Ethoxalyl chloride

Isopropylamino-3-methylaniline (275) and ethoxalyl chloride gave l-isopropyl-8-methyl-2,3(l//,47/)-quinoxalinedione (276) (EtPr N, PhMe, —78°C, 1 h then 0°C, 16 h then reflux, 24 h 45%) several analogs were made simUarly. ° ... 

Methyl-2-phenylindolizine reacts with ethoxalyl chloride to give the 1,3-diethoxalyl derivative (17). Heating in ethanolic sodium ethoxide converts 17 partly into cycl[3,2,2]azine (lu) and partly into the salt of a hydroxycycl[3,3,2]azinone (45a) (Section IV).16... 

An electrophilic substitution at the pyrroloid five-membered ring of 5-methyl-2-phenyI-indolizine with ethoxalyl chloride gave a 1,3-disubstituted derivative (2). This was converted into a mixture of the [2.2.3] cyclazine (3) and the [2.3.3]cyclazine (4) by an intramolecular condensation occurring at the activated 5-methvl group of the pyridinoid six-membered ring (see Sections 3.08.2.5 and 3.08.4 for other examples.)... 

The same one-carbon unit has been employed in a convenient isoflavone synthesis from deoxybenzoins (76S326). Other methods of ring closure of phenyl benzyl ketones to this heterocycle have been reviewed (B-62MI22400) and include triethyl orthoformate (56PIA(A)(44)36), zinc cyanide (58CB2858), ethyl formate (80BCJ831) and ethoxalyl chloride (70JCS(C)1219). 

Methyl-1,2-dihydroisoquinoline has been reacted8,66 with a variety of acid chlorides (Table III) the expected vinylogous amides (64) were isolated in most cases. 2-Benzyl-l,2-dihydroisoquinoline behaves similarly. The acylation reaction fails with simple aliphatic acid chlorides. Sometimes, the reaction of the enamine with the acid in the presence of dicyclohexylcarbodimide succeeds. The 1,2-dihydro-isoquinoline (65) also reacts with ethoxalyl chloride to yield 66.86... 

Ethoxalyl chloride, CjHjOjCCOCl, Is made either by the action of phosphorus pentachloride on ethyl oxalate or from thionyl chloride and potassium ethyl oxalate. The former procedure gives almost quantitative yields, but the latter gives a better product. ... 

Ester chlorides of dicarboxylic acids, e.g., ethoxalyl chloride afford aryl-glyoxalic esters 550,551... 

Ethoxalyl chloride (Et02C—COC1) in pyridine converted 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide to the 2-ethoxalylamino analog, which was heated at 260°C to give ethyl 5,6,7,8-tetrahydro-4-oxobenzo-thieno[2,3-d]pyrimidine-2-carboxylate (142) (moderate yield).215... 

The perchloric acid catalyzed acylation of selenophene with acetic anhydride is claimed to give solely 2-acetylselenophene <81MI 2l3-0l>. Ethoxalyl chloride reacts at the same position <83BEP896054>. Reaction with trifiuoromethylsulfenyl chloride and stannic chloride gives 2-trifluoromethylthioselenophene, and addition of trifluoromethanesulfonic acid promotes formation of the 2,5-bis(trifluoromethylthio) derivative <83JFC(23)525>. 

Ethoxalyl chloride added all at once to a stirred refluxing mixture of 1-phenyl-2-p-nitrophenylindolizine and benzene, refluxed 1.5 hrs., allowed to cool and stand overnight ethyl l-phenyl-2-p-nitrophenyl-3-indolizylglyoxylate. Y 95%. F.e. s. V. S. Venturella, J. Pharm. Sci. 53, 1166 (1964). 

A soln. of ethoxalyl chloride in chloroform added dropwise with vigorous stirring to a soln. of benzamidoxime and anhydrous pyridine in the same solvent, allowed to stand 1 hr. at room temp., then heated 1.5 hrs. at 80 with azeotropic distillation of the water formed 3-phenyl-5-carbethoxy-l,2,4-oxadiazole. Y 75%. 

The condensation product (see Volume VII, p. 316) of ethoxalyl chloride and 3,4-dimethoxyphenethylamine was cyclized with phosphoric oxide to l-carbethoxy-3,4-dihydro-6,7-dimethoxyisoquinoline which in turn was reduced with lithium aluminum hydride to dl-calycotomine (mp 134°) (20). The synthesis of calycotomine, under conditions which might prevail in the plant, from 3,4-dimethoxyphenethylamine and glycolic aldehyde, failed (21). However, if the position of ring closure is activated by a free hydroxyl this condensation readily takes place. 3-Hydroxy-4-methoxyphenethylamine hydrochloride readily condensed at pH 4.5 to 5.0 with glycolic aldehyde to give VIII (mp 200°) in 65% yield. This was methylated with diazomethane to calycotomine (22). 

Bouveault found that ethoxalyl chloride condenses with benzene and alkylbenzenes in the presence of anhydrous aluminum chloride to give esters of phenylglyoxalic acids in yields generally in excess of 70%. These could be hydrolyzed and de-carboxylated to the corresponding aldehydes (Eq 1.24). 

A soln. of isobutene and ethoxalyl chloride in cold methylene chloride added at -10° during 0.5 hr. with vigorous stirring to a soln. of SnGl4 in the same solvent, and the product isolated after 2 hrs. ethyl 4-methyl-2-oxopent-3-enoate. Y 55%. F. e. s. J. Lubochinsky and P. Maitte, G. r. 263 (G), 732 (1966). 

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