Aminations carboxylic acids, pyridine

D = Head unit (phenol, thiophene, furan, pyrrole etc.) Z=amines, carboxylic acids, pyridine etc. 

Solvents with strong hydrogen bonding (alcohols, carboxylic acids, pyridine, water, glycols, amines)... 

In the course of this study, the authors determined /Lvalues for dibenzyl, methyl phenyl, methyl p-nitrophenyl, di-p-tolyl, di-isopropyl and tetramethylene sulphoxides and for diethyl, dipropyl and dibutyl sulphites. The /Lscales are applied to the various reactions or the spectral measurements. The /Lscales have been divided into either family-dependent (FD) types, which means two or more compounds can share the same /Lscale, family-independent (FI) types. Consequently, a variety of /Lscales are now available for various families of the bases, including 29 aldehydes and ketones, 17 carboxylic amides and ureas, 14 carboxylic acids esters, 4 acyl halides, 5 nitriles, 10 ethers, 16 phosphine oxides, 12 sulphinyl compounds, 15 pyridines and pyrimidines, 16 sp3 hybridized amines and 10 alcohols. The enthalpies of formation of the hydrogen bond of 4-fluorophenol with both sulphoxides and phosphine oxides and related derivatives fit the empirical equation 18, where the standard deviation is y = 0.983. Several averaged scales are shown in Table 1588. 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Hydrogen bond donor solvents are simply those containing a hydrogen atom bound to an electronegative atom. These are often referred to as protic solvents, and the class includes water, carboxylic acids, alcohols and amines. For chemical reactions that involve the use of easily hydrolysed or solvolysed compounds, such as AICI3, it is important to avoid protic solvents. Hydrogen bond acceptors are solvents that have a lone pair available for donation, and include acetonitrile, pyridine and acetone. Kamlet-Taft a and ft parameters are solvatochromic measurements of the HBD and HBA properties of solvents, i.e. acidity and basicity, respectively [24], These measurements use the solvatochromic probe molecules V, V-die lliy I -4-n i in tan iline, which acts as a HBA, and 4-nitroaniline, which is a HBA and a HBD (Figure 1.17). 

Amination (11) and solution carbonation (8) reactions were carried out as described previously. For solid-state carbonations, a benzene solution of poly(styryl)lithium was freeze-dried on the vacuum line followed by introduction of high-purity, gaseous carbon dioxide (Air Products, 99.99% pure). Analysis and characterization of polymeric amines (11) and carboxylic acids (8) were performed as described previously. Benzoyl derivatives of the aminated polystyrenes were prepared in toluene/pyridine (2/1. v/v) mixtures with benzoyl chloride (Aldrich, 99%). 

Tertiary benzylic nitriles are useful synthetic intermediates, and have been used for the preparation of amidines, lactones, primary amines, pyridines, aldehydes, carboxylic acids, and esters. The general synthetic pathway to this class of compounds relies on the displacement of an activated benzylic alcohol or benzylic halide with a cyanide source followed by double alkylation under basic conditions. For instance, 2-(2-methoxyphenyl)-2-methylpropionitrile has been prepared by methylation of (2-methoxyphenyl)acetonitrile using sodium amide and iodomethane. In the course of the preparation of a drug candidate, the submitters discovered that the nucleophilic aromatic substitution of aryl fluorides with the anion of a secondary nitrile is an effective method for the preparation of these compounds. The reaction was studied using isobutyronitrile and 2-fluoroanisole. The submitters first showed that KHMDS was the superior base for the process when carried out in either THF or toluene (Table I). For example, they found that the preparation of 2-(2-methoxyphenyl)-2-methylpropionitrile could be accomplished h... 

Diphenylthieno[3,4-d][l,3]dioxol-2-one 5,5-dioxide (304) can serve as an activating agent for peptide synthesis (76AG(E)444). The esters (305) are formed readily on admixture of a carboxylic acid with (304) in an aprotic solvent in the presence of pyridine. The activated esters (305) are stable, crystallizable compounds which react with amines readily to furnish the corresponding amides (Scheme 65). Competition experiments reveal that the esters (305) are more effective acyl transfer agents than the p- and o-nitrophenyl esters often used in peptide synthesis. 

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