Chloro ethyl acetate

Synonyms AI3-01455 BCEXM Bis(2-chloroethyl)formal Bis(P-chloroethyl)formal BRN 1698909 Dichlorodiethyl formal Dichlorodiethyl methylal Dichloroethyl formal Di-2-chloro-ethyl acetal Di-2-chloroethyl formal 2,2-Dichloroethyl formal EINECS 203-920-2 l,l -[Meth-ylenebis(oxy)]bis(2-chloroethane) l,l -[Methylenebis(oxy)]bis(2-chloroformaldehyde) Bis(p-chloroethyl)acetal ethane Formaldehyde bis(p-chloroethylacetal) NSC 5212 RCRA waste number U024 UN 1916. 

The presence of by-products such as 1-chloro-ethyl acetate 3 and a small amoimt of ethyl acetate, suggests that the initial step is an intermolecular hydride ion transfer from cyclohexane or methylcyclopentane towards acetyl chloride-aluminium chloride complex to give 1-methylcyclopentene. From cyclohexane, the cyclohexyl cation isomerizes to 1-methyl-l-cyclopentyl carbenium ion which loses a proton. Then, the 1-chloro-ethylate-aluminium chloride... 

Dissolve 10 g. of chloro- 2,4-dinitrobenzenet in 50 ml. of dioxan in a 250 ml. conical flask. Dilute 8 ml. of hydrazine hydrate with an equal volume of water and add this slowly with shaking to the dioxan solution, keeping the temperature between zo " and 25°. Heat under reflux for 10 minutes to complete the reaction and then add 5 ml. of ethanol and heat again for 5 minutes. Cool and filter oflF the orange 2,4-dinitrophenylhydra-zine. Recrystallise the dry product from ethyl acetate m.p. 200° (decomp.). Yield, 7 g. 

Solvents. NBRs are soluble in aromatic hydrocarbons, chlorinated hydrocarbons, ketones, esters and nitroparaffin compounds. Solvents with high evaporation rate are acetone, methyl ethyl ketone, chloroform and ethyl acetate, among others. Solvents with slow evaporation rate are nitromethane, dichloropentenes, chloro-toluene, butyl acetate and methyl isobutyl ketone. 

Chloro-2-hydrazino-4-phenylquinoline A stirred mixture of 2,6-dichloro-4-phenylquino-line 12.7 g,0.01 mol) and hydrazine hydrate (6.8 g) was refluxed under nitrogen for 1 hour and concentrated in vacuo. The residue was suspended in warm water, and the solid was collected by filtration,dried and recrystallized from ethyl acetate-Skelly B hexanes to give 1.81 g (67% yield) of 6[Pg.46]

Chloro-1 -methyl-5-phenyl-s-trizolo[4,3-a]quinoline A stirred mixture of 6triethyl-orthoacetate (0.925 g,0.0057 mol) and xylene (100 ml) was refluxed, under nitrogen, for 2 hours 40 minutes. During this period the ethanol formed in the reaction was removed by distillation through a short,glass helix-packed column. The mixture was concentrated to dryness In vacuo and the residue was crystallized from methanol-ethyl acetate to give 1.28 g of 7-chloro-1-methyl-5-phenyl-s-triazolo[4,3-a]-quinoline (83.9% yield). The analytical sample was crystallized from methylene chloride methanol and had a melting point 252.5°-253.5°C. 

Chloro-1 -methyl-6-phenyl4H-s-triazolo-[4,3-a] [1,4] -benzodiazepine A stirred suspension of 5-chloro-2-[3-(bromomethyl)-5-methyl4H-1,2,4-triazol4-yl] -benzophenone (391 mg, 0.001 mol) in tetrahydrofuran (15 ml) was cooled in an ice-bat hand treated with a saturated solution of ammonia in methanol (12.5 ml). The resulting solution was allowed to warm to ambient temperature and stand for 24 hours. It was then concentrated in vacuo. The residue was suspended in water, treated with a little sodium bicarbonate and extracted with methylene chloride. The extract was washed with brine, dried with anhydrous potassium carbonate and concentrated. The residue was crystallized from methylene chloride-ethyl acetate to give... 

A suspension of 45 g 3-phenoxycarbonyloxy-1 -methyl-7-chloro-5-pheny -1,3-dihydro-2H-1,4-benzodiazepin-2-one in 450 ml methanol is treated with stirring, with 43 ml of a solution of dimethylamine in methanol (containlng31 gdimethylamine in 100 ml). Stirring ismaintained at 20°C to 25°C during 5 hours. The reaction mixture is filtered, and the filtrate is diluted with 450 ml water. The precipitate thus formed, is 3-(N,N-dimethylcarbamoyloxy)-1-methy -7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one, which is collected on a filter, dried and recrystallized from ethyl acetate, and has a melting point of 173°C to 174°C. 

The mixture is refluxed with stirring for ten hours, cooled and filtered. The filtrate is extracted three timas with 200 cc portions of 6 N acetic acid. The aqueous acetic acid solution is then made strongly basic with 10% sodium hydroxide solution, and extracted three times with 200 cc portions of ether. The ether extract is dried with anhydrous sodium sulfate, stirred with 5 g of activated carbon and filtered to provide 2-[p-chloro-a(2-di-methylaminoethoxylbenzyll pyridine in solution. Addition of a solution of 116 g (1 mol) of maleic acid in 1,500 cc of ether gives 323 g (79%) of solid which, on recrystallization from ethyl acetate, gives white solid 2-[p-chloro-a(2-dimethvlaminoethoxv)benzyl] pyridine maleate melting at 117° to 119°C. 

Preparation of 7-amino-3-chloro-3-cephem-4-carboxylic acid To a solution of 750 mg (1 55 mmol) of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride in 20 ml of tetrahydrofuran and 40 ml of methanol was added a suspension of 750 mg of prereduced 5% palladium on carbon catalyst in 20 ml of ethanol and the suspension was hydrogenated under 50 psi of hydrogen at room temperature for 45 minutes. The catalyst was filtered and washed with THF and water. The filtrate and catalyst washes were combined and evaporated to dryness. The residue was dissolved in a water-ethyl acetate mixture and the pH adjusted to pH 3. The insoluble product was filtered and triturated with acetone. The product was then dried to yield 115 mg of 7-amlno-3-chloro-3-cephem-4-carboxylic acid. 

To the crude product there was added 100 ml of ethanol with warming until a clear solution was obtained. Then 150 ml ethyl acetate was added and the resultant filtered through a glass mat and the filtrate adjusted to pH 1 by the addition of saturated ethanolic HCI. Crystallization soon occurred. The resultant was allowed to stand at 0°C for 18 hours and then filtered through a sintered glass mat. The solid was dried under vacuum at 60°C for 18 hours yielding 35 g, a 67% yield of 7(S)-chloro-7-deoxylincomycin hydrochloride as an ethanol solvate. 

After drying over sodium sulfate and concentration to vacuum the remaining residue is subjected to chromatography over silica gel. Using a benzene-ethyl acetate mixture (19 1) there is eluated 900 mg of 6-chloro-1,2a-methylene-A -pregnadiene-17o-ol-3,20-dione-17-acetate, which upon recrystallization from isopropyl ether melts at 200° to 201°C. 

A mixture of 10 parts of 7-chloro-4-fluorobutyrophenone, 5.5 parts of 1-(1,2,3,6-tetrahydro-4-pyridyl)-2-benzimidazolinone, 4 parts of sodium carbonate, and 0.1 part of potassium iodide in 176 parts of 4-methyl-2-pentanone is stirred and refluxed for 64 hours. The cooled reaction mixture is filtered and the solvent is evaporated from the filtrate to leave an oily residue which is dissolved in toluene. The toluene solution is filtered and the solvent is evaporated. The resultant residue is recrystallized from a mixture of 32 parts of ethyl acetate and 32 parts of diisopropyl ether to give 1-[1-[(4-fluorobenzoyl)propyll-1,2,3,6-tetrahydro-4-pyridyl]-2-benzimidazolinone hydrate melting at about 145°-146.5°C. 

A mixture of 2.9 grams of 5-chloro-2,4-disulfamvl-aniline in 20 ml of anhydrous diethylene-glycol dimethylether, 0.44 gram of propionaldehyde and 0.5 ml of a solution of hydrogen chloride in ethyl acetate (109.5 grams hydrogen chloride per 1,000 ml) Is heated to 80° to 90°C and maintained at that temperature for 1 hour. The reaction mixture is concentrated under reduced pressure on addition of water, the product separates and is then recrystal-lized from ethanol or aqueous ethanol to yield the desired 6-chloro-3-ethvl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide, MP 269° to 270°C. 

A solution of 0.7 g of 2-(2-amino-N-methylacetamido)-5-chlorobenzophenone in 10 ml of a 50% solution (by weight) of diketene in acetone is refluxed for 3 hours and then evaporated to give a brown oil. The oil Is chromatographed on 200 g of silica gel using a 1 1 (by volume) mixture of ethyl acetate cyclohexane 25 ml fractions are collected. Fractions 11-14 are combined, mixed with chloroform, evaporated and triturated with ether to give 0.337 g of 11-chloro-8,12b-dihydro-2,8-dimethy 1-12b-phenyl-4H-[ 1,3]oxazino[3,2-dl [1,4] benzodiazepine-4,7 (6H)-dione as a pale yellow solid, MP 174°C to 176°C. 

A) 1-(2-Amino-5-chlorophenyll-1-(2-fluorophenyll-2-a2a-but-1-en-4-ol A mixture of 40 g of 2-methylimidazole hydrochloride and of 90 g of 2-amino-5-chloro-2 -fluoro-benzophenone in 240 ml of ethanolamine is heated at 135 for 2 hours. After cooling, the reaction mixture is poured into an aqueous sodium bicarbonate solution. The mixture is extracted with ether, the organic phase is washed repeatedly with water and is dried over sodium sulfate, and the solvent is evaporated to dryness. The residual oil is chromatographed on a silica column, elution being carried out with a 50/50 mixture of cyclohexane and ethyl acetate. 

C) Preparation of 2-Methyl-3-(2,2,2-Trifluoroethyl)Thiomethyl-6-Chloro-7-Sulfamyl-3,4-Dihydro-1,2,4-Benzothiadiazine-1,1-Dioxide To 4.6 g (0.015 mol) of 4-amino-2-chloro-5-(methylsulfamyl)benzenesulfonamide in 30 ml of the dimethyl ether of ethylene glycol is added 4.08 g (0.02 mol) of 2,2,2-trifluoroethylmercaptoacetaldehyde dimethylacetal followed by 1 ml of ethyl acetate saturated with hydrogen chloride gas. The resulting solution is refluxed for 1.5 hours, cooled and then slowly added to cold water dropwise with stirring. The crude product is filtered, dried and recrystallized from isopropanol (3.2 g), MP 202° to 202.5°C. A second recrystallization from isopropanol raised the MP to 202°... 

D/chloro-5-Cyclohexyl-2-Oxo-2,3-D/hydro 1 H-Benzo(fj-Diazepine-1,4 fa) Process Using Sodium Hypochlorite — 40 ml of a solution of sodium hypochlorite of 14.5 British chloro-metric degrees are added to a suspension of 5.4 grams of 7 chloro-5 cyclohexyl-2 oxo-2,3-dihydro 1 H-benzo(f)diazepine-1,4 in BO ml of methylene chloride. The mixture is stirred at room temperature for 15 minutes the solid dissolves rapidly. The organic iayer is decanted, washed with water, dried over anhydrous Sodium sulfate and the solvent evaporated under reduced pressure without exceeding a temperature of 30 C. The residue is taken up in a little diisopropyl ether and the crystals which form are dried. They are recrystallized as rapidly as possible from ethyl acetate. Colorless crystals are obtained (3.9 grams yield, B5%) MP < = 163°C, with decomposition. 

The mixture was cooled in ice and a solution of 2-chloro-3-chloromethy I thiophene (8.8 mmol) in dry tetrahydrofuran was added. The mixture was heated at 70°C for 3 hours and allowed to stir at room temperature overnight. The solvent was removed under vacuum and the residue stirred with dry ether (200 ml). The ether solution was filtered through Celite and saturated with hydrogen chloride gas to precipitate an oil which was solidified by trituration with ether and ethyl acetate. The solid product was collected and recrystallized from a mixture of acetone and diisopropyl ether to give the product, melting point 168°C to 170°C. 

Chloro-3-methylquinoxaline 4-oxide gave 3-chloro-2-quinoxalinecarbalde-hyde 1-oxide (172) (SeOi, PhH, reflux, h 72%) dioxane may be used as solvent for such oxidations yielding, for example, 3-amino-2-quinoxaline-carbaldehyde ethyl acetate may also be so used. 

The reaction of electron deficient iV-benzenesulfonyl- 3-phenethylainines 84 with ethyl chloro(methylthio)acetate gives tetrahydroisoquinoline-1-carboxylates 85 in high yields <96H(42)141>. 

The first application of microwave irradiation in conjunction with dry media in the generation of nitrile oxide intermediates was reported by Hamelin [29]. In this example, methyl nitroacetate (170) was mixed with a dipolarophile in the presence of catalytic amounts of toluene-p-sulfonic acid (PTSA) (10% weight). Subsequent microwave irradiation led to the formation of the corresponding heterocyclic adducts (Scheme 9.52). Reactions were performed in an open vessel from which water was continuously removed [103], Likewise, irradiation in a domestic oven of a mixture of ethyl chloro(hydroxyimino)acetate (173) and a dipolarophile over alumina led to the same results in only a few minutes (Scheme 9.52) [103]. 

The reaction was followed by TLC (eluent petroleum ether-ethyl acetate 85 15). The chloroacetophenone was UV active and stained grey with p-anisaldehyde dip, R 0.5. 2-Chloro-l-phenylethanol was UV active and stained green-grey with p-anisaldehyde, R 0.39. 

The crude material was purified by flash chromatography on silica gel (30 g) using petroleum ether-ethyl acetate-triethylamine (89 10 1) as eluent to give 2-chloro-l-phenylethanol as an oil (140 mg, 90%). 

When the decomposition of the zwitterionic intermediate is rate-determining, the effect of the solvent is crucial since it may produce changes in the mechanisms and in the rate-determining step. A recent study of the kinetics of the reactions of 1-chloro-, 1-fluoro- and l-phenoxy-2,4-dinitrobenzene with piperidine, n-butylamine and benzylamine in ethyl acetate and THF indicated that these reactions resemble those in dipolar aprotic solvents when primary amines are the nucleophiles (i.e. that shown in equation 1, with... 

Mobile phase composition 1 = toluene-ethyl acetate-formic acid (30 10 10, v/v) 2 = toluene-ethyl acetate-formic acid (55 20 25, v/v) 3 = toluene-acetone-formic acid (7 6 1, v/v) 4 = benzene-ethyl acetate-formic acid (30 15 5, v/v) 5 = chloroform-methanol-formic acid (15 3 2, v/v) 6 = chloro-form-methanol-formic acid (147 30 23, v/v) 7 = Toluene-chloroform-acetone-formic acid (8 4 3 3, v/v) 8 = chloroform-methanol-formic acid (37 8 5, v/v) 9 = chloroform-methanol-formic acid (36 9 5, v/v) 10 = ethyl acetate-chloroform-formic acid (24 21 5, v/v) 11 = ethyl acetate-chloro-form-formic acid (23 21 6, v/v). 

Anodic regioselective fluorination of a-phenylsulphenylated ethyl acetates, 1-naphthalene and 2-pyridine derivatives [80], l-aryl-3-(phenylthio)oxindoles and 2-substituted-3-oxo-4-(phenylthio)-l, 2, 3,4-tetrahydroisoquinolines [81], 2-benzo-thiazolyl and 5-chloro-2-benzothiazolyl sulfides [82], a-(phenylsulfenyl)lactams [83], as well as various heterocycles such as thiolanones, oxathiolanones, dithi-olanones, 3Fl-l,4-benzoxathian-2-ones [84] in Et3N-3HF or Etr NF- HF [n = 3,4), has been reported. 

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