Furoyl chloride

Furoyl chloride is the most important derivative of fiiroic acid. From a synthetic viewpoint, it is one of the most useful derivatives of furfural, because of its stability and multiplicity of reactions. In organic chemistry, furoyl chloride is used primarily for the introduction of the furoyl group into alcohols and phenols. 

Furoyl chloride is made by reacting fiiroic acid with thionyl chloride in anhydrous 

After the addition of the thionyl chloride, the reaction mixture is refluxed for an additional 12 hours before pump 10 passes it through a filter 11 into an atmospheric distillation column 12 energized by a steam coil. In this column, the benzene solvent and the excess thionyl chloride are boiled off, liquefied in condenser 13, and collected in tank 14. 

The remaining furoyl chloride (b.p. 173 °C) is transferred into a vacuum distillation column 15 energized by a steam coil, where the furoyl chloride is obtained as the head fraction liquefied in condenser 16. The vacuum pump 17 maintains this system at a pressure of 7 mm Hg., A part of the condensate is used as reflux, while the product is collected in tank 18. The yield of furoyl chloride is in excess of 89 percent, the losses being a small fore-run collected in tank 19, a small after-run collected in tank 20, and a small quantity of a carbonaceous residue. 

The mixture of benzene and thionyl chloride in tank 14 is separated in a distillation column 21 heated by a steam coil. The sump fraction is benzene which is recycled back into tank 5 by means of pump 22. The head fraction of column 22 is thionyl chloride. It is liquefied in condenser 23 cooled by a chiller 24. A part of the condensate is used as reflux while the remainder is fed back into tank 6 by means of pump 25. 

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Preparation of 2[4-l2-Furoyll-PiperazinylI -4-Amino-6,7-Dimethoxyquinazoline To 0,10 mol 2-(1-piperazinyl)4-amino-6,7-dimethoxyquina2oline in 300 ml methanol is added with vigorous stirring, 0.10 mol 2-furoyl chloride. After addition is complete, the mixture is stirred for 3 hours at room temperature. The solids are filtered to give the desired product, MP 27B° to 2B0°C. 

Electrolysis of 2-furoyl chloride at mercury affords mainly l,2-di(2-furyl)ethene-l,2-diol di(2-furoate) however, an interesting pair of minor products are l,2-di(2-furyl)-2-hydroxy-3-cyanopropanone and 3-(2-furyl)acryloni-trile, in which a fragment of the solvent (acetonitrile) is incorporated [78]. When 2,4,6-trimethylbenzoyl chloride is reduced at carbon or mercury cathodes in acetonitrile, the major products are 2,4,6-trimethylbenzaldehyde and 3-(2,4,6-trimethylphenyl)acrylonitrile,... 

Quinfamide (19) is one of a relatively small family of antiamoebic compounds containing a dichloroacetamide function. The synthesis begins by amidation of 6-hydroxytetrahydroquino line with dichloroacetyl chloride to give 18. The sequence i completed by acylation with 2-furoyl chloride to give quinf amide (19). ... 

Alteration of the structural pattern produces a pair of adrenergic a-blocking agents which serve as anti hypertensives. These structures are reminiscent of prazocin. Reaction of piperazine with 2-furoyl chloride followed by catalytic reduction of the furan ring leads to synthon 69. This, when heated... 

Diloxanide Diloxanide, 2,2-dichloro-iV-(4-furoyloxyphenyl)-Af-methylacetamide (37.2.4), is made by acylating 2,2-dichloro-iV-(4-hydroxyphenyl)-iV-methylacetamide (37.2.3) with -2-furoyl chloride. The 2,2-dichloro-iV-(4-hydroxyphenyl)-iV-methylacetiamide (37.2.3) is made by iV-acylating 4-hydroxy-Af-methylaniline with either dichloroacetyl chloride, or by an extremely original method of using chloral cyanohydrin [41 3]. 

Prepare under argon a solution of 8 g of 4-dimethylaminopyridine in 250 ml of dry methylene chloride. Cool on an ice bath and add to the stirred solution 6.0 ml of 2-furoyl chloride. Remove from the ice bath, allow the temperature to rise to room temperature and then add 11.5 g of the 21-chloro-9p,lip-epoxy-17a-hydroxy-16a-methyl-l,4-pregnadiene-3,20-dione. After 24 hours add 500 ml of ethyl acetate saturated with water. Filter off the precipitate and then evaporate off the solvent to give the crude 21-chloro-9p,lip-epoxy-17a-hydroxy-16a-methyl-l,4-pregnadiene-3,20-dione 17-(2 -furoate). 

The present invention (Patent U.S. 6,177,560) refers to a new process for the preparation of mometasone furoate carried out by esterifiication of the 17 hydroxy group of mometasone without prior protection of the 11 hydroxy group. Mometasone (30 g) was suspended in methylene chloride (300 ml) and the resulting suspension was cooled to 0-5°C. At this temperature triethylamine (57 ml) was added. 2-Furoyl chloride (24 ml) was then added slowly. The mixture was then stirred at 8-12°C until the level of mometasone present was lower than 0.2% by HPLC. The reaction solution was then cooled to between -5-5°C and water (120 ml) was added with stirring. After stirring for 1 hour at 10-15°C the mixture was cooled to between 0-5°C and concentrated hydrochloric acid was added to adjust the pH of the aqueous layer between 1 and 2. 

The relatively low electron density at carbon, coupled with the possibility of protonation at nitrogen, makes electrophilic substitution at carbon difficult. A further problem is acid-catalyzed ring cleavage, particularly with alkyloxadiazoles. No examples of nitration or sulfonation of the oxadiazole ring have been reported and attempted brominations were unsuccessful. A low yield of 2-(2-furoyl)-5-phenyl-l,3,4-oxadiazole is obtained when 2-phenyl-l,3,4-oxadiazole is treated with 2-furoyl chloride in the presence of triethylamine (77LA159). 

A. Furan-2-ylcarbamic acid tert-butyl ester. In a 250-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar are placed 10 g (0.07 mol) of 2-furoyl chloride (Note 1), 80 mL of tert-butyl alcohol (Note 2), and 5.1 g (0.08 mol) of sodium azide (Note 3). After the flask is stirred at 25°C for 20 hr under an argon atmosphere, it is placed behind a protective shield (Note 4) and the solution is heated at reflux for 15 hr under a constant flow of argon. The solvent is removed with a rotary evaporator at aspirator vacuum to provide a white solid that is purified by flash silica gel chromatography (10% ethyl acetate/hexane) to give 10.8 g (81%) of furan-2-ylcarbamic acid tert-butyl ester as a white solid mp 98-99°C (Note 5). 

Furoyl chloride (8) 2-Furancarbonyl chloride (9) (527-69-5) tert-Butyl alcohol (8) 2-Propanol, 2-methyl- (9) (75-65-0)... 

Asymmetric acylcyanation of quinolines (Reissert-type reaction) with 2-furoyl chloride and TMSCN is successfully performed by using the chiral catalyst 168 (Scheme 10.243) [658]. In this reaction the sterically more demanding complex 168b exceeds 168a in enantioselectivity. 

Alkenylsilane acylation has been employed for the synthesis of two furano monoterpenes, dehydroel-sholzione (1) and isoegomaketone (2 Scheme 5). Acylation of isobutene with 3-methyl-2-furoyl chloride gave dehydroelsholzione in poor yield with a variety of Lewis acid catalysts (SnCU, AlCb, TiCU), but using the equivalent silane substrate, the ketone was obtained in 55% overall yield. Probably as a result of work-up conditions, the initial reaction gave a mixture of three products, the conjugated and deconjugated ketones, together with the chloro ketone addition product. Isomerization and dehydrochlorination were effected with a tertiary amine base to maximize the yield of the desired product. 

Coupling reactions of organomanganese reagents with 2- and 3- furoyl chloride in the presence of copper or iron catalysts have been used to prepare a number of naturally occurring ketones in high yields <92TL5245> and aryltrialkylstannanes have been shown to arylate 2-furoyl chloride in the presence of a palladium catalyst <92CC1440>. 

One routine method for the functionalization of quinolines is the addition of substituents to the 2-position. Further advances in the catalytic, enantioselcctive Reissert-type reaction were reported. Quinoline 63 was treated with 2-furoyl chloride and TMSCN in the presence of Lewis acid-Lewis base bifunctional catalyst 64 followed by reduction of the corresponding enamine to afford quinoline 65 in 93% ee. Quinoline 65 was subsequently converted to (-)-L-689,560, a potent NMDA receptor antagonist <01JA6801>. Additions of ally.silanes to quinolines acylated with chloroformate esters and catalyzed by various triflate salts were reported <01T109>. 

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