Condensation, acidic conditions

Formaldehyde condenses with itself in an aldol-type reaction to yield lower hydroxy aldehydes, hydroxy ketones, and other hydroxy compounds the reaction is autocatalytic and is favored by alkaline conditions. Condensation with various compounds gives methylol (—CH2OH) and methylene (=CH2) derivatives. The former are usually produced under alkaline or neutral conditions, the latter under acidic conditions or in the vapor phase. In the presence of alkahes, aldehydes and ketones containing a-hydrogen atoms undergo aldol reactions with formaldehyde to form mono- and polymethylol derivatives. Acetaldehyde and 4 moles of formaldehyde give pentaerythritol (PE) ... 

The condensation of an aldehyde with resorcinol gives rise to calix (3) arene (114). Isoprene reacts with resorcinol under acidic conditions to give ben2odipyran (24) and monochroman (25) (115). 

Examples include acetaldehyde, CH CHO paraldehyde, (CH CHO) glyoxal, OCH—CHO and furfural. The reaction is usually kept on the acid side to minimize aldol formation. Furfural resins, however, are prepared with alkaline catalysts because furfural self-condenses under acid conditions to form a gel. 

Formaldehyde may react with the active hydrogens on both the urea and amine groups and therefore the polymer is probably highly branched. The amount of formaldehyde (2—4 mol per 1 mol urea), the amount and kind of polyamine (10—15%), and resin concentration are variable and hundreds of patents have been issued throughout the world. Generally, the urea, formaldehyde, polyamine, and water react at 80—100°C. The reaction may be carried out in two steps with an initial methylolation at alkaline pH, followed by condensation to the desired degree at acidic pH, or the entire reaction may be carried out under acidic conditions (63). The product is generally a symp with 25—35% soHds and is stable for up to three months. 

Aldehydes and Ketones. Pyrrole aldehydes and ketones are somewhat less reactive than the corresponding benzenoid derivatives. The aldehydes do not undergo Cannizzaro or Perkin reactions but condense with a variety of compounds that contain active methylene groups. They also react with pyrroles under acidic conditions to form dipyrryhnethenes (26). The aldehydes can be reduced to the methyl or carbinol stmctures. The ketones undergo normal carbonyl reactions. 

In acid solution, the double bond of (203) is hydrogenated to the trans-fused sulfone (204). Presumably, this hydrogenation goes through a cis-fused intermediate that is rapidly epimerized to (204) under the acidic conditions of the reaction. Condensation of the sodium salt of 7,7-ethylenedioxy-3-oxooctanoate (205) with (204) produces (206). Cmde (206) is cyclized, hydroly2ed, and decarboxylated, producing the tricycHc compound (207). Hydrogenation of (207) followed by ketal hydrolysis and cyclization affords (208) in an overall yield of 35% from hydrindandione (203). 

These compounds are stable only under basic conditions and must be held at high pH if stored for considerable periods of time. In Step 2, these methylolureas further react under acidic conditions with urea to form the various methylene urea oligomers. Water generated from the condensation reaction is removed by evaporation when producing granular UE products. 

The epoxy cresol—novolak resins (2) are prepared by glycidylation of o-cresol—formaldehyde condensates in the same manner as the phenol—novolak resins. The o-cresol—formaldehyde condensates are prepared under acidic conditions with formaldehyde—o-cresol ratios of less than unity. 

Bis-phenol A may be produced by the condensation of phenol with acetone under acidic conditions (Figure 20.2). 

In addition to the above possible mechanisms the possibility of reaction at w-positions should not be excluded. For example, it has been shown by Koebner that o- and p-cresols, ostensibly difunctional, can, under certain conditions, react with formaldehyde to give insoluble and infusible resins. Furthermore, Megson has shown that 2,4,6-trimethylphenol, in which the two ortho- and the one para-positions are blocked, can condense with formaldehyde under strongly acidic conditions. It is of interest to note that Redfam produced an infusible resin from 3,4,5,-trimethylphenol under alkaline conditions. Here the two m- and the p-positions were blocked and this experimental observation provides supplementary evidence that additional functionalities are developed during reaction, for example in the formation of quinone methides. 

The reaction mixture is heated and allowed to reflux, under atmospheric pressure at about 100°C. At this stage valve A is open and valve B is closed. Because the reaction is strongly exothermic initially it may be necessary to use cooling water in the jacket at this stage. The condensation reaction will take a number of hours, e.g. 2-4 hours, since under the acidic conditions the formation of phenol-alcohols is rather slow. When the resin separates from the aqueous phase and the resin reaches the requisite degree of condensation, as indicated by refractive index measurements, the valves are changed over (i.e. valve A is closed and valve B opened) and water present is distilled off. 

As with the other aminoplastics, the chemistry of resin formation is incompletely understood. It is, however, believed that under acid conditions at aniline-formaldehyde ratios of about 1 1.2, which are similar to those used in practice, the reaction proceeds via p-aminobenzyl alcohol with subsequent condensation between amino and hydroxyl groups (Figure 24.10). 

This reaction, like the initial condensation, is favoured by acidic conditions and peroxides are ineffective. 

It is also possible to carry out the aldol condensation under acidic conditions. The reactive nucleophile is then the enol. The mechanism, as established in detail for acetaldehyde, involves nucleophilic attack of the enol on the protonated aldehyde. 

Coe et al. reported an efficient modification for the preparation of /-substituted indole analogs for biology screening in good yield. The intermediate P-nitrostyrene 44, prepared from the condensation of 43 with DMFDMA, underwent methanolysis and reduction to provide the aniline acetal intermediate 45. Alkylation of amine 45 was carried out employing standard conditions of reductive alkylation to provide A-alkyl analogs represented by 46. The indole 47 was generated by formation of the oxonium ion (from 46) under acidic conditions, followed by cyclization, accompanied by loss of methanol. 

Faced with the inapplicability of the standard basic conditions required for the Pfitzinger condensation in the context of their study, Lackey and Stembach developed a modified protocol which allows for the formation of quinolinic acids under acidic conditions. ... 

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

Alkylation of 1-indanone with 2-dimethylaminoethyl chloride affords the substituted ketone (1). Condensation with the lithium reagent obtained from 2-ethylpyridine affords the alcohol (2). Dehydration under acidic conditions gives dimethyl-pyrindene (3). ... 

Fischer indole condensation of Ni-benzylphenyl-hydrazine and 1-methyl-4-piperidone under the usual acid conditions affords meb-hydroline (29), an indole used as an antihistaminic agent-... 

A common case where intense general corrosion is experienced in a very restricted section of plant is where an acidic vapour is condensing. As a vapour the acid is usually non-corrosive, but when condensed it can only be handled in expensive materials. Another variation on this theme is that only at the region of initial condensation is there a corrosion problem, either the condense/reboil condition being particularly corrosive or else corrosion only takes place at or near the boiling point. Several variations in design are possible to cope with these situations ... 

Benzothiepins synthesized by a double Knoevenagel condensation (see Section 2.1.1.2.) contain free carboxylic acid groups if the reaction product is isolated under acidic conditions. Rcesterification can be performed by two methods via formation of the acid chloride and subsequent alcoholysis, or by reaction with diazomethane, e.g. the conversion of 3-benzo-thiepin-2,4-diearboxylic acid (5, R = C02H) with thionyl chloride and methanol gives the dimethyl ester 5 (R = C02Me) in 47% yield, while the diazomethane pathway provides 60% of the dimethyl ester.65 Use of excess diazomethane leads to cycloadducts (see Section 2.2.4.). 

Best results are obtained when the reaction is carried out under acidic conditions. The products are isolated in the form of their stable salts 3 with hydrochloric, perchloric or sulfuric acid.256-257 a-Hydroxymethylene ketones do not condense with benzene-1,2-diamine to give benzodiazepines if the carbonyl group is adjacent to an aromatic ring.258... 

Condensation reactions between two hydroxymethyl substituents eliminate water to form ether linkages (Fig. 7.23a) or eliminate both water and formaldehyde to form methylene linkages (Fig. 7.23b). Ether formation is favored under neutral or acidic conditions and up to 130°C above which formaldehyde departs and methylene linkages are generated. The methylene linkage formation reaction, which eliminates water and fortualdehyde, is more prevalent under basic conditions. Condensation reactions between hydroxymethyl groups and reactive... 

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