3- Chlorobutanol

Chlorobutanol is used as a plasticizer for cellulose esters, as a preservative for hypodermic solutions, and in veterinary medicine as a mild sedative and antiseptic. 

Crystalline solid with a camphor-Uke odor and taste sublimes mp 97°C (206°F) 

Chlorobutanol exhibited moderate toxicity in test animals. A lethal dose by oral intake in dogs and rabbits were 238 and 213 mg/kg, respectively (NIOSH 1986). The toxic symptoms are not reported. This compound is a mild skin and eye irritant and may be mutagenic. 

A suitable method of destruction of chlorobutanol is the burning of its solution in a combustible solvent in a chemical incinerator. 

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The hydroxy group can act as an intramolecular nucleophile. Solvolysis of 4-chlorobutanol in water gives as the product the cyclic ether tetrahydrofuran. The reaction is much faster than solvolysis of 3-chloropropanol under similar conditions. 

Hydroxy- 1-butanesulfonic acid sultone has been made through the chlorosulfonation of 1-chlorobutane,3 from 4-chlorobutyl acetate 2 4 which is prepared through the reaction of tetrahydrofuran and acetyl chloride,2 from 4-chlorobutanol,4 and from bis-4-chlorobutyl ether.2 Both 4-chlorobutanol and bis-4-chlorobutyl ether can be prepared from tetrahydrofuran.6... 

The procedure described is based on one reported by Alexander and Schniepp. 4,4 -Dichlorodibutyl ether has also been prepared by the action of thionyl chloride on tetrahydrofuran and by heating 4-chlorobutanol and hydrogen chloride under pressure. ... 

The ring may be cleaved hydrogenolytically. Halo acids afford 4-halobutanols or 1,4-dihalobutanes, depending on the reaction conditions. Acid chlorides in the presence of zinc chloride afford esters of 4-chlorobutanol, and LAH and aluminum chloride give butanol. Reaction with carbon monoxide and nickel tetracarbonyl affords adipic acid. 

The difference between the most kinetically favoured cyclisations is easily seen in the type of base needed to cyclise chloro-alcohols to three- and five-membered cyclic ethers (epoxides and THFs). Chloroethanol 19 cyclises only as the oxyanion specific base is needed, i.e. a strong enough base to remove the OH proton completely. By contrast, 4-chlorobutanol cyclises by general base catalysis the proton is removed during the cyclisation 22 and weak bases will do.1, 2... 

SYNS 4-CHLORBUTAN-l-OL (GERMAN) 4-CHLORO-l-BUTANE-OL 4-CHLOROBUTANOL TETRAMETHYLENE CHLOROHYDRIN... 

CHLOROBUTANE pOT) see BQQ750 4-CHLORO-l-BUTANE-OL see CEU500 CHLOROBUTANOL see ABDOOO 4-CHLOROBUTANOL see CEU500... 

Tetracaine hydrochloride Opticaine Tetcaine 0.5% solution 0.4% chlorobutanol... 

In addition to the above type of reaction, long-chain tertiary hypochlorites photochemically decompose - to the corresponding 5-chIoro alcohols. n-Butyl hypochlorite behaves similarly to produce 4-chlorobutanol. 

General base catalysis of Sn 2-type reactions of ordinary aliphatic alcohols by oxy-anions is observed in the cydization of 4-chlorobutanol [26], and of the sulfonium cation 2.6 [27] (Scheme 2.12) at 50 °C and 40 °C, respectively. (Amine buffers prefer to demethylate 2.6.) In all cases (including the reaction of 2.5 discussed above) catalysis by oxyanions shows a low solvent deuterium isotope effect and a Bronsted coefficient p of 0.26 + 0.1. This reaction may be something of a curiosity, but there is little doubt that it has been properly identified. 

Mercury compounds, such as phenylmercuric borate and thiomersal, can lower the ciliary beat frequency fast and irreversibly and, therefore, should be avoided, if their use is not already limited because of environmental reasons [44]. See also Sect. 23.8.4. Chlorobutanol inhibits the ciliary beat very fast, but provided the contact time is short, the ciliary movement will recover after some time. Parabens also have proved to be able to inhibit the ciliary movement in vitro studies) [45]. 

Fig. 2. Br/zinsted plot for the cyclization of 4-chlorobutanol in water at 25°C. Data points (left to right) correspond to water, 2,4-dinitrophenoxide, 2,4,6-trichlorophenoxide, 4-nitro-phenoxide, phenoxide, 2,2,2-trifluoroethoxide, and hydroxide.

As a specific example, 4-chlorobutanol 18 and the /7-tert-butylthiol 19, by refluxing with sodium hydroxide (2 hours), gave the thioalcohol (20, 85%), which by treatment with chlorosulfonic acid (one equivalent) in dichloromethane, followed by vacuum distillation at 70 °C, afforded the sulfonium salt (21, 80%) (Scheme 2). ... 

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