2,5-Dichloro-2,5-dimethylhexane

2, 5-dichloro -2, 5-dimethylhexane is an organic compound with the formula C8H16Cl2. This compound appears in a colorless to yellowish liquid state and has a unique chemical property. Due to its unique molecular structure, 2, 5-dichloro-2, 5-dimethylhexane exhibits certain reactive activity, making it one of the indispensable intermediates in the organic synthesis process. This intermediate plays an important role in chemical reactions because it is able to react specifically with other compounds to produce complex molecules with specific functions and structures. Due to its wide application in organic synthesis, 2, 5-dichloro-2, 5-dimethylhexane has an important position in chemical research and industrial production.

2, 5-Dichloro-2, 5-dimethylhexane (compound 2) was synthesized using a known procedure set forth in Bruson H et al., J Am Chem Soc, 62:36 (1940), whereby 50 g of 2, 5-dimethylhexane-2, 5-diol (compound 1 ) and 1 L of concentrated hydrochloric acid was used. Yield was measured quantitatively. Properties of compound 2 matched that reported in Bruson et al.2, 5-Dichloro-2, 5-dimethylhexane 2, 5-Dimethyl-2, 5-hexanediol (200 grams, 1.37 mole) was added as a solid portion wise to 3 liters of concentrated hydrochloric acid in a large Erlenmeyer flask. The diol quickly dissolved in the hydrochloric acid and the desired product 2, 5-dichloro-2, 5-dimethythexane precipitated out of solution as it was formed. The reaction was stirred at room temperature for 4 hours. One liter of 50percent ethyl acetate in hexanes were added and the organic later separated and washed several times with water (until neutral by pH paper). The organic solvents were removed in vacuo at room temperature The crude 2, 5-dichloro-2, 5-dimethylhexane was dissolved in hexanes and plugged through a pad of silica gel (10:1 ratio) and eluted with hexanes. This final filtration step gives a white solid after removal of the organic solvent in vacuo. Recovery of pure 2, 5-dichloro-2, 5-dimethylhexane was 230 grams 92percent yield. 1H NMR (CDCl3, delta): 1.96 (4H, s); 1.61 (12H, s).Synthesis of 2, 5-dichloro-2, 5-dimethylhexane To 2, 5-dimethyl-2, 5-hexanediol (10 g, 68.5 mmol) in a 500 mL flask was added reagent grade concentrated HCl (150 mL) and the solution was stirred at ambient temperature for 1 h. Water (100 mL) and CH2, 5-Dimethyl 2, 5-hexanediol (21) (7.31 g) was added to concentrated hydrochloric acid (100 mL) and stirred vigorously at room temperature for 30 minutes. The obtained precipitate was collected by filtration, washed with water, and dissolved in dichloromethane. After washing with water and saturated brine, the organic layer was dried with anhydrous sodium sulfate. Filtration and concentration under reduced pressure gave the title compound (22) (7.93 g, yield 86.7percent) as a white solid.Concentrated HCl (1.2 L, 14.4 mol) was added to commercial 2, 5-dimethyl-hexane-2, 5-diol (202 g, 1.4 mol) and the slurry was stirred at ambient temperature for 1.5 h.. Concentrated HCl (1.2 L, 14.4 mol) was added to commercial 2, 5-dimethyl-hexane-2, 5-diol (202 g, 1.4 mol) and the slurry was stirred at ambient temperature for 1.5 h. The mixture was filtered. The collected solid was washed with water (.x.3), dissolved in Et2O, washed successively with H2O, NaHCO3, and brine, dried over Na2SO4, and concentrated in vacuo. Recrystallization of the resulting solid residue from Et2O gave the title compound as white crystals (216 g, 85percent). 1H NMR (300 MHz, CDCl3): δ 1.60 (s, 12H), 1.95 (s, 4H).A solution of 2, 5-dimethyl-2, 5-hexanediol 19(2.0 mmol) in 37percent hydrochloric acid (42 mmol) was stirredat room temperature for 65 h. The mixture was extractedwith ethyl acetate and the organic phase was washed with5percent NaHCO3 and dried over anhydrous MgSO4. The solventwas removed under reduced pressure. The product waspurified by flash chromatography and recrystallizationusing hexane as solvent, which furnished 2, 5-dichloro-2, 5-dimethyl hexane 20 as white crystals in 85percent yield.mp 68 °C; 1H NMR (300 MHz, CDCl3) δ 1.58 (s, 12H, 3CH3), 1.93 (s, 4H, 2CH2); 13C NMR (75 MHz, CDCl3) δ 32.52, 41.14, 70.35.2, 5-dimethyl-hexane-2, 5-diol (10 g, 68.4 mmol) was placed in a reaction vessel with gentle stirring. Cone. HCI (aq, 80 mL) was added and the resulting mixture was stirred slowly for 15 mins. The resulting suspension was left standing for 2 h. It was then filtered and washed with 2x30 mL of water. A resulting solid was dried under high vacuum to afford the title compound T-1 (10.1 g, 81percent yield). The analytical data matches those reported in the literature.2, 5-Dichloro-2, 5-dimethylhexane Thionyl chloride (25 ml, 341.8 mmol) is added at ambient temperature to a solution of 2, 5-DIMETHYL-2, 5-HEXANEDIOL (20.0 g, 136.8 mmol) in 250 ml OF DICHLOROMETHANE. The reaction mixture is stirred for 4 hours. Then 250 ml of distilled water is added. The organic phase is separated and washed with 10percent NAHCO3 solution (2X250 ml), then dried over MGS04 and evaporated to dryness to give the title compound (18.37 g, 73percent). APOS;H NMR (CDCI3) : 1.57 (s, 12H, CH3) ; 1.92 (s, 4H, CH2).a) For comparison in the biological evaluation (Fig. 1 and 2) of compounds 1 - 3, [8 and 9] and 30-32, [8b and 9b] an authentic sample of bexarotene and its ketone analog (33a) were synthesized, following the reported route (Boehm, et al. 'Synthesis and Structure-Activity Relationships of Novel Retinoid X Receptor-Selective Retinoids. J. Med. Chem. 1994, 37, 2930-2941 ): a seven step, convergent synthesis that gave a 29percent overall yield of bexarotene. The first sequence of steps to bexarotene concerned the SN1 conversion of 2, 5-dimethyl-2, 5-hexanediol (33b) to 2, 5-dichloro-2, 5- dimthylhexane (34) by HCI, and the subsequent aluminum trichloride catalyzed Friedel-Crafts alkylation of toluene to give 1 , 2, 3, 4-tetrahydro-l .l A4, 6-pentamethylnapthalene (35) in 68percent yield over two steps (Scheme 1 ).2, 5-dimethylhexane-2, 5-diol (10.0 g, 68.4 mmol) was stirred in 50 mL of conc. aq. HCl for 16 hr. The reaction was diluted with 50 mL of HConcentrated HCl (400 mL) was added to 2, 5-dimethyl-2, 5-hexanediol (50.0 g, 432 mmol) dropwise with gentle swirling. The diol flakes gradually dissolved and a white precipitate formed simultaneously. The reaction mixture was stirred at room temperature (RT) for 2h; the white precipitate was filtered off and was washed with water until pH ∼7 followed by cold EtOH. The solid was dried under vacuum to afford 1 as a white solid (42.5g, 68percent), mp 63–65 C (lit.(b) 2, 5-Dichloro-2, 5-dimethylhexane (1): Concentrated HCl (400 mL) was addedto 2, 5-dimethyl-2, 5-hexanediol (50.0 g, 432 mmol) dropwise with gentleswirling. The diol flakes gradually dissolved and a white precipitate formedsimultaneously. The reaction mixture was stirred at room temperature (RT) for2 h; the white precipitate was filtered off and was washed with water until pH7 followed by cold EtOH. The solid was dried under vacuum to afford 1 as awhite solid (42.5 g, 68percent), mp 63–65 C (lit.2 63–65.8 C, lit.19 63–65 C). 1H NMR(CDCl3): d 1.95 (s, 4H), 1.60 (s, 12H).

2, 5-dichloro-2, 5-dimethylhexane is an important chemical agent that is widely used in chemical synthesis and industrial production. Especially in the pharmaceutical and pesticide industries, it is widely used as an intermediate for the synthesis of various pharmaceutical and pesticide ingredients. The unique structure of this compound makes it highly reactive in chemical reactions and can effectively promote the progress of different chemical reactions. In addition, 2, 5-dichloro-2, 5-dimethylhexane can also be used to synthesize other organic compounds, further expanding its application in chemical research and industrial production. Due to its excellent chemical properties and wide range of uses, 2, 5-dichloro-2, 5-dimethylhexane occupies an important position in the chemical industry.

Molecular Weight:183.12
XLogP3:3.4
Rotatable Bond Count:3
Exact Mass:182.0629059
Monoisotopic Mass:182.0629059
Heavy Atom Count:10
Complexity:91.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes