Hydroxylation of Alkyl Halides with Water in Ionic Liquid: Significantly Enhanced Nucleophilicity of Water

Article abstract of DOI:10.1021/jo035563i

A facile method for the nucleophilic hydroxylation of alkyl halides and mesylates with water has been developed in which the use of ionic liquid as an alternative reaction medium not only enhanced the nucleophilicity of water but also reduced the formation of elimination products predominantly formed under the conventional basic reaction conditions. For example, hydroxylation of model compound 2-(3-bromopropyl)naphthalene (1) to 2-(3-hydroxypropyl)-naphthalene (2) with water in 1-n-butyl-3-methylimidazolium tetrafluoroborate ([bmim] [BF ₄]) and 1,4-dioxane proceeded selectively in high yield (94%). The reactivity of other nucleophilic oxygen sources such as alcohol, phenol, and acetic acid in an ionic liquid was also investigated.

Full text of DOI:10.1021/jo035563i

Hyd r oxyla tion of Alk yl Ha lid es w ith Wa ter
in Ion ic Liqu id : Sign ifica n tly En h a n ced
Nu cleop h ilicity of Wa ter
F IGURE 1. Ionic liquids.
Dong Wook Kim,† Dong J in Hong,† J ai Woong Seo,†
Hoon Sik Kim,‡ Hong Kon Kim,‡ Choong Eui Song,‡ and
Dae Yoon Chi*,†
boiling points of these solvents and their solubility in both
organic and aqueous media could complicate requisite
separation and purification strategies.
Department of Chemistry, Inha University,
253 Yonghyundong Namgu, Inchon 402-751, Korea, and
Reaction Media Research Center and Life Sciences Division,
Korea Institute of Science and Technology, Cheongryang,
Seoul 130-650, Korea
As a result of their unique physical and chemical
properties, interest in ionic liquids containing imidazo-
lium cations and their counteranions as alternative
reaction media has flourished (Figure 1).6 We recently
reported a highly efficient nucleophilic substitution reac-
tion in which fluorination of alkyl halides or sulfonates
to fluoroalkanes using alkali metal fluorides proceeded
smoothly in the presence of ionic liquids. The ionic liquid
played a crucial role not only in enhancing the nucleo-
philicity of the metal salts but also in reducing the
formation of undesired byproducts as compared with
conventional methods.7 Furthermore, the immiscibility
of some ionic liquids with more traditional solvents (e.g.,
water, ether, hexane, and benzene) allowed for the
formation of bi- and triphasic reaction systems which
significantly facilitated purification and extraction of the
desired products.6a,8 In this paper, we present a highly
efficient method for the synthesis of alkyl alcohols from
alkyl halides or mesylates by a nucleophilic hydroxylation
reaction with water in various ionic liquids.9 We also
investigated the reactivity of other nucleophilic oxygen
sources such as alcohol, phenol, and acetic acid in [bmim]-
[BF4]. The use of ionic liquids significantly enhanced the
reactivities of water and alcohol as nucleophilic oxygen
sources and reduced the formation of alkenes as byprod-
ucts, resulting in excellent yields of the substituted
products.
dychi@inha.ac.kr
Received October 22, 2003
Abstr a ct: A facile method for the nucleophilic hydroxyla-
tion of alkyl halides and mesylates with water has been
developed in which the use of ionic liquid as an alternative
reaction medium not only enhanced the nucleophilicity of
water but also reduced the formation of elimination products
predominantly formed under the conventional basic reaction
conditions. For example, hydroxylation of model compound
2-(3-bromopropyl)naphthalene (1) to 2-(3-hydroxypropyl)-
naphthalene (2) with water in 1-n-butyl-3-methylimidazo-
lium tetrafluoroborate ([bmim][BF4]) and 1,4-dioxane pro-
ceeded selectively in high yield (94%). The reactivity of other
nucleophilic oxygen sources such as alcohol, phenol, and
acetic acid in an ionic liquid was also investigated.
The displacement of various alkyl halides and sul-
fonates by oxygen nucleophiles is a crucial synthetic
method1,2 for the introduction of oxygen atoms into
aliphatic organic systems. Unfortunately, the reaction
conditions typically employed in the generation of oxygen
nucleophiles (water/alcohol with strong base or alkali
metal hydroxide/alkoxide with or without phase-transfer
reagents3) often results in the formation of the undesired
elimination products, since these nucleophilic oxygens
can act as not only a nucleophile but also a base.2
Although the combination of water or alcohol with polar
aprotic solvents such as dimethyl sulfoxide (DMSO),
hexamethylphosphoric triamide (HMPA), or N-meth-
ylpyrrolidinone (NMP) could provide potent, selective,
and neutral sources of nucleophilic oxygen,4,5 the high
Table 1 illustrates the hydroxylation reaction of model
compound 2-(3-bromopropyl)naphthalene (1) with water
in ionic liquid under various reaction conditions. The
hydroxylation of bromoalkane 1 with water in organic
(4) (a) Reichardt, C. Solvents and Solvent Effects in Organic
Chemistry, 2nd ed.; VCH (UK) Ltd.: Cambridge, U.K., 1998. (b) Martin,
D.; Weise, A.; Niclas, H. Angew. Chem., Int. Ed. Engl. 1967, 6, 318-
334. (c) Normant, H. Angew. Chem., Int. Ed. Engl. 1967, 6, 1046-
1067. (d) Parker, A. J . Chem. Rev. 1969, 69, 1-32. (e) Sowinski, A. F.;
Whitesides, G. M. J . Org. Chem. 1979, 44, 2369-2376.
(5) Hutchins, R. O.; Taffer, I. M. J . Org. Chem. 1983, 48, 1360-
1362.
(6) For recent reviews on ionic liquids, see: (a) Sheldon, R. Chem.
Commun. 2001, 2399-2407. (b) Zhao H.; Malhotra S. V. Aldrichim.
Acta 2002, 35, 75-83. (c) Wasserscheid, P.; Keim, W. Angew. Chem.,
Int. Ed. 2000, 39, 3772-3789. (d) Welton, T. Chem. Rev. 1999, 99,
2071-2083.
(7) (a) Kim, D. W.; Song, C. E.; Chi, D. Y. J . Am. Chem. Soc. 2002,
124, 10278-10279. (b) Kim, D. W.; Song, C. E.; Chi, D. Y. J . Org. Chem.
2003, 68, 4281-4285. (c) Kim, D. W.; Choe, Y. S.; Chi, D. Y. Nucl.
Med. Biol. 2003, 30, 345-350.
(8) Carmichael, A. J .; Earle, M. J .; Holbrey, J . D.; McCormac, P. B.;
Seddon, K. R. Org. Lett. 1999, 1, 977-979.
(9) 1-n-Butyl-3-methylimidazolium cation [bmim] and its counter-
anionsstetrafluoroborate [BF4], hexafluorophosphate [PF6], hexafluo-
roantimonate [SbF6], triflate [OTf], and acetate [OAc]sare used.
* To whom correspondence should be addressed. Tel: +82-32-860-
7686. Fax: +82-32-867-5604.
† Inha University.
‡ Korea Institute of Science and Technology.
(1) See: Larock, R. C. Comprehensive Organic Transformation, 2nd
ed.; Wiley-VCH: New York, 1999; pp 890-895 and 970-972.
(2) See: Smith, M. D.; March, J . Advanced Organic Chemistry, 5th
ed.; Wiley-Interscience: New York, 2001; pp 462-674.
(3) (a) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis,
3rd ed.; VCH Ltd.: New York, 1993. (b) Dehmlow, E. V. Angew. Chem.,
Int. Ed. Engl. 1977, 16, 493-505. (c) Starks, C. M. J . Am. Chem. Soc.
1971, 93, 195-199. (d) Starks, C. M.; Owens, R. M. J . Am. Chem. Soc.
1973, 95, 3613-3617. (e) Gokel, G. W. Crown Ethers and Cryptands;
Royal Society of Chemistry: Cambridge, 1991. (f) Pedersen, C. J . J .
Am. Chem. Soc. 1967, 89, 7017-7036. (g) Liotta, C. L.; Harris, H. P.
J . Am. Chem. Soc. 1974, 96, 2250-2252. (h) Sam, D. J .; Simmons, H.
E. J . Am. Chem. Soc. 1974, 96, 2252-2253.
10.1021/jo035563i CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/24/2004
3186
J . Org. Chem. 2004, 69, 3186-3189

TABLE 1. Hyd r oxyla tion of Br om oa lk a n e 1 Usin g H 2O
u n d er Va r iou s Rea ction Con d ition sa
yield of productb (%)
[bmim][X]
(4 mL)
cosolvent
(2.5 mL)
time
(h)
entry
1
2
3
1
2
[BF4]
[BF4]
[BF4]
[OTf]
[PF6]
[PF6]
[SbF6]
[OAc]
[BF4]
[BF4]
[PF6]
65
31
trace
65
94
95
92
62
61
86
1,4-dioxane 65
1,4-dioxane 20
1,4-dioxane 48
1,4-dioxane 24
1,4-dioxane 72
1,4-dioxane 48
1,4-dioxane 20 (min)
3c
4
5
6
7
8
30
28
8
F IGURE 2. Two proposed mechanisms for the formation of
acetoxypropylnaphthalene 3.
98
TABLE 2. Nu cleop h ilic Su bstitu tion Rea ction s of
Br om oa lk a n e 1 w ith Va r iou s Oxygen Sou r ces in
[bm im ][BF 4]a
9
acetone
CH3CN
CH3CN
48
48
24
trace
trace
trace
92
92
84
23
10
11
12
7
68
1,4-dioxaned 48
trace
a
All reactions were carried out on a 1.0 mmol reaction scale of
b
bromoalkane 1 using 1.5 mL of H2O at 110 °C. Isolated yield.
c NaHCO3 (3 equiv) used as an acid scavenger. 1,4-Dioxane (4.5
d
mL) used.
entry
ROH
MeOH
t-BuOH
KOt-Bu
CH3COOH
phenol
time (h)
T (°C)
yieldb (%)
1
48
96
0.3
48
48
100
110
70
110
100
94
25
0
15
0
2c
3d
4
solvent (1,4-dioxane, 110 °C, entry 12) provided only trace
amounts of product after 48 h, whereas the same reaction
in [bmim][BF4] converted 65% of 1 to 2-(3-hydroxypropyl)-
naphthalene (2) in only 65 h (entry 1). The low conversion
in entry 1 can be ascribed to the low solubility of
bromoalkane 1 in the [bmim][BF4]-water mixture; when
1,4-dioxane was used as a cosolvent, the reaction afforded
alcohol 2 in excellent yield (94%, entry 2). The use of
NaHCO3 to scavenge HBr generated in situ accelerated
the reaction rate (entry 3).
5
a
All reactions were carried out on a 1.0 mmol reaction scale of
b
bromide 1 using 4 mL of ROH in 4 mL of [bmim][BF4]. Isolated
yield. c NaHCO3 (3 equiv) used. Reference 7b.
d
We next performed the nucleophilic displacement of
bromoalkane 1 using methanol, tert-butyl alcohol, phenol,
or acetic acid as both the nucleophile and the cosolvent
in [bmim][BF4] to investigate the reactivities of various
other nucleophilic oxygen sources (Table 2). The reaction
of 1 with methanol in [bmim][BF4] afforded 2-(3-meth-
oxypropyl)naphthalene (4) in excellent yield (94%, entry
1), whereas the reaction with tert-butyl alcohol in ionic
liquid gave only 25% of the substituted product 5 (entry
2). The same reaction under basic conditions (potassium
tert-butoxide) gave only the elimination product (entry
3). Acetic acid showed low nucleophilicity in the reaction
and thus gave only 15% of the acetylated product 3 (entry
4), while the phenoxylation using phenol did not proceed
at all.
In an effort to optimize the reaction conditions, we next
performed a series of hydroxylations utilizing a variety
of ionic liquids and cosolvents (entries 4-11). Although
the use of [bmim][OTf] proved favorable (92%, entry 4),
the hydroxylation using [bmim][PF6] stalled after 24 h,
affording alcohol 2 in only 62% yield (entries 5 and 6).
The use of [bmim][SbF6] provided slightly lower yields
than [bmim][OTf] (entry 7). Interestingly, while acetone
proved useful as a cosolvent (92%, entry 9), hydroxylation
in acetonitrile gave 2-(3-acetoxypropyl)naphthalene (3)
as an unexpected side product (7%) as well as the desired
alcohol (84%, entry 10). The combination of [bmim][PF6]
and acetonitrile served to further enhance this side
reaction, affording acetoxylation product 3 in 68% yield
and alcohol 2 in only 23% yield (entry 11). One can
suggest plausible mechanisms for the formation of ac-
etoxylalkane 3 via two different reaction paths: esteri-
fication of alcohol via hydroxylation or nucleophilic
acetoxylation of bromoalkane (Figure 2). In an effort to
test the feasibility of these two paths, we carried out the
esterification of alcohol 2 to acetoxyalkane 3 (path B) as
well as the nucleophilic acetoxylation of bromoalkane 1
to acetoxyalkane 3 (path C) with acetic acid in [bmim]-
[BF4] for 1 h at 100 °C. While the esterification reaction
proceeded quantitatively, the nucleophilic reaction did
not, leading us to conclude that the formation of acetoxy-
alkane 3 in entries 10 and 11 stems from the esterifica-
tion of alcohol 2 by acetic acid generated from the
hydrolysis of CH3CN under acidic catalytic conditions via
hydroxylation of bromoalkane 1.
Table 3 illustrates the hydroxylation of various pri-
mary, secondary, and benzylic halides or sulfonates with
water in the absence of base under the same reaction
conditions described previously (Table 1, entry 2). Inter-
estingly, all entries provided the corresponding alcohols
in high yield with the exception of the primary chloride
(entry 1). Primary iodoalkanes underwent hydroxylation
to alcohol 2 much more readily than the corresponding
bromoalkane (entry 2). Hydroxylation of a secondary
bromoalkane (entry 3) proceeded smoothly within 48 h,
affording the corresponding alcohol in 95% yield, and
benzyl alcohol was produced in high yield by hydroxyla-
tion of the bromide (entry 4). To investigate the possibil-
ity of reuse of [bmim][BF4], we carried out the hydroxy-
lation of 2-bromomethylnaphthalene repeatedly (5 runs).
[bmim][BF4] could be reused repeatedly, without loss of
J . Org. Chem, Vol. 69, No. 9, 2004 3187

TABLE 3. Hyd r oxyla tion of Va r iou s Alk yl Ha lid es a n d
Su lfon a te Usin g H2O in [bm im ][BF 4]a
SCHEME 1. Differ en ce betw een th e Use of
Meth a n ol in [bm im ][BF 4] a n d th e Use of P ota ssiu m
Meth oxid e in th e P r esen ce of 18-Cr ow n -6
in high yields of the substituted products. Further studies
on applications of ionic liquids in other nucleophilic
substitution reactions are under investigations.
Exp er im en ta l Section
a
Unless otherwise noted, all reactions were carried out under
b
Typ ica l P r oced u r e of th e Hyd r oxyla tion (En tr y 2 in
Ta ble 1). Water (1.5 mL) was added to the mixture of 2-(3-
bromopropyl)naphthalene (1, 249 mg, 1.0 mmol) in [bmim][BF4]
(4.0 mL) and 1,4-dioxane (2.5 mL). The mixture was stirred at
110 °C for 65 h. The reaction system is heterogeneous at 25 °C,
and it turned homogeneous at the reaction temperature. We
determined the reaction time by TLC. The reaction product was
extracted from the ionic liquid phase with ethyl ether (7 mL ×
4). The ether layer was evaporated under reduced pressure. The
residue was purified by flash column chromatography (25%
EtOAc/hexane) to provide 175 mg (0.94 mmol, 94%) of 2-(3-
hydroxypropyl)naphthalene (2) as a white solid: 1H NMR (400
MHz, CDCl3) δ 1.41 (s, 1H), 1.96-2.03 (m, 2H), 2.89 (t, J ) 7.6
Hz, 2H), 3.72 (t, J ) 6.4 Hz, 2H), 7.34-7.37 (m, 1H), 7.41-7.48
(m, 2H), 7.65 (s, 1H), 7.77-7.82 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 32.17, 34.05, 62.23, 125.16, 125.92, 126.40, 127.24,
127.37, 127.58, 127.94, 131.98, 133.58, 139.28; MS (EI) 186 (M+),
142 (100); HRMS (EI) calcd for C13H14O (M+) 186.1045, found
186.1049.
P r oced u r e for t h e Alk oxyla t ion (E n t r y 1 in Ta b le 2).
2-(3-Bromopropyl)naphthalene (1, 249 mg, 1.0 mmol) in [bmim]-
[BF4] (4.0 mL) and methanol (4.0 mL) was stirred at 100 °C for
48 h. We determined the reaction time by TLC. The reaction
product was extracted from the ionic liquid phase with ethyl
ether (7 mL × 3). The ether layer was evaporated under reduced
pressure. The residue was purified by flash column chromatog-
raphy (10% EtOAc/hexane) to provide 188 mg (0.94 mmol, 94%)
of 2-(3-methoxypropyl)naphthalene (4) as a colorless oil: 1H
NMR (400 MHz, CDCl3) δ 2.03-2.08 (m, 2H), 2.92 (t, J ) 7.6
Hz, 2H), 3.42 (s, 3H), 3.47 (t, J ) 6.2 Hz, 2H), 7.39-7.42 (m,
1H), 7.47-7.52 (m, 2H), 7.69 (s, 1H), 7.82-7.88 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 31.07, 32.36, 58.48, 71.79, 125.05,
125.80, 126.38, 127.28, 127.35, 127.53, 127.80, 131.94, 133.57,
139.40; MS (EI) 200 (M+), 168, 142 (100), 115; HRMS (EI) calcd
for C14H16O (M+) 200.1201, found 200.1204.
the same conditions as entry 2 in Table 1. Isolated yield. c NMR
determined. Methoxylations using MeOH (4 mL) were carried
out.
d
its effect and decomposition; in each cycle, 2-hydroxy-
methylnaphthalene was obtained in high yield (89-95%).
The introduction of a nucleophile to haloethyl aromatic
compounds under basic reaction conditions proves dif-
ficult since the elimination of hydrogen halide occurs
predominantly to give vinylic aromatic systems. In entry
5, however, we see that the hydroxylation of 2-(2-
bromoethyl)naphthalene in [bmim][BF4] proceeded se-
lectively to the corresponding alcohol without any elimi-
nation. The hydroxylation of R-bromoacetophenone also
gave R-hydroxyacetophenone in good yield (entry 6). As
a final example, the methoxylation of the benzyl chloride
7 containing an Fmoc protective group, which is labile
under the basic conditions, proceeded to the methoxylated
product in 83% yield, along with 13% of 9-fluorenemetha-
nol generated by the hydrolysis of 9-fluorenylmethyl
carbamate moiety. Scheme 1 demonstrated the difference
of the reactions between using methanol in the presence
of [bmim][BF4] and using potassium methoxide in the
presence of 18-crown-6.
In summary, we have described the facile hydroxyla-
tion of haloalkanes at the primary and secondary ali-
phatic and benzylic positions using water as a nucleophile
in the presence of ionic liquids. We also investigated the
reactivities of methanol, tert-butyl alcohol, phenol, and
acetic acid as nucleophilic oxygen sources in [bmim][BF4].
Using this method, the reactivities of water and methanol
as nucleophilic oxygen sources were significantly en-
hanced by ionic liquid. Moreover, the use of ionic liquid
reduced the formation of alkenes as byproducts, resulting
2-(3-ter t-Bu toxyp r op yl)n a p h th a len e (5, En tr y 2 in Ta ble
2). Prepared according to the procedure of alkoxylation except
that tert-butyl alcohol was used in the presence of NaHCO3 (252
mg, 3 mmol). 2-(3-tert-Butoxypropyl)naphthalene (5, 60 mg, 0.25
mmol, 25%) was obtained as a colorless oil: 1H NMR (400 MHz,
3188 J . Org. Chem., Vol. 69, No. 9, 2004

CDCl3) δ 1.21 (s, 9H), 1.92-1.95 (m, 2H), 2.86 (t, J ) 7.8 Hz,
2H), 3.40 (t, J ) 6.4 Hz, 2H), 7.35-7.47 (m, 3H), 7.65 (s, 1H),
7.76-7.82 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 27.61, 31.97,
32.58, 60.08, 72.57, 125.00, 125.78, 126.41, 127.38, 127.46,
127.56, 127.73, 131.94, 133.60, 139.80; MS (EI) 242 (M+), 186,
155, 141 (100), 115; HRMS (EI) calcd for C17H22O (M+), 242.1671,
found 242.1668.
2-(2-Hyd r oxyeth yl)n a p h th a len e (En tr y 6 in Ta ble 3).
Prepared according to the typical procedure of hydroxylation
starting from 2-(2-bromoethyl)naphthalene (235 mg, 1.0 mmol).
2-(2-Hydroxyethyl)naphthalene (137 mg, 0.80 mmol, 80%) was
obtained as a white solid: 1H NMR (400 MHz, CDCl3) δ 1.47
(br, 1H), 3.36 (t, J ) 6.6 Hz, 2H), 4.00 (br, 2H), 7.38-7.56 (m,
4H), 7.76-8.08 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 36.19,
63.02, 123.61, 125348, 125.64, 126.02, 127.14, 127.31, 128.84,
132.04, 133.97, 134.33. CAS Registry No. provided by the
author: 1485-07-0.
r-Hyd r oxya cetop h en on e (En tr y 7 in Ta ble 3). Prepared
according to the typical procedure of hydroxylation starting
R-bromoacetophenone (199 mg, 1.0 mmol). R-Hydroxyacetophe-
none (92 mg, 0.68 mmol, 68%) was obtained as a white solid:
1H NMR (200 MHz, CDCl3) δ 3.51 (br, 1H), 4.88 (s, 2H), 7.46-
7.68 (m, 3H), 7.90-7.96 (m, 2H); 13C NMR (50 MHz, CDCl3) δ
65.45, 127.68, 128.96, 133.42, 134.26, 198.38. CAS Registry No.
provided by the author: 582-24-1.
N-F m oc-2-m eth oxym eth yla n ilin e (En tr y 8 in Ta ble 3).
Prepared according to the typical procedure of alkoxylation
starting N-Fmoc-2-chloromethylaniline (364 mg, 1.0 mmol).
N-Fmoc-2-methoxymethylaniline (298 mg, 0.83 mmol, 83%) was
obtained as a white solid: 1H NMR (400 MHz, CDCl3) δ 3.42 (s,
3H), 4.32 (t, J ) 7.2, 1H), 4.48 (d, J ) 7.6, 2H), 4.55 (s, 2H),
7.02-7.18 (m, 2H), 7.31-7.44 (m, 5H), 7.62-7.98 (m, 5H), 8.08
(br, 1H); 13C NMR (100 MHz, CDCl3) δ 47.13, 57.75, 67.06, 73.84,
120.01, 123.11, 125.10, 127.07, 127.74, 129.31, 129.37, 137.83,
141.34, 143.86, 153.61; MS (EI) 359 (M+), 196, 178 (100), 165,
132; HRMS (EI) calcd for C23H21NO3 (M+) 359.1521, found
359.1522.
2-(3-Acetoxyp r op yl)n a p h th a len e (3, En tr y 4 in Ta ble 2).
2-(3-Bromopropyl)naphthalene (1, 249 mg, 1.0 mmol) in [bmim]-
[BF4] (4.0 mL) and acetic acid (4.0 mL) was stirred at 110 °C
for 48 h and neutralized with aqueous NaHCO3. The reaction
product was extracted from the aqueous ionic liquid phase with
ethyl ether (7 mL × 3). The ether layer was dried (Na2SO4) and
evaporated under reduced pressure. The residue was purified
by flash column chromatography (10% EtOAc/hexane) to provide
34 mg (0.15 mmol, 15%) of 2-(3-acetoxypropyl)naphthalene (3)
as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 2.04-2.11 (m,
5H), 2.88 (t, J ) 7.6 Hz, 2H), 4.16 (t, J ) 6.6 Hz, 2H), 7.34-7.36
(m, 1H), 7.45-7.50 (m, 2H), 7.65 (s, 1H), 7.79-7.84 (m, 3H); 13
C
NMR (100 MHz, CDCl3) δ 20.91, 30.02, 32.26, 63.79, 125.19,
125.92, 126.39, 127.06, 127.35, 127.54, 127.96, 131.98, 133.52,
138.62, 171.09; MS (EI) 228 (M+), 168 (100), 141, 115; HRMS
(EI) calcd for C15H16O2 (M+) 228.1150, found 228.1156.
2-(3-Hyd r oxy-n -bu tyl)n a p h th a len e (En tr y 4 in Ta ble 3).
Prepared according to the typical procedure of hydroxylation
starting from 2-(3-bromo-n-butyl)naphthalene (263 mg, 1.0
mmol). 2-(3-Hydroxy-n-butyl)naphthalene (190 mg, 0.95 mmol,
95%) was obtained as a white solid: 1H NMR (400 MHz, CDCl3)
δ 1.26 (d, J ) 6.4 Hz, 3H), 1.41 (br, 1H), 1.82-1.92 (m, 2H),
2.81-2.97 (m, 2H), 3.83-3.91 (m, 1H), 7.35-7.48 (m, 3H), 7.65
(s, 1H), 7.77-7.82 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 23.68,
32.25, 40.67, 67.48, 125.14, 125.92, 126.34, 127.28, 127.37,
127.59, 127.93, 131.98, 133.63, 139.55. CAS Registry No. pro-
vided by the author: 136240-69-2.
Ack n ow led gm en t. This work was supported by the
National Research Laboratory Program in Korea and a
KIST institutional grant. We thank Ms. Lynne Miller-
Deist for helpful discussions.
2-Hyd r oxym eth yln a p h th a len e (En tr y 5 in Ta ble 3).
Prepared according to the typical procedure of hydroxylation
starting from 2-bromomethylnaphthalene (221 mg, 1.0 mmol).
2-Hydroxymethylnaphthalene (144 mg, 0.91 mmol, 91%) was
obtained as a white solid: 1H NMR (200 MHz, CDCl3) δ 2.76
(br, 1H), 4.77 (s, 2H), 7.41-7.54 (m, 3H), 7.74-7.87 (m, 4H);
13C NMR (50 MHz, CDCl3) δ 65.14, 125.08, 125.30, 125.75,
126.40, 127.61, 127.79, 128.16, 132.81, 133.27, 138.23. CAS
Registry No. provided by the author: 1592-38-7.
Su p p or tin g In for m a tion Ava ila ble: Characterization of
1
all starting materials, reuse procedure of ionic liquid, and H
and 13C NMR spectra of 1-5, N-Fmoc-2-methoxymethyla-
niline, and corresponding starting materials. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O035563I
J . Org. Chem, Vol. 69, No. 9, 2004 3189