Acylation Thionyl chloride

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. 

Acyl chlorides are readily available They are prepared from carboxylic acids by reaction with thionyl chloride... 

Thionyl chloride reacts with carboxylic acids to yield acyl chlorides... 

In the piepaiation of ioveisol (12) (41), the key intermediate (23) is prepared from the diacid (20) by the action of thionyl chloride followed by 3-amino-l,2-propanediol. The alcohol groups of (23) are protected as the acetates (25), which is then N-acylated with acetoxyacetyl chloride and deprotected in aqueous methanol with sodium hydroxide to yield (26). N-alkylation of (26) produces ioversol (12). 

Sahcyhc acid can be converted to sahcyloyl chloride [1441 -87-8] hy reaction with thionyl chloride in boiling ben2ene. The formation of acyl haUde may also extend to reaction with the phenoHc hydroxyl. The reaction with phosphoms tri- and pentachlorides is not restricted to the formation of the acid chloride. Further interaction of the phosphoms haUde and the phenoHc hydroxyl results in the formation of the phosphoric or phosphorous esters. 

When pyrazolecarboxylic acids (Section 4.04.2.3.3(iii)) are treated with thionyl chloride instead of the acid chloride, compound (254) is isolated. This corresponds to a double iV-acylation (67HC(22)1). 

Carboxylic Thionyl acid chloride Acyl Sulfur chloride dioxide Hydrogen chloride... 

The Hurd-Mori 1,2,3-thiadiazole synthesis is the reaction of thionyl chloride with the N-acylated or tosylated hydrazone derivatives 1 to provide the 1,2,3-thiadiazole 4 in one simple step. ... 

In general, the reaction can be performed between 0-60°C with the majority of the reactions being run at room temperature. The reactivity of the hydrazones with either the acyl or tosyl leaving group with thionyl chloride depends on the substrate. However, the acylated hydrazones generally provide gaseous by-products where as the tosyl chloride reaction products have to be separated from the reaction mixture. 

A general synthesis of phosphonyl thiadiazoles has been recently disclosed starting from the hydrazone 55. The hydrazones were prepared from acyl phosphonates, which in turn were made from acid chlorides 54. Thus treatment of the hydrazone 55 with thionyl chloride in the presence of DMF and sodium chloride provided the thiadiazoles in... 

In a first step, the carboxylic acid 1 is converted into the corresponding acyl chloride 2 by treatment with thionyl chloride or phosphorous trichloride. The acyl chloride is then treated with diazomethane to give the diazo ketone 3, which is stabilized by resonance, and hydrogen chloride ... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

In the first step, 2-chloro-4-aminobenzoyl chloride hydrochloride is prepared by refluxing a mixture of 25 cc of purified thionyl chloride and 10 g of 2-chloro-4-aminobenzoic acid until all of the solid has gone into solution. To the cooled solution is added 150 cc of dry ethyl ether. A brisk stream of dry hydrogen chloride is passed into the solution until the precipitation of 2-chloro-4-aminobenzoyl chloride hydrochloride is complete. The acyl halide is removed by filtration and dried in a vacuum desiccator. 

Methyl pyrazine-2-carboxylic acid is refluxed with thionyl chloride in anhydrous benzene for approximately 12 hours. Benzene and thionyl chloride excess is removed by distillation. Then some anhydrous dioxane is added and this acid chloride solution is allowed to drop into p-(/3-aminoethyl)-benzenesulfonamide suspension in dioxane and anhydrous pyridine. The resulting mixture is then refluxed for 3 hours. Dioxane is removed by distillation and then the residue is washed with water and acetic acid. The raw acylated sulfonamide is then filtered and crystallized from 95% ethanol, thus obtaining a product of MP 200 to 203 C. 

Hydrazine 835 underwent ring closure with one carbon cyclizing reagents to afford 837 and/or /V-acyl derivatives 836. The N-acyl derivatives underwent cyclization on treatment with phosphorus oxychloride. They were also prepared by the reaction of hydrazones 838 with thionyl chloride (84JHC1565). Compound 835 underwent ring closure with carbon disulfide and ethyl chloroformate to give 839 (Scheme 169). 

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 acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl 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 acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

Acyl halides, or Non-metal halides MRH Thionyl chloride 1.63/60... 

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. 

Lan el al. [52] have reported an approach for vertically aligning multi-wall carbon nanotubes on diverse substrates treated with polyelectrolyte. The shortened multi-wall carbon nanotubes were first functionalized with acyl chloride in thionyl chloride (SOCl2). 

Amide bond is an effective anchor to connect CNTs to substrate surfaces. Lan et al. [52] covalently assembled shortened multi-walled carbon nanotubes (s-MWNT) on polyelectrolyte films. The shortened MWNT is functionalized with acyl chloride in thionyl chloride (SOCl2) before self-assembling. The FTIR spectrum of self-assem-bled MWNT (SA-MWNT) adsorbed on a CaF2 plate modified with PEI/(PSS/PEI)2 shows two characteristic absorption peaks at 1646cm-1 (amide I bond) and 1524cm-1 (amide II bond) resulting from the amide bond formed between the polyelectrolyte films and s-MWNTs. 

A wide range of A-acylbenzotriazoles 915 have been prepared under mild conditions in reactions of carboxylic acids with thionyl chloride in the presence of fourfold excess of benzotriazole, including R = alkyl, a-haloalkyl, a-alkoxyalkyl, alkenyl, alkinyl, aryl, and heteroaryl <2003S2795, 2004RQM275>. They represent convenient acylating agents for variety of nucleophiles. Synthetic applications of such compounds have been reviewed <2005SL1656>. 

The most common, convenient, and versatile synthesis of 1,2,3-thiadiazoles is the one discovered by Hurd and Mori in 1955 <1955JA5359>. This involves the reaction of thionyl chloride with acyl- or phenylsulfonylhydrazones or semicarbazones 54 that contain an a-methylene group this reaction affords a wide range of 1,2,3-thiadiazoles 55 (Equation 15). 

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. 

Acyl chlorides of the stronger acidic groups are formed by the reaction with thionyl chloride 35, 45). The amount of easily hydrolyzed chloride was equivalent to the NaHCOj neutralization or to the difference between NajCOj and NaHCOa neutralization. Both values were equal in most examples. About twice this amount of chlorine was bound at the same time in a form that was resistant to hydrolysis. The nature of the chlorine bonding is not yet known there was no sulfur in the samples. 

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. 

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