Aromatic substitution in condensation

Aromatic Substitution in Condensation Polymerization Catalyzed by Solid-Liquid Phase Transfer... 

A palladium-catalyzed amidation of halo(hetero)aromatics substituted in the ortAo-position by a carbonyl function with a primary or secondary amine has been introduced as an alternative to the Friedlander condensation for the synthesis of naphthyridinones (and quinolinones) (Scheme 32) <2004OL2433>. 

Claisen-Schmidt condensation, 720, 728 with methylamine, 673, 873 nitration, 467, 873 reductive amination, 881 with vinyllithium, 556 Benzenamine, 859. See also Aniline Benzene, 54, 399-406, 433 34 acidity of, 552, 577 Birch reduction of, 413-414 derivatives, nomenclature of, 406-408 electrophilic aromatic substitution in,... 

A halogen atom directly attached to a benzene ring is usually unreactive, unless it is activated by the nature and position of certain other substituent groups. It has been show n by Ullmann, however, that halogen atoms normally of low reactivity will condense with aromatic amines in the presence of an alkali carbonate (to absorb the hydrogen halide formed) and a trace of copper powder or oxide to act as a catalyst. This reaction, known as the Ullmant Condensation, is frequently used to prepare substituted diphenylamines it is exemplified... 

In the first century of "organic" chemistry much attention was given to the structures of carbogens and their transformations. Reactions were classified according to the types of substrates that underwent the chemical change (for example "aromatic substitution," "carbonyl addition," "halide displacement," "ester condensation"). Chemistry was taught and learned as transformations characteristic of a structural class (e.g. phenol, aldehyde) or structural subunit... 

An interesting alternative approach to the synthesis of a cryptand having nitrogen atoms in the bridges was presented by Newkome and coworkers. This group condensed triethanolamine with 2,6-dichloropyridine in a relatively straightforward but low yield (5%) nucleophilic aromatic substitution to form 7, illustrated below in Eq. (8.6). The identity of the compound was confirmed by X-ray structural analysis. 

The substitution of condensed aromatic rings is possible at various sites. This leads to regioisomerism, already when the first substituent is introduced. There are first hints that the distributions between regioisomers of condensed aromatics differ when conducted in a micro reactor as compared with conventional processing. The reason for this is not understood even suggestions on this are lacking in the literature. 

In general, if condensation polymers are prepared with methylated aryl repeat units, free radical halogenatlon can be used to introduce halomethyl active sites and the limitations of electrophilic aromatic substitution can be avoided. The halogenatlon technique recently described by Ford11, involving the use of a mixture of hypohalite and phase transfer catalyst to chlorinate poly(vinyl toluene) can be applied to suitably substituted condensation polymers. 

The synthetic route generally involves condensing two equivalents of 4,5,6,7-tetrachloroisoindoline-l-one derivatives with one equivalent of an aromatic diamine in an organic solvent. Suitable tetrachloroisoindoline-l-one derivatives are substituted in 3-position, which is occupied either by two monovalent groups (A)... 

A variety of methods have been developed for the preparation of substituted benzimidazoles. Of these, one of the most traditional methods involves the condensation of an o-phenylenediamine with carboxylic acid or its derivatives. Subsequently, several improved protocols have been developed for the synthesis of benzimidazoles via the condensation of o-phenylenediamines with aldehydes in the presence of acid catalysts under various reaction conditions. However, many of these methods suffer from certain drawbacks, including longer reaction times, unsatisfactory yields, harsh reaction conditions, expensive reagents, tedious work-up procedures, co-occurrence of several side reactions, and poor selectivity. Bismuth triflate provides a handy alternative to the conventional methods. It catalyzes the reaction of mono- and disubstituted aryl 1,2-diamines with aromatic aldehydes bearing either electron-rich or electron-deficient substituents on the aromatic ring in the presence of Bi(OTf)3 (10 mol%) in water, resulting in the formation of benzimidazole [119] (Fig. 29). Furthermore, the reaction also works well with heteroaromatic aldehydes. 

Many of the common condensation polymers are listed in Table 1-1. In all instances the polymerization reactions shown are those proceeding by the step polymerization mechanism. This chapter will consider the characteristics of step polymerization in detail. The synthesis of condensation polymers by ring-opening polymerization will be subsequently treated in Chap. 7. A number of different chemical reactions may be used to synthesize polymeric materials by step polymerization. These include esterification, amidation, the formation of urethanes, aromatic substitution, and others. Polymerization usually proceeds by the reactions between two different functional groups, for example, hydroxyl and carboxyl groups, or isocyanate and hydroxyl groups. 

A number of syntheses of pioglitazone have been disclosed (Arita and Mizuno, 1992 Fischer et al., 2005 Les et al., 2004 Meguro and Fujita, 1986, 1987 Momose et al., 1991 Prous and Castaner, 1990 Saito et al., 1998). Two related syntheses (Fischer et al., 2005 Les et al., 2004) of pioglitazone hydrochloride are described in Scheme 8.2. The tosylate of 2-(5-ethylpyridin-2-yl)ethanol (16), formed in situ with tosyl chloride, was displaced by 4-hydroxybenzaldehyde (17) by means of benzyltributylammonium chloride and NaOH to give 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde (20). Condensation of 20 with thiazolidine-2,4-dione in basic medium afforded 5-[-4-[2-(5-ethylpyridin-2-yl)ethoxy]benzylidene]thiazolidine-2,4-dione (21). Finally, this compound was hydrogenated to provide pioglitazone (2). Alternatively, a nucleophilic aromatic substitution reaction... 

The nucleophilic aromatic substitution of 6-nitropiperonal with [ F]K(Kryptofix 2.2.2)F yielded 6-[ F]fluoropiperonal that was condensed with nitromethane. Reduction and subsequent hydrolysis of the intermediate nitroalkene provided the target compound 6-[ F]FDA. In comparison to more direct approaches which utilize electrophilic aromatic substitution with positive polarized p F]fluo-rine [140-142], this type of preparation is characterized by high specific radioactivity, which is requested for human PET studies with vasopressor compounds, like 6-FDA [139,143]. 

Substituted binaphthyl compounds can be synthesized in high optical yields using nucleophilic aromatic substitution reactions in which the chiral leaving groups are alkoxy moieties derived from naturally occurring alcohols28-29. For example, the condensation of 2-(l-alkoxynaphth-2-yl)-4.5-dihydro-4,4-dimethyl-l,3-oxazole with 1-naphthyllithium or 2-methoxy-l-naphthyl 2-magnesium bromide leads to (ft)- or (.S)-(l,T-binaphthyl-2-yl)-4,5-dihydro-4,4-dimethyl-l,3-oxazole derivatives. 

In contrast to wild-type BFD, BAL accepts aromatic aldehydes substituted in the ortho position as well. Only a few aromatic aldehydes, such as pyridine 3- and 4-carbaldehyde as well as sterically exceedingly demanding aldehydes, resulted either in very low yields or in no benzoin condensation at all [62]. Moreover, mono- and dimethoxyacetaldehyde are good substrates for BAL, leading to highly functionalized enantiopure hydroxypropiophenone derivatives (Scheme 2.2.7.22) [63]. 

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