Acylated alcohols

Although the previous two sections of this chapter emphasized hydrolytic processes, two mechanisms that led to O- or N-acylation were considered. In the discussion of acid-catalyzed ester hydrolysis, it was pointed out that this reaction is reversible (p. 475). Thus, it is possible to acylate alcohols by reaction with a carboxyhc acid. To drive the reaction forward, the alcohol is usually used in large excess, and it may also be necessary to remove water as it is formed. This can be done by azeotropic distillation in some cases. 

The activated carbonyl of anhydrides can acylate alcohols or amines at the temperatures necessary for polymer processing. These reactions have been verified by HPLC using the polymer system described in Table 2. An examination of the HPLC chromatograms in Fig. 25 indicates that the phthalic anhydride peak (3.2 min) diminishes with increasing injection-molding temperatures and that two new peaks (4.6 and 6.9 min) increase in intensity. These new peaks corresponded to the half phthalate esters of 1,6-hexanediol and trans-... 

Regioselective acylation of diols.1 3-Acyl-2-oxazolones2 are useful for acylation of amines and thiols to give peptides and thioesters. They also acylate alcohols in high yield in the presence of this catalyst. With this catalyst, the reactivity for acylation of hydroxyl groups in primary >> phenolic > secondary. However, for selective acylation of primary hydroxyl groups of 1,2-diols, the Cp2ZrHCl-Mg couple is superior to Zr(acac)4. 

Ketenes in general are useful reagents for acylating alcohols, ROH, and amines, RNH2, because the reactions involve additions there are no by-products to be separated ... 

Anhydrides and esters are routinely used as acylating agents. Anhydrides, however, are the reagents of choice for acylating alcohols. For example, acetylation of cholesterol is carried out using acetic anhydride (Z = 0C(=0)CH3), and not ethyl acetate (Z = OCH2CH3). 

The dimerization of ketene leads to the formation of a lactone ( diketene ), the dimerization of dimethylketene furnishes a cyclobutanedione. In Figure 6.25, diketenes were introduced as reagents acylating alcohols to acetylacetates. 

Thus far the reaction is a normal aldol reaction, but now something quite different happens. Six atoms along the molecule from the alkoxide ion is the carbonyl group of an anhydride. An intramolecular acylation is inevitable, given that anhydrides acylate alcohols even if the two groups are in different molecules,... 

A method to synthesize substituted imidazoles starts from 1,2-aminoalcohols 1081 via a four-step procedure, as demonstrated in Scheme 263. Oxidation of acylated alcohol 1082 leads to a ketone 1083, which is transformed into imine 1084. Activation of the amide bond with dehydrating agent PCls leads to intramolecular cyclization, providing... 

Enantiopure 1,4-disubstituted 2-imidazolines 1179 can be prepared from chiral P-amino alcohols 1175. The acylated alcohols, iV-hydroxyethylamides 1176, are reacted with excess thionyl chloride (or with thionyl chloride followed by phosphorus pentachloride) to yield A -chloroethylimidoyl chlorides 1177. Treatment of 1177 with amines or anilines produces iV-chloroamidines 1178, which were converted into imidazolines 1179 upon work-up with aqueous hydroxide (Scheme 287) <2002JOC3919>. 

In general, thiocarbonyl halides (59) function as thioacylation reagents with a variety of nucleophiles to yield the appropriate thio derivatives (60) (Scheme 31). For example, (59) on condensation with thiols, amines, potassium cyanide or potassium thiocyanide yields the corresponding thio compounds (60). Thiolocarboxylic acids (50) characteristically acylate alcohols and amines with desulfuration (Scheme 32). Dithiocarboxylic acid esters (54b) react with organolithium or Grignard reagents to give the dithioketals (61) after treatment with an alkyl halide (Scheme 33). 

Acylated alcohols and alcohols of Table 11.1-6, which can be obtained with other hydrolases as such or of opposite configuration, are contained in Tables 11.1-15, 11.1-16,11.1-20 and 11.1-21. 

A broad structural range of racemic secondary mono-, bi- and tricyclic acylated alcohols are substrates in lipase-catalyzed enantiomer-differentiating hydrolysis as the examples 1-90 of Table 11.1-16 reveal. A large number of cis- and trans-cycloalkanols bearing a functional group in 2-position (1-20, 25, 26, 58-62) is thereby available in enantiomerically pure form. Enantiomer selectivity in the case of cyclic allylic alcohols where the double bond bears no other substituent in the exposition is frequently low. Through a temporary substrate modification such as mono- or dibromination, enantiomerically pure cyclic allylic alcohols may also be obtained in these cases (51, 52). 

Acylated alcohols and alcohols of Table 11.1-16 which can be obtained with other... 

Lipase-catalyzed enantiomer-differentiating inter- and intramolecular alcoholysis of acylated alcohols and lactones in organic solvents may most advantageously be used instead of hydrolysis in aqueous solution in those cases where insufficient stability, high solubility or low functional group selectivity is observed or may be anticipated in the latter case (1-16) (TSble 11.1-22). 

O-Acylation. Alcohols, including tertiary alcohols, are acylated readily with Sc(OTf)3 as a catalyst. The catalyst is superior to DMAP and Bu P. 

Acylation. Alcohols undergo acylation with either anhydrides or free carboxylic acids in the presence of ScCNTfjlj, which is prepared from Sc(OAc)j and Tf NH. 

High-yield aq lations of hindered alcohols are of considerable current interest [ 142 ]. Older methods for such reactions involve acetic anhydride, acetyl chloride, and the use of -butyUithium in the presence of an acid chloride. More contemporary approaches include catalysts such as DMAP [143], BujP [144], and 4-pyrrohdinopyridine (PPY),with DMAP being the most popular. Although both BujP and DMAP provide good yields of acylated alcohols, these catalysts have disadvantages. For example, BU3P has a low flash point and DMAP is fairly toxic. 

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