1,1,4,4,6-Pentamethyl-1,2,3,4-tetrahydronaphthalene

White Solid

1, 1, 4, 4, 6-pentamethyl-1, 2, 3, 4-tetrahydronaphtalene 4: The synthesis of compound 8 is outlined below : To a solution of 2, 5 dichloro-2, 5 [DIMETHYLHEXANE, ] 2, (10 g, 54.7 [MMOL)] in toluene (270 mL 0.2 M) was slowly added aluminum trichloride (5.47 g, 41 [MMOL)] as a solid over 15 minutes time. The reaction was complete after 10 minutes as assayed by TLC in hexanes. The unreacted aluminum trichloride was quenched slowly with water over 10 minutes. Additional toluene (250 mL) was added to extract the product from the aqueous layer. The organic layer was passed through a pad of silica gel (40 [G)] and eluted with toluene. The organic layer was [EVAPORATED IN VACUO] to dryness to yield 1, 1, 4, 4, [6-PENTAMETHYL-1, ] 2, 3, 4-tetrahydronaphtalene, 4 (11g, 97percent yield). To a solution containing 1, 1, 4, 4, [6-PENTAMETHYL-1, ] 2, 3, 4-tetrahydronaphtalene, 4, (20 g, 99 [MMOL)] and methyl 5- (chloromethyl)-2-furoate, 5, (17.28 g, 99 [MMOL)] in methylene chloride (500 mL 0.2 M aluminum trichloride (16.46 g, 124 [MMOL)] was added slowly as a solid at the reflux temperature. The solution was refluxed for an additional two hours. The reaction was monitored by TLC in 10percent ethyl acetate/hexanes solution. The reaction was cooled to room temperature and the unreacted aluminum trichloride was quenched with water over 15 minutes. The crude product was extracted with methylene chloride and passed through silica gel (80 [G)] and eluted with methylene chloride. The solvent was [EVAPORATED IN VACUO] to syrup. The crude product was purified with silica gel (300g) via a plug [FILTERATION] column. Methyl [5- [ (3, ] 5, 5, 8, [8-PENTAMETHYL-5, ] 6, 7, 8-tetrahydro-2- naphthalenyl) methyl]-2-furoate, 6, was eluted with 2 percent ethyl acetate/hexanes to afford 15.4 [G] (46 percent yield). To a solution containing Methyl [5- [ (3, ] 5, 5, 8, 8-pentamethyl-5, 6, 7, 8-tetrahydro-2-naphthalenyl) methyl]-2-furoate, 6, (15.1 g, 44 [MMOL)] in MeOH (175 mL) and water (175 mL), a solution of [NAOH] (3.53 g, 88.3 [MMOL)] in water (29 mL) was added. The reaction was stirred overnight at room temperature. After completion as judged by TLC, the solution was acidified with 1 M HCI to pH 2. The crude product was extracted in to organic layer using ethyl acetate and concentrated to afford 5- [[ (3, 5, 5, 8, 8-PENTAMETHYL-5, 6, 7, 8-TETRAHYDRO-2-NAPHTHALENYL) METHYL]-2-FUROIC] acid, 7 (15.0 g, 99 percent yield). To a solution containing [5- [ (3, ] 5, 5, 8, [8-PENTAMETHYL-5, ] 6, 7, [8-TETRAHYDRO-2-NAPHTHALENYL)] methyl]- 2-furoic acid, 7, (20.15 g, 61.77 [MMOL)] in methylene chloride (310 mL), thionyl chloride (45 mL, 617. mmol) was added. The reaction was heated under reflux for 5 hours and another batch of thionyl chloride (45 mL, 617 [MMOL)] was added. The reaction was stirred overnight at room temperature. The solution was concentrated to a syrup and filtered through a pad of silica gel [(50G), ] eluted with 3percent ethyl acetate in hexanes, and [CONCENTRATED IN VACUO] to afford [5- [ (3, ] 5, 5, 8, [8-PENTAMETHYL-5, ] 6, 7, 8- tetrahydro-2-naphthalenyl) methyl]-2-furoyl chloride, 8 (17g, 80percent yield).(1)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 CHTo a 1000 mL round-bottomed flask fitted with water condenser were added compound 1 (30.0 g, 165 mmol), toluene (35.1 mL, 330 mmol) and CH(c) 1, 1, 4, 4, 6-Pentamethyl-1, 2, 3, 4-tetrahydronaphthalene (2): To a 1000 mLround-bottomed flask fitted with water condenser were added compound 1(30.0 g, 165 mmol), toluene (35.1 mL, 330 mmol) and CH2Cl2 (150 mL). To thisvigorously stirred solution was added aluminum chloride (1.92 g, 1.4 mmol)slowly in portionwise, which resulted in rapid evolution of gaseoushydrochloride acid. The reaction mixture was stirred at RT for 30 minfollowed by additional aluminum chloride (400 mg). After the reactionmixture was stirred and heated to reflux for 15 min, it was cooled in an icebath and quenched with 20percent HCl aqueous solution (150 mL). The mixture wasextracted with hexanes; the combined organic layers were washed with waterand brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo.The crude product was purified by column chromatography with hexanes toafford 2 as a white solid (28.3 g, 85percent), mp 34–35 C (lit.2 34–36 C). 1H NMR(CDCl3): d 7.40 (d, J = 8.0 Hz, 1H), 7.31 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 2.49 (s, 3H), 1.87 (s, 4H), 1.48(s, 6H), 1.47 (s, 6H).In a 250 ml_ round-bottomed flask was weighed T-1 (1.8 g, 10 mmol). Dry DCE (20 ml_) was added followed by dry toluene (921 mg, 10 mmol, 1 equiv). Then AICI3 (133 mg, 1 mmol, 10 molpercent) was added in portions. The resulting mixture was stirred under argon for 16 h. The mixture was cooled to room temperature, and then poured on ice-water (50 ml_). The organic layer was separated and the aqueous layer was extracted with Et22, 3-Dimethyl-butane-2, 3-diol (20.0 g, 0.14 mol) was added portionwise to 100 mL of conc. HCl at room temperature. After stirring for 1 h, a viscous white slurry was formed. The mixture was cooled with an ice bath, 50 mL of ice-water was added, the mixture filtered and dried at reduced pressure. The residue was then dissolved in a mixture of dichloromethane (100 mL) and toluene (25.8 g, 0.28 mol). Aluminum chloride (200 mg 1.50 mmol) was added slowly and the mixture was stirred at room temperature for 3 h. The mixture was then poured to 100 mL of ice-water, extracted with dichloromethane (3*10 mL), washed with saturated sodium bicarbonate (1*10 mL) and brine (1*110 mL). After the extract was dried (MgSO1, 1, 4, 4, 6-pentamethyl-1, 2, 3, 4-tetrahydronaphtalene 4: To a solution of 2, 5 dichloro-2, 5 dimethylhexane 2 (10 g, 54.7 mmol) in toluene (270 Ml, 0.2 M) is slowly added aluminum trichloride (5.47 g, 41 mmol) as a solid over a 15-minute period. The reaction is complete after 10 minutes as assayed by tlc in hexanes. The unreacted aluminum trichloride is quenched slowly with water over 10 minutes. Additional toluene (250 mL) is added to extract the product from the aqueous layer. The organic layer is passed through a pad of silica gel (40 g) and eluted with toluene. The organic layer is evaporated in vacuo to dryness to yield 1, 1, 4, 4, 6-pentamethyl-1, 2, 3, 4-tetrahydronaphtalene4 (11g, 97percent yield). NMR 1.29 (s, 6H), 1.28 (s, 6H), 1.69 (s, 4H), 2.32 (s, 3H), 7.22 (d, 1H), 7.12 (s, 1H), 6.97 (dd, 1H).

Targretin analog, has been shown to induce apoptosis in certain leukemia cell lines.

Molecular Weight:202.33
XLogP3:5.4
Exact Mass:202.172150702
Monoisotopic Mass:202.172150702
Heavy Atom Count:15
Complexity:236
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes