Acyl chlorides using thionyl chloride

Synthesis of Acyl Chlorides Using Thionyl Chloride... 

A MECHANISM FOR THE REACTION ] Synthesis of Acyl Chlorides Using Thionyl Chloride 787... 

Carboxylic acids (RCO2H) can be converted into acid chlorides (acyl chlorides) using thionyl chloride (SOCI2) or phosphorus trichloride (PCI3). 

Any carboxylic acid derivative can be converted to any other using one or more of the reactions discussed in the previous sections. If the conversion requires going from a less reactive derivative to a more reactive one, then an indirect route may be necessary. Remember that any derivative can be hydrolyzed to a carboxylic acid using water and acid or base. Also remember that the carboxylic acid can be converted to the acyl chloride with thionyl chloride, providing access to the other derivatives. 

The liquid phosphorus oxychloride, b.p. 107°, is a by-product and is removed by fractional distillation under normal pressure. Unless the b.p. of the acid chloride differs very considerably (say, <] 100°) from that of the phosphorus oxychloride, the acyl halide is liable to contain traces of the latter. In such circumstances it is preferable to use thionyl chloride for the preparation of the acid chloride. 

Difficult N-acylations, such as those of A-alkylanilines or a-alkylamino acid derivatives, are most conveniently performed with acyl halides in non-nucleophilic solvents (e.g. DCM, DCP) in the presence of pyridine or DIPEA [13]. Acyl halides can be prepared on insoluble supports under conditions similar to those used in solution. Typical reagents for the preparation of acyl chlorides include oxalyl chloride [19-21], thionyl chloride [22,23], and triphosgene [13]. Anhydrous solvents must be used for all wash-... 

Pentafluorophenyl 61 and 4-oxo-3,4-dihydrobenzotriazin-3-yl 65 esters (see Table 16) can be obtained from acid 59 and hydroxy compounds using thionyl chloride the intermediate is the Fmoc amino acid chloride 64 (Scheme 17). In the case of the pentafluorophenyl esters 61, the acid chloride 64 is generated in the absence of the nucleophile and acylation is promoted in the presence of pyridine. While in the case of the 4-oxo-3,4-dihydrobenzotriazin-3-yl esters 65, condensation is achieved by heating the reactants in refluxing dichloromethane. The method is not applicable to derivatives with acid-sensitive side-chain protectors. 

The thiazetine (49) is in thermal equilibrium with the ring-opened heterodiene (50), and on exposure to Sb2Te3 at elevated temperature gives the novel A -l,2,4-thiatellurazoline system (51). A number of 1,2-thiazetine 5-oxides (52) have been prepared by thermolysis of diazo-ketones in the presence of A-suIphinyl-amines and from the reaction of 2-acyl-acetamides and thionyl chloride in the presence of base/ l,2-Thiazet-2-yls (53), a new class of stable radicals, are obtained by photolysis and thermolysis of (54) and sulphur amides, for example (55). They are useful as catalysts, regulators, or inhibitors in radical-initiated reactions. ... 

The hydroxyl group on carboxylic acids may be replaced with a chlorine atom using thionyl chloride to give acyl chlorides. In nature, carboxylic acids are converted to thioesters. 

The HCl salt of A-butyl-iV-(cyclohexylethyl)amine (2 HC1) was synfiiesized firom commercially available cyclohexylacetic acid (11). Acid chloride formation using thionyl chloride in toluene with catalytic DMF was followed by amine acylation under Schotten-Baumann conditions to give the amide (8). After workup, the resulting toluene solution was azeotropically dried and the amide was reduced with BH3 SMe2. The crude reaction mixture was quenched with HCl in MeOH and the resulting salt was crystallized from toluene/MTBE. The salt was isolated in 80% yield for the 3 steps. 

The traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acid chloride. Molecules devoid of acid-sensitive functional groups can be converted to acid chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acid chloride. When a salt is used, the reaction solution remains essentially neutral. 

We recall that the best way to replace hydroxyl group of an alcohol with chlorine is to convert the hydroxyl group into a better leaving group. Similarly, we can use thionyl chloride to convert a carboxylic acid to an acyl halide. It reacts with an alcohol to give a chlorosulfite ester (Section 15.3). 

Explain why acyl halides of hydroxy acids cannot be prepared using thionyl chloride. 

Another example has been provided by Ito et al., who described the use of methanofullerene derivatives as powerful and stable precursors for glycofullerenes.217 Their study was based on the use of [60]fullerenoacetyl chloride (227), obtained from the ferf-butyl [60]fullerenoacetate derivative 226, which had been prepared in 56% yield by treatment of corresponding stabilized sulfonium ylides 225 with C6o-218 Subsequent transformation with p-TsOH in toluene gave [60]full-erenoacetic acid, which was directly converted into the corresponding acyl chloride 227 by using thionyl chloride. Standard ester formation with methyl 2,3,4-tetra-O-benzyI -/<-d-gl ucopyranoside (228) and 4-(dimethylamino)pyridine (DMAP) afforded the desired hybrid derivative 229 in 66% yield. 

The carboxylic functionalities inserted onto the tubes can be used as platforms to obtain further transformations (Fig. 3.5). A commonly utilized route is the reaction of carboxylic groups with thionyl chloride or oxalyl chloride to prepare the corresponding acyl chlorides, which are useful intermediates for amidation or esterification reactions. Amides can also be prepared directly from the acids by means of standard solution chemistry conditions, using carbodiimide derivatives in the presence of the selected amine. 

There are several chemical reactions that can be used as an alternative to achieve covalent functionalization of CNTs. Two of them are amidation and/or esterification reactions. Both reactions take advantage of the carboxylic groups sitting on the side-walls and tips of CNTs. In particular, they are converted to acyl chloride groups (-C0-C1) via a reaction with thionyl (SO) or oxalyl chloride before adding an alcohol or an amine. This procedure is very versatile and allows the functionalization of CNTs with different entities such as biomolecules [154-156], polymers [157], and organic compounds [158,159] among others. 

The formation of an acyl halide involves the reaction of a carboxylic acid with a halogen source. The common halogen sources tire compounds like PX3, PXj, ClOCCOCl (oxalyl chloride), or SO.V2> where. Y is a halogen. The most commonly used acyl halides are the chlorides, and the simplistic reaction is RCOOH —> RCOCl. Figure 12-15 illustrates the mechanism using thionyl... 

Although introduced over 40 years ago, Hurd and Mori s synthesis of 1,2,3-thiadiazoles remains the most widely used for the synthesis of 1,2,3-thiadiazoles. The simplicity of the method has contributed to its popularity. A variety of ketones and aldehydes have been converted into their corresponding hydrazones (tosyl and acyl), and thioamides have been converted into thio-carbazonate esters. The carbonyl derivatives are then treated with thionyl chloride to yield 1,2,3-thiadiazoles in high yields. When one is faced with the task of synthesizing new 1,2,3-thiadiazoles, Hurd and Mori s method should always receive attention. 

Various 2,5-disubstituted furans 1 have been converted into 5-acyl-3-substituted isothiazoles 2 by treatment with ethyl carbamate, thionyl chloride and pyridine. The reactive species produced by this combination of reagents may be the highly reactive thiazyl chloride, NSCl, or a related species such as its trimer (NSCPa. This mixture of reagents was reported to be much more convenient to use than (NSC1)3 and in many cases produced higher yields of isothiazole <99S757>. 

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