Intermolecular reactions carboxylic acids

Choi and Sakakura et al. reported that iron(III) triflate, in situ formed from FeCls and triflic acid, efficiently catalyzes the intermolecular addition of carboxylic acids to various alkenes to yield carboxylic esters. The reaction is applicable to the synthesis of unstable esters, such as acrylates (Scheme 40) [50]. 

J Steffans et al., 1973, 1975. The reference reaction is the attack of the anion of a carboxylic acid of pK, 3.91 on methyl 2,4-dinitrophenyl phosphate at 39° (Kirby and Younas, 1970). The intramolecular reaction is corrected for the better leaving group using y LO=1.26 (Khan et al., 1970), and to 39° using the activation energy measured for the intermolecular reaction with acetate (Kirby and Younas, 1970). 

Capon and Walker, 1971. The reference intermolecular reaction is the mutarotation of D-glucose, catalysed by a carboxylic acid of pK, 4.3... 

In 50% dioxan (Fife and Przystas, 1977). The reference intermolecular reaction is the hydrolysis of the acetal group of the corresponding methyl ester by a carboxylic acid of p/f. 5.56. The value of k2 was calculated from the buffer catalysis data given for three carboxylic acids using buffer pK. s measured in 50% dioxan (at 50°) by Fife and Brod (1970)... 

Alkoxy-VCP 163 was found to be a very competent reagent in the intermolecular [5+2] cycloaddition (Tab. 13.12). With some minor optimization of the previous reaction conditions, namely the use of 1,2-dichloroethane (DCE) as solvent at a higher concentration (0.5 M) and reaction temperature (80 °C), the reaction was found to be complete in minutes in some cases with 0.5 mol% [RhCl(CO)2]2, while still providing good to excellent yields of cycloheptenone products. Significantly, reactive functionahty, including unprotected alcohols and carboxylic acids, is tolerated in the reaction. The reaction is also readily scaled, with comparable isolated yields over a 100-fold increase in scale. The formation of products in minutes is of consequence, as such reactions allow for the more time-efficient reahzation of synthetic goals. 

In organic reactions, ionic interactions may serve as intermolecular or intramolecular forces. In some cases, these may involve metal cations, such as Na% or anions, such as Cl. Cations may include an ammonium ion from an amino group, such as RNH3. The anion may be from a carboxylic acid, such as RCOO. The oppositely charged ions attract each other very strongly. 

The halogenated derivatives of six membered heterocycles, like their carbacyclic analogues, usually participate readily in coupling reactions that involve the incorporation of an olefin or carbon monoxide. The insertion of carbon monoxide commonly leads to the formation of either a carboxylic acid derivative or a ketone, depending on the nature of the other reactants present. Intermolecular and intramolecular variants of the insertion route are equally popular, and are frequently utilized in the functionalization of heterocycles or the formation of annelated ring systems. 

Intermolecular Markovnikov-type addition of phenols (ArOH), carboxylic acids (RCO2H), and protected amines (TsNH2) to alkenes, such as 4-MeOC6H4CH2CH= CH2, can be catalysed by triflic acid in low concentrations (1-5%). Functional groups, such as the methoxyl on aromatics, can be tolerated if the concentration of triflic acid and the reaction temperature are controlled appropriately. This reaction provides one of the simplest alkene addition methods and can serve as an alternative to metal-catalysed reactions.33... 

Ameline, G. Vaultier, M. Mortier, J. Directed metalation reactions. Intermolecular competition of the carboxylic acid group and various substituents. Tetrahedron Lett. 1996, 37, 8175— 8176. 

B as an ester- or lactone-substituted aldehyde enolate. Such enolates undergo condensations with all kinds of aldehydes, including paraformaldehyde. An adduct E is formed initially, acy-lating itself as soon as it is heated. The reaction could proceed intramolecularly via the tetrahedral intermediate D or intermolecularly as a retro-Claisen condensation. In both cases, the result is an acyloxy-substituted ester enolate. In the example given in Figure 13.50, this is the formyloxy-substituted lactone enolate C. As in the second step of an Elcb elimination, C eliminates the sodium salt of a carboxylic acid. The a,/)-unsaturated ester (in Figure 13.50 the 0J,/3-unsaturated lactone) remains as the aldol condensation product derived from the initial ester (here, a lactone) and the added aldehyde (here, paraformaldehyde). 

A one-pot synthesis of 3,5-disubstituted 7-hydroxy-3//-l,2,3-triazolo[4,5-d]pyrimidines (130) has been carried out by using benzyl azide, cyano-acetamide, ethyl or methyl esters of the appropriate carboxylic acid, and sodium ethoxide as catalyst. The reaction proceeds via a 5-amino-l-benzyltriazole-4-carboxamide intermediate (85JHC1607). 7-Amino-3H-l,2,3-triazolo[4,5-d]pyrimidines 133 (R2 = H) were prepared starting from benzyl azide, malononitrile, and an aliphatic or aromatic nitrile, or by reaction of 130 with phosphorus oxychloride followed by amination. Compound 132 was formed in most reactions from two molecules of the 5-amino-4-cyano-l-benzyltriazole intermediate by an intermolecular nucleophilic at-... 

For intramolecular reactions, treatment of a carboxylic acid with sulfuric acid or polyphosphoric acid is sometimes used to generate the acyl cation electrophile. This method is usually too mild for intermolecular acylations but works well for intramolecular examples, as shown in the following equation ... 

The cyclodehydration of 2-substituted-A/-acylthiazolidine-4-carboxylic acids yields bicyclic munchnones. This mesoionic ring system acts as a cyclic azomethine ylid and can undergo 1,3-dipolar cycloaddition reactions with dipolarophiles. A range of chiral pyrrolo[l,2-c]thiazoles have been prepared by this method both intermolecularly and intramolecularly. 

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