Self-condensation, avoiding

Lateral lithiation of nitriles can be achieved—and self-condensation avoided—if LiTMP is used in THF at —78°C (Scheme 199/ . 

In commercial practice, chlorination may be carried out either in batches or continuously. Glass-lined or nickel reactors may be used. Because certain metallic impurities such as iron catalyze ring chlorination and self-condensation, their presence must be avoided. The cmde product is purged of dissolved... 

As is the case during manufacture, contact with those metallic impurities that catalyze Friedel-Crafts condensation reactions must be avoided. The self-condensation reaction is exothermic and the reaction can accelerate producing a rapid buildup of hydrogen chloride pressure in closed systems. 

Self-condensing monomers of the form AMB avoid a stoichiometry restriction. The idea is to synthesize the monomer using conditions where the A and B endgroups are not reactive but to polymerize the monomer under conditions where the endgroups do react. An important example is the polymerization of PET. A large excess of ethylene glycol is reacted with terephthalic acid to form a nominal trimer, diglycol terephthalate ... 

A mixture of the alcohol with formic acid rapidly self-heated, then reacted violently [1], A stirred mixture with cyanoacetic acid exploded violently after application of heat [2], Contact with acids causes self-condensation of the alcohol, which may be explosively violent under unsuitable physical conditions. The general mechanism has been discussed [3], The explosion hazards associated with the use of acidic catalysts to polymerise furfuryl alcohol may be avoided by using as catalyst the condensation product of 1,3-phenylenediamine and l-chloro-2,3-epoxypropane [4], See Nitric acid Alcohols (reference 6)... 

A sequential cycloaddition, tandem cycloreversion-cycloaddition process is more efficient than the direct cycloaddition, especially in case of aliphatic aldehydes, where the corresponding ylides are rather unstable. The cycloreversion strategy lowers the concentration of the free ylide in the reaction mixture and avoids side reactions such as self-condensation of this reactive species. In some cases, this tandem cycloreversion-cycloaddition sequence provides improved chemical yields without any loss of diastereoselectivity. For example, compound 476 treated with methyl fumarate, methyl maleate, and methyl acrylate provides acceptable yields of compounds 477-479 (Scheme 80) <2000S1170, 2002S1885>. 

To improve the product yields in Lossen rearrangement, mesyloxycarbamates have been used as alternative reagents . The use of A-acyl-O-mesylhydroxamic acids (558) avoids the competing formation of self-condensation by-products (560). These are obtained from the accumulation of isocyanate (559) before complete consumption of the hydroxamic acid (557) as observed in the classical Lossen rearrangement (equation 249). 

Undesirable intermolecular reactions can be avoided during certain synthetic conversions. Thus it is often useful to carry out C-alkylation and C-acylation of compounds that form enolate anions, for example, esters with a-hydrogens. Such reactions are often complicated by self-condensation since the enolate anion can attack the carbonyl group of a second ester molecule. Attachment of the enolizable ester to a polymer support at low loading levels allows the alkylation and acylation reactions (Eq. 9-79) to be performed under... 

Alkylation of the simplest 7-lactone, butyrolactone (5), has been described by the use of lithium cyclohexylisopropylamide and iodomethane or an alkyl bromide10. In this paper the low temperature ( — 78 °C) was explicitly recommended in order to avoid self-condensation. It was noted that more than one equivalent of base increased the yield. 

On an industrial scale, cinnamaldehyde is prepared almost exclusively by alkaline condensation of benzaldehyde and acetaldehyde. Self-condensation of acetaldehyde can be avoided by using an excess of benzaldehyde and by slowly adding acetaldehyde [154]. 

The generation of alkyl-substituted monomeric metaphosphoric acid esters (254) has been described using two different methods and the metaphosphate produced spontaneously self-condensed to give polymeric P—O—P bonds, hi the presence of styrene polymerization is avoided and happing occurs instead to give a diastereomeric mixture of 2-alkoxy-l,3,2-dioxophospholane-2-oxides with (254 R = Me).232 Pyridine A -oxidc-tricthylaminc mixtures individually or together catalyse the phosphorylation of... 

If a compound cannot enolise because it has no protons on the a-carbon atoms then it can take part in a carbonyl condensation only as the electrophile. This will be useful only if it is strongly electrophilic (to avoid self-condensation of the other compound, see point 3 above) so you will see mainly aldehydes and acid chlorides in this list. 

As Patchornik (54,55) showed the competitive self-condensation of an ester can be avoided if the ester molecules are separated by fixation on the polymer. According to Scheme 3,0.1 to 0.2 meq ester groups were fixed at the chloromethylated polymer. Pure monoalkylation can be achieved and no self-condensation is observed if the load is kept small. 

The following example shows the self-condensation of ethyl acetate to give ethyl ace-toacetate (ethyl 3-oxobutanoate). Ethoxide is used as the base to avoid transesterification or hydrolysis of the ethyl ester (see Problem 22-34). The initial product is the enolate of ethyl acetoacetate, which is reprotonated in the final step. 

Typical experimental conditions for reactions of kinetic enolates involve formation of the enolate at very low temperature (-78°C) in THF. Remember, the strong base LDA is used to avoid self-condensation of the carbonyl compound but, while the enolate is forming, there is always a chance that self-condensation will occur. The lower the temperature, the slower the self-condensation reaction, and the fewer by-products there are. Once enolate formation is complete, the electrophile is added (still at -78°C the lithium enolates may not be stable at higher temperatures). The reaction mixture is then usually allowed to warm up to room temperature to speed up the rate of the S 2 alkylation. 

The use of acidic conditions avoids base-catalyzed self-condensation and retro-Michael reactions and tolerates base-sensitive groups, as exemplified by the triflic-acid (CF3S03H)-catalyzed Michael addition shown below. ... 

A feature distinguishing Reformatsky enolates from base-generated enolates is that zinc enolates add to highly hindered as well as to easily enolizable ketones, such as cyclopentanones, thus avoiding formation of condensation products. Moreover, there is no danger of a Claisen-type self-condensation since zinc-enolates do not react with esters but react readily with aldehydes and ketones to furnish aldol-type products. 

Our interest in this area has been in synthesizing a variety of silanetriols where silicon is bonded to carbon, nitrogen, or oxygen in order to assess their relative stabilities as well as the differences in their reactivities. The C-bonded silanetriol tBuSi(0H)3 (12) was synthesized from the commercially available /BuSiCb (Scheme 3) [23]. The bulky t-butyl group afforded the desired steric protection needed to avoid the self-condensation. However, it should be mentioned that the hydrolysis of tBuSiCla in the presence of KOH leads to the isolation of the primary condensation product of the /-butylsilanetriol, [tBuSi(OH)2]20 [2]. 

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