Synthesis of trifluoromethylnaphthalenes

Article abstract of DOI:10.1016/S0040-4020(00)00977-7

Reaction of 1-(3,4-dihydro-2H-5-pyranyl)-2,2,2-trifluoro-1-ethanone with benzylic Grignard reagents affords by 1,2-addition unsaturated allylic alcohols. These alcohols readily undergo dehydration and cyclisation to give trifluoromethylnaphthalenes. The generality of this procedure was established by reaction with diverse benzyl and allyl Grignard reagents and by reaction of a number of unsaturated ketones. The resulting trifluoromethylnaphthalenes were oxidised to give substituted acetic- and propionic acids. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00977-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 10067±10074
Synthesis of Tri¯uoromethylnaphthalenes
a
b
c
John M. Mellor,a, Afaf H. El-Sagheer, El-Sayed H. El-Tamany and Reda N. Metwally
*
aDepartment of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
bDepartment of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt
cDepartment of Science and Maths., Faculty of Petroleum and Mining Engineering, Suez Canal University, Suez, Egypt
Received 18 July 2000; revised 14 September 2000; accepted 12 October 2000
AbstractÐReaction of 1-(3,4-dihydro-2H-5-pyranyl)-2,2,2-tri¯uoro-1-ethanone with benzylic Grignard reagents affords by 1,2-addition
unsaturated allylic alcohols. These alcohols readily undergo dehydration and cyclisation to give tri¯uoromethylnaphthalenes. The generality
of this procedure was established by reaction with diverse benzyl and allyl Grignard reagents and by reaction of a number of unsaturated
ketones. The resulting tri¯uoromethylnaphthalenes were oxidised to give substituted acetic- and propionic acids. q 2000 Elsevier Science
Ltd. All rights reserved.
Introduction
benzyl organometallic reagent to afford a 1,2-adduct, which
on dehydration affords aromatic products. In order that this
procedure might be applied to tri¯uoromethylketones, thus
giving tri¯uoromethyl substituted aromatic compounds
(Scheme 1), it is essential that the benzyl organometallic
reagent should undergo 1,2-addition with, for example, a
b-alkoxy-a,b-unsaturated ketone, rather than the possible
1,4-addition. Earlier13,14 we have shown that benzyl mag-
nesium bromide reacts with the ketone (1) by 1,2-addition in
high yield. There are a number of protocols using organo-
metallic reagents to favour 1,2-addition and minimise 1,4-
addition. In the favourable case of allyl derivatives, not only
do allyl Grignard reagents preferentially add15 by 1,2-
addition, but direct reaction of an allyl halide with indium
metal leads to in situ formation of an indium allyl16 and
hence to selective 1,2-addition. We ®nd that either this
protocol, or the related Barbier conditions17 whereby an
allyl Grignard reagent is generated in situ, are effective. In
the case of 1,2-addition of benzyl groups, although the
Acyclic ¯uorinated building blocks1 have been used widely
in the synthesis of ¯uorinated heterocyclic compounds.
Routes to ¯uorinated carbocyclic aromatic compounds
have relied more on either direct ¯uorination2 or the intro-
duction of tri¯uoromethyl groups from tri¯uorobromo-
methane,3 tri¯uoroiodomethane,4 tri¯uoromethyltrimethyl-
silane5 and other silanes,6 silver tri¯uoroacetate,7 sodium
tri¯uoroacetate,8 N-tri¯uoromethyl-N-nitrosotri¯uoromethane-
sulfonamide,9 or bistri¯uoromethylmercury.10 Introduction
of tri¯uoromethyl side chain substituents into aromatic
carbocycles via a building block approach permitting
construction of the ring with incorporation of the tri¯uoro-
methyl substituent is little developed. The possibility that
the [313] benzannulation procedures, recently developed
by Junjappa et al.11 and reviewed by Katritzky et al.,12
might be used to give ¯uorinated naphthalenes, is attractive.
In this methodology an unsaturated ketone is reacted with a
Scheme 1.
Keywords: Grignard reagents; naphthalenes; tri¯uoromethylketones.
* Corresponding author. Tel.: 1238059-2392; fax: 1238059-6805; e-mail: jmm4@soton.ac.uk
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00977-7

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J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
procedures using organocerium intermediates18 have been
well described, we ®nd no advantage relative to the use of
Grignard reagents. In this paper we describe the synthesis of
a series of 1,2-adducts by reaction of benzyl Grignard
reagents with the cyclic ketone (1) and related ketones.
By subsequent dehydration of the resulting alcohols, and
of an alcohol obtained via addition of allyl magnesium
bromide, and cyclisation through [3,3] benzannulation, the
resulting intermediate 1,2-adducts are transformed to
tri¯uoromethyl substituted aromatics.
We ®nd that method A by prior preparation of the Grignard
reagent in ether followed by addition of the ketone (3) is
markedly less ef®cient than method B, using Barbier con-
ditions of in situ preparation and reaction of the Grignard
reagent. In these reactions with ketone (3) signi®cant
amounts of the alcohols (12) and (13), products derived
via 1,4-addition, were observed using method B. In par-
ticular using method A in ether reaction of p-methylbenzyl
magnesium bromide with ketone (3) gave, in addition to the
alcohol (11), the tertiary alcohol (14). Analogous obser-
vations23 have been made in addition of other Grignard
reagents to the ketone (3). From ketone (4) the crystalline
1,2-adduct (15) was obtained in 25% yield under Barbier
conditions (method B), but in lower yield by method A.
However by reaction with benzyl lithium the 1,2-adduct
(15) was obtained in 35% yield. The 1,2-adducts (16±18)
derived by addition of the Grignard reagents from allyl
bromide and cinnamyl chloride to ketones (1) and (3),
have been described13 in the accompanying paper, where
we have used Barbier conditions. In the preparation of
1,2-adducts from allyl and benzyl Grignard reagents, whilst
recognising the advantages of using Barbier conditions, as
described elsewhere,13 we also note that the nature of the
ketone is a factor in the choice of reaction conditions. Thus
the acyclic ketone (3) and the ketone (4) give higher yields
under Barbier conditions (method B) and the cyclic ketone
(1) gives satisfactory yields under the conditions of method
A with benzyl Grignard reagents.
Results and Discussion
Our study has been based on cyclic ketones (1) and (2),
which are readily prepared19 by Friedel and Crafts acylation
of dihydropyran and dihydrofuran respectively. Similarly
the acyclic ketone (3) is easily prepared19,20 by acylation
of ethyl vinyl ether. Recently the ketone (4) has become
available21 by the reaction of an N-protected proline with
tri¯uoroacetic anhydride. In the accompanying paper,22 we
have described the 1,4-addition reactions of phenyl and
other aryl Grignard reagents with e.g. the cyclic ketone
(1). In a further paper13 we have found that benzyl mag-
nesium bromide afforded by 1,2-addition the alcohol (5) in
93% yield. Under similar reaction conditions we found that
the Grignard reagent derived from p-methoxybenzyl
bromide did not add ef®ciently to ketone (1). Self-coupling
in the course of attempted reactions of Grignard reagents
derived from benzyl halides, and in particular p-methoxy-
benzyl halides, is a serious limitation to their use. We found
that attempts to vary the reaction conditions to avoid self-
coupling led in ether-tetrahydrofuran to 1,4-additions rather
than the desired 1,2-addition. Consequently we have not
found conditions permitting ef®cient 1,2-addition of
p-methoxybenzyl magnesium bromide to ketone (1). Fortu-
nately the behaviour of p-methoxybenzyl magnesium
bromide proved to be the exception. Reaction of the
Grignard reagents derived from p-methylbenzyl bromide,
p-bromobenzyl bromide and p-chlorobenzyl chloride with
ketone (1) give the desired 1,2-adducts (6±8) in good yield
following method A in ether. The structure of alcohol (7)
was established14 by a single crystal X-ray diffraction study.
We have reported13 that the addition of benzyl magnesium
bromide to the ketone (2) is less ef®cient under the same
conditions. The alcohol (9) was obtained as a minor product,
as, in this case, 1,4-addition was the dominant pathway. In
reactions with the acyclic ketone (3) the major pathway is
via 1,2-addition affording the alcohols (10) and (11) from
benzyl magnesium bromide and p-methylbenzyl mag-
nesium bromide respectively.

J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
10069
Katritzky et al.12 have reviewed methods of [3,3] benzannu-
lation. An ef®cient method of dehydration of alcohols
derived from additions of benzyl Grignard reagents to
ketones, and subsequent cyclisation, has been developed
by Junjappa et al.11 using boron tri¯uoride etherate. We
have found that this method and a further procedure using
p-toluenesulfonic acid as the promoter of dehydration and
cyclisation, are effective. The course of the reaction path-
way is established by the reaction of alcohol (5) with
p-toluenesulfonic acid in toluene at re¯ux for a short period.
The dehydration products, a mixture of the alkenes (19) are
isolated in 84% yield. Either reaction of these alkenes (19)
or of the alcohol (5) under more vigorous conditions gives
the desired naphthalene (20) in good yield. Using p-tolu-
enesulfonic acid, reaction of the alcohol (5) gave the naph-
thalene (20) in 70% yield, alongside two minor products, the
ester (21) and the ether (22). With boron tri¯uoride etherate
the naphthalene (20) is obtained in 82% yield. Similarly the
naphthalenes (23±25) are obtained by ef®cient cyclisations.
The major signi®cance of these results is the development of
a route to 2-tri¯uoromethyl benzenes and naphthalenes,
which de®nes speci®cally the position of the ¯uorinated
substituent relative to other substituents. Although
2-tri¯uoromethylnaphthalene (28) is known,24±27 the
preparation from naphthalene is characterised by separation
problems9,28 from 1-tri¯uoromethylnaphthalene. Other
routes require the use of HF,24SF4 or XeF2 and have
not been shown to be applicable to more substituted
naphthalenes. 3,6-Disubstituted 2-tri¯uoromethyl- naphtha-
lenes have not been prepared prior to our work. The interest
in the side-chain alcohols is enhanced by their possible
transformation to other substituents, thus offering a wider
range of aromatic end-groups, which might be used to
modify polarity and hence properties of biologically active
molecules. The point is illustrated by oxidation using Jones
reagent of the alcohols (20) and (24±26) to the naphthyl-
propionic acids (31±33) and the naphthylacetic acid (34) in
good yield. 3-Substituted-2-tri¯uoromethylnaphthalenes
have already been prepared30 in a study of candidate drugs
to be used against diabetes. Hence our access to a series of
tri¯uoromethyl-substituted naphthalenes carrying additional
alcohol, acid and amine endgroups promises much scope for
subsequent structural elaboration.
26
29
Using the procedure with p-toluenesulfonic acid, the
cyclisation of the alcohols (9) and (15) gave respectively
the naphthalenes (26) and (27) having side-chain alcohol
and protected amine functionality. The procedure based
on p-toluenesulfonic acid is particularly ef®cient for trans-
forming the alcohols (10) and (11) derived from the acyclic
ketone (3) to 2-tri¯uoromethylnaphthalene (28) and
2-methyl-6-tri¯uoromethylnaphthalene (29) respectively.
The cyclisation of the alcohol (17), obtained by 1,2-allyl-
ation of the ketone (1) could only be achieved under forcing
conditions, which resulted in the formation of the tosylate
(30) in 60% yield. The cyclisation of the alcohol (16) was
studied under a variety of conditions without success.
Experimental
General experimental procedures are described elsewhere.31
4-(Ethoxy)-1,1,1-tri¯uoro-3-butene-2-one (3).19,20 To a
stirred solution of 4-dimethylaminopyridine (12.0 mg,
0.10 mmol) and tri¯uoro acetic anhydride (3.28 gm,
15.62 mmol) in dichloromethane (20.00 ml), ethyl vinyl
ether (1.06 g, 14.70 mmol) was added dropwise at 2108C.
The reaction mixture was stirred for 19 h at 08C, allowed to
warm to room temperature and the solvent was evaporated
in vacuo. The reaction mixture was poured into sodium
bicarbonate solution (the deep violet colour changed to a
yellow colour), the two phases were separated and the
organic phase was washed with water, dried over anhydrous
sodium sulfate and the solvent was evaporated in vacuo to
give the crude title compound (3) as a yellow oil (2.00 gm,
81%). The crude product was used directly in subsequent
Grignard reactions.
Alcohols prepared by 1,2-addition of Grignard reagents
Method A. To a 100 ml round bottomed ¯ask (with an

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J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
addition funnel, magnetic stirrer bar and re¯ux condenser
carrying a calcium chloride tube), magnesium turnings
(0.54 g, 22.22 mmol), dry ether (4.2 ml) and a crystal of
iodine were added. A few drops of benzyl halide
(22.22 mmol) in dry ether (4.2 ml) were added dropwise,
and the solution was stirred until the formation of the
Grignard reagent. The remainder of the benzyl halide was
diluted with dry ether (8.4 ml) and the solution was added at
such a rate as to maintain gentle re¯ux. After the complete
addition of the benzyl halide, the reaction mixture was
heated under re¯ux with stirring on a warm water bath for
20 min. The reaction mixture was cooled and a solution of
the ketone (1) (1.00 g, 5.55 mmol) in dry ether (4.2 ml) was
added dropwise. The reaction mixture was stirred for
30 min, followed by heating under re¯ux for another
30 min, allowed to cool to room temperature and 2 M
hydrochloric acid was added until pH2. The two phases
were separated and the aqueous phase extracted with ether
(3£15 ml), the combined organic phases were collected,
washed with water (2£20 ml), dried over MgSO4 and the
solvent evaporated in vacuo to afford a crude product.
128.8 and 126.6 (Ph±C), 124.45 (q, JC±Fˆ281.4, CF3),
123.5 (CHvCH), 71.5 (q, Jˆ31.65 Hz, CH±CF3), 38.8
(CH2Ph); ymax (®lm, cm21) 3550±3100 (OH), 1603
(CvC); LRMS (Scan AP1): m/zˆ216 (M1, 12%), 199
(M12OH, 12), 198 (M12H2O, 100); HRMS (EI1): M1
found 216.0768; C11H11F3O requires 216.0762.
Following method A, reaction of ketone (3) with benzyl
magnesium bromide (2.5 equiv.) afforded the alcohol (10)
in 40% yield, (analytical data as described above).
(E)-4-Ethoxy-1,1,1-tri¯uoro-2-(p-methylbenzyl)-3-buten-
2-ol (11). Following method B reaction of ketone (3) with
p-methylbenzyl magnesium bromide afforded after chroma-
tography [silica gel, hexane: ethyl acetate (90:10)] two
fractions. The title compound (11) was isolated ®rst as a
1
pale yellow oil (0.68 g, 45%) H NMR (300 MHz, CDCl3)
dˆ7.15 (4H, m, Ar-H), 6.42 (1H, d, Jˆ12.5 Hz, CHvCH),
4.88 (1H, d, Jˆ12.5 Hz, CHvCH), 3.72 (2H, q, Jˆ7.0 Hz,
OCH2), 3.11 (1H, d, Jˆ13.2 Hz, CH2-Ar), 2.97 (1H, d,
Jˆ13.2 Hz, CH2-Ar), 2.38 (3H, s, CH3), 2.12 (1H, s, OH),
1.31 (3H, t, Jˆ7.0 Hz, CH3); 13C NMR (75 MHz, CDCl3)
dˆ151.0 (±O±CH), 137.1 (C0), 131.0 and 129.1 (Ar-H),
100.6 (CHvCH), 65.5 (CH2CH3), 41.1 (CH2-Ar), 21.2
(CH3), 14.7 (CH2CH3); ymax (CH2Cl2, cm21) 3563 and
3438 (OH), 1653 and 1515 (CvC); LRMS (Scan AP1):
m/zˆ257 (M12OH, 47%), 228 (M12C2H5OH, 23), 205
(M12CF3, 100) HRMS (EI1): M1 found 274.1176,
C14H17F3O2 requires 274.1181. (E)-1,1,1-tri¯uoro-5-(p-
methylphenyl)-3-penten-2-ol (13) was isolated as a pale
yellow oil (0.27 g, 21%) 1H NMR (300 MHz, CDCl3)
dˆ7.19 (2H, d, Jˆ8.1 Hz, Ar-H), 7.11 (2H, d, Jˆ8.1 Hz,
Ar-H), 6.17 (1H, dt, Jˆ14.7, 7.5, 7.5 Hz, CH±CH2), 5.60
(1H, dd, Jˆ14.7, 6.6 Hz, CHvCH), 4.43 (1H, pent.,
Jˆ6.6 Hz, CH±CF3), 3.44 (2H, d, Jˆ6.6 Hz, CH2-Ar),
2.55 (1H, s, OH), 2.35 (3H, s, CH3); 13C NMR (75 MHz,
CDCl3) dˆ137.75 (CHvCH), 136.2, 135.9 (C0-Ar), 129.5,
128.7 (Ar-C), 124.5 (q, JC±Fˆ281.4, CF3), 123.25
(CHvCH), 71.6 (q, JC±Fˆ31.65, CH±CF3), 38.4 (CH2-
Ar), 21.2 (CH3); ymax (®lm, cm21) 3550±3100 (OH);
LRMS (Scan AP1): m/zˆ230 (M1, 60%), 213
(M12OH, 15), 212 (M12H2O, 100), 160 [(M121)2CF3,
13], HRMS (EI1): M1 found 230.0924, C12H13F3O requires
230.0918.
Method B. To magnesium turnings (0.44 gm, 18.11 mmol)
in dry ether (1.5 ml), the benzyl bromide (0.20 mmol) was
added, the reaction mixture was heated with vigorous
stirring to initiate the reaction. A solution of the ketone
(3) (0.93 gm, 5.54 mmol) and the benzyl bromide (6.58
mmol) in dry ether (3.0 ml) was added dropwise to maintain
re¯ux. The reaction mixture was heated under re¯ux for 3 h,
allowed to cool to room temperature and poured into cold
saturated aqueous ammonium chloride (100 ml). The two
phases were separated and the aqueous phase extracted with
ether (3£15 ml), the combined organic phases were
collected, washed with water (2£20 ml), dried over
MgSO4 and the solvent evaporated in vacuo to afford a
crude product.
(E)-2-Benzyl-4-ethoxy-1,1,1-tri¯uoro-3-buten-2-ol (10).
Following method B, reaction of ketone (3) with benzyl
magnesium bromide afforded after chromatography [silica
gel, hexane: ethyl acetate (95:5)] two fractions. The title
compound (10) was isolated as a pale yellow oil (0.79 g,
1
55%) H NMR (300 MHz, CDCl3) dˆ7.33 (3H, m, Ph),
7.22 (2H, m, Ph), 6.38 (1H, d, Jˆ12.5 Hz, OCH), 4.85
(1H, d, Jˆ12.5 Hz, CHvCH), 3.70 (2H, q, Jˆ7.0 Hz,
OCH2), 3.15 (1H, d, Jˆ14.0 Hz, CH2Ph), 2.95 (1H, d, Jˆ
14.0 Hz, CH2Ph), 2.00 (1H, s, OH), 1.24 (3H, t, Jˆ7.0 Hz,
CH3); 13C NMR (75 MHz, CDCl3) dˆ151.05 (±O±CH),
133.9 (C0-1), 131.2, 128.4 and 127.45 (Ph-C), 125.6 (q,
JC±Fˆ285.9, CF3), 100.5 (CHvCH), 75.0 (C±CF3), 65.6
(CH2CH3), 41.5 (CH2±Ph), 14.7 (CH2CH3); ymax (®lm,
cm21) 3500±3100 (OH), 1630, 1590 (CvC); LRMS
(Scan AP1): m/zˆ243 (M12OH, 60 %), 191 (M12CF3,
100); HRMS (CI1): (M11NH4) found 278.1369;
C13H15F3O2 requires 278.1368.
(E)-1,1,1-Tri¯uoro-2-(p-methylbenzyl)-5-(p-methylphenyl)-
3-penten-2-ol: (14). Following method A reaction of ketone
(3) with (p-methylbenzyl) magnesium bromide afforded
after chromatography [silica gel, hexane: ethyl acetate
(90:10)] two fractions: (E)-4-ethoxy-1,1,1-tri¯uoro-2-(p-
methylbenzyl)-3-buten-ol (11) which was isolated as a
pale yellow oil (0.45 g, 30%) (analytical data as described
above); and the title compound (14) which was isolated as a
1
pale yellow oil (0.38 g, 20%) H NMR (300 MHz, CDCl3)
dˆ7.10 (6H, m, Ar-H), 6.90 (2H, d, Jˆ7.4 Hz, Ar-H), 5.82
(1H, dt, Jˆ15.4, 6.6, 6.6 Hz, CH±CH2), 5.60 (1H, d,
Jˆ15.4 Hz, CHvCH), 3.34 (2H, d, Jˆ6.6 Hz, CHCH2-
Ar), 3.12 (1H, d, Jˆ13.5 Hz, CH2-Ar), 2.95 (1H, d, Jˆ
13.5 Hz, CH2-Ar), 2.35 (3H, s, CH3), 2.34 (3H, s, CH3),
2.08 (1H, s, OH); 13C NMR (75 MHz, CDCl3) dˆ137.0,
136.2, 135.9 and 130.6 (C0-Ar), 133.8, 131.05, 129.2,
129.1, 128.65 and 127.2 (Ar-C and CHˆvCH), 125.6 (q,
JC±Fˆ286.0, CF3), 76.1 (q, JC±Fˆ55.4 Hz, C±CF3), 40.2 and
(E)-1,1,1,-Tri¯uoro-5-phenyl-3-penten-2-ol (12). The
compound was isolated as a pale yellow oil (0.30 g, 25%);
1H NMR (300 MHz, CDCl3) dˆ7.30±7.00 (5H, complex,
Ph±H), 6.03 (1H, dt, Jˆ14.7, 7.5, 7.5 Hz, CH±CH2), 5.49
(1H, dd, Jˆ14.7, 6.6 Hz, CHvCH), 4.35 (1H, Pent.,
Jˆ6.6 Hz, CH±CF3), 3.38 (2H, d, Jˆ6.6 Hz, CH2Ph); 13C
NMR (75 MHz, CDCl3) dˆ139.0 (C0), 137.4 (CHvCH),

J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
10071
38.1 (2C, CH2-Ar), 21.3 and 21.2 (2C, CH3); ymax (®lm,
cm21) 3600±3400 (OH); LRMS (Scan AP1): m/zˆ334
(M1, 61 %), 316 [(M121)2OH, 100%)], 265 (M12CF3,
38), HRMS (EI1): M1 found, 334.1547; C20H21F3O
requires, 334.1544.
94); HRMS (EI1): M1 found 306.0634, C14H14ClF3O2
requires 306.0634.
Ethyl 4-(1-benzyl-2,2,2-tri¯uoro-1-hydroxyethyl)-2,3-
dihydro-1H-1-pyrrolecarboxylate (15) prepared by 1,2-
addition of benzyl lithium (Method C). To a mixture of
toluene (0.930 g, 9.00 mmol) and TMEDA (0.380 g,
3.72 mmol), a solution of butyl lithium in hexanes (1.6 m/
l) (1.88 ml, 3.00 mmol) was added dropwise under nitrogen.
The reaction mixture was heated under gentle re¯ux for
about 30 min (until all the gas evolution stopped) and the
red solution allowed to cool to room temperature. The
benzyl lithium was added dropwise via syringe to a solution
of the ketone (4) (0.237 g, 1.00 mmol) in tetrahydrofuran
(2.5 ml), the reaction mixture was stirred for 30 min,
allowed to warm to room temperature, diluted with tetra-
hydrofuran (25.0 ml) and poured into saturated ammonium
chloride solution (50 ml). The two phases were separated
and the aqueous phase extracted with ether (3£15 ml), the
combined organic phases were collected, washed with water
(2£20 ml), dried over MgSO4 and the solvent evaporated in
vacuo. The title compound (15) was isolated as a white solid
which was recrystallised from petroleum ether to give white
crystals (0.120 g, 35%) mp 99±1008C 1H NMR (300 MHz,
CDCl3) dˆ7.29 (3H, m, Ph-H), 7.21 (2H, m, Ph-H), 6.66
and 6.50 (1H, s, H-6), 4.11 (2H, m, CH2CH3), 3.77 (2H, m,
H-2), 3.10 (2H, m, CH2-Ph), 2.85±2.50 (3H, complex, H-3,
OH), 1.23 (3H, m, CH2CH3); 13C NMR (75 MHz, CDCl3)
dˆ133.5 (C0-1), 130.7, 128.6 and 127.6 (Ph-C), 118.7
(C-4), 75.8 (C±CF3), 61.8 (CH2CH3), 46.1 (C-2), 39.6
(CH2-Ph), 30.2 and 29.2 (C-3), 14.75(CH3); ymax (®lm,
cm21) 3500±3200 (OH), 1681 (CvO), 1600 (CvC);
LRMS (Scan AP1): m/zˆ330 [(M111), 58%], 312 (M12
OH, 28), 260 (M12CF3, 100); HRMS (CI1): (M11NH4);
found, 347.1587 C16H18F3NO3 requires 347.1583. Found C,
58.35; H, 5.39; N, 4.17. C16H18F3O3N requires C, 58.35; H,
5.51; N, 4.25%.
2-(3,4-Dihydro-2H-5-pyranyl)-1,1,1-tri¯uoro-3-(p-methyl-
phenyl)-2-propanol (6). Following method A reaction of
ketone (1) with p-methylbenzyl magnesium bromide
afforded after chromatography [silica gel, hexane: ethyl
acetate (95:5)] the title compound (6) as a pale yellow oil
(1.54 g, 97%) 1H NMR (300 MHz, CDCl3) dˆ7.18 (2H, d,
Jˆ8.5 Hz, Ar-H), 7.09 (2H, d, Jˆ8.5 Hz, Ar-H), 6.51 (1H, s,
H-6), 4.00, (1H, m, H-2), 3.91 (1H, m, H-2), 3.08 (2H, s,
CH2-Ar), 2.33 (3H, s, CH3), 2.13 (2H, m, H-4), 2.00 (1H, s,
OH), 1.85 (2H, m, H-3); 13C NMR (75 MHz, CDCl3)
dˆ144.6 (C-6), 137.2 and 130.5, (C0-1, C0-4), 130.7 and
129.3 (Ar-C), 125.9 (q, JC±Fˆ287.1, CF3), 108.2 (C-5),
76.8 (C-CF3), 65.5 (C-2), 38.6 (CH2-Ar), 21.95 (C-3),
21.2 (CH3), 20.8 (C-4); ymax (®lm, cm21) 3550±3200
(OH), 1657 (CvC); LRMS (Scan AP1): m/zˆ269 (M12
OH, 64 %), 217 (M12CF3, 100); HRMS (CI1): (M11NH4)
found 304.1529, C15H17F3O2 requires 304.1525.
3-(p-Bromophenyl)-2-(3,4-dihydro-2H-5-pyranyl)-1,1,1-
tri¯uoro-2-propanol (7). Following the method A reaction
of ketone (1) with p-bromobenzyl magnesium bromide
afforded after chromatography [silica gel, hexane: ethyl
acetate (95:5)] the title compound (7) as a white solid
(1.45 g, 74%) which was recrystallised from petroleum
1
ether mp 69±708C H NMR (300 MHz, CDCl3) dˆ7.45
(2H, d, Jˆ8.1 Hz, Ar-H), 7.09 (2H, d, Jˆ8.1 Hz, Ar-H),
6.45 (1H, s, H-6), 3.95 (1H, m, H-2), 3.88 (1H, m, H-2),
3.09 (1H, d, Jˆ13.9 Hz, CH2-Ar), 3.04 (1H, d, Jˆ13.9 Hz,
CH2-Ar), 2.20±2.00 (3H, complex, H-4, OH), 1.80 (2H, m,
H-3); 13C NMR (75 MHz, CDCl3) dˆ144.6 (C-6), 133.1
and 121.5, (C0-1, C0-4), 132.7 and 132.5 (Ar-C), 125.8 (q,
JC±Fˆ287.1, CF3), 107.8 (C-5), 65.5 (C-2), 38.4 (CH2-Ar),
21.8 (C-3), 20.8 (C-4); ymax (CH2Cl2, cm21) 3567 (OH),
1663 (CvC); LRMS (Scan AP1): m/zˆ335 [(M11
2)2OH, 22%], 333 (M12OH, 20), 283 [(M112)2CF3,
9], 281(M12CF3, 9); HRMS (CI1): (M11NH4) found
368.0474, C14H14BrF3O2 requires 368.0473. Found C,
47.90; H, 4.03; Br, 22.78. C14H14F3O2Br requires C,
47.88; H, 4.02; Br, 22.75%. The structure of alcohol (7)
has been established14,32 by X-ray diffraction.
Dehydration of alcohols with p-toluene sulfonic acid in
toluene
Method C. To a solution of the alcohol (0.385 mmol) in
toluene (7.65 ml) was added under nitrogen p-toluenesul-
fonic acid (0.134 mmol). The reaction mixture was heated
under re¯ux for 2 h and poured into sodium bicarbonate
solution (30 ml). The two layers were separated and the
organic layer was washed with water (2£20 ml), dried
over anhydrous sodium sulfate and the solvent was evapo-
rated in vacuo to afford a crude product.
3-(p-Chlorophenyl)-2-(3,4-dihydro-2H-5-pyranyl)-1,1,1-
tri¯uoro-2-propanol (8). Following method A reaction of
ketone (1) with p-chlorobenzyl magnesium chloride
afforded after chromatography [silica gel, hexane: ethyl
acetate (95:5)] the title compound (8) as a pale yellow oil
(1.36 g, 80%); 1H NMR (300 MHz, CDCl3) dˆ7.28 (2H, d,
Jˆ8.1 Hz, Ar-H), 7.13 (2H, d, Jˆ8.1 Hz, Ar-H), 6.44 (1H, s,
H-6), 3.96 (1H, m, H-2), 3.84 (1H, m, H-2), 3.10 (1H, d,
Jˆ14.0 Hz, CH2-Ar), 3.02 (1H, d, Jˆ14.0 Hz, CH2-Ar),
2.20±1.98 (3H, complex, H-4, OH), 1.78 (2H, brm, H-3);
13C NMR (75 MHz, CDCl3) dˆ144.6 (C-6), 133.35 and
132.5 (C0-1, C0-4), 132.1, and 128.5 (Ar-C), 125.8 (CF3),
107.8 (C-5), 65.5 (C-2), 38.4 (CH2-Ar), 21.8 (C-3), 20.8
(C-4); ymax (®lm, cm21) 3500±3150 (OH), 1655 (CvC);
LRMS (Scan AP1): m/zˆ291 [(M112)2OH, 38%], 289
(M12OH, 100), 239 [(M112)2CF3, 30], 237 (M12CF3,
Dehydration of alcohols with BF3/benzene
Method D. To a solution of the alcohol (0.10 mmol) in dry
benzene (0.34 ml), boron tri¯uoride etherate (0.013 ml) was
added and the reaction mixture was re¯uxed for 50 min. The
mixture was poured into sodium bicarbonate solution
(50 ml), the two layers were separated and the organic
layer was washed with water (2£20 ml), dried over
anhydrous sodium sulfate and the solvent was evaporated
in vacuo to afford a crude product.
5-[(E) and (Z)-2-Phenyl-1-(tri¯uoromethyl)-1-ethenyl]-
3,4-dihydro-2H-pyran (19). Following the method C alcohol

10072
J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
(5) (0.60 g, 2.2 mmol) in toluene (70 ml) was heated under
re¯ux for 20 min and the title compounds (19) were isolated
after chromatography [silica gel, petroleum ether: ethyl
acetate (90:10)] as a pale yellow oil [mixture of the two
H0-4), [7.90 (2H, d, Jˆ8.1 Hz) and 7.86 (2H, d, Jˆ8.1 Hz),
H0-5 and H0-8], 7.84 (2H, s, H0-1), 7.6527.48 (4H,
complex, H0-6 and H0-7), 3.63 (4H, m, H-1), 3.12 (4H, m,
H-3), 2.10 (4H, m, H-2); 13C NMR (75 MHz, CDCl3)
dˆ136.6, 134.85, 130.7 and 123.2 (Ar-C0), 129.75±126.4
(Ar-C), 125.05 (CF3), 70.3 (C-1), 31.6 and 29.3 (C-2 and
C-3); ymax (®lm, cm21): 1638 and 1600 (CvC); LRMS
(Scan AP1): m/zˆ491 [(M111), 44%], 490 (M1, 100),
254 [(M12(C14H11F3, 21)], 236 [M12(C14H13F3O), 52];
HRMS (EI1): M1 found 490.1728, C28H24F6O requires
490.1731.
1
isomeric dienes (19)] (0.47 g, 84%) H NMR (300 MHz,
CDCl3) dˆ7.44 (2H, m, Ph-H), 7.31±7.14 (8H, complex,
Ph-H), [6.91 (1H, s), 6.73 (1H, s), 6.64 (1H, s) and 6.39 (1H,
s), vinylic-H], 3.94 (4H, m, H-2), 2.16 (2H, m, H-4), 2.01
(2H, m, H-4), 1.84 (4H, m, H-3); 13C NMR (75 MHz,
CDCl3) dˆ145.7, 144.7, 133.5 and 132.9 (vinylic-c),
135.7, 134.5, 133.5 and 132.9 (C±CF3 and C0-Ar), 129.6,
129.0, 128.7, 128.6, 128.1 and 127.9 (Ph-C), 124.2 (q,
JC±Fˆ273.5, CF3) 123.8 (q, JC±Fˆ276.9, CF3), 110.7 and
105.0 (C-5), 65.7 and 65.5 (C-2), 23.3, 23.1, 22.3, and
22.1 (C-3 and C-4); ymax (®lm, cm21) 1644 and 1620
(CvC); LRMS (Scan AP1): m/zˆ255 [(M111), 13%],
254 (M1, 100) HRMS (EI1): M1 found 254.0915,
C14H13F3O requires 254.0918.
Following method C, a mixture of the two isomeric trienes
(19) (0.050 g, 0.2 mmol) in toluene (1 ml) was heated under
re¯ux for 1.5 h and afforded after chromatography [silica
gel, petroleum ether:ethyl acetate (90:10)] the alcohol (20)
(0.030 g, 65%), the tosylate (21) (0.010 g, 13%) and the
ether (22) (0.019 g, 21%).
3-[3-(Tri¯uoromethyl)-2-naphthyl]-1-propanol
(20).
3-[7-Methyl-3-(tri¯uoromethyl)-2-naphthyl]-1-propanol
(23). Following method D, alcohol (6) (0.20 g, 0.70 mmol),
afforded after chromatography [silica gel, hexane: ethyl
acetate (70:30)] the title compound (23) as a white solid
(0.17 g, 90%) which was recrystallised from petroleum
Following method D, alcohol (5) (0.30 g, 1.1 mmol)
afforded after chromatography [silica gel, petroleum ether:
ethyl acetate (70:30)] the title compound (20) as a white
solid (0.23 g, 82%) mp 50±528C 1H NMR (300 MHz,
CDCl3) dˆ8.18 (1H, s, H0-4), [7.88 (1H, d, Jˆ8.1 Hz)
and 7.81 (1H, d, Jˆ8.1 Hz), H0-5 and H0-8], 7.80 (1H, s,
H0-1), 7.68±7.42 (2H, complex, H0-6 and H0-7), 3.80 (2H, t,
Jˆ6.5 Hz, H-1), 3.02 (2H, t, Jˆ8.1 Hz, H-3), 2.01 (2H, m,
H-2), 1.80 (1H, s, OH); 13C NMR (75 MHz, CDCl3) dˆ
136.4, 134.8 and 130.7 (Ar-C0), 129.75, 128.7, 128.4,
127.3, 127.2, 127.1 and 126.6 (Ar-C), 125.05 (CF3), 62.5
(C-1), 34.5 (C-2), 28.8 (C-3); ymax (CH2Cl2, cm21) 3616
(OH), 1637 and 1600 (CvC); LRMS (Scan AP1):
m/zˆ255 [(M111), 11%], 254 (M1, 100), 236 [(M12
H2O), 26]. Found C, 66.15; H, 4.96. C14H13F3O requires
C, 66.14; H, 5.15%.
1
ether, mp 40±418C; H NMR (300 MHz, CDCl3) dˆ8.12
(1H, s, H0-4), 7.79 (1H, d, Jˆ8.1 Hz, H0-5), 7.70 (1H, s,
H0-1), 7.59 (1H, brs, H0-8), 7.36 (1H, dd, Jˆ8.1, 1.5 Hz,
H0-6), 3.81 (2H, t, Jˆ6.6 Hz, H-1), 3.02 (2H, t, Jˆ8.1 Hz,
H-3), 2.55 (3H, s, CH3), 2.02 (2H, m, H-2), 1.52 (1H, s,
OH); 13C NMR (75 MHz, CDCl3) dˆ138.4, 136.35,
135.05, 126.7 and 123.2 (Ar-C0), 129.1, 128.9, 128.5,
126.8 and 126.3 (Ar-C), 62.6 (C-1), 34.5 (C-2), 28.85
(C-3), 22.0 (CH3); ymax (CH2Cl2, cm21) 3615 (OH), 1640
and 1600 (CvC); LRMS (Scan AP1): m/zˆ269 [(M111),
14%], 268 (M1, 100), 250 [(M12H2O), 7]. Found C, 66.95;
H, 5.67. C15H15F3O requires C, 67.16; H, 5.64%.
Following method C, alcohol (5) (0.270 g, 0.99 mmol) in
toluene (16 ml) was heated under re¯ux for 8 h and afforded
after chromatography [silica gel, petroleum ether:ethyl
acetate (90:10)] three fractions. 3-[3-(Tri¯uoromethyl)-2-
naphthyl]-1-propanol (20) was isolated as a white solid
(0.175 g, 70%) (analytical data as described above). 3-[3-
(tri¯uoromethyl)-2-naphthyl]propyl p-methyl-1-benzene-
sulfonate (21) was isolated as a white solid (0.06 g, 16%),
which was recrystallised from ethyl acetate/petroleum ether
3-[7-Bromo-3-(tri¯uoromethyl)-2-naphthyl]-1-propanol
(24). Following method D, alcohol (7) (0.300 g, 0.86 mmol),
afforded after chromatography [silica gel, hexane: ethyl
acetate (70:30)] the title compound (24) as a white solid
(0.264 g, 92%) which was recrystallised from petroleum
ether to give white crystals, mp 81±828C; 1H NMR
(300 MHz, CDCl3) dˆ7.98 (1H, s, H0-4), 7.82 (1H, d,
Jˆ1.5 Hz, H0-8), 7.59 (1H, d, Jˆ8.6 Hz, H0-5), 7.53 (1H,
s, H0-1), 7.44 (1H, dd, Jˆ8.6, 1.5 Hz, H0-6), 3.65 (2H, t,
Jˆ6.5 Hz, H-1), 2.89 (2H, t, Jˆ8.0 Hz, H-3), 1.96 (1H, s,
OH), 1.88 (2H, m, H-2); 13C NMR (75 MHz, CDCl3)
dˆ137.75, 135.7, 129.0, 126.9 and 122.7 (Ar-C0), 130.2,
130.1, 129.4, 128.7, and 126.8 (Ar-C), 124.7 (CF3), 62.4
(C-1), 34.3 (C-2), 28.8 (C-3); ymax (CH2Cl2, cm21) 3615
and 3466 (OH), 1637 and 1591 (CvC); LRMS (Scan
AP1): m/zˆ334 [(M112), 58%], 332 (M1, 48), 314
[(M12H2O), 33]. Found C, 50.76; H, 3.47, Br, 24.06.
C14H12F3OBr requires C, 50.47; H, 3.63; Br, 23.98%.
1
to give white crystals mp 91±928C H NMR (300 MHz,
CDCl3) dˆ8.18 (1H, s, H0-4), [7.90 (1H, d, Jˆ8.1 Hz)
and 7.79 (1H, d, Jˆ8.8 Hz), H0-5 and H0-8], 7.82 (2H, d,
Jˆ8.1 Hz, Ar-H), 7.69 (1H, s, H0-1), 7.57 (2H, m, H0-6,
H0-7), 7.35 (2H, d, Jˆ8.1 Hz, Ar-H), 4.18 (2H, t, Jˆ
6.0 Hz, H-1), 2.95 (2H, t, Jˆ8.0 Hz, H-3), 2.48 (3H, s,
CH3), 2.06 (2H, m, H-2); 13C NMR (75 MHz, CDCl3)
dˆ145.0, 134.8, 134.7, 133.2 and 130.8 (Ar-C0), 130.05,
128.7, 128.5, 128.1, 127.4, 127.3 and 127.2 (Ar-C), 124.6
(CF3), 69.8 (C-1), 30.6 and 28.5 (C-2, C-3), 21.8 (CH3); ymax
(CH2Cl2, cm21) 1639 and 1599 (CvC); LRMS (Scan AP1):
m/zˆ409 [(M111), 15%], 408 (M1, 75), 254 [(M11
1)2(CH3±C6H4±SO2), 12], 236 [M12(CH3±C6H4±
SO3H), 53]. Found C, 61.59; H, 4.53. C21H19F3O3S requires
C, 61.75; H, 4.69%. Di{3-[3-(tri¯uoromethyl)-2-naph-
thyl]propyl} ether (22) was isolated as a yellow oil
3-[7-Chloro-3-(tri¯uoromethyl)-2-naphthyl]-1-propanol
(25). Following method D, alcohol (8) (0.40 g, 1.31 mmol)
afforded after chromatography [silica gel, hexane: ethyl
acetate (70:30)] the title compound (25) as a white solid
(0.36 g, 94%) which was recrystallised from petroleum
ether to give white crystals mp 67±688C; 1H NMR
(300 MHz, CDCl3) dˆ8.13 (1H, s, H0-4), 7.81 (1H, d,
1
(0.03 g, 6%) H NMR (300 MHz, CDCl3) dˆ8.21 (2H, s,

J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
10073
Jˆ8.8 Hz, H0-5), 7.79 (1H, m, H0-1), 7.70 (1H, brs, H0-8),
7.46 (1H, dd, Jˆ8.8, 2.2 Hz, H0-6), 3.79 (2H, t, Jˆ6.5 Hz,
H-1), 3.02 (2H, t, Jˆ8.1 Hz, H-3), 2.00 (2H, m, H-2), 1.65
(1H, s, OH); 13C NMR (75 MHz, CDCl3) dˆ137.8, 135.4
and 134.3 (Ar-C0), 130.2, 128.9, 127.6, 126.9, and 126.1
(Ar-C), 124.7 (CF3), 62.4 (C-1), 34.35 (C-2), 28.8 (C-3);
ymax (CH2Cl2, cm21) 3616 (OH), 1640 (CvC); LRMS
(Scan AP1): m/zˆ290 [(M112), 49%], 288 (M1, 100),
272 [(M112)2H2O, 28], 270 [(M12H2O), 75]. Found C,
58.28; H, 4.11; Cl, 12.40. C14H12F3OCl requires C, 58.25;
H, 4.19; Cl, 12.28%.
7.58 (1H, s, H0-1), 7.50 (1H, dd, Jˆ8.0, 1.5 Hz, H0-7),
7.32 (1H, dd, Jˆ8.0, 1.5 Hz, H0-3), 2.46 (3H, s, CH3); 13C
NMR (75 MHz, CDCl3) dˆ138.25, 135.0 and 130.55
(Ar-C0), 129.6, 128.7, 128.4, 127.0 and 125.5 (Ar-C),
124.1 (CF3), 22.0 (CH3); ymax (CH2Cl2, cm21) 1620 and
1600 (CvC); LRMS (Scan AP1): m/zˆ211 [(M111),
7%], 210 (M1, 55). Found C, 68.85; H, 4.21; C12H9F3
requires C, 68.57; H, 4.32%.
2-(Tri¯uoromethyl)naphthalene (28). Following method
C, alcohol (10) (0.150 g, 0.58 mmol) afforded the title
compound (28) as white solid (0.096 g, 84%), which was
recrystallised from ethanol/water to give a white crystals mp
2-[3-(Tri¯uoromethyl)-2-naphthyl]-1-ethanol (26). Follow-
ing method C, alcohol (9) (0.070 g, 0.27 mmol) was heated
under re¯ux for 4 h and the title compound (26) was isolated
after chromatography [silica gel, petroleum ether: ethyl
acetate (70:30)] as a white solid (0.060 g, 92%) which
was recrystallised from petroleum ether to give white crys-
tals mp 66±678C; 1H NMR (300 MHz, CDCl3) dˆ8.20 (1H,
s, H0-4), [7.90 (1H, d, Jˆ8.1 Hz) and 7.85 (1H, d, Jˆ
8.1 Hz), H0-5 and H0-8], 7.89 (1H, s, H0-1), [7.68 (1H, m)
and 7.48 (1H, m), H0-6 and H0-7], 3.97 (2H, t, Jˆ6.6 Hz,
H-1), 3.20 (2H, t, Jˆ6.6 Hz, H-2), 1.68 (1H, s, OH); 13C
NMR (75 MHz, CDCl3) dˆ134.6, 132.6, 130.85 and 127.3
(Ar-C0), 130.85, 128.7, 128.5, 127.4, 127.25 and 126.9
(Ar-C), 124.8 (CF3), 63.2 (C-1), 36.0 (C-2); ymax (CH2Cl2,
cm21) 3611 (OH), 1639 (CvC); LRMS (Scan AP1):
m/zˆ241 [(M111), 6%], 240 (M1, 43); HRMS (CI1):
(M11NH4) found, 258.1109, C13H11F3O requires
258.1106. Found C, 64.78; H, 4.57. C13H11F3O requires C,
65.00; H, 4.62%.
1
64±658C (lit.27 mp 63±648C) H NMR (300 MHz, CDCl3)
dˆ8.08 (1H, s, H0-1), 7.92±7.78 (3H, m, Ar-H), 7.61±7.45
(3H, m, Ar-H); 13C NMR (75 MHz, CDCl3) dˆ134.7.0 and
132.3 (Ar-C0), 129.1, 129.0, 128.3, 128.0, 127.3, 125.8 and
121.6 (Ar-C); ymax (CH2Cl2, cm21) 1640 and 1606 (CvC);
LRMS (Scan AP1): m/zˆ196 (M1, 100).
3-[2-(Tri¯uoromethyl)phenyl]propyl p-methyl-1-benzene-
sulfonate (30). Following method C, alcohol (17) (0.30 g,
1.35 mmol) was reacted with p-toluene sulfonic acid
(0.76 g, 4.0 mmol) in toluene (10 ml) and was heated
under re¯ux for 22 h to afford after chromatography [silica
gel, petroleum ether:ethyl acetate (90:10)] the title
1
compound (30) as a yellow oil (0.29 g, 60%); H NMR
(300 MHz, CDCl3) dˆ7.82 (2H, d, Jˆ8.8 Hz, Ar-H), 7.60
(1H, d, Jˆ7.4 Hz, H0-3), [7.45 (1H, t, Jˆ7.4 Hz) and 7.28
(1H, t, Jˆ7.4 Hz) H0-4 and H0-5], 7.39 (2H, d, Jˆ8.1 Hz,
Ar-H), 7.32 (1H, d, Jˆ7.4 Hz, H0-6), 4.09 (2H, t, Jˆ5.9 Hz,
H-1), 2.79 (2H, t, Jˆ8.0 Hz, H-3), 2.46 (3H, s, CH3), 1.95
(2H, m, H-2); 13C NMR (75 MHz, CDCl3) dˆ145.0, 139.4
and 133.1 (Ar-C0), 132.0, 131.2, 130.05, 128.0, 126.5 and
126.3 (Ar-C), 124.5 (CF3), 69.8 (C-1), 30.75 and 28.7 (C-2,
C-3), 21.8 (CH3); ymax (®lm, cm21) 1620, 1583 (CvC);
LRMS (Scan AP1): m/zˆ376 (M11NH4, 3%), 186 (M12
p-CH3±C6H4±SO3H, 100); HRMS (CI1): (M11NH4) found
376.1164,. C17H17F3O3S requires 376.1194.
Ethyl N-{2-[3-(tri¯uoromethyl)-2-naphthyl]ethyl}carba-
mate (27). Following method C, alcohol (15) (0.12 g,
0.36 mmol) was heated under re¯ux for 3 h and the title
compound (27) was isolated after chromatography [silica
gel, petroleum ether:ethyl acetate (80:20)] as a white solid
(0.07 g, 63%) which was recrystallised from ethyl acetate/
petroleum ether to give white crystals mp 56±578C 1H NMR
(300 MHz, CDCl3) dˆ8.20 (1H, s, H0-4), [7.90 (1H, d,
Jˆ8.1 Hz) and 7.85 (1H, d, Jˆ8.1 Hz), H0-5 and H0-8],
7.83 (1H, s, H0-1), [7.66 (1H, m) and 7.50 (1H, m), H0-6
and H0-7], 4.85 (1H, brs, NH), 4.15 (2H, q, Jˆ7.4 Hz,
CH2CH3), 3.53 (2H, q, Jˆ7.0 Hz, H-1), 3.19 (2H, t, Jˆ
7.0 Hz, H-2), 1.29 (3H, t, Jˆ7.0 Hz, CH3); 13C NMR
(75 MHz, CDCl3) dˆ156.8 (CvO), 134.7, 133.0, 130.9
and 127.2 (Ar-C0), 130.7, 128.7, 128.55, 127.4, 127.3 and
126.9 (Ar-C), 124.8 (CF3), 61.0 (OCH2CH3), 42.1 (C-1),
Oxidations using Jones reagent
To a cold solution of the alcohol (20) (0.13 g, 0.51 mmol) in
dry acetone (2 ml), Jones reagent (0.2 ml) was added under
nitrogen, the reaction mixture was stirred for 1 h, diluted
with water (20 ml) and extracted with dry ether (3£15 ml).
The combined organic phases were collected, washed with
water (2£20 ml), dried over MgSO4 and the solvent evapo-
rated in vacuo. The resulting solid was puri®ed by ¯ash
column chromatography [silica gel, hexane: ethyl acetate
(70:30)].
33.1 (C-2), 14.8 (CH2CH3); ymax (CH2Cl2, cm21
)
3447(NH), 1716(CvO), 1630 and 1590 (CvC); LRMS
(Scan AP1): m/zˆ312 [(M111), 25%], 265 [(M12
C2H5OH), 6]; HRMS (CI1): (M11NH4) found, 329.1487,
C16H16F3O2N requires, 329.1477. Found C, 61.75; H, 5.05;
N, 4.37%. C16H16F3O2N requires C, 61.73; H, 5.18; N,
4.50%.
3-[3-(Tri¯uoromethyl)-2-naphthyl]propanoic acid (31).
Oxidation of alcohol (20) (0.13 g, 0.51 mmol) gave the
title compound (31) as a white solid (0.124 g, 90%) which
was recrystallised from petroleum ether to give white
crystals mp 117±1188C. 1H NMR (300 MHz, CDCl3)
dˆ8.20 (1H, s, H0-4), [7.92 (1H, d, Jˆ8.1 Hz) and 7.86
(1H, d, Jˆ8.1 Hz), H0-5 and H0-8], 7.83 (1H, s, H0-1),
7.67±7.50 (2H, complex, H0-6 and H0-7), 3.30 (2H, t,
Jˆ8.0 Hz, H-3), 2.81 (2H, t, Jˆ8.0 Hz, H-2); 13C NMR
(75 MHz, CDCl3) dˆ179.0 (CvO), 134.8, 134.5, 130.9
and 127.4 (Ar-C0), 129.8, 128.7, 128.6, 127.4, 127.3 and
2-Methyl-6-(tri¯uoromethyl)naphthalene (29). Follow-
ing method C, alcohol (11) (0.28 g, 1.0 mmol) afforded
the title compound (29) as a yellowish white solid (0.20 g,
95%), which was recrystallised from ethanol/water to give a
yellowish white crystals mp 101±1028C; 1H NMR
(300 MHz, CDCl3) dˆ8.00 (1H, s, H0-5), [7.75 (1H, d,
Jˆ8.1 Hz) and 7.71 (1H, d, Jˆ8.1 Hz), H0-8 and H0-4],

10074
J. M. Mellor et al. / Tetrahedron 56 (2000) 10067±10074
127.0 (Ar-C), 124.8 (q, JC±Fˆ273.5, CF3), 35.5 (C-2), 27.4
(C-3); ymax (CH2Cl2, cm21) 3036±2800 (OH), 1712 (CvO),
1640 and 1600 (CvC); LRMS (Scan AP1): m/zˆ268 (M1,
36 %), 222 [M12(HCOOH), 9], 194 [M12
(CH3CH2COOH), 10]; HRMS (CI1): (M11NH4) found,
286.1060, C14H11F3O2 requires, 286.1055. Found C,
62.67; H, 4.15%. C14H11F3O2 requires C, 62.69; H, 4.13%.
References
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2-[3-(Tri¯uoromethyl)-2-naphthyl]acetic acid (34).
Oxidation of alcohol (26) (0.24 g, 1.0 mmol) gave the title
compound (34) as a white solid (0.21 g, 85%) which was
recrystallised from ethyl acetate/petroleum ether to give
white crystals mp 150±1518C; 1H NMR (300 MHz,
CDCl3) dˆ8.21 (1H, s, H0-4), [7.92 (1H, d, Jˆ8.1 Hz)
and 7.88 (1H, d, Jˆ8.1 Hz), H0-5 and H0-8], 7.85 (1H, s,
H0-1), 7.68±7.53 (2H, complex, H0-6 and H0-7), 4.10 (2H, s,
H-1); 13C NMR (75 MHz, CDCl3) dˆ177.2 (CvO), 134.5,
131.4 and 128.7 (Ar-C0), 132.3, 128.8, 127.7, 127.5, 127.4
and 127.3 (Ar-C), 124.4 (CF3), 38.2 (C-1); ymax (CH2Cl2,
cm21): 3250±2800 (OH), 1707 (CvO), 1640 and 1600
(CvC); LRMS (Scan AP1): m/zˆ255 [(M111), 8%], 254
(M1, 65), 236 [(M12H2O), 7], 210 [(M12CO2), 7]. Found
C, 61.39; H, 3.35. C13H9F3O2 requires C, 61.42; H, 3.57%.
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3-[7-Bromo-3-(tri¯uoromethyl)-2-naphthyl]propanoic
acid (32). Oxidation of alcohol (24) (0.070 g, 0.21 mmol)
gave the title compound (32) as a white solid (0.065 g, 88%)
which was recrystallised from ethyl acetate/petroleum ether
to give white crystals mp 158±1598C; 1H NMR (300 MHz,
DMSO) dˆ8.42 (1H, s, H0-4), 8.23 (1H, brs, H0-8), 8.08
(1H, d, Jˆ8.8 Hz, H0-5), 7.99 (1H, s, H0-1), 7.73 (1H, dd,
Jˆ8.8, 1.5 Hz, H0-6), 3.10 (2H, t, Jˆ8.0 Hz, H-3), 2.68 (2H,
t, Jˆ8.0 Hz, H-2), 2.5 (1H, s, OH); 13C NMR (75 MHz,
DMSO) dˆ173.5 (CvO), 135.95, 135.5, 128.85 and
122.4 (Ar-C0), 131.0, 130.1, 129.2, 128.6 and 127.2
(Ar-C), 34.5 (C-2), 26.9 (C-3); ymax (CH2Cl2, cm21):
3200±2900 (OH), 1712 (CvO), 1637 and 1591 (CvC);
LRMS (Scan AP1): m/zˆ348 (M112, 72%), 347 (M111,
72%), 302 [(M12CO2), 10]; Found C, 48.44; H, 2.93.
C14H10F3O2Br requires C, 48.44; H, 2.90%.
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3-[7-Chloro-3-(tri¯uoromethyl)-2-naphthyl]propanoic
acid (33). Oxidation of alcohol (25) (0.10 g, 0.347 mmol)
gave the title compound (33) as a white solid (0.093 g, 89%)
which was recrystallised from ethyl acetate/petroleum ether
to give white crystals mp 137±1388C; 1H NMR (300 MHz,
CDCl3) dˆ8.18 (1H, s, H0-4), 7.83 (1H, d, Jˆ8.8 Hz, H0-5),
7.81 (1H, s, H0-1), 7.73 (1H, brs, H0-8), 7.49 (1H, dd, Jˆ8.8,
2.2 Hz, H0-6), 3.31 (2H, t, Jˆ8.0 Hz, H-3), 2.82 (2H, t,
Jˆ8.0 Hz, H-2); 13C NMR (75 MHz, CDCl3) dˆ178.7
(CvO), 135.9, 135.35, 134.6, 129.2 and 126.8 (Ar-C0),
130.3, 128.9, 128.0, 127.2 and 126.2 (Ar-C), 35.3 (C-2),
27.4 (C-3); ymax (CH2Cl2, cm21): 3300±2900(OH), 1710
(CvO), 1640 (CvC). LRMS (Scan AP1): m/zˆ304
(M112, 10%), 302 (M1, 33). Found C, 55.42; H, 3.07;
Cl, 11.86. C14H10F3O2Cl requires C, 55.55; H, 3.33; Cl,
11.71%.
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Acknowledgements
31. Andrew, R. J.; Mellor, J. M.; Reid, G. Tetrahedron 2000, 56,
7255.
32. Coles, S. J.; Hursthouse, M. B. private communication.
We thank the Egyptian Government for a research student-
ship (A. H. El-S.) and EPSRC for X-ray facilities.