2-chloroacetaldehyde

Colorless liquid, bp 103°C (217.4°F) freezes at -91.5 C (-132.7 F) density 0.8095 at 20°C (68°F) slightly soluble in water but mixes readily with alcohol and ether. 

LD50 value, skin (rabbits) 4857 mg/kg LD50 value, oral (rats) 3200 mg/kg 

Inhalation toxicity is very low. Exposure to 4000 ppm for air was lethal to rats. 

Highly flammable flash point (open cup) 12°C (54°F) autoignition temperature 222°C (432°F) vapor density 3 (air = 1). Vapor-air mixture is explosive. Fire-extinguishing agent dry chemical, foam, or CO2. 

The derivative valeraldehyde oxazolidine (9-butyl-l-aza-8-oxabicyclo[4.3.0]nonane) is desorbed with toluene and analyzed by GC-FID (NIOSH 1984, Suppl. 1989, Method 2536). 

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Chloroacetaldehyde is unstable and lachrymatory it is therefore usually generated in situ by the action of water upon ap-dichloroethyl ethyl ether ... 

The replacement of selenoamide by selenourea in the Hantzsch s synthesis. (1st method) leads to 2-aminoselenazoles 2, 14. 15). This series of compounds has been well developed, mainlv because selenourea is much more easily accessible than the selenoamides, but also because a wide variety of a-halogenated carbonyl compounds are available for the Hantzsch s evdization reaction (Scheme 5). 2-Aminoselenazole itself was prepared from commercially available chloroacetaldehyde semihydrate... 

A. Chloroacetaldehyde and Derivatives (Thiazole and its 2-Monosubstituted Derivatives) (Table II-l)... 

Another difficulty in this reaction lies in the preparation of pure chloroacetaldehyde. The low yield observed is due to simultaneous formation of by-products (polyhalogenation). So vinylchloride was used as a starting material for this synthesis (449). A simpler method is to react chlorine with vinylchloride in aqueous solution and then to dehydrate the semihydrated chloroacetaldehyde by distillation through a column of calcium chloride heated to 70 to 90 C (451). 

When chloroacetaldehyde is condensed with higher thioamides prepared from amides and phosphorus pentasulfide according to Schwarz s method (222), 2-substituted thiazoles are obtained (4, 10,"22, 175). 

It is also possible to start from chloroacetaldehyde derivatives such as 1,2-dihalogeno ethyl acetate yields can reach 90% (356). These compounds can be easily obtained by addition of halogen to the double bond of vinylacetate at 0 to 10°C. 

Aminothiazole itself (104a), R, = R2 = H (an intermediate in the preparation of sulfathiazole), was synthetized as early as 1888 from a,p-dihalogenoethylethers, which give chloroacetaldehyde in addic medium (8). Many other derivatives have now been used for this synthesis, and they are listed in Table IT12. All give excellent yields. 

The N,N-disubstituted thioureas (135) condensed with a-halocarbonyl compounds give 2-disubstituted aminothiazoies (136) but in lower yields (30 to 70%) (Scheme 65 and Table 11-20) (518). For example, N,N-dialkylthioureas condensed with chloroacetaldehyde or dibromoether lead to Ar,At-dialkyl-2-aminothiazoles in 136, Ri=R2 = methyl (342, 404, 436, 637), ethyl (343, 436), n-propyl (518), n-butyl (518), ally] (518), and benzyl (26, 29). When chloroacetone and dichloroacetone are the carbonyl reactants the corresponding 4-methyl (518) and 4-chloromethyl derivatives (572) were obtained. 

The results initially obtained were due to the formation in both aqueous and alcoholic solution of resinous by-products. This formation results from the decomposition of the ammonium dithiocarbamate, or from the self-condensation of chloroacetaldehyde or the formation of intermediate products. 

A recent study instigated by Kolosova (521) and taken up and proved by Chanon and Metzger (597) increased the yield of this reaction to 70% in the case of chloroacetaldehyde and to 50% in the case of di-bromoether, whereas other authors have been either unable to obtain the product in this way or in very low yield (11%) (316). 

Reaction with triplet oxygen 0( P) atoms [17778-80-2] gives high yields of CO and chloroacetaldehyde [107-20-0], with smaller amounts of acetyl chloride [75-36-5], HCl, methane [74-82-8], and polymer. The rate of the gas-phase reaction of vinyl chloride with 0( P) atoms has also been reported (41). 

Vinyl chloride can be completely oxidized to CO2 and HCl using potassium permanganate [7722-64-7] in an aqueous solution at pH 10. This reaction can be used for wastewater purification, as can ozonolysis, peroxide oxidation, and uv irradiation (42). The aqueous phase oxidation of vinyl chloride with chlorine yields chloroacetaldehyde (43). 

Addition of HOCl to vinyl chloride yields chloroacetaldehyde (106) addition to acetylenic compounds produces dichloroketones (107) (see... 

Oxidation. Monochloroacetic acid [79-11-8] may be synthesized by the reaction of ethylene chlorohydrin with nitric acid [7697-37-2]. Yields of greater than 90% are reported (41). >Beta-chlorolactic acid (3-chloro-2-hydroxypropanoic acid) [1713-85-5] is produced by the reaction of nitric acid with glycerol monochlorohydrin (42). Periodic acid [10450-60-9] and glycerol monochlorohydfin gives chloroacetaldehyde [107-20-0] ia 50% yield (43). 

AminothiaZoles. In contrast to the pyrazolones, pyridones, and indoles just described, aminotliiazoles are used as diazo components. As such they provide dyes that ate more bathochromic than their benzene analogues. Thus aminothiazoles are used chiefly to provide dyes in the red-blue shade areas. The most convenient synthesis of 2-aminothiazoles is by the condensation of thiourea with an a-chlorocarbonyl compound for example, 2-aminothiazole [96-50A-] (94) is prepared by condensing thiourea [62-56-6J with a-chloroacetaldehyde [107-20-0J both readily available intermediates. 

Chloroacetaldehyde diethyl acetal was used as obtained from Aldrich Chemical Company, Inc. 

Chloro-1 -nitropropane Chloroacetaldehyde a-Chloroacetophenone Chlorobenzene (monochlorobenzene) o-Chlorobenzylidine malononitrile Chlorobromomethane Chlorodiphenyl (42% chlorine) Chlorodiphenyl (54% chlorine) 2-Chloroethanol (ethylene chlorohydrin) Chloroform... 

Chlorinated camphene Chlorinated diphenyl oxide Chlorine Chlorine dioxide Chlorine trifluoride Chloroacetaldehyde... 

Charcoal screenings, wet Charcoal, wet Chlorine azide Chlorine dioxide Chloroacetaldehyde Chloroacetone (unstabilized) Chloroacetonitrile Chloroformates, n.o.s. Chloroprene, uninhibited Chlorosulphonic acid Coal briquettes, hot Coke, hot Copper acetylide... 

Although bromo derivatives have been used, the two most common ot-halocarbonyl compounds for this reaction are chloroacetaldehyde and chloroacetone. The dicarbonyl component is typically ethyl acetoacetate or one of its derivatives. A variety of bases including triethylamine and potassium hydroxide can promote the reaction however, the most popular base is pyridine. Conversion to the furan takes place either at room temperature or upon heating to 50°C with reaction times varying from four hours to five days and yields ranging from 30-86%. 

In 1911 Benary reported a modification of Feist s original procedure. He reacted chloroacetaldehyde (8), generated in situ from the ammonia promoted decomposition of 1,2-dichloroethyl ethyl ether (7), with ethyl acetoacetate (9) and ammonia to yield ethyl 2-methyl 3-furoate (10). ... 

The mechanism of the Feist-Benary reaction involves an aldol reaction followed by an intramolecular 0-alkylation and dehydration to yield the furan product. In the example below, ethyl acetoacetate (9) is deprotonated by the base (B) to yield anion 10 this carbanion reacts with chloroacetaldehyde (8) to furnish aldol adduct 11. Protonation of the alkoxide anion followed by deprotonation of the [i-dicarbonyl in 12 leads to... 

Other aldehydes which have been used in the reaction are pro-panal, butanal, glycolaldehyde, 3-hydroxybutanal, and a number of phenylacetaldehydeand benzaldehyde derivatives. Whereas condensation of tryptophan with acetaldehyde takes place even at room temperature and pH 6.7, the reactions with chloral, chloroacetaldehyde, and crotonaldehyde fail entirely. 

As demonstrated above, nitro derivatives of five-membered heterocycles have found extensive use as antiinfective agents. It is therefore of interest that the nitro derivative of a substituted thiazole was at one time used as an antitrichomonal agent. Bro-mination of 2-aminothiazole (136) (obtained from condensation of thiourea with chloroacetaldehyde) gives the 4-bromo derivative (138) this is then acetylated to 139. Treatment of 139 with nitric acid leads to an interesting displacement of bromine by a nitro group to afford aminitrazole (140)... 

Aj Preparation of 3-Chloromethyl-6-Chloro-7-Sulfamyl-3,4-Dihydro-Benzothiadizine-1,1-Dioxide—Jo 8 ml of 40-50% chloroacetaldehyde aqueous solution and 7 ml of dimethyl-formamide are added 10 grams of 2,4-disulfamvl-5-chloroaniline. The mixture is heated on a steam bath for 2 hours after which it Is concentrated at reduced pressure. The residue Is triturated with water. The solid material is recrystallized from methanol-ether after-treatment with activated carbon to give 7.2 grams of product, MP 229°-230°C. 

Acetazolamide Bucloxic acid Butalamine HCI Chlorotrianisene Chlorquinaldol Clenbuterol Diazoxide Enflurane Floxacillin Flucloronide Isoflurophate Lindane Methazolamide Metoclopramide HCI Oxacillin sodium Chloroacetaldehyde Benzthiazide... 

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