Acyl chlorides, conversion

Figure 13.5. Stractme of mitotane, its acyl chloride conversion product formed by the enzyme cytochrome P450 1 IB (CYPl IB), and the reaction products of the latter with amino groups in proteins or nucleic acids. CYP1 IB occurs in the mitochondria within the adrenal cortex, rendering this tissne (and its derived tissues) selectively susceptible to mitotane.

Conversion of Acyl Chlorides to Other Carboxylic Acid Derivatives... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

Acylation (Section 12 7 and Chapter 20) Reaction in which an acyl group becomes attached to some structural unit in a molecule Examples include the Fnedel-Crafts acylation and the conversion of amines to amides Acyl chloride (Sections 4 1 and 20 1) Compound of the type... 

Conversion of acyl chlorides to lunctlonalized (OH, OCH3, OPh, SCH3) ketones by means ol tns(tnmethylsilyloxy)ethylene 4... 

The most appar ent chemical property of car boxylic acids, then- acidity, has already been examined in earlier sections of this chapter. Three reactions of carboxylic acids—conversion to acyl chlorides, reduction, and esterification—have been encountered in previous chapters and are reviewed in Table 19.5. Acid-catalyzed esterification of carboxylic acids is one of the fundfflnental reactions of organic chemistry, and this portion of the chapter begins with an exanination of the mechanism by which it occurs. Later, in Sections 19.16 and 19.17, two new reactions of carboxylic acids that are of synthetic value will be described. 

Section 19.13 Among the reactions of carboxylic acids, their conversions to acyl chlorides, primary alcohols, and esters were introduced in earlier chapters and were reviewed in Table 19.5. 

FIGURE 20.1 Structure, reactivity, and carbonyl-group stabilization in carboxylic acid derivatives. Acyl chlorides are the most reactive, amides the least reactive. Acyl chlorides have the least stabilized carbonyl group, amides the most. Conversion of one class of compounds to another is feasible only in the direction that leads to a more stabilized carbonyl group that is, from more reactive to less reactive. 

The Rosenmund reduction is usually applied for the conversion of a carboxylic acid into the corresponding aldehyde via the acyl chloride. Alternatively a carboxylic acid may be reduced with lithium aluminum hydride to the alcohol, which in turn may then be oxidized to the aldehyde. Both routes require the preparation of an intermediate product and each route may have its advantages over the other, depending on substrate structure. 

An alternative reported in the same publication involves the in situ conversion of the carboxylic acids to the corresponding acyl chlorides using PS-PPh3 and CCI3CN (THE, 10 °C, 5 min) before treatment with the amidoxime in the presence of DIEA (THE, 150 °C, 15 min). The resin-bound phosphine not interfering with the second step, and THF being the best solvent for both steps, the two-steps sequence could be performed one-pot with yields comparable to those obtained using the HBTU/PS-BEMP combination (Scheme 12). 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

Acyl chlorides containing an a hydrogen are smoothly converted to alkenes, with loss of HCI and CO, on heating with chlorotris(triphenylphosphine)rhodium, with metallic platinum, or with certain other catalysts. The mechanism probably involves conversion of RCH2CH2COCI to RCH2CH2—RhCO(Ph3P)2Cl2 followed by a concerted syn elimination of Rh and H. See also 14-39 and 19-12. 

Chloroacylation of terminal aryl, alkyl or alkenyl alkynes [Le. the addition of RC(=0)-C1 across the CC triple bond] with aromatic acyl chlorides was catalysed by [IrCl(cod)(lPr)] (5 mol%) in good conversions (70-94%) in toluene (90°C, 20 h). Z-addition products were observed only, hitemal alkynes were umeactive. Surprisingly, a phosphine/[lr(p-Cl)(l,5-cod)]2 system under the same conditions provides decarbonylation products (Scheme 2.34) [117]. 

Carboxylic acids can be converted to acyl chlorides and bromides by a combination of triphenylphosphine and a halogen source. Triphenylphosphine and carbon tetrachloride convert acids to the corresponding acyl chloride.100 Similarly, carboxylic acids react with the triphenyl phosphine-bromine adduct to give acyl bromides.101 Triphenviphosphine-iV-hromosuccinimide also generates acyl bromide in situ.102 All these reactions involve acyloxyphosphonium ions and are mechanistically analogous to the alcohol-to-halide conversions that are discussed in Section 3.1.2. 

Conversion of acyl chlorides to aldehydes occurs upon reaction with HOTf and [Cp(CO)3WH] [32]. The reaction of HOTf with benzoyl chloride and [Cp(CO)3WH] led to the isolation of [Cp(CO)3W(PhCHO)]+OTf (Eq. (25)), in which the aldehyde is bound to the metal [32]. The spectroscopic properties and... 

Monoalkylation of a vic-glycol.1 Selective monoalkylation or monoacylation of the vic-glycol group of dimethyl L-tartrate is possible by conversion to the O-stannylene acetal (1) by reaction with dibutyltin oxide. The acetal is converted selectively to a mono derivative (3) by reaction with an alkyl halide or acyl chloride (excess) and CsF (about 2 equiv.). KF or Bu4NF are less effective than CsF. 

The conversion of acyl chlorides, sulphonyl chlorides and phosphoryl chlorides into the corresponding fluorides using potassium fluoride in the presence of a quaternary ammonium salt has been recorded [44-47]. Optimum yields are obtained when the dry potassium fluoride contains ca. 1% water. 

The procedure for synthesizing sulfanilamide (a sulfa drug) is a multistep procedure as illustrated in Figure 13-50. The first step also works if you substitute an acyl chloride for the acid anhydride. The conversion of the amine to an amide converts the strong activator into a medium activator, limiting multiple attacks. The last step converts the amide back into an... 

One of the more difficult partial reductions to accomplish is the conversion of a carboxylic acid derivative to an aldehyde without over-reduction to the alcohol. Aldehydes are inherently more reactive than acids or esters so the challenge is to stop the reduction at the aldehyde stage. Several approaches have been used to achieve this objective. One is to replace some of the hydrogens in a group III hydride with more bulky groups, thus modifying reactivity by steric factors. Lithium tr i - / - b u to x y a I u m i n u m hydride is an example of this approach.42 Sodium tri-t-butoxyaluminum hydride can also be used to reduce acyl chlorides to aldehydes without over-reduction to the alcohol.43 The excellent solubility of sodium bis(2-methoxyethoxy)aluminum hydride makes it a useful reagent for selective... 

A homogeneously catalyzed (49) route for the conversion of acyl chlorides to unsymmetrical ketones catalyzed by [Rh(PPh3)2(CO)Cl] has been modified by using the supported catalyst [(j —PPh RhfPPhsXCOjCl] (91) ... 

Thallium(I) fluoride is, furthermore, used for the conversion of acyl chlorides to acyl fluorides6 and the preparation of a-fluorocarbonyl compounds.7,8... 

However, it is often better to "activate" the carboxylic acid by conversion to an acyl chloride or an anhydride ... 

The successful conversion of polystyrene-bound acyl chlorides into ketones by treatment with organocadmium compounds has also been reported (Entry 4, Table... 

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