Aldehydes base-catalyzed condensations

Synthesis and Properties. Polyquinolines are formed by the step-growth polymerization of o-aminophenyl (aryl) ketone monomers and ketone monomers with alpha hydrogens (mosdy acetophenone derivatives). Both AA—BB and AB-type polyquinolines are known as well as a number of copolymers. Polyquinolines have often been prepared by the Friedlander reaction (88), which involves either an acid- or a base-catalyzed condensation of an (9-amino aromatic aldehyde or ketone with a ketomethylene compound, producing quinoline. Surveys of monomers and their syntheses and properties have beenpubhshed (89—91). 

In the base-catalyzed condensation of diethyl ethylsulfonylmethylphosphate with aldehydes or ketones, the corresponding a, /1-unsaturated sulfones were obtained in good yields297,364,365. 

Boiadjiev and Lightner synthesized fluorescent tricyclic-bridged pyrrinones such as 31 by base-catalyzed condensation-cyclization of pyrrolin-2-one 112 with pyrrole aldehyde 113 (Equation 24) <2005M553, 2005JOC689>. 

The Friedlander reaction is the acid- or base-catalyzed condensation of an ortho-acylaniline with an enolizable aldehyde or ketone. Henichart and coworkers have described microwave-assisted Friedlander reactions for the synthesis of indoli-zino[l,2-b]quinolincs, which constitute the heterocyclic core of camptothecin-type antitumor agents (Scheme 6.238) [421], The process involved the condensation of ortho-aminobenzaldehydcs (or imines) with tetrahydroindolizinediones to form the quinoline structures. Employing 1.25 equivalents of the aldehyde or imine component in acetic acid as solvent provided the desired target compounds in 57-91% yield within 15 min. These transformations were carried out under open-vessel conditions at the reflux temperature of the acetic acid solvent. 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Scheme 33 Base catalyzed condensation of aldehydes by electrogenerated bases (EGB s) R alkyl, yields 72-77%, very high current efficiency.

Hydroxycyclopentenones.2 A new synthesis involves addition of aldehydes to l Cetoxy-3-butene-2-one catalyzed with this salt (1), followed by base-catalyzed Condensation of the resulting 1,4-diketone. 

Base-catalyzed condensation of 2-(acetyl)thioindoxyl with aromatic aldehydes affords compounds with the general formula 330, which give the adducts 331 with aryl mercaptans in the presence of piperidine.582... 

Cyclopentenones can also be used for condensation, with o-substituted aldehydes or ketones (110) serving as reaction partners (Scheme 13). In this way thialenes 41 and 45, which have sulfur directly bonded to an aromatic ring, can be produced in one step by base-catalyzed condensation from o-mercaptobenzaldehyde and from a,/ -unsaturated cyclopentenones.110,131 Under the same conditions salicylic aldehyde gives only open-chained products fill).5,72,73 99,1 >6,1 27,128 finerai acids are required for further condensation. Thereby, pyrylium salts (90 Y = CH, X = O) are produced, from which oxalenes are formed by deprotonation (see Section I1I,A,1). 

A common side reaction during Oppenauer oxidations consists of the base-catalyzed condensation of the carbonyl compound, resulting from the oxidation, with the carbonyl compound used as oxidant. Sometimes, advantage is taken from this side reaction for synthetic purposes. For example, oxidation of primary alcohols with an aluminium alkoxide and acetone results in the formation of an intermediate aldehyde that condenses with acetone, resulting in a synthetically useful formation of an enone.59... 

The aldehydes 346 and 347 were prepared from the methoxyl derivatives by osmic acid sodium chlorate oxidation and deketalization followed by base-catalyzed condensation in an overall yield of 50%. Acetalization of 346 with /i-toluenesulfonic acid and ethylene glycol in refluxing benzene afforded the acetal 348. The latter has an active site at C-6 suitable for the introduction of oxygen substituents at this position. 

The base-catalyzed condensation of a-azido esters and ketones with aromatic aldehydes has recently been developed as a new vinyl azide synthesis.42,43 The yields range from moderate to excellent in some cases. The thermal decomposition of ethyl a-azidocinnamate (87) in xylene gives only 2-ethoxycarbonylindole (88).44 The unstable 2-ethoxycarbonyl-3-phenyl-l-azirine could be detected if the thermolysis was carried out at a lower temperature. This fact indicates that the 1-azirine is probably an intermediate leading to the indole, although the intermediacy of the vinyl nitrene could not be established. This result is similar to that observed by Isomura et al. on the pyrolysis of terminal vinyl azides.27,28... 

Calixarenes [77] are defined as [l.n]metacyclophanes with its basic structural unit consisting of phenolic groups linked by ortho-methylene groups. Two examples are shown in Fig. 25. Several reviews are available on this subject [77-79]. These compounds can be synthesized by the acid- or base-catalyzed condensation reaction of a substituted phenol with formaldehyde or an aldehyde (Fig. 26). Calixarenes have also been synthesized by a stepwise reaction that sequentially add phenolic groups followed by a cyclization step. More efficient convergent synthesis have also been developed [80-82], The bowl-like structural conformation generally... 

Further kinetic evidence for the importance of enols comes from work on the base-catalyzed condensations of carbonyl-containing compounds. There are a number of such reactions characteristic of aldehydes, ketones, carboxylic acids, esters, amides, etc. Of these the most elementary appear to be the aldol condensations, which are prototypes of the others. These reactions can be represented by the equation... 

The addition of malonic ester to benzalacetophenone is an illustration of a very general base-catalyzed condensation. The olefinic compound taking part in the reaction may be one in which the double bond is in the alpha position of an aldehyde, ketone, " ester,... 

The general approach was a base catalyzed condensation of the diketopiperazine with an aldehyde, followed by hydrogenation and hydrolysis. The glycine-L-aspartic acid diketopiperazine ester (5) can be prepared by standard peptide coupling procedures, but our preferred method at scale is to prepare the glycine unit from chloroacetyl chloride and ammonia (Scheme 11). 

Cyclopentenones can also be used for condensation, with o-substituted aldehydes or ketones (110) serving as reaction partners (Scheme 13). In this way thialenes 41 and 45, which have sulfur directly bonded to an aromatic ring, can be produced in one step by base-catalyzed condensation from... 

These syntheses have resulted from application of two well-known general reactions of nitroparaffins to the sugar field. The base-catalyzed condensation of primary or secondary nitroparafiins with aldehydes gives nitro alcohols the sodium salts of these decompose in dilute mineral acid... 

Several 1,3,5-triazine mono- and dialdoximes 5 can be prepared by the base-catalyzed condensation of the corresponding methyl-1,3,5-triazines 4 with alkyl nitrites. The formation of either the mono- or the dialdoxime is dependent on the reaction conditons used. Hydrolysis of the oximes to 1,3,5-triazinecarbaldehydes 6 can only be achieved for 4,6-diaryl-l, 3,5-triazine 2-al-doximes. These aldehydes can also be obtained by reaction of 4,6-diaryl-2-methyl-l,3,5-triazi-nes with sodium nitrite in concentrated sulfuric acid.162... 

Having demonstrated the preparation of an array of small organic compounds in high purity and yield, multistep reactions were then conducted by spatially incorporating two supported reagents into a continuous flow reactor. As Fig. 14.11 illustrates, the first step of the reaction consists of an acid-catalyzed acetal deprotection to afford the respective aldehyde and the second step involves the base-catalyzed condensation of the aldehyde with an activated methylene. Using this approach, 100% deprotection of the acetal to aldehyde was observed and 99% conversion of the aldehyde to the desired unsaturated product was observed to an give analytically pure product in 99.6% yield. 

Methylanthranilium salts condense readily with aldehydes, ketones, orthoesters, and diazonium salts to yield styryl, cyanine, and azo dyes, respectively.235 An interesting aspect of these anthranilium salts is their bifunctionality, the 3-methyl group being nucleophilic whereas the C-3 position is electrophilic. As a consequence, base-catalyzed condensation with aldehydes bearing a nucleophilic function at the ortho position (e.g.,... 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

It is known that under the influence of dilute base two molecules of an aldehyde or a ketone may combine to form a 3-hydroxyaldehyde or a 6-hydroxyketone. Such a reaction is called an aldol condensation. Using acetaldehyde as an example, the mechanism for the base-catalyzed condensation may be written as follows ... 

The synthesis of 2-arylpyrimidines carrying fluoroalkyl groups in 4- and 6-position can be achieved through base-catalyzed condensation of fluorinated imines 38, 40, and 43 with the corresponding aromatic aldehydes 44 (Fig. 7.13). ... 

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