Tetrahydrofuran acid chlorides

Contrary to Brown s results, a later paper claims that chloral, esters and acid chlorides are readily reduced by diborane in tetrahydrofuran it is suggested that diborane can complex with tetrahydrofuran before effecting reduction. 

Preparation of 2-Cyclopropylcarbony/amido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropane-carboxylic acid chloride. The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonyl-amido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoal-treating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

Sodium cyanide, Glacial acetic acid, Chlorine gas. Carbon tetrachloride Benzene, Aluminum chloride, 2-Chloroacetyl chloride. Hydrochloric acid. Sodium hydroxide. Methylene chloride. Calcium chloride. Hexanes Methanol, MalononitrUe, o-Chlorobenzaldehyde, Piperdine Tetrahydrofuran, Hydrogen chloride, Chloropicrin, Powdered tin Benzene, Arsenic trichloride. Aluminum chloride. Hexanes Acetone, Sulfuric acid. Chlorine, Calcium chloride Isopropylamine, Glyoxal, Diethyl ether Benzene, Pyridine, Diphenylamine, Arsenic trichloride Tetraethyl lead. Arsenic trichloride... 

The order of reactivities of various functional groups determined under standard conditions (using externally generated diborane, and tetrahydrofuran as solvent) is acid > alkene > ketone > nitrile > epoxide > ester > acid chloride.33 Acids, aldehydes, ketones, epoxides, nitriles, lactones and azo compounds are reduced rapidly, esters more slowly and chloral, acid chlorides and nitro compounds are inert. Double bonds undergo the hydroboration reaction,25 nitriles and azo compounds are reduced to amines, and the remaining groups to alcohols. Ketones can be reduced selectively in the presence of epoxides. Contrary to the order of reactivities given above, it has been claimed that nitriles are reduced more rapidly than ketones.223... 

The treatment of 4-oxo-4Z/-pyrido[ 1,2-a]pyrimidine-3-carboxylic acid 429 with phosphorus pentachloride in dichloromethane at 0°C gave acid chloride 430, which reacted with amine 431 in tetrahydrofuran in the presence of /V-methyl-TV-trimethylsilyl trifluoroacetamide at room temperature overnight to give /-substituted 3-carboxamide 432 (88USP4777252). After catalytic debenzylation, the 3-substituent of 4//-pyrido[l, 2-a]py-rimidin-4-one 433 was involved in different reactions to give antibacterial derivative 434 (see Scheme 25). 

Guanidinocaproic acid p-tosyl salt and thionyl chloride were mixed together to react at the room temperature. An endothermic reaction occurred and the caproic acid gradually dissolved. Then the reaction mixture was left standing for 1 to 2 h and was extracted with ether. The lower oily layer and the ether layer were separated from each other and the lower layer was repeatedly washed with ether. Then the oily substance (caproic acid chloride) was added with benzoic acid ethyl ester in tetrahydrofuran, and the mixture was stirred. After the mixture became a uniform solution, of pyridine were gradually added. An exothermic reaction occurred and an oily substance came to be separated in the lower layer. After the completion of the reaction, the oily substance was washed with water and then recrystallized from hot water once or twice. Thus 4-(6-guanidino-hexanoyloxy)-benzoic acid ethyl ester salt was obtained as white crystals. 

The crude 3-(4-biphenylyl)-2-butenoic acid is dissolved in 200 ml of dry tetrahydrofuran and 4 ml (0.055 mole) of thionyl chloride is added. The solution is refluxed under a nitrogen atmosphere for 3 hours and the solvent and excess thionyl chloride then distilled off. The resulting residue is flash distilled in a microdistillation apparatus at 145-153°C/0.075 mm to yield the 3-(4-biphenylyl)-2-butenoic acid chloride, substantially in trans form. 

RCu/S(CHj)2. Various alkylcoppers are more thermally stable and also more reactive in dimethyl sulfide than in ether or tetrahydrofuran. This solvent can improve yields in conjugate additions and in alkylation of acid chlorides.2... 

Acid chloride (about 4 mg) is added to a solution of the amino acid ester (about 1 mg) dissolved in tetrahydrofuran (0.8 ml) and containing pyridine (0.2 ml). The reaction products are injected directly together with an excess of the reagent 1.5% of SE-30,... 

Assay for enantiomeric purity To a magnetically stirred suspension of diphenylprolinol sulfate (30 mg) in tetrahydrofuran (1 mL) is added 1 M aqueous sodium hydroxide (210 pL). The mixture is stirred for 15 min, then (R)-Mosher acid chloride (20 pL) is added. By TLC (EM Si-60, 8 2 hexane/EtOAc, R diphenylprolinol = 0.05, Rf Mosher amide = 0.4) the reaction is complete in 1 hr. The reaction mixture is diluted into hexane (9 mL). then eluted through a Baker Silica SPE (1 g) column (previously washed with hexane). The column was eluted with additional 9 1 hexane/tetrahydrofuran (5 mL). The combined eluates were than analyzed by capillary GC Column 0.33 mm x 30 m DB-23 (J W Scientific) Oven Temperature 250°C Injector/Detector Temperature 275°C Carrier Gas Helium (21 lbs/in2), ca. 30 1 split Injection 1 pL Detection FID Retention Times (R.R)-Mosher amide 25.9 min (R.S)-Mosher amide 29.6 min. The enantiomeric purity is 99 1. 

Li[(tBuO)3AlH] Tetrahydrofuran -78 acid chloride —> aldehyde... 

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