Similarity acyl chlorides

Alkylation of the ambident anion derived from hydroxythiophenes has been discussed exhaustively <86HC(44/3)l>. In general, soft electrophiles like methyl iodide lead to C-methylation, while the hard electrophile, dimethyl sulfate, gives predominantly the ( -methylated product. Similarly acyl chlorides and acid anhydrides give only the 0-acylated products. In conformity with the above, it has recently been reported that treatment of (243 R = = H) with acetyl chloride and... 

When jS-hydrogens are present in the substrate aldehyde, olefins and H2 are produced, but in substantially smaller quantities than observed with analogous acid chlorides. For example, decarbonylation of heptanal yields 14% hexene, whereas exclusive formation of alkene is observed from similar acyl chlorides. This difference is due to the ease with which hydride transfer (as opposed to chloride transfer) occurs in the respective alkyl intermediates. 

Carboxylic acid anhydrides react similarly to acyl chlorides... 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

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. 

Transformations through 1,2-addition to a formal PN double bond within the delocalized rc-electron system have been reported for the benzo-l,3,2-diazaphospholes 5 which are readily produced by thermally induced depolymerization of tetramers 6 [13] (Scheme 2). The monomers react further with mono- or difunctional acyl chlorides to give 2-chloro-l,3,2-diazaphospholenes with exocyclic amide functionalities at one nitrogen atom [34], Similar reactions of 6 with methyl triflate were found to proceed even at room temperature to give l-methyl-3-alkyl-benzo-l,3,2-diazaphospholenium triflates [35, 36], The reported butyl halide elimination from NHP precursor 13 to generate 1,3,2-diazaphosphole 14 upon heating to 250°C and the subsequent amine addition to furnish 15 (Scheme 5) illustrates another example of the reversibility of addition-elimination reactions [37],... 

Similarly, acylation of the dipeptide 410 with bromoacetyl chloride followed by base-induced cyclization gives the pyrazinylacetate ester 411 <2001BML1251>. Compound 410 is itself cyclized with />-toluenesulfonic acid to give the (iV-alkylated indole) equivalent of 406 <200JME3518>. 

Heterocyclic ring systems are also used to connect two anthraquinone groups. Typical examples include Cl Vat Red 10 (6.106), which is an oxazole derivative obtained from 2-amino-3-hydroxyanthraquinone and the appropriate acyl chloride, the similar thiazole derivative Cl Vat Blue 31 (6.107) and the oxadiazole derivative Cl Vat Blue 64 (6.108). 

Methods for the A-acylation of similar heterocycles, such as simple thiazolidinethiones, have been reported since 1977, namely acyl chlorides in miscellaneous conditions,586 or carboxylic acids under DCC-activation.60,61 However the easiest and most effective method involves acyl chlorides or carboxylic anhydrides in the presence of an amine.47 Applying that procedure on carbohydrate scaffolds Rollin and co-workers62 reported the synthesis of diverse /V-acylated OZTs. The reactions were performed with good yields and the /V-selective acylation was ascertained by NMR— namely the thiocarbonyl 13C chemical shift (Scheme 41). Thanks to the dual nature of the carbanion drifting in the reaction,596 60 no competitive formation of the thioester, as mentioned by Plusquellec el al. in the case of benzothiazole, was observed. 

A similar reaction was also observed with acyl chlorides, which afforded polysub-stituted furans 79 [39]. An intramolecular version of this reaction behaved similarly to afford anellated furan products 81. 

Acyl chlorides are converted in good yield into symmetrical carboxylic acid anhydrides upon treatment with dilute aqueous sodium hydroxide at -I0°C in the presence of a tetra- -butylammonium salt [76, 77]. Yields are considerably lower when Aliquat is used. In a similar manner, chloroformates and ethyl oxalyl chloride are converted into carbonic hemi-ester anhydrides. 

Bis-acyl sulphides are obtained in only low yield by the standard reaction of sodium sulphide with an acyl chloride, but the addition of Adogen results in their viable synthesis with yields >70%. Examples using quaternary phosphonium salts provide the optimum yields (> 90%) [63]. Similarly, thiophenols have been benzoylated using benzoyl chloride under basic conditions in the presence of ammonium salts [12]. 

Acyl chlorides themselves may be synthesized by a similar type of reaction, in which we invoke nucleophilic attack of an acid onto thionyl chloride as shown. As we shall see later (see Section 7.13.1), the S=0 group behaves as an electrophile in the same way as a C=0 group. 

After removal of the carboxylic acid portion of the original amide, a new amide linkage is generated, e.g. by reaction with a suitable acyl chloride. One of the first commercial semi-synthetic penicillins, methicillin, was produced as shown. Other agents, e.g. ampicillin, may be produced by similar means, though sensitive functional groups in the new side-chain will need suitable protection. 

Procedures for synthesis of ketones based on coupling of organostannanes with acyl chlorides have also been developed.152 153 The catalytic cycle is similar to that involved in the coupling with alkyl or aryl halides. The scope of compounds to which the procedure can be applied is wide and includes successful results with tetra-n-buty lstannanc. This example implies that the reductive elimination step in the mechanism can compete successfully with -elimination. 

Reaction with acetyl chloride yields diacetyl peroxide. Similar diacyl peroxides are formed from other acyl chlorides ... 

Under high dilution conditions (81JCR(S)314) bis-acyl chlorides react with diols to generate the corresponding tetralactones (41) (77TL2573). This procedure has most commonly been applied to the synthesis of crown ethers with subunits (79CRV37). Lactams have been prepared similarly from suitable diamines (76TL2603). 

These reactions are most important for the preparation of acyl fluorides.1061 Acyl chlorides and anhydrides can be converted to acyl fluorides by treatment with polyhydrogen fluoride-pyridine solution996 or with liquid HF at -10°C.1062 Formyl fluoride, which is a stable compound, was prepared by the latter procedure from the mixed anhydride of formic and acetic acids.1063 Acyl fluorides can also be obtained by reaction of acyl chlorides with KF in acetic acid1064 or with diethylaminosulfur trifluoride (DAST).1065 Carboxylic esters and anhydrides can be converted to acyl halides other than fluorides by the inorganic acid halides mentioned in 074, as well as with Ph3PX2 (X = Cl or Br), 066 but this is seldom done. Halide exchange can be carried out in a similar manner. When halide exchange is done, it is always acyl bromides and iodides that are made from chlorides, since chlorides are by far the most readily available.1067... 

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