Condensation of 2-naphthol and naphthalenediols with o-dichlorobenzene in the presence of aluminum halides

Article abstract of DOI:10.1248/cpb.60.722

It is known that 1-naphthol, as a result of superelectrophilic (dicationic) activation in superacid media, is able to react with such deactivated aromatic compound as o-dichlorobenzene to give 4-(3,4-dichlorophenyl)-1-tetralone (2), which is a highly valuable intermediate in the synthesis of the antidepressant, sertraline (1) and other useful derivatives. However, the analogous reactivity of 2-naphthol and a variety of naphthalenediols towards o -dichlorobenzene has not been investigated thus far, although the corresponding tetralones, bearing dichlorophenyl moiety, could be of great pharmacochemical interest. In present work, we disclose that 1,5-, 1,6-, and 1,7- naphthalenediols (6a-c) react smoothly with o -dichlorobenzene in the presence of an excess of aluminum chloride or aluminum bromide to give the pairs of isomeric 4-(3,4- dichlorophenyl)- and 4-(2,3-dichlorophenyl)- 5-, 6-, and 7-hydroxy-1-tetralones (10a-c and 11a-c) in high overall yields. 2-Naphthol and 2,7-naphthalenediol (6d) exhibited comparatively lower reactivity, which however was sufficient to obtain the corresponding dichlorophenyl-2-tetralones in moderate yields. The mechanism of these reactions involving superelectrophilic dicationic or even tricationic intermediates, is discussed.

Full text of DOI:10.1248/cpb.60.722

722
Regular Article
Chem. Pharm. Bull. 60(6) 722–727 (2012)
Vol. 60, No. 6
Condensation of 2-Naphthol and Naphthalenediols with
o-Dichlorobenzene in the Presence of Aluminum Halides
Konstantin Yuryevich Koltunov,a,b,c Aleksey Nikolaevich Chernov,a,b
,c
Gubbi Krishnamurthy Surya Prakash,* and George Andrew Olahc
b
a Boreskov Institute of Catalysis; Pr. Akademika Lavrentieva, 5, Novosibirsk 630090, Russia: Novosibirsk State Uni-
c
versity; Pirogova, 2, Novosibirsk 630090, Russia: and Loker Hydrocarbon Research Institute and Department of
Chemistry, University of Southern California; University Park, Los Angeles, California 90089–1661, U.S.A.
Received December 14, 2011; accepted March 28, 2012; published online April 11, 2012
It is known that 1-naphthol, as a result of superelectrophilic (dicationic) activation in superacid media, is
able to react with such deactivated aromatic compound as o-dichlorobenzene to give 4-(3,4-dichlorophenyl)-
1-tetralone (2), which is a highly valuable intermediate in the synthesis of the antidepressant, sertraline (1)
and other useful derivatives. However, the analogous reactivity of 2-naphthol and a variety of naphthalene-
diols towards o-dichlorobenzene has not been investigated thus far, although the corresponding tetralones,
bearing dichlorophenyl moiety, could be of great pharmacochemical interest. In present work, we disclose
that 1,5-, 1,6-, and 1,7- naphthalenediols (6a–c) react smoothly with o-dichlorobenzene in the presence of an
excess of aluminum chloride or aluminum bromide to give the pairs of isomeric 4-(3,4-dichlorophenyl)- and
4-(2,3-dichlorophenyl)- 5-, 6-, and 7-hydroxy-1-tetralones (10a–c and 11a–c) in high overall yields. 2-Naph-
thol and 2,7-naphthalenediol (6d) exhibited comparatively lower reactivity, which however was sufficient to
obtain the corresponding dichlorophenyl-2-tetralones in moderate yields. The mechanism of these reactions
involving superelectrophilic dicationic or even tricationic intermediates, is discussed.
Key words superacid; superelectrophilic activation; 2-naphthol; naphthalenediol; tetralone
Tetralones are useful molecules as starting material for N,C-diprotonation in superacids and reacted with benzene and
the synthesis of biologically active compounds and pharma- cyclohexane under the influence of aluminum halides through
ceutical substances.1–8) For example, one of the major com- dications 5 to give 5-amino-3-phenyl-1-tetralone and 5-amino-
mercial pharmaceutical agents, sertraline ((+)-cis-(1S,4S)-1- 1-tetralone, respectively32) (Chart 3).
methylamino-4-(3,4-dichlorophenyl)tetralin, 1), an antidepres-
Based on this background, in continuation of our interest in
sant known under the trade name Zoloft, is a competitive superelectrophilic activation of naphthols and their derivatives,
inhibitor of synaptosomal serotonin uptake.9,10) The current a study on the reactivity of 2-naphthol and isomeric 1,5-, 1,6-,
commercial process for the production of sertraline involves 1,7-, and 2,7-naphthalenediols (6a–d)33) towards o-dichloroben-
the synthesis of ( )-1 followed by resolution.1,3,11–14)
key intermediate in the synthesis of
zene is reported with the aim of synthesizing the correspond-
is ing dichlorophenyl-1- and 2-tetralones, which are considered
A
1
4-(3,4-dichlorophenyl)-1-tetralone (2), which has been pre- as promising intermediates for medicinal chemistry.8,34) The
pared by a few synthetic routes.15–17) The most efficient route main aim of the work was also to determine the regioselectiv-
to tetralone 2 is based on one-stage condensation reaction of ity of these reactions.
1-naphthol with o-dichlorobenzene under the influence of alu-
minum halides.3,16,17)
Results and Discussion
Originally, a similar method for the synthesis of 4-aryl-
Reactions of 2-Naphthol Until now, attempts to involve
1-tetralones had been demonstrated for reactions of 1-naph- 2-naphthol in reaction with o-dichlorobenzene were not suc-
thol with benzene, chlorobenzene, fluorobenzene and toluene cessful.23) Thus, 2-naphthol did not give any product at condi-
under the influence of aluminum halides or in the HF–SbF5 tions, essential for the reaction of 1-naphthol, which reacted
superacid medium18–22) (Chart 1). Analogously, 2-naphthol with o-dichlorobenzene in the presence of an excess of AlCl3
°
reacts with benzene in the presence of aluminum halides to (or AlBr3) at elevated temperature, normally at 100–120 C
3,16,17)
give 4-phenyl-2-tetralone19,23) (Chart 1). Furthermore, selective (65 C), to give tetralone 2 in 65–80% yield over 1–2h.
°
ionic reduction of naphthols by alkanes leads to tetralones un- Therefore, at the time it was concluded that dicationic in-
der similar reaction conditions24,25) (Chart 1).
termediate 4 is not electrophilic enough to react with such
The mechanism of these reactions was recognized to in-
volve superelectrophilic26) dications (structures 3 and 4, Chart
1) as the key intermediates formed by C,C-diprotonation and
a number of analogous dications have indeed been generated
as long-lived species by dissolving naphthols and/or their de-
rivatives in liquid superacids.27,28) Moreover, a set of isomeric
naphthalenediols was reacted similarly with benzene and
cyclohexane in the presence of AlBr3 and AlCl3 to afford the
corresponding hydroxytetralones29–31) (Chart 2).
In addition, it has been found that, in contrast to 1-naph-
thol and naphthalenediols, 5-amino-1-naphthol is activated by
*To whom correspondence should be addressed. e-mail: gprakash@usc.edu
© 2012 The Pharmaceutical Society of Japan

June 2012
723
Chart 2. Reactions of Naphthalenediols with Benzene and Cyclohexane
Chart 1. Reactions of Naphthols with Arenes (ArH) and Alkanes
(AlkH).
deactivated aromatic compound as o-dichlorobenzene. Indeed,
according to density functional theory (DFT) calculations,
dication 4 is less electrophilic compared to the diprotonated
form of 1-naphthol35) (structure 3).
Nevertheless, 2-naphthol was observed to react with o-
dichlorobenzene to give isomeric 4-(3,4-dichlorophenyl)- and
4-(2,3-dichlorophenyl)-2-tetralones 7 and 8 in ca. 9:1 ratio,
respectively, in a moderate overall yield. A condition, favor-
able to ensure the successful result, appeared to be a long
term reaction performed at room temperature (Table 1).
The plausible mechanism of the reaction includes genera-
tion of dications 4, similar to that described in Chart 1. Di-
Chart 3. Reactions of 5-Amino-1-naphthol with Benzene and Cyclo-
hexane
1
cations 4 (X=H) have been previously detected by H- and
Table 1. Electrophilic Reactions of 2-Naphthol
13C-NMR spectroscopy as long-lived species in HF-SbF5-
28)
°
SO2ClF superacid system at −40 C. However, in the pres-
ence of aluminum halides, participation of dicationic species 4
(X=AlnHal−3n, Hal=Cl, Br) seems more probable, as 2-naphthol
is converted quantitatively into complexes 9 upon action of
AlCl3 and AlBr3.36) The subsequent C-protonation of 9 results
in formation of 4 (X=AlnHal−3n) in equilibrium with 9. A cata-
lytic amount of protic superacid (HHal–AlnHal3n or H2O–Aln-
Hal3n), which is required for C-protonation of intermediate
species 9, is normally present in such reaction media due to
presence of traces of water in the starting materials. The acid
strength of HHal–AlnHal3n (Hal=Br, Cl) is estimated to be
−15 to −18 in the Ho scale.37–39) So, additional saturation of
the reaction mixture with gaseous HHal, which usually accel-
erates similar reactions,40) is not generally needed.
Taking into account a quantitative recovery of unreacted
2-naphthol, it is very likely that the moderate yield of te-
tralones 7 and 8 (no more than 36%, Table 1) is close to the
equilibrium concentration of the product. The sensitivity of
the reaction to the reverse process is in agreement with the
known reactivity of 2-naphthol towards benzene. Thus, in
spite of a 90% yield of 4-phenyl-2-tetralone in reaction of
Reaction conditions
7 and 8 overall
yielda) (%)
°
Acid (eq)
Time (d)
T ( C)
AlCl3 (3.0)
7
14
14
14
1
25
25
11
19
35
24
1
AlCl3 (3.0)
AlCl3 (5.0)
25
AlCl3 (5.0)
60
AlCl3 (5.0)
110
25
HCl–AlCl3 (3.0)
HCl–AlCl3 (3.0)
AlBr3 (3.5)
AlBr3 (3.5)
7
29
36
24
1
14
7
25
25
1
60
a) Based on 1H-NMR spectroscopic data. The balance is mainly unreacted 2-naph-
thol. The ratio of 7/8 is about 9:1 in each case.
2-naphthol with benzene in the presence of a 2.5-fold molar diols 6a–c with the electrondeficient o-dichlorobenzene gave
19)
°
excess of AlCl3 (20 C, 16h), the equilibrium of a similar products similar to 1-naphthol. Reactions took place under
°
reaction is shifted completely to 2-naphthol, when HF-SbF5 the influence of a 3-fold molar excess of AlCl3 at 110 C
23,41)
°
°
°
The or AlBr3 at 25 C to give pairs of 5-, 6-, and 7-hydroxy-
superacid at −20 C or HUSY-zeolites at 130 C used.
observed poor reactivity of 2-quinolinol (heterocyclic analog substituted 4-(3,4-dichlorophenyl)-1-tetralones (10a–c) and
of 2-naphthol) towards benzene is also relevant to this case.42)
4-(2,3-dichlorophenyl)-1-tetralones (11a–c), respectively, in
Reactions of Naphthalenediols 6a–c For isomeric ca. 95% overall yields (Table 2).
naphthalenediols, the possibility of superelectrophilic activa-
The ratio of isomers 10a–c and 11a–c in the obtained mix-
tion has been demonstrated earlier only for their reactions tures is about 4:1, in each case. The same ratio of product 2
with cyclohexane and benzene29–31) (Chart 2). Reactions of and isomeric 4-(2,3-dichlorophenyl)-1-tetralone was found,

724
Vol. 60, No. 6
previously, for the reaction of 1-naphthol with o-dichloroben-
zene.17) This is to be expected based on these reactions having
a common mechanism. Dicationic electrophiles 12 (Y=OH),
which are the key intermediates of the reactions studied, may
also be additionally protonated (or coordinated with aluminum
halide) to give tricationic 12 (Y=OHX+) in the limiting cases.
Differences in the activation of naphthalenediols 6a–c com-
pared to 5-amino-1-naphthol (Chart 3) can be explained by reported.20)
the weaker basicity of hydroxy group in relation to the amino-
Based on the structure–activity relationship of 1 and its
group. As a consequence, higher equilibrium concentration of derivatives, it is well known that the presence of 3,4-dichloro-
C,C-diprotonated forms can be found in the first case. On the phenyl group is actually necessary to induce the biological ac-
other hand, O,C-diprotonated dications 13 (X=H) and similar tivities and the attempts to improve the activities by variation
complexes 13 (X=AlnHal−3n), which are comparatively more of 4-aryl-group were unsuccessful.45) Nevertheless, the proper-
easily formed,43,44) than C,C-diprotonated forms 12, do not ties of 1 should likely be improved by structural changes in
react with o-dichlorobenzene, probably, because of the dimin- the tetraline aromatic ring. Literature precedence exists for
ished electrophilicity. Therefore, intermediates 12 are stronger this contention as 4-(4-chlorophenyl)-1-methylaminotetralin
electrophiles and could react predominantly despite their (the close analog of 1) has been reported to exhibit close or
relatively low equilibrium concentrations. Calculational esti- even enhanced therapeutic properties due to introduction of
mations of electrophilicity of a number of dications showed, 7-methoxy group.45) This provides an incentive that similar
for example, that C,C-diprotonated naphthols are more electro- functionalized derivatives of 1 can be pharmaceutically im-
philic than N,C-diprotonated 5-amino-1-naphthol (structure 5) portant. From this point of view, the presently obtained prod-
and isomeric hydroxyquinolines.32,35)
ucts 10a–c or their close derivatives, as alkyl or aryl ethers
The main products 10 can be isolated from the reaction and others may serve as useful synthons for the synthesis of
mixture by simple recrystallization. Moreover, undesired te- analogs of 1.
tralones 11 can also be transformed into the useful isomers
Reactions of Naphthalenediol 6d Since 6d represents
10. For example, the mixture of isomers 10b and 11b with exclusively derivatives of 2-naphthol, its poor reactivity to-
the ratio 45:55 (obtained from the mother liquor after recrys- ward o-dichlorobenzene could be anticipated. However, 6d re-
tallization of the initial mixture) gave the equilibrium ratio acted more readily, than the parent 2-napthol to give isomeric
78:22 after 15h reaction in o-dichlorobenzene with AlCl3 at 4-(3,4-dichlorophenyl)- and 4-(2,3-dichlorophenyl)-7-hydroxy-
°
120 C. Such isomerisation of aryltetralones have earlier been 2-tetralones 14 and 15 (9:1) in 56% overall yield (Chart 4).
Table 2. Condensation of Naphthalenediols 6a–c with o-Dichlorobenzene
Reaction conditions
10 and 11 overall yield
Naphthalenediol
Products
and (ratio)a)
°
Acid (eq)
AlBr3 (3)
Time (h)
100
T ( C)
25
95% (77:23)
AlCl3 (3)
AlBr3 (3)
20
72
110
25
98% (79:21)
95% (78:22)
AlCl3 (3)
AlBr3 (3)
20
72
110
25
93% (78:22)
94% (85:15)
1
a) Based on H-NMR spectroscopic data.

June 2012
725
Chart 4. Condensation of Naphthalenediol 6d with o-Dichlorobenzene
Notably, the reaction proceeded slowly, for 7d, in the pres-
ence of a 4-fold molar excess of AlBr3 at room temperature,
whereas attempts to replace AlBr3 by AlCl3 were not success-
ful. This is probably due to the lack of solubility of complexes
of 6d with AlCl3 in o-dichlorobenzene at room temperature.
Increasing the reaction time from one to two weeks did not
change either the yield or the ratio of 14 and 15, which indi-
cates the achievement of equilibrium values influencing both
of these parameters.
A higher reactivity of 6d compared to that of 2-naphthol
can be explained by invoking the intermediacy of tricationic
species 16 (Chart 5), which is more electrophilic than dications
4. The intermediate O,C-diprotonated forms 17 (X=H) and
similar complexes 17 (X=AlnBr−3n) have been generated earlier
as long-lived species in HF-SbF5-SO2ClF and AlBr3-CH2Br2
Chart 5. Superelectrophilic Activation of Naphthalenediol 6d Proposed
superacid systems.43,44) Alternatively, dicationic species 18, bromide, aluminum chloride, o-dichlorobenzene, 2-naphthol
which is effectively stabilized by positive charge delocaliza- and naphthalendiols 6a–d were purchased from suppliers and
tion over an intact hydroxyl group, may also contribute to the used as received.
reaction. Owing to a higher concentration of 18 (compared to
4-(3,4-Dichlorophenyl)-2-tetralone (7) and 4-(2,3-Di-
16), the equilibrium of reaction with o-dichlorobenzene could chlorophenyl)-2-tetralone (8) To a stirred suspension of
be shifted to tetralones 14 and 15 in spite of the diminished AlCl3 (freshly sublimed, 8.0g, 60mmol) in o-dichlorobenzene
electrophilicity of 18.
(15mL) was added 2-naphthol (2.9g, 20mmol). The mixture
°
From a synthetic point of view, the studied reactions of 6d was saturated with gaseous HCl at 25 C for 20min. The re-
°
and 2-naphthol may represent a convenient way to access di- sulting suspension was stirred at 25 C for 2 weeks, and then
chlorophenyl-2-tetralones. The close derivative of product 14, poured onto ice. The resulting mixture was extracted with
4-(3,4-dichlorophenyl)-7-methoxy-2-tetralone, as well as the ether. The organic phase was washed with dilute HCl and then
parent product 7 are regarded as important intermediates in several times with water. The organic solution was subjected
medicinal chemistry.8,34) These materials were produced pre- to steam distillation to remove solvents and the rest of 2-naph-
viously by using inefficient multistep procedures. Therefore, thol. The residue was dissolved in ether, dried over anhydrous
the results obtained on the reactivity of 2-naphthols may be MgSO4 and concentrated in vacuo to give a brown, viscous
1
of practical interest. We suggest also that analogous reactions oil [2.11g (36%), mixture of 7/8 (89:11), according to H-
1
can be followed to obtain 2-tetralones with other deactivated NMR spectroscopic data]. Compound 7: H-NMR (500MHz,
(halogenated) aromatic compounds.
CD3OD) δ: 2.78 (1H, dd, J=16.5, 7Hz), 2.85 (1H, dd, J=16,
5.5Hz), 3.5 (1H, d, J=20.5Hz), 3.68 (1H, d, J=20.5Hz), 4.46
(1H, dd, J=6.5, 6Hz), 6.92 (1H, d, J=7.5Hz), 6.99 (ddd, J=8,
Conclusions
In summary, we have found that 2-naphthol and naphtha- 2, 0.5Hz, 1H), 7.16–7.24 (4H, m), 7.4 (1H, d, J=8Hz). 13C-
lenediol 6d are able to react with o-dichlorobenzene under NMR (125MHz, CD3OD) δ: 45.1, 45.3, 46.6, 127.1, 127.2,
the influence of aluminum halides, which provide a new 128.2, 128.7, 129.9, 130.4, 131.2, 131.9, 133.6, 136.4, 139.3,
one-step procedure for the preparation of dichlorophenyl- 144.3, 211.5. GC-MS [M]+: 290. The tetralone 7 is a known
2-tetralones. Naphthalenediols 6a–c condense with o-dichlo- compound; spectroscopic data are listed here as an update.8)
robenzene to give as the main products hydroxy substituted Compound 8 (fragmentary data were taken from the spectrum
4-(3,4-dichlorophenyl)-1-tetralones 10a–c. Since the starting of the mixture of products 7 and 8): 1H-NMR (500MHz,
materials are commercially readily available the reactions of- CD3OD) δ: 2.81 (1H, dd, J=16.5, 7Hz), 2.87 (1H, dd, J=16,
fer a convenient one step synthetic approach for preparation of 5.5Hz), 3.62 (1H, d, J=20.5Hz), 3.79 (1H, d, J=20.5Hz), 5.0
novel derivatives of 2.
(1H, t, J=6.5Hz). GC-MS [M]+: 290.
4-(3,4-Dichlorophenyl)-6-hydroxy-1-tetralone (10b) and
4-(2,3-Dichlorophenyl)-6-hydroxy-1-tetralone (11b). Meth-
Experimental
1
General Remarks The H- and 13C-NMR spectra were od a To a stirred suspension of AlCl3 (4.2g, 37.5mmol) in
recorded on a Varian 300 (300, 75MHz) or Bruker Avance o-dichlorobenzene (6mL) was added naphthalendiol 6b (2g,
°
III 500 (500, 125MHz) NMR spectrometers. GC-MS spectra 12.5mmol). The resulting mixture was stirred at 110 C for
recorded on Agilent 5973N electron ionization/positive chemi- 20h, then cooled and poured over several grams of ice. Af-
cal ionization instrument. High-resolution mass spectra were ter stirring the quenched mixture for 10min, hexane (20mL)
measured at the Southern California Mass Spectrometry Fa- was added and stirring continued for 1h. The crude reaction
cility at the University of California at Riverside. Aluminum product was filtered off, washed with water and hexane and

726
Vol. 60, No. 6
dried to give 3.75g (98%) of 10b and 11b mixture (the ratio 7.47 (1H, dd, J=7.8, 1.4Hz), 7.61 (1H, dd, J=7.8, 1.2Hz), 8.77
79:21, respectively, according to 1H-NMR spectroscopic (1H, s).
data). Recrystallization of the mixture from aqueous ethanol
(twice) and toluene (twice) gave tetralone 10b (2.33g, 61%) as 4-(2,3-Dichlorophenyl)-7-hydroxy-2-tetralone (15) To
4-(3,4-Dichlorophenyl)-7-hydroxy-2-tetralone (14) and
a
°
white crystals. Compound 10b: mp 240–241 C. IR (CHCl3): solution of AlBr3 (28.4g, 0.105mol) in o-dichlorobenzene
ν=1655cm−1. 1H-NMR (300MHz, acetone-d6) δ: 2.22–2.46 (30mL) was added 6d (4.2g, 0.026mol). The resulting solu-
°
(2H, m), 2.51–2.59 (2H, m), 4.36 (1H, dd, J=8.54, 4.63Hz), tion was stirred at 25 C for 1 week, and then poured onto ice.
6.34 (1H, d, J=2.44Hz), 6.86 (1H, dd, J=8.55, 2.44Hz), 7.2 The resulting mixture was extracted with ether. The organic
(1H, dd, J=8.3, 2.2Hz), 7.45 (1H, d, J=2.2Hz), 7.57 (1H, d, phase was washed with dilute HCl and then several times with
J=8.3Hz), 7.94 (1H, d, J=8.55Hz), 9.13 (s, 1H). 13C-NMR water. The organic solution was subjected to steam distillation
(75MHz, acetone-d6) δ: 32.1, 37.0, 45.2, 115.5, 115.6, 126.4, to remove solvents and the rest of 6d (which is soluble in a
129.5, 130.3, 130.7, 131.4, 131.5, 132.6, 146.1, 148.8, 162.7, hot water). After removing of a hot water solution and cooling
195.4. High resolution (HR)-MS Calcd for C16H12Cl2O2 [M]+: the residue, a brown solid was isolated to give a mixture of
306.0214; Found 306.0225. Compound 11b (data were taken title compounds, 14 and 15 (89:11) in 56% overall yield. Re-
from the spectrum of the mixture of products 10b and 11b): crystallization of the mixture from hexane gave 2.99g (37%)
1H-NMR (300MHz, acetone-d6) δ: 2.2–2.65 (4H, m), 4.85 of 14 as a pale-yellow crystalline product. Compound 14: mp
1
°
(1H, t, J=8Hz), 6.34 (1H, d, J=2.2Hz), 6.88 (1H, dd, J=8.2, 93–95 C. H-NMR (500MHz, CD3OD) δ: 2.8 (1H, dd, J=16.5,
2.2Hz), 7.05 (1H, dd, J=8, 1.6Hz), 7.32 (1H, t, J=8Hz), 7.54 7Hz), 2.89 (1H, dd, J=16, 5.5Hz), 3.45 (1H, d, J=20.5Hz),
(1H, dd, J=8, 1.6Hz), 7.95 (1H, d, J=8.2Hz), 9.16 (1H, s).
3.64 (1H, d, J=20.5Hz), 4.43 (1H, t, J=6Hz), 6.63–6.68 (2H,
Method b To a solution of AlBr3 (10g, 37.5mmol) in o- m), 6.79 (1H, d, J=8Hz), 7.02 (1H, dd, J=8.5, 2.5Hz), 7.24
dichlorobenzene (7mL) was added 6b (2g, 12.5mmol). The (1H, d, J=2Hz), 7.42 (1H, d, J=8.5Hz). 13C-NMR (125MHz,
°
resulting mixture was stirred at 25 C for 72h, followed by the CD3OD) δ: 43.6, 44.6, 45.2, 115.2, 116.2, 128.9, 130.0, 130.2,
workup, as described above, to give 3.63g (95%) of 10b and 131.1, 131.6, 131.8, 133.5, 136.1, 145.2, 157.9, 211.7. HR-MS
11b (78:22) mixture.
Calcd for C16H12Cl2O2 [M]+: 306.0214; Found 306.0210. Com-
4-(3,4-Dichlorophenyl)-7-hydroxy-1-tetralone (10c) and pound 15 (fragmentary data were taken from the spectrum
1
4-(2,3-Dichlorophenyl)-7-hydroxy-1-tetralone (11c) Using of the mixture of products 14 and 15): H-NMR (500MHz,
the a and b methods, the mixtures of title compounds, 10c CD3OD): δ: 2.76 (1H, dd, J=16.5, 7Hz), 2.87 (1H, dd, J=16,
and 11c (the ratios 78:22 and 85:15, respectively) were pre- 5.5Hz), 3.54 (1H, d, J=20.5Hz), 3.7 (1H, d, J=20.5Hz), 4.92
pared in 93–94% yields. Recrystallization of the mixtures (1H, dd, J=6.5, 6Hz). GC-MS [M]+: 306.
from toluene (twice) and ethanol (twice) gave 10c (60%) as
°
a white crystalline product. Compound 10c: mp 192–193 C.
Acknowledgments Financial support of the work by the
IR (CHCl3): ν=1664cm−1. 1H-NMR (300MHz, acetone-d6) National Science Foundation and the Loker Hydrocarbon Re-
δ: 2.2–2.5 (2H, m), 2.55–2.65 (2H, m), 4.37 (1H, dd, J=8.06, search Institute is gratefully acknowledged.
3.42Hz), 6.85 (1H, d, J=8.54Hz), 7.02 (1H, dd, J=8.54,
2.93Hz), 7.16 (1H, dd, J=8.3, 2.2Hz), 7.41 (1H, d, J=2.2Hz),
7.47 (1H, d, J=2.93Hz), 7.54 (1H, d, J=8.3Hz), 8.68 (s, 1H).
13C-NMR (75MHz, acetone-d6) δ: 32.3, 36.9, 44.2, 112.6,
122.0, 129.4, 130.6, 131.3, 131.4, 131.5, 132.5, 134.6, 137.2,
146.6, 157.2, 196.9. HR-MS Calcd for C16H12Cl2O2 [M]+:
306.0214; Found 306.0214. Compound 11c (data were taken
from the spectrum of the mixture of products 10c and 11c):
1H-NMR (300MHz, acetone-d6) δ: 2.2–2.65 (4H, m), 4.85
(1H, dd, J=6.84, 1.95Hz), 6.85 (1H, d, J=8.3Hz), 6.92 (1H,
dd, J=7.82, 1.47Hz), 7.04 (1H, dd, J=8.3, 2.9Hz), 7.28 (1H,
t, J=7.82Hz), 7.49 (1H, d, J=2.9Hz), 7.55 (1H, dd, J=7.82,
1.47Hz), 8.77 (1H, s).
References and Notes
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4-(3,4-Dichlorophenyl)-5-hydroxy-1-tetralone (10a) and
4-(2,3-Dichlorophenyl)-5-hydroxy-1-tetralone (11a) Using
the b method (completion of the reaction required 100h), the
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