5-Bromo-1-tetralone

Preparation of 7-Bromo-l-tetralone; 7-bromo-1-tetralone was prepared according to the procedure described in Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994, 24, 2777-2788. The above isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-bromo-1-tetralone (11.59 g, 51percent) and 7-bromo-1-tetralone (9.45 g, 42percent).A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.34 g, 250 mmol) and heated to 75-80 °C. 1- Tetralone (14.6 g, 13.3 ML, 100 mmol) was added dropwise over 10 min. The resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51percent) and 7- BROMO-1-TETRALONE (9.45 g, 42percent).A 500 mL three-necked flask fitted with an addition funnel, reflux condenser and thermometer was charged with aluminum chloride (33.-34 g, 250 mmol) and heated to 75-80 °C. 1- Tetralone (14.6 g, 13.3 mL, 100 mmol) was added dropwise over 10 MIN. THE resulting brown slurry was stirred for 3 min before dropwise addition of bromine (19.21 g, 6.15 ml, 120 mmol) over 15 min. The mixture was stirred for 5 min and then poured into a mixture of ice (300 g) and 12N HC1 (40 mL). The mixture was stirred until the aluminum chloride was dissolved and then diluted with water (200 mL). The mixture was extracted with diethyl ether (3 X 300 mL) and the combined organics were washed with water (2 X 300 mL), dried (sodium sulfate), filtered and evaporated in vacuo to give a dark brown mixture of 5-and 7- BROMO-1-TETRALONE. The isomers were separated using silica gel flash chromatography (Biotage Flash 75, elution solvent 20/1 hexanes: MTBE) to yield 5-BROMO-1-TETRALONE (11.59 g, 51percent) and 7- BROMO-1-TETRALONE (9.45 g, 42percent). [Note 1. Procedure: Cornelius, L. A. M.; Combs, D. W. Synthetic Communications 1994, 24, 2777-2788].Example III To prepare this compound, 1-tetralone (10.2 g, 70 mmol) was added dropwise to a slurry of aluminum trichloride (23.3 g, 175 mmol) heated to 70 °C in a 3-neck flask with an outlet tube connected to a 2 M sodium carbonate solution. The slurry was stirred with a spatula. After the addition of 1-tetralone, the slurry was removed from heat and allowed to cool to room temperature. Bromine (12.3 g, 77 mmol) was added dropwise over 15 minutes. After that addition was complete, the slurry was heated at 80 °C for 10 minutes, then it was poured into a mixture of 200 grams of ice and 25 mL concentrated HC1. The 3-neck flask was rinsed with water and that rinse water was also added to the ice and slurry solution. That solution was extracted twice with ether (200 mL each) and those two extracts were combined. The combined ether extract was washed sequentially with water (50 mL), saturated sodium bicarbonate (25 mL), and brine (100 mL), and then was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford an oil. The oil was subjected to flash chromatography (12percent THF/hexanes), and the resultant product was recrystallized from hexanes to afford 4.4 g (27percent) of 5-bromo-3, 4-dihydro-2No.-naphthalen-l-one. Anhydrous AlCl3 (66.67 g, 0.50 mol, 99.99percent) under N2 was stirred vigorously as 1-tetralone (29.83 g, 0.20 mol) was added dropwise over 7 min. The evolved HCl gas was scrubbed through 5 N NaOH. The resulting mixture was a dark brown oil that exothermed to 75° C. When the temperature had cooled to 50° C., Br2 was added dropwise over 15 min. The mixture, which had cooled further to 40° C., was heated to 80° C. for 5 min, then poured into a mixture of ice (600 g) and 12 N HCl (80 mL). All the ice melted, leaving a cool dark mixture which was diluted with H2O (200 mL) and extracted with CH2Cl2 (200 mL, 100 mL). The combined extracts were dried with MgSO4 and concentrated in vacuo (30-60° C.) to a dark brown oil (45.6 g; theory=45.02 g).[0085] Chromatography over silica gel 60 with 8:1 heptane:THF did not prove effective, but two passes through the Biotage radially pressured silica gel cartridges using 9:1 heptane:MTBE as eluent produced acceptably pure fractions. [0086] 5-Bromo-3, 4-dihydro-1(2H)-naphthalenone was isolated as an orange oil (12.27 g, 28.3percent). HPLC showed an apparent wide divergence in absorbances at 230 nm for the two regioisomers, and was therefore not reliable for a potency check. TLC on silica gel (4:1 heptane:MTBE) confirmed modest contamination with 7-bromo-3, 4-dihydro-1(2H)-naphthalenone. [0087] 7-Bromo-3, 4-dihydro-1(2H)-naphthalenone was isolated as a yellowish-white solid (15.48 g, 35.8percent); mp 69.5-75° C. (lit 74-75° C.). 1H NMR (CDCl3) corresponded to the literature description, plus a trace of heptane and an undefined by-product. TLC showed it to be cleaner than 5-bromo-3, 4-dihydro-1(2H)-naphthalenone. [0088] A third fraction of orange oil (9.06 g, 20.9percent) was isolated. TLC showed it to be a nearly 1:1 ratio of 5-bromo-3, 4-dihydro-1(2H)-naphthalenone, and 7-bromo-3, 4-dihydro-1(2H)-naphthalenone.General procedure: A freshly prepared heterogeneous iron catalyst (10 mol%), tBuOK (8 mol%), sec.alcohol (0.5 mmol) and 2 mL of mesitylene were added to a 15 mL Schlenk flask under an atmosphere of argon. The flask was equipped with a reflux condenser and the solution was heated at 155C with stirring in an open system under argon for 36 hr (Table 4). The reaction products were analyzed by GC-MS. After cooling to room temperature, m-xylene was added as internalstandard to the reaction mixture and the products were quantitatively analyzed by GC.To prepre this compound, 90% fuming nitric acid (0.115 gram, 0.165 mmol) was added to a solution of 5-bromo-3, 4-dihydro-2No.-naphthalen-l-one (0.34 g, 1.50 mmol) in 3 mL concentrated sulfuric acid at 0 C. After 45 minutes, the mixture waspoured into ice, and 6 N aqueous sodium hydroxide (9 mL) was added very slowly. That mixture was extracted twice with EtOAc (40 mL each), and the two extracts were combined. The combined EtOAc extract was washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was subjected to flash chromatography (40% EtOAc/hexanes) and recrystallization (EtOAc/hexanes) to afford 0.15 g (38%) of 5-bromo-3, 4-dihydro-8-nitro-2H-naphthalen-l-one. *H NMR (500 MHz, CDC13) 5 7.84 (d, J = 8.2, 1H), 7.25 (d, J = 8.2, 1H), 3.07 (t, J = 6.2, 2H), 2.74 (t, J = 6.7, 2H), 2.18-2.25 (m, 2H).

Molecular Weight:225.08
XLogP3:3.2
Hydrogen Bond Acceptor Count:1
Exact Mass:223.98368
Monoisotopic Mass:223.98368
Topological Polar Surface Area:17.1
Heavy Atom Count:12
Complexity:190
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes