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Org. Synth. 2013, 90, 153-163
DOI: 10.15227/orgsyn.090.0153
Synthesis of 1-Naphthol via Oxidation of Potassium 1-Naphthyltrifluoroborate
Submitted by Gary A. Molander, Sabahat Zahra Siddiqui, and Nicolas Fleury-Brégeot1.
Checked by David Hughes
1. Procedure
A. Potassium 1-Naphthyltrifluoroborate (2). A 1-L round-bottomed flask equipped with a 4-cm oval PTFE-coated magnetic stir bar and a thermocouple thermometer (Note 1) is charged with 1-naphthaleneboronic acid (22.0 g, 128 mmol, 1.0 equiv) and methanol (80 mL) (Notes 2 and 3). The solution is cooled to 5 ºC using an ice-bath. A solution of KHF2 (30.3 g dissolved in 100 mL water, 388 mmol, 3.0 equiv) is added in 5 portions over 10 min, resulting in a thick white slurry (Note 4). The ice bath is removed and the mixture is stirred for 20 min (Note 5). The stir bar is removed and the mixture is concentrated by rotary evaporation (45 ºC bath temp, 100 to 20 mmHg) (Note 6). Acetonitrile (2 x 200 mL) flushes are used to azeotropically remove the remaining water, with the mixture concentrated by rotary evaporation after each flush (45 ºC bath temp, 100 to 20 mmHg) (Notes 7 and 8). The flask is equipped with a 3-cm oval PTFE-coated magnetic stir bar and acetonitrile (300 mL) is added. The flask is placed in a heating mantle and the stirred mixture is heated at reflux for 90 min (Notes 9 and 10). After cooling to ambient temperature over 90 min, the resulting solids are removed by filtration through a 150-mL medium porosity sintered glass funnel and rinsed with acetonitrile (2 x 50 mL) (Note 11). The filtrate is concentrated by rotary evaporation (55 ºC bath temp, 70 mmHg) to afford potassium 1-naphthyltrifluoroborate (2) as a white solid (29.9 g) as a hemi-acetonitrile solvate (Note 12). The solid is heated under vacuum (70 mmHg) for 18-24 h at 90 ºC to provide the de-solvated product (26.5 g, 89% yield) (Notes 13 and 14).
B. 1-Naphthol (3). A 1-L 3-necked round-bottom flask is equipped with a 3-cm oval PTFE-coated magnetic stir bar and a 500-mL addition funnel. The two side necks are sealed with septa, one of which is pierced with a thermocouple thermometer (Note 1). The flask is charged with potassium 1-naphthyltrifluoroborate (26.0 g, 111 mmol, 1.0 equiv) and acetone (300 mL) (Note 15). The mixture is stirred to dissolve all solids, then cooled to 3 ºC using an ice bath. The addition funnel is charged with a solution of Oxone® (72 g dissolved in 300 mL water, 117 mmol, 1.05 equiv), which is added to the flask over 10 min (Note 16). The reaction mixture is stirred for an additional 5 min, then quenched with aq HCl (0.1 M, 360 mL, 0.3 equiv), added in one portion. The contents are transferred to a 2-L separatory funnel and extracted with dichloromethane (3 x 250 mL). The combined organic layers are washed with half-saturated aq. NaCl (200 mL), then dried by filtering through a bed of Na2SO4 (150 g) in a 350-mL sintered glass funnel. The filtrate is concentrated in portions in a 1-L flask by rotary evaporation (40 ºC, 200 to 20 mmHg) to an orange oil, then flushed with toluene (75 mL) and concentrated (50 ºC, 20 mmHg) to provide a brown wet solid (40 g). The product is recrystallized in the same flask by adding 15 mL of toluene and warming in a 60 ºC water bath to dissolve all solids. A 3-cm oval PTFE-coated magnetic stir bar is added and the flask is equipped with a 150-mL addition funnel. The stirred mixture is allowed to cool to room temperature, upon which crystallization occurs. n-Heptane (140 mL) is added via the addition funnel over 1 h. After stirring for 4 h, the suspension is filtered through a 150-mL medium porosity sintered glass funnel, washed with 4:1 n-heptane:toluene (2 x 15 mL), and air-dried to afford 1-naphthol (12.0 g) as an off-white to slightly pink solid. A second crop of product is obtained as follows. The filtrate and washes from the initial crystallization are concentrated by rotary evaporation (50 ºC, 20 mmHg) in a l-L flask to afford 4 g of solids. Toluene (15 mL) is added along with a 3-cm oval PTFE-coated magnetic stir bar. The mixture is warmed in a 60 ºC water bath to dissolve all solids, then allowed to cool to room temperature, upon which crystallization occurs. n-Heptane (60 mL) is added via a 150-mL addition funnel over 1 h, then the mixture is stirred for 14 h at room temperature. The suspension is filtered through a 150-mL medium porosity sintered glass funnel, washed with 4:1 n-heptane:toluene (2 x 10 mL), and air-dried to afford 1-naphthol as a pink solid (2.32 g). The two crops are combined (14.3 g, 89 % yield) (Notes 17 and 18).
2. Notes
1. The internal temperature was monitored using a J-Kem Gemini digital thermometer with a Teflon-coated T-Type thermocouple probe (12-inch length, 1/8 inch outer diameter, temperature range -200 to +250 °C).
2. The following reagents and solvents were used as received for Step A: 1-naphthaleneboronic acid (Oakwood), methanol (Fisher Optima), acetonitrile (Fisher Optima, water content 80 ppm based on Karl Fischer titration) and KHF2 (Acros 99+%). Potassium hydrogen fluoride must be handled carefully as it is corrosive. In the presence of water, it slowly releases HF. As a consequence, when using normal glassware, etching of the flask may occur with time. The solution of KHF2 was prepared fresh just prior to use. The submitters report the synthesis of organotrifluoroborates has also been carried out in Nalgene® bottles with a screw-cap lid fitted with a mechanical stirrer.
3. The submitters prepared 1-naphthaleneboronic acid as follows. An oven-dried 500-mL, 3-necked, round-bottomed flask, equipped with a stirring bar and a reflux condenser, is charged with oven-dried magnesium turnings (11.5 g, 459 mmol, 2.8 equiv, activated in an oven at 160 ºC for 48 h) and flushed with N2. The magnesium turnings are covered with dry tetrahydrofuran (50 mL) and stirred at 470 rpm. The reaction is initiated by the addition of iodine crystals (60 mg, 0.14 mol %) and a small portion (approximately 0.5 mL) of neat 1-bromonaphthalene. If necessary, the reaction flask can be further warmed using an oil bath. Once the reaction is started (as evident by the disappearance of the yellowish color of iodine) the flask is heated in a 75 ºC oil bath, and 1-bromonaphthalene (34.0 g, 164 mmol, 1 equiv) in dry THF (155 mL) is added dropwise over 25 min. The dark green solution is refluxed for 17 h. The reaction is allowed to cool over 40 min, then the solution of 1-naphthalenemagnesium bromide is transferred by cannula in a dropwise fashion over 1 h to an N2-flushed 1-L round-bottom flask containing a stirred solution of triethyl borate (42 mL, 246 mmol, 1.5 equiv) in dry THF (100 mL) placed in a dry-ice/acetone bath. After the addition is complete, the cold bath is removed and the resulting brownish green solution is stirred for 5 h at room temperature. The color of the solution changes from dark brown to white and a precipitate is formed. The reaction flask is then placed in an ice bath and aqueous HCl (100 mL, 2 M, 1.2 equiv) is added dropwise over 10 min. The white precipitate dissolves to form a light yellow, clear solution. After 1 h stirring at room temperature, the reaction mixture is extracted with diethyl ether (2 x 150 mL) and the combined organic layers are washed with distilled water (3 x 300 mL). The organic layer is dried over anhydrous sodium sulfate (50 g) and the solvents are removed on a rotary evaporator at 35 ºC at 75 mmHg. After drying under vacuum overnight, 1-naphthaleneboronic acid is obtained as a white solid (22.0-22.9 g, 78-81% yield). If necessary, the product may be recrystallized using 200 mL of distilled water and 20 mL of THF, sonicated for 5-7 min, refrigerated overnight, filtered, and dried under vacuum. Analytical data: mp: 194-196 °C. IR (cm-1): 3261, 1575, 1508, 1348, 1318, 807, 778; 1H NMR (500 MHz, DMSO-d6) d: 7.62-7.49 (m, 3 H), 7.78-7.76 (m, 1 H), 8.02-7.91 (m, 2 H), 8.35 (m, 3 H); 13C NMR (125 MHz, acetone-d6) d: 125.6, 125.9, 126.1, 128.7, 129.3, 129.7, 132.6, 133.4, 136.1; 11B NMR (128 MHz, acetone-d6) d: 30.6.
4. The reaction is run open to air. The temperature rose to 15 ºC at the end of the addition. If the slurry becomes too thick to stir, it should be broken up with a spatula.
5. The submitters monitored completion of the reaction by 11B-NMR. The disappearance of the boronic acid peak at 30.7 ppm indicated the completion of the reaction.
6. The pressure is reduced gradually to minimize bumping. About 120 mL of solvent was removed, leaving a residue of 97 g of wet solids in the flask.
7. The pressure is reduced gradually to minimize bumping. After each acetonitrile flush, the mixture was concentrated to 50-52 g of solids.
8. The submitters removed water by lyophilization for 24 h.
9. The mixture remains heterogeneous as the product dissolves, but the residual KHF2 remains undissolved.
10. The submitters subjected the crude material to Soxhlet extraction using 700 mL of acetonitrile in a 1-L round-bottomed flask placed in an oil bath (102 ºC and 280 rpm) for 6 h. The filtrate was concentrated on a rotary evaporator under reduced pressure at (40 ºC, 150 mmHg) until dry material was obtained.
11. The water content of the acetonitrile solution was determined to be 570 ppm based on Karl Fischer titration. Higher levels of water can result in some dissolution of KHF2.
12. The hemi-solvate was determined based on 1H NMR analysis in acetone-d6. The solvate remained intact upon vacuum drying 2 days at 40 ºC.
13. The submitters report the crude product can be purified by dissolving the material in acetonitrile (50 mL) and precipitating with diethyl ether (300 mL).
14. Potassium 1-naphthyltrifluoroborate has the following physical and spectroscopic properties: mp: > 300 ºC. IR (cm-1): 2980, 2884, 2360, 1382, 940, 668, 651; 1H NMR pdf (400 MHz, acetone-d6) δ: 7.30-7.36 (m, 3 H), 7.64 (d, J = 8.2 Hz, 1 H), 7.74-7.77 (m, 2 H), 8.57-8.59 (m, 1 H); 13C NMR pdf (100 MHz, acetone-d6) δ: 124.5, 124.8, 125.9, 126.7, 128.4, 130.0 (q, JC-F = 3.2 Hz), 131.4, 134.5, 138.1, 147 (very broad); 11B NMR (128 MHz, acetone-d6) δ: 4.06; 19F NMR pdf (377 MHz, acetone-d6) δ: -138.6; HRMS (ESI) m/z calcd. for C10H7BF3 (M-K) 195.0593, found 195.0593. Anal calcd for C10H7BF3K: C, 51.31; H, 3.01; Found: C, 51.50; H, 2.81.
15. The following reagents and solvents were used as received for Step B: acetone (Fisher certified ACS), Oxone® (Sigma-Aldrich), toluene (Fisher Optima), n-heptane (99%, ReagentPlus, Sigma-Aldrich), dichloromethane (Fisher, certified ACS reagent, stabilized) and 6 N HCl (Fisher). The solution of Oxone was prepared fresh just prior to use.
16. The reaction was carried out open to air. The temperature rose to 32 ºC during the addition. The reaction mixture becomes milky white during the addition.
17. 1-Naphthol has the following physical and spectroscopic properties: mp: 95-96 ºC (lit. mp 95 ºC2a, 94 ºC2b); IR (cm-1): 3300, 1597, 1358, 1269, 1083, 789, 765; Rf: 0.4 (hexanes/EtOAc 4:1); 1H NMR pdf (400 MHz, CDCl3): δ: 5.17 (s, 1 H), 6.83 (dd, J = 7.4, 0.7 Hz, 1 H), 7.30-7.34 (m, 1 H), 7.43 (d, J = 8.3 Hz, 1 H), 7.48-7.53 (m, 2 H), 7.81-7.85 (m, 1 H), 8.17-8.20 (m, 1 H); 13C NMR pdf (100 MHz, CDCl3): δ: 108.8, 121.0, 121.7, 124.6, 125.5, 126.0, 126.7, 127.9, 135.0, 151.5; MS (EI, 70eV) 144 (M+, 100), 116 (62), 115 (81), 89 (22), 63 (18); Purity by GC: 99% (tR = 11.2 min, conditions: Agilent DB35MS column; 30 m x 0.25 mm; initial temp 60 °C, ramp at 20 °C/min to 280 °C, hold 15 min)
18. A yield of 87% was obtained at half scale.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
Boron containing reagents are among the most versatile building blocks used in chemistry. Historically, boranes and boronic acids are the most encountered, but over the past decades, modified boron compounds, which overcome some of the limitations associated with the earlier boron reagents, have emerged.3
Potassium organotrifluoroborates, quaternary boron salts, represent a relatively new class of reagents that are air and moisture stable and are efficient partners in boron-based chemical transformations.4 They are easily prepared by addition of KHF2 to various organoboron reagents,5 and once synthesized they can be stored indefinitely without particular precaution. The organotrifluoroborate group acts as a boronic acid surrogate that can be carried through several chemical transformations6 before being reacted or deprotected to yield the boronic acid.7 These features make them very attractive reagents, and they are the subject of many studies. They are mainly used as coupling partners in the Suzuki-Miyaura reaction8 but are also very useful reagents in other transformations.9
Treatment of organotrifluoroborate salts with oxone10 represents a very efficient and practical method to oxidize these boron reagents. Oxone is an inexpensive reagent that readily oxidizes a large range of organotrifluoroborates in high yields within minutes. The rapidity, ease of execution, and non-toxicity of the oxidizing agent, associated with the advantages inherent to the potassium organotrifluoroborates, make the procedure described above a very convenient, environmentally sound, and attractive transformation. The process is exceedingly general. Aromatic trifluoroborates are transformed to phenols, alkyltrifluoroborates are converted to the corresponding alcohols in a stereospecific manner (complete retention of configuration), and alkenyltrifluoroborates can be used to access aldehydes (Table 1). These transformations occur with great chemoselectivity, as other oxidizable groups such as alkenes, aldehydes, as well as sulfides and amines remain untouched under the mild reaction conditions.
Table 1. Oxidation of Various Organotrifluoroborates with Oxone
Table 1. Oxidation of Various Organotrifluoroborates with Oxone

References and Notes
  1. Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104-6323
  2. (a) Paul, R.; Ali, M. A.; Punniyamurthy, T. Synthesis 2010, 4268-4272. (b) Hoffmann, R. W.; Ditrich, K. Synthesis 1983, 107-109.
  3. (a) Hall, D. G., Ed. Boronic Acids; Wiley-VCH: Weinheim, 2005; (b) Onak, T. Organoborane Chemistry; Academic Press: New York, 1975.
  4. (a) Molander, G. A., Figueroa, R. Aldrichim. Acta 2005, 38, 49-56; (b) Molander, G. A., Ellis, N. Acc. Chem. Res. 2007, 40, 275-286; (c) Stefani, H. A., Cella, R., Adriano, S. Tetrahedron 2007, 63, 3623-3658; (d) Darses, S., Genêt, J.-P. Chem. Rev. 2008, 108, 288-325; for mechanistic details on the advantages of organotrifluoroborates over other boron reagents in the Suzuki reaction see: (e) Butters, M., Harvey, J. N., Jover, J., Lennox, A. J. J., Lloyd-Jones, G. C., Murray, P. M. Angew. Chem. Int. Ed. 2010, 49, 5156-5160.
  5. (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020: (b) Molander, G. A.; Cooper, D. J. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons: New York, 2006; DOI 10.1002/047084289X.rn00628.
  6. For some examples see: (a) dihydroxylation: Molander, G. A., Figueroa, R. Org. Lett. 2006, 8, 75-78; (b) nucleophilic substitution: Molander, G. A., Ham, J. Org. Lett. 2006, 8, 2031-2034; (c) dipolar cycloaddition: Molander, G. A., Ham, J. Org. Lett. 2006, 8, 2767-2770; (d) oxidation: Molander, G. A., Petrillo, D. E. J. Am. Chem. Soc. 2006, 128, 9634-9635; (e) metalation: Molander, G. A., Ellis, N. M. J. Org. Chem. 2006, 71, 7491-7493; (f) ozonolysis: Molander, G. A., Cooper, D. J. J. Org. Chem. 2007, 72, 3558-3560; (g) olefination: Molander, G. A., Figueroa, R. J. Org. Chem. 2006, 71, 6135-6140; Molander, G. A., Ham, J., Canturk, B. Org. Lett. 2007, 9, 821-824; (h) reductive amination: Molander, G. A., Cooper, D. J. J. Org. Chem. 2008, 73, 3885-3891; (i) cross-coupling: Molander, G. A., Sandrock, D. L. J. Am. Chem. Soc. 2008, 130, 15792-15794; Molander, G. A., Sandrock, D. L. Org. Lett. 2009, 11, 2369-2372; (j) condensation: Molander, G. A., Febo-Ayala, W., Jean-Gerard, L. Org. Lett. 2009, 11, 3830-3833.
  7. Molander, G.A., Cavalcanti, L. N., Canturk, B., Pan, P.S., Kennedy, L. E. J. Org. Chem. 2009, 74, 7364-7369.
  8. Molander, G.A., Canturk, B. Angew. Chem. Int. Ed. 2009, 48, 9240-9261.
  9. For bromodeboronation see: (a) Kabalka, G. W., Mereddy, A. R., Organometallics, 2004, 23, 4519-4521; (b) for iododeboronation, see: Kabalka, G. W., Mereddy, A. R. Tetrahedron Lett., 2004, 45, 343-345; Kabalka, G. W., Mereddy, A. R. Tetrahedron Lett., 2004, 45, 1417-1419; (c) for chlorodeboronation see: Molander, G. A., Cavalcanti, L. N. J. Org. Chem. 2011, 76, 7195-7203.
  10. Molander, G. A., Cavalcanti, L.N. J. Org. Chem. 2011, 76, 623-630.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

1-Bromonaphthalene; (90-11-9)

Triethyl borate; (150-46-9)

Magnesium; (7439-95-4)

Iodine; (7553-56-2)

1-Naphthaleneboronic acid; (13922-41-3)

Potassium hydrogen fluoride; (7789-29-9)

Potassium 1-Naphthyltrifluoroborate: Borate(1-), trifluoro-1-naphthalenyl-, potassium (1:1), (T-4)-; (166328-07-0 )

Oxone; (70693-62-8)

1-Naphthol; (9 0-15-3)

Professor Gary Molander received his B.S. degree at Iowa State University in 1975, working with Professor Richard C. Larock. He obtained his Ph.D. degree in 1979 under the direction of Professor Herbert C. Brown. He joined Professor Barry Trost's group at the University of Wisconsin, Madison as a National Institutes of Health postdoctoral fellow in 1980, and in 1981 he accepted an appointment at the University of Colorado, Boulder. In 1999 he joined the faculty at the University of Pennsylvania. His research interests focus on the development of new synthetic methods for organic synthesis and natural product synthesis.
Sabahat Zahra Siddiqui was born in Lahore, Pakistan. She received her B.Sc degree from Lahore College for Women University (Roll of Honor), M.Sc degree in Organic Chemistry from Government College University, Lahore (Certificate of Merit) and M.Phil in Organic Chemistry from Punjab University, Lahore (Certificate of Merit). Currently, she is a Lecturer and a PhD scholar at Government College University, Lahore. She won an IRSIP scholarship 2011-2012 from the Higher Education Commission of Pakistan to visit the University of Pennsylvania, USA as a visiting research scholar where her research focused on synthetic methods using organotrifluoroborates under the guidance of Prof. Gary Molander.
Dr. Nicolas Fleury-Brégeot studied chemistry in France at the ESCOM (Ecole Supérieure de Chimie Organique et Minérale), where he received a Master of Science degree in 2005. He then joined the ICSN (Institut de Chimie des Substances Naturelles) in Gif-sur-Yvette where he obtained his Ph.D. in 2008 under the supervision of Dr. Angela Marinetti. After working for one year as a postdoctoral research associate in Tarragona (Spain) with Prof. Carmen Claver on asymmetric hydrogenation, he moved to Philadelphia. He is currently pursuing research in the group of Prof. Gary Molander as a postdoctoral research associate at the University of Pennsylvania. His research focuses on the development of new synthetic methods involving organotrifluoroborates.