12 outlines how hydantoin is produced during the synthesis of methionine depicted in Figure 7.11. Initially, the aminonitrile B is formed. With its amino group it adds to carbon dioxide, which—under the weakly basic reaction conditions—is followed by the formation of the carbamate ion D. In a fully analogous fashion, ammonia reacts with carbon dioxide to give ammonium carbamate (cf. Section 8.2). The intermediate D in Figure 7.12 permits the intramolecular and thus kinetically favored—i.e., fast—addition of the oxyanion to the C=N triple bond. The addition product is the negatively charged heterocycle F, which in...

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

Simultaneous treatment of a carbonyl compound with a Lewis acid and a tertiary amine or another weak base ( soft enolization ) can sometimes be used to generate enolates of sensitive substrates which would have decomposed under strongly basic reaction conditions [434]. Boron enolates, which readily react with aldehydes at low temperatures, can also be prepared in situ from sensitive, base-labile ketones or carboxylic acid derivatives [293, 295, 299]. Unwanted decomposition of a carbanion may also be prevented by generating it in the presence of an electrophile which will not react with the base (e.g. silyl halides or silyl cyanides [435]). 

Non-deprotonated amides are weak nucleophiles and are only alkylated by trialkyl -oxonium salts or dimethyl sulfate at oxygen or by some carbocations at nitrogen [16, 83]. Alkylation with primary or secondary alkyl halides under basic reaction conditions is usually rather difficult, because of the low nucleophilicity and high basicity of deprotonated amides. Non-cyclic amides are extremely difficult to N-alkylate, and few examples of such reactions (mainly methylations, benzylations, or allyla-tions) have been reported (Scheme 6.21). 4-Halobutyramides, on the other hand, can often be cyclized to pyrrolidinones in high yield by treatment with bases (see Scheme 1.8) [84—86]. 

Unsaturated lactones lacking substitution at C-4 are the simi est ones available via this general type of cycloaddition. Several syntheses of these lactones are of practical value, including two Pd-based meth-ods. However, the considerable utility of metal carbonyl anions in lactone synthesis is illustrated by a rhodium carbonyl anion catalyst system which gives very high yields upon reaction with a variety of internal alkynes under weakly basic aqueous conditions, essentially water-gas shift conditions. These conditions were established to maximize chemoselectivity with respect to other possible alkyne carbonylation products. Regioselectivity is modest in this process, but was not examined systematic ly (equation 13). ... 

The role of the inorganic salts in this reaction was also examined. Potassium carbonate, silver carbonate, or silver nitrate was respectively used in this experiment (Table 6.2). We found that the addition of 0.3-0.4 equivalent of potassium carbonate could effectively increase the reaction rate (Table 6.2, entries 3 ). It was surprising that the addition of 0.04 equivalent of silver carbonate could significantly accelerate this reaction. This reaction was completed in 2 h (Table 6.2, entries 8). Other silver-containing compounds such as silver nitrate (a weak acid), had a slight negative effect on this reaction (Table 6.2, entries 10-14). The results showed that basic reaction conditions favored the formation of phosphite anion, and the addition of these three inorganic salts did not affect enantioselectivity (Table 6.2). 

Torgov introduced an important variation of the Michael addition allylic alcohols are used as vinylogous a -synthons and 1,3-dioxo compounds as d -reagents (S.N. Ananchenko, 1962, 1963 H. Smith, 1964 C. Rufer) 1967). Mild reaction conditions have been successful in the addition of ],3-dioxo compounds to vinyl ketones. Potassium fluoride can act as weakly basic, non-nudeophilic catalyst in such Michael additions under essentially non-acidic and non-basic conditions (Y. Kitabara, 1964). 

Acylation of pyridazinones and related compounds in the presence of weakly basic catalysts such as pyridine or sodium acetate produces IV-acylated products, while O-acylated products are obtained under strongly basic conditions. However, the reaction between 6-chloropyridazin-3(2//)-one with chlorocarbonates and that of maleic hydrazide with unsaturated acid chlorides or chloromethylsulfonyl chloride gives preferentially N-substituted products. 

It has already been mentioned that monobromination of 5a-3-ketones gives 2a-bromo compounds (18). Further bromination occurs under acidic or distinctly basic conditions (the reaction is not satisfactory in weakly basic... 

Volcanic gases contain up to 47% sulphur dioxide (SO2). A group from the University of Hong Kong studied the ability of SO2 to support condensation reactions. Under weakly basic conditions, SO2 dissolved in water forms SO2- ions. Oxidation of these to SO4- proceeds via SO3. The experiments suggest the following reaction mechanism ... 

Compound 51 was found to be unstable and difficult to purify, as described in the literature [93—95]. Therefore, 51 was not isolated, but was instead converted to the stable pinacol 1-acetamido-l-hexylboronate derivative 52. However, the acylated derivative 52 could not be purified by column chromatography as it was destroyed on silica gel and partially decomposed on alumina. Fortunately, we found that it dissolves in basic aqueous solution (pH > 11) and can then be extracted into diethyl ether when the pH of the aqueous layer is 5—6. Finally, pure 52 was obtained by repeated washing with weak acids and bases. It should be mentioned here that exposure to a strongly acidic solution, which also dissolves compound 51, results in its decomposition. Compared with other routes, the present two-step method involves mild reaction conditions (THF, ambient temperature) and a simple work-up procedure. It should prove very useful in providing an alternative access to a-aminoboronic esters, an important class of inhibitors of serine proteases. 

Scheme 5.6). The reaction can be conducted under basic liquidiliquid conditions but, in order to minimize hydrolysis of the phosphite and to prevent carbene formation, a milder solid (KHCO, liquid system with tetra-/i-butyIammonium bromide is preferred. Under these conditions, yields are almost quantitative [38]. Tetra-bromomethane is generally recommended, in preference to tetrachloromethane, for reactions with weakly basic aryl-amines. 

A disadvantage of the traditional synthesis of A -alkyl-A -tosylhydrazones, particularly in the reaction of the tosylhydrazine with weakly electrophilic carbonyl compounds, is the instability of the hydrazine under the reaction conditions. However, A -alkylation of the tosylhydrazone (Table 5.23) under weakly basic condi-... 

The carbon nucleophiles in amine-catalyzed reaction conditions are usually rather acidic compounds containing two electron-attracting substituents. Malonic esters, cyanoacetic esters, and cyanoacetamide are examples of compounds which undergo condensation reactions under Knoevenagel conditions.115 Nitroalkanes are also effective nucleophilic reactants. The single nitro group sufficiently activates the a hydrogens to permit deprotonation under the weakly basic conditions. Usually, the product that is isolated is... 

Triazole opens the sulbactam (50) ring systems under weakly basic conditions (Equation (18)) <85CPB4923>. This reaction can be used to determine the concentration of sulbactam in urine and plasma by monitoring the absorbance at 326 nm. 

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