1-Bromo-l-chloropropane

Hydrogen hahdes normally add to form 1,2-dihaLides, though an abnormal addition of hydrogen bromide is known, leading to 3-bromo-l-chloropropane [109-70-6], the reaction is beUeved to proceed by a free-radical mechanism. Water can be added by treatment with sulfuric acid at ambient or lower temperatures, followed by dilution with water. The product is l-chloro-2-propanol [127-00-4]. 

Reactions of this type have been widely used for the synthesis of 1,5-benzoxazepines by the reactions of o-aminophenols and their derivatives with a variety of functionalized three-carbon chains. Thus reaction with 3-bromo-l-chloropropane gives (360) and reaction with 3-chloropropionyl chloride gives the analogous 4-oxo derivative. Similarly a,/3-unsatur-ated Icetones give (361), /3-ketoesters give (362), l,3-oxazolid-5-ones give (363), and the reaction of the sodium salt of N-methanesulfonyl-o-aminophenol with epichlorohydrin gives... 

The quaternary bromide 25, obtained from DBU and 3-bromo-l-chloropropane in diethyl ether, was reduced with lithium aluminum hydride (LAH) in tetrahydrofuran (THF) at ambient temperature to give a perhydro bicycle (26), which was then cyclized in refluxing acetonitrile to a tricyclic salt (27)(82TL1121). 

A systematic study of the alkylation of benzene with optically active 1,2-, 1,3-, 1,4-, and 1,5-dihaloalkanes showed that the stereochemical outcome depends on the halogens and the chain length.142 Retention of configuration in alkylation with (S)-1,2-dichloropropane was explained by invoking double inversion and the involvement of a bridged cation such as 27. (S)-l-Bromo-2-chloropropane, in contrast,... 

Oxatomide (ill, R = Xj = X2 = X3 = H), the selected compound of the series, is currently prepared according to Scheme 2. Alkylation of 1,3-dihydro-l-(1-methylethenyl)-2H-benzimidazol-2-one (IV) ) with I-bromo-3-chloropropane afforded V, which... 

Na-methoxide added to a soln. of 7-chloro-l,3-dihydro-5-phenyl-2H-l,4-benzo-diazepin-2-one in anhydrous dimethylformamide, stirred and heated 0.5 hr. on a steam bath, cooled to 30, treated with l-bromo-3-chloropropane, and stirred 66 hrs. at 20° -> 7-chloro-l-(3-chloropropyl)-l,3-dihydro-5-phenyl-2H-l,4-benzodiazepin-2-one. Y 86%. L. H. Sternbach et al., J. Med. Ghem. 8, 815 (1965). 

To a solution of 0.35 mol of allenyllithium in 240 ml of hexane and 200 ml of THF (see Chapter II, Exp. 13) were added 25 g of dry HMPT at -80°C. Subsequently 0.30 mol of l-bromo-3-chloropropane were added in 10 min. The reaction was very exothermic, but could be kept under control by occasional cooling in a bath with liquid nitrogen. After an additional 10 min the cooling bath was removed and the temperature was allowed to rise to -30°C. The solution was then poured into 500 ml of water. The organic layer and three ethereal extracts were dried over magnesium sulfate. The solvents were distilled off as thoroughly as possible at... 

Dialkylation of an amine or sulfonamide with a 1,3-dihalide provides a further route to azetidines <79CRV33l, 64HC( 19-2)88 5). Examples of this approach are the formation of N-tosylazetidine from tosylamide and l-bromo-3-chloropropane and the formation of N-alkylazetidinyl esters (36). The latter reaction works well except for R=Me the former provides a useful route to azetidine since the tosyl group can be removed by reductive methods. 

Chloropropyl bromide (l-bromo-3-chloropropane) [109-70-6] M 157.5, b 142-145 , n 1.4732. Washed with cone H2SO4, water, 10% Na2C03 soln, water again and then dried with CaCl2 and fractionally distd just before use [Akagi, Oae and Murakami J Am Chem Soc 78 4034 1956]. 

The propyne (b.p. —23.2°) is precondensed to the mark in a volumetric flask cooled by acetone-dry ice. Evaporation of some propyne during addition will lead to a moderate molar excess of l-bromo-3-chloropropane, regarded as desirable in preventing formation of diyne product. 

Gas chromatographic analysis at 79° using a flame detector in conjunction with a 183 x 0.32 cm. stainless-steel column containing Dow-Corning 550 fluid on silanized support gave peaks for l-bromo-3-chloropropane (6.5 minutes) and 6-chloro-2-hexyne (9.3 minutes) whose areas were shown to be proportional to the mole fractions. The latter were determined by integration of the expanded (50 Hz sweep width)... 

The 3tf,9tf-diazaperylenium dication 33 was synthesized for the first time in two steps from />-phenylenediamine. When reacted with l-bromo-3-chloropropane, this diamine gave the diazaperylene 359, containing two quinolizidine fragments <2001CC1742>, and this product was oxidized with HgO in acetic acid to give a low yield of a mixture of quinolizinium products 33 and 360 in a 1 3 molar ratio (Scheme 81) <20020L4113>. 

Pyrrolizines fused to a pyridine ring can be prepared from pyrrolopyridinones such as 118. These can be alkylated both at the amide nitrogen and at the carbon a to that nitrogen, and so reaction of 118 with l-bromo-3-chloropropane and sodium hydroxide under phase-transfer conditions gives the tetrahydropyrido[2,3-tf]pyrrolizinone 119 <1990BCJ3047> (Equation 6). 

Dithiane, with l-bromo-3-chloropropane and n-butyl-lithium to give 5,9-dithi-aspiro[3.5]nonane, 51, 76... 

Available from K K Laboratories or may be prepared in 89% yield by the following procedure. To a solution of 393 g. (2.63 moles) of sodium iodide in 1 1. of reagent grade acetone is added 394 g. (2.50 moles) of l-bromo-3 chloropropane (Aldrich Chemical Co.). After stirring 2 hours at room temperature, the mixture is filtered, the sodium bromide is washed with acetone, and the acetone is evaporated at reduced pressure. A dark iodine color is present along with some solid sodium salts. The oil is dissolved in ether, and the solution is washed with a 10% aqueous sodium thiosulfate solution. The ethereal layer is separated, dried over anhydrous sodium sulfate, and evaporated at reduced pressure to yield 454 g. of an oil that can be used without further purification. 

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