Carboxylic acids => alkyl halides

Numerous binary and ternary diene polymerization initiator systems with neodymium as the rare-earth metal component have been designed empirically and investigated since the early discoveries in the 1960s. Commercially used neodymium-based catalysts mostly comprise Nd(III) carboxylates, aluminum alkyl halides, and aluminum alkyls or aluminum alkyl hydrides [43, 48,50-52]. Typically, the carboxylic acids, which are provided as mixtures of isomers from petrochemical plants carry solubilizing aliphatic substituents R. They are treated with the alkylaluminum reagents to generate the active catalysts in situ (Scheme 11). 

Hydrides from carboxylic acids Carboxylic acids from hydrides Carboxylic acids from hydrides Esters from hydrides Hydrides from aldehydes Hydrides from aldehydes Alkyls from aldehydes Ketones from methylenes Ketones from ketones Alkyls from olefins Acetylenes from halides also acetylenes from acetylenes Esters from alcohols also esters from carboxylic acids Alkyls from olefins Alkyls from olefins... 

Alkynes from halides also alkynes from alkynes Esters from alcohols also esters from carboxylic acids Alkyls from alkenes (Conjugate Reduction)... 

Although carboxylic acids generally form 1 1 adducts with alkenes, the resulting esters are easily ionized in the presence of either Lewis or protonic acids. The higher efficiency of chlorinated acetic acids relative to hydrogen halides is ascribed to the ability of their 1 1 adducts to coordinate with excess acid. Alkyl halides are eventually formed when carboxylic acids are used to initiate polymerization in the presence of a Lewis acid due to migration of the carboxylate moiety to the Lewis acid [Eq. (25)]. Similarly, styrene and isobutene polymerizations initiated by preformed alkyl acetate adducts in the presence of BC13 always produce Cl-terminated chains [104,105]. 

The reaction of potassium carboxylates with alkyl halides without the use of a solvent in the presence of catalytic amounts of a tetraalkylammonium salt proceeds smoothly to give the corresponding esters in good to excellent yields, except for cyclohexyl bromide where elimination mainly takes place. Alkylation of o- and p-hydroxybenzoic acid selectively takes place at the CO2K group. ... 

Microwaves Alkylation of ethylphenyl sulfonyl acetate, diethyl malonate, anions derived from active methylene Dihalocyclopropanation of substituted olefins under LLPTC and SLPTC conditions Ethoxylation of o,p-nitrochlorobenzene Reactions of carboxylic acids with halides Wang and Jiang (1992), Wang et al. (1995) Villemin and Labiad (1992) Yuan et al. (1992a) Yuan et al. (1992b)... 

The pentachloride is most used. It will convert snlphonic acids to snlphonyl halides (12.276), alcohols to halides (12.277) and carboxylic acids to halides (12.278). Af-alkyl-substituted amides (12.279) and ketoximes (12.280) can be converted to nitriles and the Beckmann rearrangement promoted (12.281). 

Overall the carboxylation of Grignard reagents transforms an alkyl or aryl halide to a carboxylic acid in which the carbon skeleton has been extended by one carbon atom... 

Primary and secondary alkyl halides may be converted to the next higher carboxylic acid by a two step synthetic sequence involving the preparation and hydrolysis of nitriles Nitnles also known as alkyl cyanides are prepared by nucleophilic substitution... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

One-electron oxidation of carboxylate ions generates acyloxy radicals, which undergo decarboxylation. Such electron-transfer reactions can be effected by strong one-electron oxidants, such as Mn(HI), Ag(II), Ce(IV), and Pb(IV) These metal ions are also capable of oxidizing the radical intermediate, so the products are those expected from carbocations. The oxidative decarboxylation by Pb(IV) in the presence of halide salts leads to alkyl halides. For example, oxidation of pentanoic acid with lead tetraacetate in the presence of lithium chloride gives 1-chlorobutane in 71% yield ... 

Section 19.12 Nitriles, which can be prepared from primary and secondary alkyl halides by nucleophilic substitution with cyanide ion, can be converted to carboxylic acids by hydrolysis. 

PCI5 chlorinates alcohols to alkyl halides and carboxylic acids to the corresponding RCOCl. When heated with NH4CI the phosphonitrilic chlorides are obtained (p. 536). These and other reactions are summarized in the diagram. 

Chiral oxazolines developed by Albert I. Meyers and coworkers have been employed as activating groups and/or chiral auxiliaries in nucleophilic addition and substitution reactions that lead to the asymmetric construction of carbon-carbon bonds. For example, metalation of chiral oxazoline 1 followed by alkylation and hydrolysis affords enantioenriched carboxylic acid 2. Enantioenriched dihydronaphthalenes are produced via addition of alkyllithium reagents to 1-naphthyloxazoline 3 followed by alkylation of the resulting anion with an alkyl halide to give 4, which is subjected to reductive cleavage of the oxazoline moiety to yield aldehyde 5. Chiral oxazolines have also found numerous applications as ligands in asymmetric catalysis these applications have been recently reviewed, and are not discussed in this chapter. ... 

Electrochemical reduction of oxazolinium salts 36 gives the anions 37, which add efficiently to alkyl halides or, in the presence of McsSiCl, to methyl acrylate, methyl vinyl ketone, and acrylonitrile. Simple acid hydrolysis then gives the ketone products 38 and 39, and this method is quite general since the starting salts are readily prepared from carboxylic acids, R C02H (87TL4411). 

Differences in solubility of the reactants may for example be utilized as follows. Sodium iodide is much more soluble in acetone than are sodium chloride or sodium bromide. Upon treatment of an alkyl chloride or bromide with sodium iodide in acetone, the newly formed sodium chloride or bromide precipitates from the solution and is thus removed from equilibrium. Alkyl iodides can be conveniently prepared in good yields by this route. Alkyl bromides are more reactive as the corresponding chlorides. Of high reactivity are a-halogen ketones, a-halogen carboxylic acids and their derivatives, as well as allyl and benzyl halides. 

Yet another nonsedating zwitterionic H-1 antihistamine consists of the product from metabolism of the terminal hydroxyl of the potent antihistamine hydroxyzine terminating in hydroxymethyl instead of a carboxylic acid. This compound, cetirzine (123), can be obtained in straightforward fashion by alkylation of the monosubstituted piperazine 120 with halide 121, via the amide 122 [27]. 

Carboxylic acids can be prepared from nitriles by reaction with hot aqueous acid or base by a mechanism that we ll see in Section 20.9. Since nitriles themselves are usually made by Sts 2 reaction of a primary or secondary7 alkyl halide with CN , the two-step sequence of cyanide displacement followed by nitiile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr —> RC=N RC02H). 

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