Hexane, 1-bromo, reaction with

To a 2 L, 3-neck Morton flask fitted with a thermometer, a mechanical stirrer, and an addition funnel was added the methyl 3-hydroxy-2-methylene-3-phenylpropionate (305.9 g, 1.585 mol) followed by addition of 48% HBr (505 ml, 4.46 mol) in one portion. The flask was immersed in an ice-water bath, at which time concentrated sulfuric acid (460 ml, 8.62 mol) was added dropwise over 90 min and the internal temperature of the reaction mixture was maintained at 23°-27°C throughout the addition process. After removal of the ice-water bath, the mixture was allowed to stir at room temperature overnight. The solution was then transferred to a separatory funnel and the organic layer was allowed to separate from the acid layer. The acids were drained and the organic layer was diluted with 2 L of a 1 1 ethyl acetate/hexane solution, washed with saturated aqueous sodium bicarbonate solution (1 L), dried over sodium sulfate, and concentrated to yield 400.0 g (99%) of the desired (Z)-l-bromo-2-carbomethoxy-3-phenyl-2-propene as a light yellow oil, which was used without any additional purification, boiling point 180°C (12 mm). 

Since the pyridinyl radical is soluble in n-hexane, and BrCHjBr has a dipole moment of l.OD, the initial state is not very polar and the transition state can thus not be very polar. A free-energy versus reaction coordinate diagram (Fig. 24a) illustrates the point. The rate-limiting step must be the transfer of a bromine atom from the halocarbon to the pyridinyl radical, yielding a bromomethyl radical and one or two bromodihydropyridines. The latter dissociate to the pyridinium bromide, while the former combines with a second pyridinyl radical to form two bromo-methyldihydropyridines. The mechanism is shown in Fig. 25 for the reaction with BrCH Cl. 

Diethyl 3-bromo-3-chloromethylcyclopropane-trans-l,2-dicarboxylate was formed in good yield (76%) from the corresponding 3-bromomethylcyclopropane on reaction with lithium chloride at elevated temperature. However, dimethyl 3-bromo-3-bromomethylcyclo-propane- ra i-l,2-dicarboxylate gave the corresponding chloride in low yield under the same conditions, in part due to formation of methyl 1 -bromo-4-oxo-m-3-oxobicyclo[3.1.0]hexane-6-carboxylate. ... 

The reported synthesis for (5Z,9Z)-14-methylpentadeca-5,9-dienoic acid (14) started with commercially available 4-methylpentan-l-ol, which upon reaction with phosphorous tribromide afforded l-bromo-4-methylpentane [52], Commercially available pent-4-yn-l-ol was also protected as the tetrahydropyranyl ether as shown in Fig. (18). Formation of the lithium acetylide with n-BuLi in THF and subsequent addition of 1-bromo-4-methylpentane in hexamethylphosphoric acid triamide resulted in the isolation of the tetrahydropyranyl protected 9-methyldec-4-yn-l-ol. Hydrogenation of the alkyne with Lindlar s catalyst and quinoline in dry hexane afforded the cis hydropyranyl-protected 9-methyldec-4-en-l-ol. Deprotection of the alcohol with />-toluenesulfonic acid afforded (Z)-9-methyldec-4-en-l-ol. Pyridinium chlorochromate oxidation of the alcohol resulted in the isolation of the labile (Z)-9-methyldec-4-enal. Final Wittig reaction with (4-carboxybutyl) triphenylphosphonium bromide in THF/DMSO resulted in the desired (5Z,9Z)-14-methylpentadeca-5,9-dienoic acid (14). 

Alkyl-l-alkynes. Reaction of 1-bromo-l-alkynes (1) with at least 2 eq. of n-butyllithium in hexane gives 3-butyl-1-alkynes (2) in excellent yields. The favored mechanism involves metal-halogen exchange (a) and further reaction with n-butyllithium to give the dUithioalkyne (b), which is then alkylated at the propargylic carbon atom ... 

Suggest a reason why treating 2-bromo-bicyclo[2.1.1]hexane (draw it) with KOH and ethanol leads to the less substituted alkene rather than the more substituted alkene (draw both alkenes)—despite the fact that these are E2 conditions. This observation led to what is known as Bredt s rule for reactions that produce an alkene unit in small bicyclic molecules. 

Now let s draw the forward scheme. The 3° alcohol is converted to 2-methylpropene using strong acid. Anti-Markovnikov addition of HBr (with peroxides) produces l-bromo-2-methylpropane. Subsequent reaction with sodium acetylide (produced from the 1° alcohol by dehydration, bromination and double elimation/deprotonation as shown) produces 4-methyl-1-pentyne. Deprotonation with sodium amide followed by reaction with 1-bromopentane (made from the 2° alcohol by tosylation, elimination and anfi -Markovnikov addition) yields 2-methyl-4-decyne. Reduction using sodium in liquid ammonia produces the E alkene. Ozonolysis followed by treatment with dimethylsulfide produces an equimolar ratio of the two products, 3-methylbutanal and hexanal. 

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... 

A suspension of 17a,21-dihydroxypregna-4,9(ll)-diene-3,20-dione 21-acetate (0.77 g) and iV-bromoacetamide (0.3 g) in anhydrous methylene dichloride (40 ml) is added over 2-3 min with stirring to a mixture of anhydrous hydrogen fluoride (10.19 g), and anhydrous tetrahydrofuran (18 g) in a polyethylene bottle at —80° (acetone-dry ice). After 1 hr at —80° the reaction mixture is kept for a further 1 hr at 0° and then added cautiously to an excess of an ice-cold solution of sodium carbonate. Extraction with methylene dichloride and crystallization from acetone-hexane furnish 9a-bromo-ll -fluoro-17a,21-dihydroxypregn-4-ene-3,20-dione 21-acetate (0.69 g), mp 205-208°, raised by several crystallizations from acetone-hexane to 215-217° [aju 142° (CHCI3) max 240-242 mju (e 15,500). 

To a solution of 2a-bromo-5a-cholestan-3-one (7.1 g, 15.2 mmol) in 175 ml dry acetone is added dropwise a solution of potassium ethyl xanthate (2.6 g, 16.2 mmol) in 90 ml acetone. The reaction mixture is stirred at 20° for 12 hr and then evaporated to dryness under vacuum. The resulting solid is treated with 100 ml hexane to dissolve the organic material and the inorganic salts are removed by filtration. The hexane filtrate is concentrated under vacuum and the resulting yellow solid ca. 7.5 g) is crystallized from chloroform-ethanol to give the xanthate (137) as white needles, ca. 5 g mp 114-115°. 

An aryllithium reagent, prepared from 1-bromo-2,6-diethylbenzene and butyllithium, reacts with SnCl2 in THF at 0°C to produce hexakis(2,6-diethylphenyl)tristannacyclopro-pane, 47, in 50-55% yield883. If the reaction above is performed at 0°C in Et20, the 1-butyl-2,2,3,3,4,5,5,6,6-nonakis(2,6-diethylphenyl)hexastannabicyclo[2,2,0]hexane, 48, can be isolated in 1.5% yield. This compound turns out to be the first example of a polycyclic polystannane88b. 

A mixture of diethyl 2-bromo-l-phenylethenylphosphonite (30.3 g, 0.1 mol) and dimethyl maleate (14.4 g, 0.1 mol) was stirred for 4 h at room temperature under an argon atmosphere. At this time, hexane was added to the reaction mixture sufficient for complete precipitation, and the resultant crystals (unreacted dimethyl maleate) were removed by filtration. The oily residue was treated on a silica gel column (40/100 pm) using a pentane/acetone (8 2) mixture, allowing the elution and isolation after evaporation of pure l-ethoxy-2-phenyl-4,5-dimetho x yea rb o n y I - A2-X5-phospholene 1-oxide (8.9 g, 27%), which exhibited spectra and analytical data in accord with the proposed structure. 

Preparation of 2-bromo-3-(p-tolyl)propene (typical procedure) A three-necked, 50 mL flask equipped with an argon inleL a rubber septum and an internal thermometer was charged with bis(p-bromophenyl)ditelluride (1.7 g, 3.0 mmol, 1 equiv) and Ni(acac)2 (77 mg, 0.3 mmol, 10 mol%). The reaction mixture was cooled to -40°C and THF (6 mL) was added. It was further cooled to -78°C and Et2Zn (1.5 mL, 15 mmol, 5 equiv) was slowly added via syringe. The reaction was allowed to warm to room temperature and was stirred for 6 h. Meanwhile, a mixture of copper cyanide (2.68 g, 23 mmol) and lithium chloride (2.54 g, 60 mmol) was dried under vacuum (130°C, 2 h) and dissolved in THF (10 mL). This solution was added to the reaction mixture at -60°C, followed by 2,3-dibro-mopropene (6.0 g, 30 mmol, 10 equiv). The reaction mixture was warmed up to room temperature and worked up as usual. The crude oil obtained after evaporation of the solvents was purified by flash chromatography (hexanes), affording the product (1.45 g, 5.2 mmol, 88% yield) as a colourless oil. 

A mixture of 0.10 mol of l-bromo-5-hexyne (Chap. XII, exp. 1.5) and 70 ml of THF is cooled to between -60 and -80 C. A solution of 0.105 mol (slight excess) of BuLi in hexane is added drop wise over -15 min, while maintaining the temperature range indicated. Two minutes after this addition, derivatization reactions can be carried out with the clear solution. 

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