With chloracetyl chloride

A compound closely related to classical adrenergic agonists in which the para hydroxy function is however replaced by an amino group has been investigated for its activity as a growth promoter in domestic animals. Acylation of the aniline derivative 26 with chloracetyl chloride will afford acetophenone 27 the amino-ketone 28 is obtained on reaction with isopropylamine. Removal of the protecting group (29) followed by reduction of the ketone affords cimaterol (30) 5J. 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

Di(epoxyethyl)diphenyl was obtained from diphenyl by Friedel-Crafts reaction with chloracetyl chloride. Meerwein-Ponndorf reduction gave the dichlorohydrin, and treatment with alcoholic potassium hydroxide gave 97% of the theoretical yield of diepoxide, (f.p., 161 °C.). The stabilizing effect was about one-fourth that of dibutyltin laurate. 

Dithiolanes with a carbon-carbon double bond or carbon-heteroatom double bond at C-2 are good Michael acceptors. As an example, cyclocondensation reactions of the compound 342 with chloracetyl chloride and mercaptoa-cetic acid gave the corresponding azetidinone 343 and 4-thiazolidinone 344, respectively (Scheme 44) <2000PS259>. 

Hydroxy-1 4-benzisoxazine-5-arsinic acid. — 20 grams of 2-amino-8-hydroxyphenylarsinic acid in 50 c.c. of 2N sodium hydroxide are treated alternately with chloracetyl chloride (15 c.c. in all) and 25 per cent, sodium hydroxide at 50° C. The mixture is then made strongly alkaline and heated for ten minutes at 90° C., more alkali being added as the acidity develops. A 60 per cent, yield of the arsinic acid (I) is obtained by acidifying the liquor, and subsequent crystallisation ftom water yields colourless rhombs, M.pt. 245° to 248° C. with decomposition. The cdLcvum, barium and magnesium salts are amorphous, white solids. 

Startg. m. allowed to react with chloracetyl chloride in dry benzene in the presence of 2-methylimidazole -> 3-diloroacetamidoquinazoline deriv. (startg. m. f. 455). Y 86%. K. Meguro, H. Tawada, and Y. Kuwada, Chem. Pharm. Bull. 2i, 1619 (1973). 

B g of o-emino-N-preacted with an ethereal solution of 3.9 g of chloracetyl chloride with cooling in a mixture of... 

Into a stirred, cooled (10°-15°C) solution of 26.2 grams (0.1 mol) of 2-amino-5-chlorobenzo-phenone (3-oxime in 150 ml of dioxane were introduced in small portions 12.4 grams (0.11 mol) of chloracetyl chloride and an equivalent amount of 3 N sodium hydroxide. The chlor acetyl chloride and sodium hydroxide were introduced alternately at such a rate so as to keep the temperature below 15°C and the mixture neutral or slightly alkaline. The reaction was completed after 30 minutes. The mixture was slightly acidified with hydrochloric acid, diluted with water and extracted with ether. The ether extract was dried and concentrated in vacuo. Upon the addition of ether to the oily residue, the product, 2-chloroacetamido-5-chlorobenzophenone (3-oxime, crystallized in colorless prisms melting at 161°-162°C. 

One mol of 2,6-xylidine is dissolved in 800 ml glacial acetic acid. The mixture is cooled to 10°C, after which 1.1 mol chloracetyl chloride is added at one time. The mixture is stirred vigorously during a few moments after which 1,000 ml half-saturated sodium acetate solution, or other buffering or alkalizing substance, is added at one time. The reaction mixture is shaken during half an hour. The precipitate formed which consists of cj-chloro-2,6-di-methyl-acetanilide is filtered off, washed with water and dried. The product is sufficiently pure for further treatment. The yield amounts to 70 to 80% of the theoretical amount. 

The reaction between the copper derivative of pentafluorobenzene and chloracetyl chloride (ammonia as base) produces a little of the highly stable furan 8, an unusual result that has been regarded very tentatively as a Feist-Benary reaction with Cf,F5COCH2Cl as substrate.48... 

Fortunately 81 is phenylalaninol—the alcohol from the amino acid phenylalanine. The workers decided to acylate at nitrogen first and so used chloracetyl chloride to make 77 which cyclised on treatment with base. 

Chloracetyl-p-arsanilic acid is prepared by the interaction of chloracetyl chloride and p-arsanilic acid, whilst the corresponding iodoacetyl derivative (M.pt. 196° C.) and the iodopropionyl derivative (M.pt. 224° C.) are formed by treating sodium hydroxide solutions of the acid with the respective acid chloride. ... 

The chlorination of thb compound with sulfur monochloride and chlorine to obtain chloracetyl chloride according to the equation... 

In a related method, also shown in Figure 10, water can be removed via an azeotrope with another solvent. In the example used, broth derivatized with chloroacetyl chloride is added to cyclohexanone after vacuum distillation of the water the cyclohexanone contains insoluble solids as well as dissolved N-chloracetyl cephalos-... 

CHLORACETYL CHLORIDE (79-04-9) Forms corrosive vapors with air. Violent decomposition in water, producing chloroacetic acid and hydrogen chloride gas. Violent reaction with combustibles, alcohols, metal powders, sodium amide, many organic materials and compounds, causing toxic fumes and the danger of fire and explosion. Aqueous solution is incompatible with caustics, alkalis, alcohols, aliphatic amines, alkanolamines, ammonia, caustics, epichlorohydrin, isocyanates, alkylene oxides, sulfuric acid. 

An equimolar amount of chloracetyl chloride in dry dioxane added at 0° with vigorous stirring as fast as possible to 1.5 g. dl-dihydrocycloheximide (prepn. s. 81) in the same solvent containing 1 equivalent of pyridine, stirring continued 1 hr. at 0°, and 15 hrs. at room temp. 0.894 g. dl-dihydrocycloheximide chlor-acetate. — Any excess of base causes formation of large amounts of the isomeric chloracetate. F. Johnson et al.. Am. Soc. 88, 149 (1966) acoxycarboxylic acids s. W. O. McClure, Biochem. Prep. 11, 54 (1966). 

Chloracetyl chloride added dropwise with stirring to 2-aminobenzohydroxamic acid, and refluxed 10 min. -> 2-chloromethyl-3-hydroxy-4(3H)-quinazolinone. Y 85%. F. e. s. C. B. Schapira and S. Lamdan, J. Heterocyclic Chem. 9, 569 (1972). 

A soln. of 3,5-dimethoxytoluene in CSg added with shaking and cooling to AICI3, chloracetyl chloride in tihe same solvent added rapidly to the mixture after most of theAlClg has dissolved, and refluxed 46 hrs. 6-methoxy-4-methylbenzofuran-3(2H)-one. Y 90%. J.D. Brewer and J. A. Elix, Australian J. Chem. 25, 545 (1972). 

Chloracetyl chloride dropped rapidly at 10-30° into isopropyl dithiocarbazate in anhydrous benzene, and refluxed vigorously for 1 hr. with azeotropic water entrainment -> 2-isopropylthio-5-chloromethyl-l,3,4-thiadiazole. Y 77%. F. e. s. K. Riifenacht, Helv. 55, 1979 (1972). 

The third way for the synthesis emanates from 2-methylamino-5-chlorobenzophenone (5.1.5), which is acylated by chloracetic acid chloride, forming 2-chloracetylmethylamido-5-chlorbenzophenone (5.1.6). Reaction of this product with hexamethylenetetramine replaces the chlorine atom in the chloracetyl part of the molecule, giving a hexamethyl-enetetramino derivative of 2-aminoacetyhnethylamido-5-chlorbenzophenone, which upon hydrolysis in an hydrochloric acid ethanol solution undergoes cyclocondensation and gives diazepam (5.1.2) [6,7]. 

This follows, since, if step C is slow, step B must also be slow and thus the addition intermediate would accumulate. Satchell found no spectrophoto-metric or kinetic evidence for this with either chloracetyl or /3-chloropropionyl chlorides. This conclusion is obviously of wide potential significance in the hydrolyses of acyl derivatives and even the observation of oxygen exchange during solvolysis (one of the main supports of the tetrahedral intermediate postulate) does not rule reaction (26) out, since the acylation could remain synchronous in part. 

To a hot solution 199.3 g (0.1 mol) of phenothiazine in 2 L of dry benzene was added a little quantity of bromine and then were added dropwise 136 g (0.1 mol) of chloroacetyle chloride. Then a mixture was refluxed for 5 hours. After cooling the mixture was concentrated in vacuo. Product was dissolved at reflux in ethanol absolute and filtered. At room temperature was crystallized chloracetyl-10-phenothiazine with 123°C yield 242 g. 

A soln. of N,2-dichloracetamide and 1-dodecene in methylene chloride irradiated 27 hrs. at 10-20° under Ng with 3500 A light 2-chloro-N-chloracetyl-n-dodecyl-amine. Y 95%. F. e. s. D. Touchard and J. Lessard, Tetrah. Let. 1971, 4425. 

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