Chlorination of ethanol

Chloral hydrate Chloral hydrate, 2,2,2-trichloro-l,l-ethandiol (4.3.1), is synthesized either by chlorination of ethanol or chlorination of acetaldehyde and the subsequent addition of water molecules to the resulting trichloroacetic aldehyde [31],... 

Derivation Chlorination of ethanol and condensation with chlorobenzene. 

Trichloroacetaldehyde (chloral), b.p. 97.8°/760 mm, is formed on chlorination of ethanol with irradiation and stirring. Absolute ethanol is no longer used, as in Liebig s procedure,624 but, instead, aqueous 70-80% ethanol which leads directly to chloral hydrate ... 

ORIGIN/INDUSTRY SOURCES/USES derivation is from chlorination of ethanol and condensation with chlorobenzene used to kill pests, but its use has also been banned formerly used medically to treat cancer of the adrenal gland non-degradable pesticide and a nonsystemic... 

Chlorination of Acetaldehyde. In some commercial processes for chloral, acetaldehyde, or its condensation product, paraldehyde is chlorinated under hydrous conditions. In some cases this has an advantage over the chlorination of ethanol as only 3 moles of chlorine are required as compared with the 4 moles used in the ethanol process ... 

Chlorination of Ethanol. Ethyl alcohol either absolute or containing water is chlorinated to form the hemiacetal of trichloroacetaldehyde from which chloral is liberated by treatment with concentrated sulfuric acid. Ferric chloride may be employed as a chlorination catalyst, but its use does not appear necessary. Five moles of hydrogen chloride is liberated for each mole of chloral produced, and the other by-products include ethyl chloride, ethylene dichloride, and ethyl ether. 

Chloral hydrate was first obtained by Liebig (1832) from the reaction of water with chloral, the latter obtained via the chlorination of ethanol. Industrially, chloral is prepared by passing chlorine into cooled ethanol (either absolute or 95 percent) to form the hemiacetal of trichloroacetaldehyde, from which chloral is liberated by treatment with sulfuric acid. 

Crude chloral, obtained by the liquid-phase chlorination of ethanol, has been assayedl26 by a procedure involving the volumetric measurement of the chloroform formed after hydrolysis with strong KOH solution. 

Chlorination of ethanol to produce trichloroacetaldehyde, CCI3CHO, was first described in 1832. Its hydrated form is called chloral and is a powerful hypnotic with the nickname knockout drops. Chloral is a key reagent in the synthesis of DDT, which was first prepared in 1874 and was demonstrated by Paul Mueller in 1939 to be a powerful insecticide. The use of DDT in the suppression of insect-home diseases was perhaps best described in a 1970 report by the U.S. National Academy of Sciences To only a few chemicals does man owe as great a debt as to DDT.. .. In little more than two decades, DDT has prevented 500 million human deaths, due to malaria, that otherwise would have been inevitable. DDT effectively kills the Anopheles mosquito, the main carrier of the malaria parasite. Malaria afflicts hundreds of millions of people worldwide and claims... 

CCls CHO. A colourless oily liquid with a pungent odour b.p. 98°C. Manut actured by the action of chlorine on ethanol it is also made by the chlorination of ethanal. When allowed to stand, it changes slowly to a white solid. Addition compounds are formed with water see chloral hydrate), ammonia, sodium hydrogen sulphite, alcohols, and some amines and amides. Oxidized by nitric acid to tri-chloroethanoic acid. Decomposed by alkalis to chloroform and a methanoate a convenient method of obtaining pure CHCI3. It is used for the manufacture of DDT. It is also used as a hypnotic. 

When chlorine is passed into boiling ethanol, both chlorination of the methyl group and oxidation of the primary alcohol group to an aldehyde occur, giving trichloro-acetaldehyde or chloral ... 

Three industrial processes have been used for the production of ethyl chloride hydrochlorination of ethylene, reaction of hydrochloric acid with ethanol, and chlorination of ethane. Hydrochlorination of ethylene is used to manufacture most of the ethyl chloride produced in the United States. Because of its prohibitive cost, the ethanol route to ethyl chloride has not been used commercially in the United States since about 1972. Thermal chlorination of ethane has the disadvantage of producing undesired by-products, and has not been used commercially since about 1975. 

Reduction of indolenines with sodium and ethanol gives indolines. The pentachloropyr-role, obtained by chlorination of pyrrole with sulfuryl chloride at room temperature in anhydrous ether, was shown by spectroscopic methods to have an a-pyrrolenine (2H-pyrrole) structure (222). It is necessary, however, to postulate that it is in equilibrium with small but finite amounts of the isomeric /3-pyrrolenine form (3//-pyrrole 223), since pentachloropyrrole functions as a 2-aza- rather than as a 1-aza-butadiene in forming a cycloadduct (224) with styrene (80JOC435). Pentachloropyrrole acts as a dienophile in its reaction with cyclopentadiene via its ene moiety (81JOC3036). 

The residue of crystalline putrescine dihydrochloride is rinsed onto a Buchner funnel with the aid of 100-200 ml. of absolute ethanol used in several portions. The last portions of ethanol are used as wash liquid for the crystals. The crystals are finally pressed dry and washed with 25 ml. of ether. The air-dried product weighs 53-55 g. (72-74%) and melts above 275. Analysis for chlorine indicates that the salt is anhydrous. Concentration of the filtrate to a volume of about 25 ml. yields an additional 1-2 g. total yield 73-77%. The entire synthesis may be completed in one day. 

Although 16-methylene-17a-hydroxy-20-ketopregnanes can be brominated at C-21 in excellent yield in chloroform containing a small amount of methanol,with A -17a-hydroxy-20-ketopregnanes the use of ethanol alone (containing hydrogen chloride) is far superior. Isolated double bonds (e.g., A, A ) may also be protected prior to bromination by the addition of chlorine. 

An interesting variation of this theme starts with the a-chlorination of dicyclohexylketone (58). Treatment of the halo-genated intermediate with base leads to the acid, 60, by the Favorski rearrangement. Esterification of the acid with 2(1-pyrolidino)ethanol yields dihexyrevine (61). Both this agent and its earlier congener are recommended for use in GI spasms. 

Another remarkable reaction is the nucleophilic substitution of the chlorine by alkoxy or sulfido groups using the alcohol or the thiol and the weak base Na2C03 in situ. For example, in the case of ethanol, the reaction proceeds in 12 h at reflux Eq. (23), Table 3. 

CH2 CH.CH2.OH mw 58.09 OB to C02 -220.35% colorl, mobile liq with a pungent odor mp —129° bp 96.9°, d 0.8520g/cc at 20/4° RI 1.4127, 1.4133, 1.4135 (Sep values). V sol in w, ethanol and ether. Prepn is by the high temp chlorination of propene, followed by hydrolysis of allyl chloride. Thus,. . Allyl chloride is hydrolyzed at 200psi pressure, 150°C and a pH range of 10—12. Injection of steam forms a water-allyl alcohol azeotrope, which is then treated with diallyl ether to remove water. Final purification by distn leads to a 98% min assay. . (Ref 2). Using procedures such as the above, ... at least two American companies (Shell Chemical Co and Dow Chemical Co) produce a total of several million lbs per year... (Ref 2)... 

Sato A, Nakajima T, Koyama Y. 1981. Dose-related effects of a single dose of ethanol on the metabolism in rat liver of some aromatic and chlorinated hydrocarbons. Toxicol Appl Pharmacol 60 8-15. 

Several min after addition of ethanol to a mixture of the amide chloride ( fusible white precipitate ) and iodine, an explosion occurs. Addition of the compound to chlorine gas or bromine vapour leads to a delayed violent or explosive reaction. Amminemetal salts behave similarly, and formation of A-halogen compounds is involved in all cases. 

Chlorination of pyrido[2,3- 1pyridazines 108 and 109 with POCI3 in pyridine at 110 °C afforded the respective 8- and 5-chloro derivatives 110 and 112, which upon reaction with hydrazine hydrate in boiling ethanol gave the hydrazine derivatives 111 and 113, respectively <1998SC2871>. 

Ethyl hypochlorite is a yellow liquid, the boiling point of which is 36°C (Sandmeyer [1]). It was prepared by introducing chlorine gas into a cooled mixture composed of 1 part of sodium hydroxide, 1 part of ethanol and 9 parts of water. 

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