Friedel Crafts with oxalyl chloride

The isomeric benzo[l,2-A4,3- ]dithiophene-4,5-quinone is prepared in reasonable yields by a one-step Friedel-Crafts reaction of 3,3 -bithienyl with oxalyl chloride in refluxing 1,2-dichloroethane over 7-10 days (Equation 85) <2001JA11899>. 

Some acyl halides are reactive enough to effect Friedel-Crafts acylation on the neutral heterocycles without a catalyst. For pyrrole such reactions are known, for example, with trifluoroacetyl chloride and trichloroacetyl chloride. Indole reacts smoothly in cold ether with oxalyl chloride and on heating with acetic anhydride. Some examples of these types of acylation are collected in Table 10. 

Yuan XH, Chen M, Dai QX et al (2009) Friedel-Crafts acylation of euithracene with oxalyl chloride catalyzed by ionic liquid of [BMIMja/AlClj. Chem Eng J 146 266-269... 

Friedel-Crafts acylation. A synthesis of chilenine is completed by a two-fold Friedel-Crafts acylation of an A-(arylethyl)amide with oxalyl chloride. ... 

Hydroxynaphthoquinones. Under Friedel-Crafts reaction conditions aroy-lacetic esters react with oxalyl chloride to give the quinone skeleton. The ester group is removable through saponification. 

Mild Lewis acids can also be used to effect Friedel-Crafts cyclization, which is particularly important with synthetic targets bearing other functional groups. An example is the cyclization of 205 (after initial conversion to the acid chloride with oxalyl chloride) to give a 94% yield of 206 in the Rapoport and co-workers... 

The formation of aromatic a-diketo compounds through either inter- [939] or intramolecular [940, 941] Friedel-Crafts reaction with oxalyl chloride is limited to just a few examples. 

Intermolecular Friedel-Crafts acylation of various substituted alkyl alkoxyben-zenes 1257 with oxalyl chloride using 1,2-dichloroethane [942] or carbon disulfide [943] as solvent gives rise to benzils 1258. 

Under Friedel-Crafts conditions (AICI3, CS2), oxalyl chloride reacts with aromatic hydrocarbons to give carbonyl chlorides, which are hydrolyzed by water to give carboxylic acids. The AICI3-mediated chlorocarbonylation of arenes with oxalyl chloride has been used in the preparation of symmetrical and unsymmetrical diaryl ketones [946] (see also Section 4.3.6). 

Alternatively, isatins 1784 can be synthesized from secondary aromatic amines with oxalyl chloride followed by a Friedel-Crafts cyclization [1311]. 

Preparation of Arylcarboxylic Acids and Derivatives. The general Friedel-Crafts acylation principle can be successfully appHed to the preparation of aromatic carboxyUc acids. Carbonyl haUdes (phosgene, carbonyl chloride fluoride, or carbonyl fluoride) [353-50-4] are diacyl haUdes of carbonic acid. Phosgene [75-44-5] or oxalyl chloride [79-37-8] react with aromatic hydrocarbons to give aroyl chlorides that yield acids on hydrolysis (133) ... 

The rather different scheme used to prepare the propionic acid side chain in cicloprofen (52-5) leads to the inclusion of this tricyclic compound in the present chapter, which is intended to deal with monocychc compounds. The synthesis starts with the Friedel-Crafts acylation of the hydrocarbon fluoiene (52-1), with the half-ester of oxalyl chloride to give the a-ketoester (52-2) as the product. The required side chain methyl group is then added by reaction of the product with methylmagnesium bromide this apparently proceeds selectively... 

The most important method for the preparation of aryl ketones is known as Friedel-Crafts acylation. The reaction is of wide scope. Reagents other than acyl halides can be used," including carboxylic acids," anhydrides, and ketenes. Oxalyl chloride has been used to give diaryl 1,2-diketones." Carboxylic esters usually give alkylation as the predominant product (see 11-11)." A-Carbamoyl p-lactams reacted with naphthalene in the presence of trifluoromethanesulfonic acid to give the keto-amide." ... 

Hydroxy-5,6,7-trimethoxyxanthone, which was isolated for the first time from H. ericoides, was successfully synthesized by Gil et aL [59]. The synthesis was performed from the new benzophenone precursor 25 (Fig. 13). Compound 25 was prepared by Friedel-Crafts acylation of 1, 3,4-tetramethoxy-benzene with 2,5-dibenzyloxybenzoic acid and oxalyl chloride. When benzophenone 25 was heated with Me4NOH, 5-benzoyloxy-2-hydroxy-2, 3, 4, 5 -tetramethoxybenzophenone (25) underwent cychzation to 2-benzyloxy-5,6,7-trimethoxyxanthone (26) [60]. Hydrogenolysis of this compound with H2/Pd-C [61] finally afforded 2-hydroxy-5,6,7-trimethoxyxanthone (27) which is identical to natural xanthone [60]. 

Reactions of Benzolb]thiophens. Reaction of (318), prepared from p-thiocresol and oxalyl chloride, gave (319) with chloroacetic acid and sodium hydride. (319) was converted to many other benzolb]-thiophen derivatives, including (320), which was obtained via side-chain bromination and Friedel-Crafts alkylation. Desulphurization of (320) gave (321),223 compounds (322) were obtained from the reaction... 

A related synthesis produces indolones by a different Friedel-Crafts route. The Stolle synthesis reacts with a secondary aryl amine such as diphenylamine with an a-chloro acid chloride or an a-bromo acid bromide to give an a-bromoamide (such as 315) or an a-chloroamide. An early version of the reaction used oxalyl chloride, but a more typical example is the reaction of 2-bromopropanoyl bromide with 314 to give 315. Friedel-Crafts cyclization (with AICI3) led to the indolone 316.1 ... 

The Friedel-Crafts reaction of oxalyl chloride with aromatic compounds offers a useful means of generating aromatic carboxylic acids. The reaction essentially proceeds via a chloroglyoxylate intermediate 1278, which decomposes on heating to give the corresponding acid chloride 1279. The similar preparation of heteroaryl carboxylic acids 1282 from substrates 1281 is also reported. Yields are generally high [958]. 

Also obtained by Friedel-Crafts acylation of phenol with propionyl chloride in the presence of aluminium chloride (37%) [6579] or at 125-130° for 1 h (22%) [6580,6581] according to the method [6582], N,B. This same reaction in carbon disulfide, using propionyl chloride formed in situ by action of oxalyl chloride with sodium propionate (method B), for 1 h at 70°, yield 65% [6671],... 

A final synthetic effort in the yohimbine alkaloid area concerns the studies reported by Loewenthal and his coworkers (Scheme 3.92) (143). The aim was to develop an efficient method to prepare the bicyclic enone 21, which serves as a key intermediate in the Woodward reserpine synthesis strategy (19). The route for preparation of 21 began with Friedel Crafts reaction of 2-methoxynaphthalene (523) with the oxalyl chloride equivalent 524, a process which afforded the acenaphthenoquinone 525. Oxidative-decarboxylation of 525 yielded the naphthalene-carboxylic acid 526 which was transformed by Birch reduction and esterification to the dihydro-derivative 527. Carboxyla-tion then provided geminal diester 528 which was epoxidized. Sequential lactonization and methylation afforded tricyclic lactone 529. Ester cleavage with subsequent decarboxylation gave lactone 530 which was demethylated to provide 531. While no further effort was given to the development of this... 

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