General Condensation Reactions

Arangeof 1,3-dialkylimidazoliumand l-H-3-alkylimidazoliumionicliquidswere used in the condensation of ketones with 2-aminoacetophenones to give quinolines [253] (the Friedlander annulation). The authors discuss how the basicity of the 

Yields in the 85-99% range were observed by Yang et al. [257] without the need for a catalyst. 

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Improvements in the traditional aryl C-1 cyclization reaction were reported (Scheme 11). Generally, condensation reactions of phenethylamine derivatives do not perform well with electron-withdrawing groups. Reaction of sulfamoyl- 3-phenethylamines 46, even containing an aryl nitro group, with chloro(methylthio)acetate <99H(51)103> or a-... 

For the general condensation reaction of secondary amines with ketones to yield enamines, pyrrolidine, piperidine, or morpholine is generally used. The rate of enamine formation depends on the basicity of the secondary amine and the steric environment of the carbonyl group [12a, b, 29], Pyrrolidine, which is more basic, usually reacts faster than morpholine. The investigation of piperazine, a disecondary amine, has only been reported recently by Benzing [45, 46] and Sandler [41]. Surprisingly, the reaction of excess -butyraldehyde with piperazine in tetrahydrofuran at — 20°C to 0°C gave mainly AM-butenyl-piperazine [41] (see Eq. 13). 

A variety of substituted uranyl superphthalocyanine complexes, such as the more soluble methyl 161 and butyl 162 substituted systems [118, 17] can be obtained from the general condensation reaction (Scheme 22). However, when the condensation reaction was carried out using 1,2-dicyanobenKnes with electron withdrawing substituents, or those which impose a greater steric congestion, no five subunit-containing macrocyclic products could be detected. 

Figure 1. General condensation reaction in polyketide biosynthesis. The starter units are attached to thiol groups of the ketosynthase (KS), and extender units to thiol groups of either acyl carrier protein or acetyl coenzyme A (X).

Generally condensation reactions, such as (5.7)-(5.10), are reversible, so that the eliminated water must be removed if a high polymeric product is to be formed. The rate of a step polymerization is the sum of the rates of reaction between molecules of various sizes, that is, the sura of the rates for reactions such as (5.7)-(5.10). To describe the course of these reactions in terms of reaction kinetics would seem at first sight to be a very complicated task. However, fortunately it is possible to introduce simplifying approximations that make the kinetic problem tractable. 

Figure 3.12 General condensation reaction for polysilane preparation. Tol, toluene.

In principle, the heterocyclization between these p-substituted ketones and monosub-stitnted hydrazines proceeds by a Michael addition-elimination on the p-carbon atom by the more nncleophilic nitrogen of the hydrazine, followed by cyclodehydration to give mixtnres of 3-triflnoromelhyl and 5-trifluoromethylpyrazoles. In general, condensation reactions with melhylhydrazine lead to the 3-trifluoromethylpyrazole derivatives as only or major regioisomers, whereas with aryl or heterocyclic aromatic hydrazines, the formation of 5-trifluoromethylpyrazole prevails. 

M. Nardi, A. Cozza, L. Mainolo, M. OHverio, A. Procopio, 1,5-Benzoheteroazepines through eco-friendly general condensation reactions. Tetrahedron Lett. 52 (2011) 4827-4834. 

Synthesis of large heterocycles usually involves condensation reactions of two difunctional molecules. Such molecules tend to polymerize. So far two special techniques have been described above to avoid this important side-reaaion , namely high dilution and use of templates. The general procedure to avoid polymerizations in reactions between difunctional molecules is, of course, the application of protecting groups as described in sections 4.1.2 and 2.6. 

Poly(butylene Terephthalate). Poly(butylene terephthalate) is prepared in a condensation reaction between dimethyl terephthalate and 1,4-butanediol and its repeating unit has the general structure... 

Discussion of ladder polymers also enables us to introduce a step-growth polymerization that deviates from the simple condensation reactions which we have described almost exclusively in this chapter. The Diels-Alder reaction is widely used in the synthesis of both ladder and semiladder polymers. In general, the Diels-Alder reaction occurs between a diene [XVI] and a dienophile [XVll] and yields an adduct with a ring structure [XVlll] ... 

Synthesis and Properties. Several methods have been suggested to synthesize polyimides. The predominant one involves a two-step condensation reaction between aromatic diamines and aromatic dianhydrides in polar aprotic solvents (2,3). In the first step, a soluble, linear poly(amic acid) results, which in the second step undergoes cyclodehydration, leading to an insoluble and infusible PL Overall yields are generally only 70—80%. 

The common synthetic route to bismaleimides or maleimide functionalized oligomers is the condensation of diamines or amino-terminated oligomers with maleic anhydride. Another possibiUty is the use of an AB-type monomer of the following general formula to build the polymaleimide, where X represents a functional group that can be employed in condensation reactions. 

Aromatic compounds that are sufftciendy nucleophilic to condense with benzenediazonium chloride and form azo compounds generally condense with TCNE, eg, the reaction of /V, /V- dim ethyl a n i1 in e proceeds stepwise (21,22). 

In practice, the taffy process is generally employed for only medium molecular-weight resins (1) (n = 1-4). The polymerization reaction results in a highly viscous product (emulsion of water and resin) and the condensation reaction becomes dependent on agitation. At the completion of the reaction, the heterogeneous mixture consists of an alkaline brine solution and a water—resin emulsion and recovery of the product is accompHshed by separation of phases, washing of the taffy resin with water, and removal of water under vacuum. 

These processes have supplanted the condensation reaction of ethanol, carbon monoxide, and acetylene as the principal method of generating ethyl acrylate [140-88-5] (333). Acidic catalysts, particularly sulfuric acid (334—338), are generally effective in increasing the rates of the esterification reactions. Care is taken to avoid excessive polymerisation losses of both acryflc acid and the esters, which are accentuated by the presence of strong acid catalysts. A synthesis for acryflc esters from vinyl chloride (339) has also been examined. 

As these condensation reactions can occur at the two ortho and the para positions in phenol, w-cresol and 3,5-xylenol, cross-linked structures will be formed. It has been pointed out by Megson that because of steric hindrance the amount of cross-linking that can take place is much less than would involve the three reactive groups of all the phenolic molecules. It is now generally considered that the amount of cross-linking that actually takes place is less than was at one time believed to be the case. 

The general definition of a condensation reaction is a one that involves product formation by expulsion of water (or other small molecule) as a by-product. By this definition, activation and methylolation are also condensations. In more precise terms the chain-building process should be described as a condensation polymerization, however, in the jargon of the phenolics industry, the term condensation is usually reserved for the chain-building process. This terminology is not necessarily observed in the literature [88]. Many literature reports correctly refer to methylolation as a condensation reaction. The molecular weight development of the phenol alcohol adducts may also be classified as a step-polymerization. 

A general route to benzo-2,l,3-selenadiazoles involves the condensation reaction between 1,2-diaminobenzene and selenium tetrachloride. This method has also been used recently for the synthesis of 4,5,6,7-tetrafluoro-2,l,3-benzotelluradiazole (Eq. 2.9) ... 

The mechanism of this reaction is generally understood to consist of subsequent Claisen condensation reactions to produce an intermediate diketone 12, which readily tautomerizes to the fully conjugated dihydroxythiophene 13. ... 

A variation of the general method for the synthesis of 2-amino-selenazoles is to avoid the use of the free a-halogenocarbonyl compound and in its place react the corresponding ketone and iodine with selenourea.This procedure is also taken from thiazole chemistry. By contrast with thiourea, the reaction with selenourea needs a longer reaction time and the work up of the reaction mixture is somewhat more difficult. Usually an excess of the ketone is used. In the preparation of 2-amino-4-( n-nitrophenyl)selenazole, a very high yield, calculated on the amount of iodine used, was obtained. To explain this peculiar result, the oxidative action of the nitro group was invoked. This liberates free iodine from some of the hydrogen iodide eliminated in the condensation reaction, and the free iodine then re-enters into the reaction. 

A general method for the construction of a pyridine ring is the Hantzsch synthesis. A condensation reaction of two equivalents of a /3-ketoester 1 with an aldehyde 2 and ammonia leads to a 1,4-dihydropyridine 3, which can be oxidized to the corresponding pyridine 4—for example by nitric acid ... 

We ve now studied three of the four general kinds of carbonyl-group reactions and have seen two general kinds of behavior. In nucleophilic addition and nucleophilic acyl substitution reactions, a carbonyl compound behaves as an electrophile. In -substitution reactions, however, a carbonyl compound behaves as a nucleophile when it is converted into its enol or enolate ion. In the carbonyl condensation reaction that we ll study in this chapter, the carbonyl compound behaves both as an electrophile and as a nucleophile. 

We ll see later in this chapter and again in Chapter 29 that carbonyl condensation reactions occur frequently in metabolic pathways. In fact, almost all classes of biomolecules—carbohydrates, lipids, proteins, nucleic acids, and many others—are biosynthesized through pathways that involve carbonyl condensation reactions. As with the or-substitution reaction discussed in the previous chapter, the great value of carbonyl condensations is that they are one of the few general methods for forming carbon-carbon bonds, thereby making it possible to build larger molecules from smaller precursors. We ll see how and why these reactions occur in this chapter. 

Active Figure 23.1 MECHANISM The general mechanism of a carbonyl condensation reaction. One partner becomes a nucleophilic donor and adds to the second partner as an electrophilic acceptor. 

Aldehydes and ketones with an a hydrogen atom undergo a base-catalyzed carbonyl condensation reaction called the aldol reaction. For example, treatment of acetaldehyde with a base such as sodium ethoxide or sodium hydroxide in a protic solvent leads to rapid and reversible formation of 3-hydroxybutanal, known commonly as aldol (aidehyde + alcohol), hence the general name of the reaction. 

Resole syntheses entail substitution of formaldehyde (or formaldehyde derivatives) on phenolic ortho and para positions followed by methylol condensation reactions which form dimers and oligomers. Under basic conditions, pheno-late rings are the reactive species for electrophilic aromatic substitution reactions. A simplified mechanism is generally used to depict the formaldehyde substitution on the phenol rings (Fig. 7.21). It should be noted that this mechanism does not account for pH effects, the type of catalyst, or the formation of hemiformals. Mixtures of mono-, di-, and trihydroxymethyl-substituted phenols are produced. 

Resole resins are generally crosslinked under neutral conditions between 130 and 200° C or in the presence of an acid catalyst such as hydrochloric acid, phosphoric acid, p-toluenesulfonic acid, and phenolsulfonic acid under ambient conditions.3 The mechanisms for crosslinking under acidic conditions are similar to acid-catalyzed novolac formation. Quinone methides are the key reaction intermediates. Further condensation reactions in resole resin syntheses under basic conditions at elevated temperatures also lead to crosslinking. 

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