Regioselective [3+3] cyclization of 1,3-Bis(silyloxy)buta-1,3-dienes with 1,1,1-Trifluoro-4-(silyloxy)alk-3-en-2-ones: New and Convenient synthesis of functionalized 5-alkyl-3-(trifluoromethyl)phenols

Article abstract of DOI:10.1002/hlca.201200056

Functionalized 5-alkyl-3-(trifluoromethyl)phenols were prepared by formal [3+3] cyclization of 1,3-bis(silyloxy)buta-1,3-dienes with 1,1,1-trifluoro-4- (silyloxy)alk-3-en-2-ones derived from 1,1,1-trifluoroalkane-2,4-diones. The latter were prepared by co

Full text of DOI:10.1002/hlca.201200056

44
Helvetica Chimica Acta – Vol. 96 (2013)
Regioselective [3 þ 3] Cyclization of 1,3-Bis(silyloxy)buta-1,3-dienes with
1,1,1-Trifluoro-4-(silyloxy)alk-3-en-2-ones: New and Convenient Synthesis of
Functionalized 5-Alkyl-3-(trifluoromethyl)phenols
by Stefan Bꢀttnera), Alina Bunescua)b), Sebastian Reimanna)b), T. H. Tam Danga), Thomas Pundta),
Renske Klassena), Andreas Schmidta), Nazken K. Kelzhanovaa)c), Zharylkasyn A. Abilovc),
Tariel V. Ghochikyand), Ashot S. Saghiyand)e), Alexander Villingera), Helmut Reinkea),
Anke Spannenbergb), and Peter Langer*a)b)
a) Institut fꢀr Chemie, Universitꢁt Rostock, Albert-Einstein-Str. 3a, DE-18059 Rostock
(fax: þ 3814986412; e-mail: peter.langer@uni-rostock.de)
b) Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock, Albert-Einstein-Str. 29a,
DE-18059 Rostock
c) Al-Farabi Kazakh National University, Al-Farabi ave. 71, 050040 Almaty, Kazakhstan
d) Faculty of Chemistry, Yerevan State University, Alex Manoogian 1, 0025 Yerevan, Armenia
e) CJSC Scientific Research Institute of Biotechnology, Gyurjyan Str. 14, 0056, Yerevan, Armenia
Functionalized 5-alkyl-3-(trifluoromethyl)phenols were prepared by formal [3 þ 3] cyclization of
1,3-bis(silyloxy)buta-1,3-dienes with 1,1,1-trifluoro-4-(silyloxy)alk-3-en-2-ones derived from 1,1,1-tri-
fluoroalkane-2,4-diones. The latter were prepared by condensation of the dianion of 1,1,1-trifluoro-
pentane-2,4-dione with alkyl halides.
Introduction. – In 2006, we published a preliminary communication related to the
synthesis of 5-methyl-3-(trifluoromethyl)phenols by formal [3 þ 3] cyclocondensation
of 1,3-bis(silyloxy)buta-1,3-dienes1) with 1,1,1-trifluoro-4-(silyloxy)prop-3-en-2-one
[2]. This methodology was later extended to the synthesis of 5-aryl-3-(trifluorome-
thyl)phenols [3], 5-hetaryl-3-(trifluoromethyl)phenols [4], 5-alkyl-3-(perfluoroalkyl)-
phenols, and 5-aryl-3-(perfluoroalkyl)phenols [5]. We also reported the synthesis of 5-
unsubstituted 3-(trifluoromethyl)phenols by cyclization of 1,3-bis(silyloxy)buta-1,3-
dienes with 4-ethoxy-1,1,1-trifluoroalk-3-en-2-ones [6]. Here, we report full details of
the synthesis of functionalized 5-alkyl-3-(trifluoromethyl)phenols by cyclization of 1,3-
bis(silyloxy)buta-1,3-dienes with 1,1,1-trifluoro-4-(silyloxy)alk-3-en-2-ones. With re-
gard to our preliminary communication [2], the preparative scope has been consid-
erably extended. While the method was initially restricted to the synthesis of 5-methyl-
3-(trifluoromethyl)phenols, we were able to realize the synthesis of various 5-alkyl-3-
(trifluoromethyl)phenols. In this context, we report an efficient synthesis of the
required starting materials, 1,1,1-trifluoroalkane-2,4-diones, by condensation of the
dianion of 1,1,1-trifluoropentane-2,4-dione with alkyl halides. While in our preliminary
communication only very few variations of substituent R1 were studied, the present
paper includes a variety of different groups. In addition, chloroalkyl substituents were
introduced in different position of the molecule.
1
)
For a review of 1,3-bis(silyl enol ethers) in general, see [1].
ꢂ 2013 Verlag Helvetica Chimica Acta AG, Zꢀrich

Helvetica Chimica Acta – Vol. 96 (2013)
45
Results and Discussion. – The condensation of the dianion of 1,1,1-trifluoropen-
tane-2,4-dione (2a) with alkyl iodides 1a – 1e afforded the 1,1,1-trifluoroalkane-2,4-
diones 2b – 2f in 41 – 59% yield (Table 1). 1,1,1-Trifluoro-4-(trimethylsilyloxy)alk-3-en-
2-ones 3a – 3f were prepared by silylation of the corresponding CF3-substituted 1,3-
diones 2a – 2f. The reactions with simple aliphatic alkyl iodides afforded products 3b
and 3d – 3f in excellent yields (92 – 95%). 1,3-Dione 3c, containing a remote Cl
substituent, was isolated in 77% yield. Commercially available 1,1,1,3,3,3-hexafluoro-
pentane-2,4-dione (2g) was transformed to 3g (Scheme).
Table 1. Synthesis of 3a – 3f
R1
Compound
Yield of 2 [%]a)
Compound
Yield of 3 [%]a)
C6H13
Cl(CH2)6
C8H17
C10H21
C12H25
2b
2c
2d
2e
2f
42
49
59
41
55
3b
3c
3d
3e
3f
94
77
92
95
93
a) Yields of isolated products.
Scheme. Synthesis of 3g
The TiCl4 mediated cyclization of 3a – 3g with 1,3-bis(silyloxy)buta-1,3-dienes 4a –
4u, prepared by known procedures [7 – 9], afforded the desired 5-alkyl-3-(trifluoro-
methyl)phenols 5a – 5al in 26 – 76% yield (Table 2). For reaction optimization, (high)
concentration and stoichiometric amounts of the starting materials, and low temper-
ature (ꢀ 788) were decisive. All products were formed with excellent regioselectivity
and contained the CF3 group in ortho position to the ester (or Ac) group. The other
possible regioisomers (CF3 group para to the ester group) could not be detected in the
crude product mixture (1H-NMR evidence). In some cases, the product yields were
moderate, due to practical problems. The individual quality (purity) of the enones and
dienes, which cannot be purified owing to their labile nature, played an important role.

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Helvetica Chimica Acta – Vol. 96 (2013)
Table 2. Synthesis of 5-Alkyl-3-(trifluoromethyl)phenols 5a – 5al
3
4
5
R1
R2
R3
Yield of 5 [%]a)
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3c
3d
3d
3d
3d
3e
3e
3e
3e
3e
3f
3f
3f
3f
3f
3g
4a
4b
4c
4d
4e
4f
4g
4h
4j
5a
5b
5c
5d
5e
5f
5g
5h
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
5t
5u
5v
5w
5x
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
C7H15
C7H15
C7H15
C7H15
C7H15
C7H15
Cl(CH2)7
C9H19
C9H19
C9H19
C9H19
C11H23
C11H23
C11H23
C11H23
C11H23
C13H27
C13H27
C13H27
C13H27
C13H27
CF3
H
Me
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
EtO
76
48
49
49
31
50
47
26
69
43
68
40
75
72
60
66
65
66
57
80
60
44
32
66
60
62
39
51
47
49
67
34
35
43
45
66
35
Cl(CH2)3
C4H9
C6H13
Cl(CH2)6
C7H15
C8H17
PhCH2
Ph(CH2)2
Ph(CH2)3
H
Me
Et
H
H
Me
Et
Pr
H
MeO
H
H
Me
Et
H
H
Me
Et
Pr
H
H
Me
Et
Pr
H
H
4k
4l
4m
4n
4o
4p
4a
4b
4q
4r
EtO
EtO
Me
MeO
MeO
MeO
MeO
Me
MeO
EtO
MeO
MeO
MeO
Me
MeO
MeO
MeO
MeO
Me
MeO
MeO
MeO
MeO
C6H5
Me
4p
4s
4m
4a
4b
4q
4p
4a
4b
4q
4t
4p
4a
4b
4q
4t
5y
5z
5aa
5ab
5ac
5ad
5ae
5af
5ag
5ah
5ai
5aj
5ak
5al
4u
4a
a) Yield of isolated products.

Helvetica Chimica Acta – Vol. 96 (2013)
47
In some cases, hydrolysis of the starting materials is observed during the reaction. In
addition, TiCl4-mediated oxidative dimerization of the diene gives rise to the formation
of side-products. Both ester-, Ac- and PhCO(Bz)-substituted phenols were successfully
prepared. While dienes 4p and 4u were prepared from acetyl- and benzoylacetone,
respectively, all other dienes were prepared from b-keto esters. Despite the fact that, in
general, the reactivity of dienes derived from 1,3-diones is lower than the reactivity of
dienes derived from b-keto esters, excellent yields were obtained for the products
derived from 4p and 4u. Likewise, substituents R1 and R2 do not have a major influence
on the yield. Interestingly, products 5c, 5f, and 5w, containing a side chain at C(5) or
C(6) with a remote Cl substituent, were isolated in acceptable yields. In fact, we have
observed earlier that dienes containing a remote Cl substituent can be successfully
employed in formal [3 þ 3] cyclizations [9].
The structure of 5q was established by 2D-NMR experiments (NOESY and
HMBC) (Fig. 1). Additional evidence was obtained from analysis and comparison of
the C,F coupling pattern for all derivatives. The structures of 5a, 5k, 5w, and 5al were
independently confirmed by X-ray crystal-structure analyses (Figs. 2 – 5)2). Inspection
of the crystal lattice of 5al revealed that the H-atom of the OH group is involved in
intermolecular bonds to the C¼O groups of adjacent molecules.
Fig. 1. NOESY and HMBC of 5q
Compounds 5a – 5al show some interesting spectroscopic features. The 19F-NMR
chemical-shift values of all compounds containing an ester group are in the range of
58 – 59 ppm, while for compounds with an Ac group the signals are observed in the
range of 55 – 56 ppm. The chemical shift is influenced by through-bond or through-
space interactions with the neighboring group.
In conclusion, we have reported a versatile synthesis of 5-alkyl-3-(trifluorome-
thyl)phenols by cyclization reactions of 1,3-bis(silyloxy)buta-1,3-dienes. The starting
materials, 1,1,1-trifluoroalkane-2,4-diones, were prepared by condensation of the
dianion of 1,1,1-trifluoropentane-2,4-dione with alkyl halides.
2
)
CCDC-884948 – 884951 contain all crystallographic details of this publication and are available free
of charge at www.ccdc.cam.ac.uk/conts/retrieving.html, or can be ordered from the following
address: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, U.K.; fax:
(þ44)1223-336-033; or deposit@ccdc.cam.ac.uk.

48
Helvetica Chimica Acta – Vol. 96 (2013)
Fig. 2. Crystal structure of 5a
Fig. 3. Crystal structure of 5k
Fig. 4. Crystal structure of 5w

Helvetica Chimica Acta – Vol. 96 (2013)
49
Fig. 5. Crystal structure and intermolecular interactions of 5al
Experimental Part
General Procedure for the Synthesis of Diones 2b – 2f. To a soln. of BuLi (2.3 equiv.) in THF (3 ml
per 1.0 mmol of 1) iPr2NH (2.3 equiv.) was added at 08, and the mixture was stirred for 30 min, followed
by dropwise addition of 1,1,1-trifluoropentane-2,4-dione (1.0 equiv.) and subsequent stirring for
additional 60 min at 08. The mixture then was cooled to ꢀ 788 and the iodoalkane (1.0 equiv.) was
added. The temp. of the mixture was allowed to rise to 208 during 14 h, and, subsequently, HCl (10%,
40 ml) was added. The org. layer was separated and extracted with Et2O (3 ꢁ 40 ml). The combined org.
layers were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified
by column chromatography (CC; SiO2; heptane/AcOEt 20 :1) or by distillation.
1,1,1-Trifluoroundecane-2,4-dione (2b). Starting with 1,1,1-trifluoropentane-2,4-dione (1; 4.623 g,
i
30 mmol), 1-iodohexane (6.362 g, 30 mmol), BuLi (27.6 ml of a 2.5m soln. in hexanes), and Pr2NH
(9.7 ml, 69 mmol) in THF (90 ml), 2b was isolated as a colorless liquid (2.968 g, 42%) by distillation.
B.p. 73 – 758/0.9 Torr. IR (ATR): 3117w, 2958w, 2929m, 2858w, 1594m, 1459m, 1379w, 1277w, 1197m,
1150s, 1107m. 1H-NMR (250 MHz): 0.88 (t, J ¼ 6.7, Me); 1.21 – 1.41 (m, 4 CH2); 1.57 – 1.73 (m, CH2); 2.43
(t, J ¼ 7.6, COCH2CH2); 5.91 (s, CH). 13C-NMR (75 MHz): 14.0 (Me); 22.6 (CH2); 25.5 (CH2); 28.9
(CH2); 29.0 (CH2); 31.6 (CH2); 38.4 (CH2); 95.6 (q, 3J ¼ 1.9, CH); 117.0 (q, 1J ¼ 282.8, CF3); 175.6 (q, 2J ¼
36.2, COCF3); 197.6 (CO). 19F-NMR (235 MHz): ꢀ 76.7 (CF3). EI-MS (70 eV): 238 (6, Mþ), 196 (13),
169 (48), 154 (100), 139 (90). HR-EI-MS (70 eV): 238.1176 (Mþ, C11H17F3O2þ ; calc. 238.1181).
11-Chloro-1,1,1-trifluoroundecane-2,4-dione (2c). Starting with 1 (1.000 g, 6.49 mmol), 1-chloro-6-
iodohexane (1.600 g, 6.49 mmol), BuLi (6.0 ml of a 2.5m soln. in hexanes), and iPr2NH (2.1 ml,
14.93 mmol) in THF (16 ml), 2c was isolated as a colorless liquid (0.864 g, 49%) by CC. 1H-NMR
(250 MHz): 1.21 – 1.84 (m, 5 CH2); 2.41 (t, J ¼ 7.6, CH2); 3.55 (t, J ¼ 7.6, CH2); 5.93 (s, CH). 13C-NMR
(75 MHz): 25.3 (CH2); 26.6 (CH2); 28.5 (CH2); 28.9 (CH2); 32.4 (CH2); 38.4 (CH2); 45.0 (CH2); 95.7
(CH); 117.0 (q, 1J ¼ 283.0, CF3); 175.3 (CCF3); 197.4 (CO). 19F-NMR (235 MHz): ꢀ 76.7 (CF3). EI-MS
(70 eV): 272 (3, Mþ), 203 (22), 167 (27), 154 (100), 139 (68), 85 (44). HR-EI-MS (70 eV): 272.0788 (Mþ,
C11H16ClF3Oþ2 ; calc. 272.0791).
1,1,1-Trifluorotridecane-2,4-dione (2d). Starting with 1 (1.541 g, 10 mmol), 1-iodooctane (2.401 g,
i
10 mmol), BuLi (9.2 ml of a 2.5m soln. in hexanes), and Pr2NH (3.2 ml, 23 mmol) in THF (30 ml), 2d
was isolated as a colorless liquid (1.569 g, 59%) by distillation. B.p. 95 – 998/0.6 Torr. IR (ATR): 2956w,
2926m, 2856w, 1595m, 1459m, 1378w, 1276w, 1197m, 1151s, 1107m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7,

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Helvetica Chimica Acta – Vol. 96 (2013)
Me); 1.20 – 1.40 (m, 6 CH2); 1.58 – 1.73 (m, CH2); 2.43 (t, J ¼ 7.6, COCH2CH2); 5.91 (s, CH). 13C-NMR
(75 MHz): 14.1 (Me); 22.6 (CH2); 25.5 (CH2); 29.1 (CH2); 29.2 (CH2); 29.2 (CH2); 29.3 (CH2); 31.8
3
1
2
(CH2); 38.4 (CH2); 95.6 (q, J ¼ 2.0, CH); 117.0 (q, J ¼ 283.0, CF3); 175.7 (q, J ¼ 36.2, COCF3); 197.6
(CO). 19F-NMR (282 MHz): ꢀ 76.7 (CF3). EI-MS (70 eV): 266 (5, Mþ), 197 (34), 167 (30), 154 (100),
139 (73). HR-EI-MS (70 eV): 266.1491 (Mþ, C13H21F3O2þ ; calc. 266.1494).
1,1,1-Trifluoropentadecane-2,4-dione (2e). Starting with 1 (6.164 g, 40 mmol), 1-iododecane
i
(10.727 g, 40 mmol), BuLi (36.8 ml of a 2.5m soln. in hexanes), and Pr2NH (12.9 ml, 92 mmol) in
THF (120 ml), 2e was isolated as a colorless liquid (4.814 g, 41%) by CC and subsequent distillation.
B.p. 1108/0.2 Torr. IR (ATR): 2924w, 2855w, 1595m, 1459m, 1377w, 1277w, 1198m, 1151s, 1107m.
1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, Me); 1.20 – 1.38 (m, 8 CH2); 1.59 – 1.71 (m, CH2); 2.43 (t, J ¼ 7.6,
COCH2CH2); 5.91 (s, CH). 13C-NMR (75 MHz): 14.1 (Me); 22.7 (CH2); 25.5 (CH2); 29.1 (CH2); 29.2
(CH2); 29.3 (CH2); 29.4 (CH2); 29.6 (CH2); 29.6 (CH2); 31.9 (CH2); 38.4 (CH2); 95.6 (q, 3J ¼ 1.8, CH);
117.0 (q, 1J ¼ 283.7, CF3); 175.7 (q, 2J ¼ 36.2, COCF3); 197.6 (CO). 19F-NMR (282 MHz): ꢀ 76.7 (CF3).
EI-MS (70 eV): 294 (4, Mþ), 228 (28), 167 (29), 154 (100), 139 (66). HR-EI-MS (70 eV): 294.1805 (Mþ,
C15H25F3Oþ2 ; calc. 294.1807).
1,1,1-Trifluoroheptadecane-2,4-dione (2f). Starting with 1 (4.623 g, 30 mmol), 1-iodododecane
i
(8.887 g, 30 mmol), BuLi (27.6 ml of a 2.5m soln. in hexanes), and Pr2NH (9.7 ml, 69 mmol) in THF
(90 ml), 2f was isolated as a colorless liquid (5.316 g, 55%) by CC and subsequent distillation. B.p. 112 –
1
1158/0.08 Torr. IR (ATR): 2923w, 2854w, 1596m, 1465m, 1377w, 1277w, 1198m, 1152s, 1107m. H-NMR
(300 MHz): 0.88 (t, J ¼ 6.7, Me); 1.19 – 1.39 (m, 10 CH2); 1.58 – 1.70 (m, CH2); 2.43 (t, J ¼ 7.6,
COCH2CH2); 5.91 (s, CH). 13C-NMR (75 MHz): 14.1 (Me); 22.7 (CH2); 25.5 (CH2); 29.1 (CH2); 29.2
(CH2); 29.3 (CH2); 29.4 (CH2); 29.6 (CH2); 29.6 (CH2); 29.6 (CH2); 29.7 (CH2); 31.9 (CH2); 38.4 (CH2);
95.6 (q, 3J ¼ 1.8, CH); 117.0 (q, 1J ¼ 283.5, CF3); 175.7 (q, 2J ¼ 36.2, COCF3); 197.6 (CO). 19F-NMR
(282 MHz): ꢀ 76.7 (CF3). EI-MS (70 eV): 322 (5, Mþ), 253 (21), 192 (19), 167 (32), 154 (100), 139 (57).
HR-EI-MS (70 eV): 322.2110 (M, C17H29F3Oþ2 ; calc. 322.2120).
General Procedure for the Synthesis of Compounds 3a – 3g. To a stirred Et2O soln. (2 ml per 1.0 mmol
of 2) of 2a – 2g (1.0 equiv.) were added Et3N (1.0 equiv.) and TMSOTf (0.95 equiv.) at 08 under Ar. The
soln. was stirred for 30 min at 08. The temp. of the mixture was allowed to rise to 208, and stirring was
continued for 3 d. A liquid salt layer separated at the bottom of the flask. The upper layer (Et2O soln.,
containing the product) was transferred to a dry flask by syringe under Ar. Et2O (1.5 ml per 1.0 mmol of
2) was added to the liquid salt layer, the mixture was stirred for 2 min, and the layers were allowed to
separate in a period of 2 h. The Et2O solns. were combined and concentrated in vacuo to give 3a – 3f,
which were not further purified and, due to their unstable nature, immediately used for the synthesis of
phenols 5 (without detailed spectroscopic characterization).
General Procedure for the Synthesis of 5-Alkyl-3-(trifluoromethyl)phenols 5a – 5al. To a CH2Cl2 soln.
(5 ml) of 4 (2.4 mmol) and 3 (2.2 mmol) was added TiCl4 (2.4 mmol) at ꢀ 788 under Ar. The temp. of the
mixture was allowed to rise to 208 during 14 h, and, subsequently, HCl (10%, 20 ml) was added. The org.
layer was separated and extracted with CH2Cl2 (3 ꢁ 20 ml). The combined org. layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by CC (SiO2;
heptane/AcOEt 20 :1).
Methyl 2-Hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5a). Starting with 3a (0.498 g, 2.2 mmol),
4a (0.625 g, 2.4 mmol), and TiCl4 (0.26 ml, 2.4 mmol) in CH2Cl2 (5 ml), 5a was isolated as a white solid
(0.390 g, 76%). M.p. 68 – 698. IR (Nujol): 1671m (n(C¼O)). 1H-NMR (250 MHz): 2.38 (s, Me); 3.97 (s,
MeO); 7.01 (s, 1 arom. H); 7.13 (s, 1 arom. H); 10.76 (s, OH). 13C-NMR (63 MHz): 21.5 (Me); 52.7
(MeO); 120.4 (q, 3J ¼ 7, CH); 122.0 (CH); 123.1 (q, 1J ¼ 274, CF3); 130.1 (q, 2J ¼ 32, CCF3); 145.1 (C);
147.3 (C); 162.0 (COH); 169.7 (CO). 19F-NMR (235 MHz): ꢀ 58.8 (CF3). EI-MS (70 eV): 234 (31, Mþ),
202 (100). Anal. calc. for C10H9F3O3 (234.17): C 51.29, H 3.87; found: C 50.93, H 4.24.
Methyl 2-Hydroxy-3,4-dimethyl-6-(trifluoromethyl)benzoate (5b). Starting with 3a (0.226 g,
1.0 mmol), 4b (0.549 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (2 ml), 5b was isolated as a
white solid (0.120 g, 48%). M.p. 56 – 588. Rf (heptanes/AcOEt 3 :2) 0.80. IR (ATR): 3030w, 2970w, 2861w,
1660s, 1612w, 1439w, 1390m, 1341m, 1125m, 1099m, 933m, 809m, 707s. 1H-NMR (300 MHz): 2.22 (s, Me);
2.33 (s, Me); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.08 (s, OH). 13C-NMR (100 MHz): 11.9, 20.5 (2 Me);
52.7 (MeO); 107.7 (C); 120.4 (q, 3J ¼ 6.7, CH); 123.6 (q, 1J ¼ 271.0, CF3); 126.8 (q, 2J ¼ 31.5, CCF3); 129.7,

Helvetica Chimica Acta – Vol. 96 (2013)
51
142.9 (C); 160.0 (COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.2 (CF3). EI-MS (70 eV): 248 (30, Mþ),
217 (16), 216 (40), 197 (11), 196 (100). Anal. calc. for C11H11F3O3 (248.07): C 53.23, H 4.47; found: C
53.31, H 4.50.
Methyl 3-(3-Chloropropyl)-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5c). Starting with 3a
(0.226 g, 1.0 mmol), 4c (0.674 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (2 ml), 5c was isolated
as a white solid (0.152 g, 49%). M.p. 56 – 588. Rf (heptanes/AcOEt 3 :2) 0.78. IR (ATR): 2958w, 1660s,
1613w, 1439m, 1394w, 1341w, 1239w, 1126w, 959w, 815w, 728s. 1H-NMR (300 MHz): 1.98 – 2.05 (m, CH2);
2.05 (s, Me); 2.86 (t, J ¼ 7.8, CH2Ar); 3.60 (t, J ¼ 6.4, CH2Cl); 3.96 (s, MeO); 7.12 (s, 1 arom. H); 11.12 (s,
OH). 13C-NMR (75 MHz): 20.0 (Me); 24.0, 31.1, 45.0 (3 CH2); 52.7 (MeO); 108.0 (C); 120.9 (q, 3J ¼ 6.7,
1
2
CH); 123.4 (q, J ¼ 271.0, CF3); 127.5 (q, J ¼ 31.7, CCF3); 132.4, 142.9 (C); 160.1 (COH); 170.2 (CO).
19F-NMR (282 MHz): ꢀ 58.3 (CF3). EI-MS (70 eV): 310 (15, Mþ), 244 (13), 243 (100), 216 (17), 215
(14), 196 (17). Anal. calc. for C13H14ClF3O3 (310.70): C 50.25, H 4.54; found: C 50.49, H 4.72.
Methyl 3-Butyl-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5d). Starting with 3a (0.975 g,
4.31 mmol), 4d (1.500 g, 4.74 mmol), and TiCl4 (0.52 ml, 4.7 mmol) in CH2Cl2 (5 ml), 5d was isolated as a
colorless liquid (0.611 g, 49%). IR (neat): 3657m, 2970m, 2929m, 2868m, 1928s, 1674m, 1612m, 1576m,
1440m, 1382s, 1342w, 1305w, 1236w, 1194m, 1141w, 1046w, 1005w, 974w, 935w, 873w, 841w, 812s, 751m,
710m, 677m, 659m, 582m, 553m, 540s. 1H-NMR (300 MHz): 0.95 (t, J ¼ 7.1, Me), 1.35 – 1.54 (m, 2 CH2);
2.36 (s, Me); 2.69 (t, J ¼ 7.6, CH2Ar); 3.96 (s, MeO); 7.10 (s, 1 arom. H); 11.02 (s, OH). 13C-NMR
(75 MHz): 14.3 (Me); 20.3 (MeAr); 23.4, 26.7, 30.9 (3 CH2); 53.0 (MeO); 108.3 (C); 121.1 (q, 3J ¼ 6.4,
1
2
CH); 123.9 (q, J ¼ 273.3, CF3); 127.3 (q, J ¼ 28.3, CCF3); 134.8 (C), 142.8 (C); 160.4 (COH); 170.7
(CO). 19F-NMR (282 MHz): ꢀ 58.2 (CF3). EI-MS (70 eV): 291 (6, Mþ), 290 (37), 259 (12), 258 (10), 244
(13), 243 (100), 241 (17), 229 (18), 217 (8), 216 (69), 215 (44), 197 (7), 196 (62), 187 (9), 159 (9), 109 (9).
HR-EI-MS (70 eV): 290.1122 (Mþ, C14H17F3Oþ3 ; calc. 290.1130).
Methyl 3-Hexyl-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5e). Starting with 3a (0.226 g,
1.0 mmol), 4e (0.689 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (2 ml), 5e was isolated as a
slightly yellow solid (0.100 g, 31%). M.p. 40 – 418. Rf (hexane/CH2Cl2 3 :2) 0.88. IR (ATR): 2952w,
2924m, 2855w, 1660s, 1613w, 1439m, 1342m, 1305m, 1127m, 955s, 884m, 814m, 711s. 1H-NMR (300 MHz):
0.89 (t, J ¼ 6.9, Me); 1.25 – 1.52 (m, 4 CH2); 2.35 (s, Me); 2.68 (t, J ¼ 7.8, CH2Ar); 3.95 (s, MeO); 7.10 (s, 1
arom. H); 11.01 (s, OH). 13C-NMR (75 MHz): 14.1, 20.0 (2 Me); 22.6, 26.6, 28.4, 29.6, 31.7 (5 CH2); 52.6
3
1
2
(MeO); 107.9 (C); 120.7 (q, J ¼ 6.7, CH); 123.6 (q, J ¼ 271.2, CF3); 126.8 (q, J ¼ 31.5, CCF3); 134.4,
142.4 (C); 160.0 (COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.2 (CF3). EI-MS (70 eV): 318 (26, Mþ),
272 (15), 271 (100), 229 (13), 216 (66), 215 (44), 196 (46). Anal. calc. for C16H21F3O3 (318.33): C 60.37, H
6.65; found: C 60.44, H 6.66.
Methyl 3-(6-Chlorohexyl)-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5f). Starting with 3a
(0.814 g, 3.60 mmol), 4f (1.500 g, 3.96 mmol), and TiCl4 (0.43 ml, 4.0 mmol) in CH2Cl2 (5 ml), 5f was
isolated as a colorless oil (0.633 g, 50%). IR (neat): 3640w, 2945m, 2852m, 1936s, 1673m, 1612m, 1576s,
1440m, 1383s, 1340s, 1291w, 1236w, 1194s, 1140w, 1099w, 1047s, 975m, 936m, 874m, 843m, 813m, 729m,
710m, 677m, 654m, 582m, 555m, 540s. 1H-NMR (300 MHz): 1.36 – 1.57 (m, 3 CH2); 1.77, 1.81 (tt, J ¼ 6.9,
6.7, CH2); 2.36 (s, Me); 2.69 (t, J ¼ 7.6, CH2Ar); 3.54 (t, J ¼ 6.7, CH2Cl); 3.96 (s, MeO); 7.11 (s, 1 arom.
H); 11.03 (s, OH). 13C-NMR (75 MHz): 20.3 (MeAr); 26.8, 27.1, 28.5, 29.5, 32.9, 45.4 (6 CH2); 53.0
(MeO); 108.3 (C); 121.1 (q, J ¼ 6.8, CH); 123.9 (q, 1J ¼ 272.8, CF3); 127.3 (q, 2J ¼ 31.7, CCF3); 134.5 (C);
142.8 (C); 160.4 (COH); 170.7 (CO). 19F-NMR (282 MHz): ꢀ 58.3 (CF3). EI-MS (70 eV): 355 (2, Mþ,
37Cl), 353 (5, Mþ, 35Cl), 352 (26), 320 (16), 307 (22), 306 (11), 305 (67), 285 (32), 243 (11), 229 (14), 217
(12), 216 (100), 215 (54), 197 (7), 196 (59), 187 (10), 159 (8). HR-EI-MS (70 eV): 352.1041 (Mþ,
C16H20ClF3Oþ3 ; calc. 352.1048). Anal. calc. for C16H20ClF3O3 (352.78): C 54.47, H 5.71; found: C 54.4, H
5.93.
Methyl 3-Heptyl-2-hydroxy-4-methyl-6-(trifluormethyl)benzoate (5g). Starting with 3a (0.860 g,
3.80 mmol), 4g (1.500 g, 4.18 mmol), and TiCl4 (0.46 ml, 4.2 mmol) in CH2Cl2 (5 ml), 5g was isolated as a
white solid (0.600 g, 47%). M.p. 47 – 488. IR (KBr): 3452w, 2958w, 2921w, 2848w, 1663w, 1614s, 1578m,
1473m, 1463m, 1440m, 1396s, 1347m, 1311m, 1294m, 1272m, 1243m, 1203m, 1190m, 1162s, 1135s, 1050m,
1002m, 985m, 961m, 936m, 909m, 885m, 844m, 816m, 795s, 773m, 735m, 712m, 678m, 658m, 556s, 538m,
485s. 1H-NMR (300 MHz): 0.89 (t, J ¼ 6.8, Me); 1.29 – 1.55 (m, 5 CH2); 2.36 (s, Me); 2.68 (t, J ¼ 7.8,
CH2Ar); 3.96 (s, MeO); 7.10 (s, CH); 11.02 (s, OH). 13C-NMR (75 MHz): 14.4 (Me); 20.3 (MeAr); 23.0,

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1
27.0, 28.8, 29.5, 30.3, 32.2 (6 CH2); 53.0 (MeO); 108.3 (C); 121.1 (q, J ¼ 6.8, CH); 123.9 (q, J ¼ 272.7,
CF3); 127.2 (q, 2J ¼ 31.8, CCF3); 134.8 (C); 142.8 (C); 160.4 (COH); 170.7 (CO). 19F-NMR (282 MHz):
ꢀ 58.2 (CF3). EI-MS (70 eV): 333 (5, Mþ), 332 (26), 301 (10), 286 (17), 285 (100), 283 (10), 243 (9), 229
(14), 216 (68), 215 (42), 196 (46), 187 (7). HR-EI-MS (70 eV): 332.1597 (Mþ, C17H23F3O3þ ; calc.
332.1599). Anal. calc. for C17H23F3O3 (332.36): C 61.43, H 6.98; found: C 61.2, H 6.90.
Methyl 2-Hydroxy-4-methyl-3-octyl-6-(trifluoromethyl)benzoate (5h). Starting with 3a (0.226 g,
1.0 mmol), 4h (0.754 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (2 ml), 5h was isolated as a
slight yellow solid (0.090 g, 26%). M.p. 49 – 518. Rf (hexane/CH2Cl2 3 :2) 0.80. IR (ATR): 2957w, 2923m,
2852w, 1660s, 1613s, 1473s, 1461w, 1439m, 1343m, 1304m, 1128m, 964m, 934m, 814m, 711s. 1H-NMR
(300 MHz): 0.88 (t, J ¼ 6.7, Me); 1.26 – 1.55 (m, 6 CH2); 2.35 (s, Me); 2.68 (t, J ¼ 7.8, CH2Ar); 3.95 (s,
MeO); 7.10 (s, 1 arom. H); 11.01 (s, OH). 13C-NMR (75 MHz): 14.1, 20.0 (2 Me); 22.6, 26.6, 28.4, 29.3,
29.4, 30.0, 31.9 (7 CH2); 52.6 (MeO); 107.9 (C); 120.7 (q, 3J ¼ 6.7, CH); 123.5 (q, 1J ¼ 271.0, CF3); 126.8
(q, 2J ¼ 31.7, CCF3); 134.4, 142.4 (2 C); 160.0 (COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.2 (CF3).
EI-MS (70 eV): 346 (21, Mþ), 300 (17), 299 (100), 229 (12), 216 (63), 215 (41), 196 (40). Anal. calc. for
C18H25F3O3 (346.38): C 62.41, H 7.27; found: C 62.44, H 7.50.
Methyl 3-Benzyl-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5j). Starting with 3a (0.453 g,
2.0 mmol), 4j (0.771 g, 2.2 mmol), and TiCl4 (0.24 ml, 2.2 mmol) in CH2Cl2 (5 ml), 5j was isolated as a
colorless solid (0.444 g, 68%). M.p. 57 – 588. IR (neat): 3644m, 3076m, 3023m, 2950m, 2852m, 1932s,
1672m, 1612s, 1577m, 1497m, 1440m, 1396m, 1383s, 1344s, 1302w, 1236w, 1194m, 1140w, 1088w, 1068w,
1030w, 962w, 936w, 907w, 875w, 843w, 813s, 745m, 700m, 659m, 621m, 579m, 540m, 494s. 1H-NMR
(300 MHz): 2.34 (s, Me); 3.97 (s, MeO); 4.12 (s, CH2); 7.14 – 7.27 (m, 6 arom. H); 11.12 (s, OH). 13C-NMR
(75 MHz): 20.8 (MeAr); 32.2 (CH2); 53.2 (MeO); 108.7 (C); 121.3 (q, 3J ¼ 6.7, CH); 123.8 (q, 1J ¼ 273.3,
CF3); 127.8 (q, 2J ¼ 30.6, CCF3); 126.5, 128.5, 128.8, 139.3 (Ph); 132.4 (C); 144.1 (C); 160.5 (COH); 170.6
(CO). 19F-NMR (282 MHz): ꢀ 58.3 (CF3). EI-MS (70 eV): 325 (11, Mþ), 324 (61), 304 (11), 293 (34),
292 (100), 291 (23), 284 (23), 272 (50), 271 (30), 269 (49), 264 (56), 263 (43), 244 (10), 215 (21), 201 (15),
195 (12), 165 (25), 152 (10). HR-EI-MS (70 eV): 324.0964 (Mþ, C17H15F3O3þ ; calc. 324.0973). Anal. calc.
for C17H15F3O3 (324.29): C 62.96, H 4.66; found: C 63.4, H 4.72.
Methyl 2-Hydroxy-4-methyl-3-(2-phenylethyl)-6-(trifluoromethyl)benzoate (5k). Starting with 3a
(0.226 g, 1.0 mmol), 4k (0.729 g, 2.0 mmol), and TiCl4 (0.1 ml, 1.0 mmol) in CH2Cl2 (2 ml), 5k was
isolated as a white solid (0.145 g, 43%). M.p. 70 – 718. Rf (hexane/CH2Cl2 3 :2) 0.68. IR (ATR): 3086w,
3026w, 2949w, 2857w, 1673m, 1604m, 1494w, 1440m, 1309s, 1231m, 1121s, 949s, 878m, 695s. 1H-NMR
(300 MHz): 2.21 (s, Me); 2.80 (t, J ¼ 7.8, CH2); 2.99 (t, J ¼ 8.1, CH2); 3.97 (s, MeO); 7.08 (s, 1 arom. H);
7.18 – 7.31 (m, 5 arom. H); 11.15 (s, OH). 13C-NMR (75 MHz): 19.9 (Me); 29.0, 34.4 (2 CH2); 52.7
(MeO); 108.0 (C); 120.7 (q, 3J ¼ 6.4, CH); 123.5 (q, 1J ¼ 271.1, CF3); 126.0 (Ph); 127.2 (q, 2J ¼ 31.5,
CCF3); 128.4, 128.5 (Ph); 133.1, 141.8, 142.8 (3 C); 160.2 (COH); 170.3 (CO). 19F-NMR (282 MHz):
ꢀ 58.2 (CF3). EI-MS (70 eV): 338 (21, Mþ), 306 (21), 247 (22), 216 (11), 215 (100), 91 (44). Anal. calc.
for C18H17F3O3 (338.32): C 63.90, H 5.06; found: C 64.06, H 5.01.
Methyl 2-Hydroxy-4-methyl-3-(3-phenylpropyl)-6-(trifluoromethyl)benzoate (5l). Starting with 3a
(0.453 g, 2.0 mmol), 4l (0.833 g, 2.2 mmol), and TiCl4 (0.24 ml, 2.2 mmol) in CH2Cl2 (5 ml), 5l was
isolated as a colorless oil (0.479 g, 68%). IR (neat): 3644m, 3076m, 3023m, 2950m, 2852m, 1932s, 1672m,
1612s, 1577m, 1497m, 1440m, 1396m, 1383s, 1344s, 1302w, 1236w, 1194m, 1140w, 1088w, 1068w, 1030w,
1
962w, 936w, 907w, 875w, 843w, 813s, 745m, 700m, 659m, 621m, 579m, 540m, 494s. H-NMR (300 MHz):
1.84, 1.88 (tt, J ¼ 7.8, CH2CH2CH2); 2.29 (s, Me); 2.75 (t, J ¼ 8.2, 2 CH2Ar); 3.97 (s, MeO); 7.11 (s, 1 arom.
H); 7.18 – 7.31 (m, 5 arom. H); 11.06 (s, OH). 13C-NMR (75 MHz): 20.2 (MeAr); 26.6, 30.1, 36.4 (3 CH2);
3
1
2
53.0 (MeO); 108.3 (C); 121.1 (q, J ¼ 6.7, CH); 123.9 (q, J ¼ 272.9, CF3); 127.4 (q, J ¼ 31.7, CCF3);
126.2, 128.6, 128.7 (Ph); 134.2 (C); 142.4 (C); 142.9 (C); 160.4 (COH); 170.6 (CO). 19F-NMR
(282 MHz): ꢀ 58.2 (CF3). EI-MS (70 eV): 353 (9, Mþ), 352 (42), 321 (13), 320 (15), 229 (12), 228 (10),
217 (11), 216 (100), 215 (18), 208 (32), 196 (64), 193 (15), 105 (18), 91 (21). HR-EI-MS (70 eV):
352.1277 (Mþ, C19H19F3Oþ3 ; calc. 352.1281). Anal. calc. for C19H19F3O3 (352.35): C 64.77, H 5.44; found: C
64.9, H 5.52.
Ethyl 2-Hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5m). Starting with 3a (0.453 g, 2.2 mmol),
4m (0.659 g, 2.4 mmol), and TiCl4 (0.26 ml, 2.4 mmol) in CH2Cl2 (5 ml), 5m was isolated as a colorless
solid (0.220 g, 40%). M.p. 288. IR (Nujol): 1672 (n(C¼O)). 1H-NMR (300 MHz): 1.41 (t, J ¼ 7.6,

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MeCH2O); 2.38 (s, Me); 4.43 (q, J ¼ 7.2, MeCH2O); 7.01 (s, CH); 7.13 (s, CH); 10.90 (s, OH). 13C-NMR
(63 MHz): 13.4 (MeCH2); 21.5 (Me); 62.3 (CH2); 108.6 (C); 120.4 (q, 3J ¼ 7, CH); 122.0 (CH); 123.2 (q,
2
1J ¼ 275, CF3); 130.1 (q, J ¼ 34, CCF3); 145.0 (C); 162.1 (COH); 169.3 (CO). 19F-NMR (282 MHz):
ꢀ 58.0 (CF3). EI-MS (70 eV): 248 (16, Mþ), 202 (100). Anal. calc. for C11H11F3O3 (248.20): C 53.23, H
4.47; found: C 52.85, H 4.69.
Ethyl 2-Hydroxy-3,4-dimethyl-6-(trifluoromethyl)benzoate (5n). Starting with 3a (0.453 g,
2.2 mmol), 4n (0.692 g, 2.4 mmol), and TiCl4 (0.26 ml, 2.4 mmol) in CH2Cl2 (5 ml), 5n was isolated as
a colorless oil (0.430 g, 75%). IR (Nujol): 1669 (n(C¼O)). 1H-NMR (250 MHz): 1.40 (t, J ¼ 7.6,
MeCH2O); 2.21 (s, Me); 2.33 (s, Me); 4.43 (q, J ¼ 7.2, MeCH2O); 7.11 (s, CH); 11.21 (s, OH). 13C-NMR
(63 MHz): 11.9 (MeAr); 13.5 (MeAr); 20.5 (MeCH2O); 62.3 (CH2O); 108.0 (q, 3J ¼ 2, C); 120.4 (q, J ¼ 7,
CH); 123.6 (q, 1J ¼ 274, CF3); 126.8 (q, 2J ¼ 32, CCF3); 129.7 (C); 142.8 (C); 160.1 (COH); 169.9 (CO).
19F-NMR (235 MHz): ꢀ 57.7 (CF3). EI-MS (70 eV): 262 (29, Mþ), 216 (55). HR-EI-MS (70 eV):
262.0809 (Mþ, C12H13F3Oþ3 ; calc. 262.0817). Anal. calc. for C12H13F3O3 (262.23): C 54.96, H 5.00; found:
C 54.46, H 4.99.
Ethyl 3-Ethyl-2-hydroxy-4-methyl-6-(trifluoromethyl)benzoate (5o). Starting with 3a (0.453 g,
2.2 mmol), 4o (0.726 g, 2.4 mmol), and TiCl4 (0.26 ml, 2.4 mmol) in CH2Cl2 (5 ml), 5o was isolated as
a colorless oil (0.435 g, 72%). IR (Nujol): 1669 (n(C¼O)). 1H-NMR (250 MHz): 1.13 (t, J ¼ 7.5,
MeCH2Ar); 1.40 (t, J ¼ 7.5, MeCH2O); 2.36 (s, Me); 2.73 (q, J ¼ 7.4, MeCH2Ar); 4.42 (q, J ¼ 7.2,
MeCH2O); 7.10 (s, CH); 11.16 (s, OH). 13C-NMR (63 MHz): 12.6 (MeCH2); 13.5 (MeCH2O); 19.6
(MeAr); 62.3 (CH2O); 108.3 (C); 120.7 (q, 3J ¼ 7, CH); 123.5 (q, 1J ¼ 272, CF3); 126.8 (q, 2J ¼ 32, CCF3);
135.5 (C); 142.0 (C); 160.0 (COH); 169.9 (CO). 19F-NMR (235 MHz): ꢀ 57.7 (CF3). EI-MS (70 eV): 276
(39, Mþ), 230 (86). HR-EI-MS (70 eV): 276.0958 (Mþ, C13H15F3Oþ3 ; calc. 276.0973).
1-[2-Hydroxy-4-methyl-6-(trifluoromethyl)phenyl]ethanone (5p). Starting with 3a (0.453 g,
2.2 mmol), 4p (0.587 g, 2.4 mmol), and TiCl4 (0.26 ml, 2.4 mmol) in CH2Cl2 (5 ml), 5p was isolated as
1
a colorless solid (0.290 g, 60%). M.p. 120 – 1218. IR (Nujol): 3311 (n(OH)), 1687 (n(C¼O)). H-NMR
(250 MHz): 2.37 (s, Me); 2.62 (q, J ¼ 1.8, COMe); 6.98 (s, CH); 7.07 (s, CH); 10.04 (s, OH). 13C-NMR
(63 MHz): 21.5 (Me), 31.4 (q, J ¼ 6, COMe); 118.9 (q, 3J ¼ 2, C); 119.9 (q, 3J ¼ 6, CH); 122.3 (CH); 123.7
(q, 1J ¼ 274, CF3); 128.7 (q, 2J ¼ 30, CCF3); 144.3 (C); 158.8 (COH); 204.9 (CO). 19F-NMR (235 MHz):
ꢀ 55.3 (CF3). EI-MS (70 eV): 218 (24, Mþ), 203 (100). HR-EI-MS (70 eV): 218.0545 (Mþ, C10H9F3Oþ2 ;
calc. 218.0555).
Methyl 4-Heptyl-2-hydroxy-6-(trifluoromethyl)benzoate (5q). Starting with 3b (0.458 g, 1.48 mmol),
4a (0.430 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5q was isolated as a red solid
(0.308 g, 66%). M.p. 35 – 368. IR (ATR): 2958m, 2855w, 1679m, 1620m, 1580m, 1487m, 1461w, 1441w,
1362w, 1338w, 1286w, 1204m, 1170m, 1127s, 1026w, 1004m. 1H-NMR (250 MHz): 0.88 (t, J ¼ 6.9,
MeC6H12); 1.18 – 1.41 (m, 4 CH2); 1.51 – 1.72 (m, CH2CH2Ar); 2.62 (t, J ¼ 7.7, CH2Ar); 3.97 (s, MeO);
7.01 (s, 1 arom. H); 7.13 (s, 1 arom. H); 10.76 (s, OH). 13C-NMR (75 MHz): 14.0 (MeCH2); 22.6 (CH2);
29.0 (CH2); 29.1 (CH2); 30.4 (CH2); 31.7 (CH2); 35.9 (CH2Ar); 52.7 (MeO); 108.4 (q, 3J ¼ 1.2, CCO2Me);
119.8 (q, 3J ¼ 6.7, CHCCF3); 121.3 (CHCOH); 123.4 (q, 1J ¼ 273.7, CF3); 130.1 (q, 2J ¼ 31.7, CCF3); 150.1
(CC7H15); 162.0 (COH); 169.7 (CO). 19F-NMR (282 MHz): ꢀ 58.8 (CF3). EI-MS (70 eV): 318 (17, Mþ),
286 (28), 215 (13), 202 (100), 173 (10). HR-EI-MS (70 eV): 318.1436 (Mþ, C16H21F3O3þ ; calc. 318.1443.
Anal. calc. for C16H21F3O3 (318.33): C 60.37, H 6.65; found: C 60.48, H 6.67.
Methyl 4-Heptyl-2-hydroxy-3-methyl-6-(trifluoromethyl)benzoate (5r). Starting with 3b (0.466 g,
1.50 mmol), 4b (0.453 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5r was isolated as
a pale red oil (0.322 g, 65%). IR (ATR): 2956w, 2927m, 2857w, 1671m, 1611m, 1578w, 1440w, 1400w,
1329m, 1280s, 1245s, 1232s, 1194m, 1134s, 1077s, 1012m. 1H-NMR (300 MHz): 0.89 (t, J ¼ 6.9, MeC6H12);
1.22 – 1.40 (m, 4 CH2); 1.49 – 1.62 (m, CH2CH2Ar); 2.24 (s, Me); 2.64 (t, J ¼ 7.9, CH2Ar); 3.96 (s, MeO);
7.10 (s, 1 arom. H); 11.10 (s, OH). 13C-NMR (125 MHz): 11.6 (MeAr); 14.0 (MeCH2); 22.6 (CH2); 29.1
(CH2); 29.5 (CH2); 30.0 (CH2); 31.8 (CH2); 34.1 (CH2Ar); 52.6 (MeO); 107.6 (CCOOMe); 119.7 (q, 3J ¼
6.7, CHCCF3); 123.7 (q, 1J ¼ 273.4, CF3); 126.9 (q, 2J ¼ 31.7, CCF3); 129.3 (CMe); 147.5 (CC7H15); 160.4
(COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 332 (34, Mþ), 300 (100), 229
(74), 216 (86), 187 (16). HR-EI-MS (70 eV): 332.1595 (Mþ, C17H23F3O3þ ; calc. 332.1599).
Methyl 3-Ethyl-4-heptyl-2-hydroxy-6-(trifluoromethyl)benzoate (5s). Starting with 3b (0.480 g,
1.55 mmol), 4q (0.476 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5s was isolated

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Helvetica Chimica Acta – Vol. 96 (2013)
as a pale red oil (0.351 g, 66%). IR (ATR): 2957w, 2928m, 2873, 2857w, 1671m, 1609w, 1439m, 1400w,
1337m, 1292s, 1247s, 1228s, 1194m, 1136s, 1111s, 1062m. 1H-NMR (300 MHz): 0.89 (t, J ¼ 7.0, MeC6H12);
1.15 (t, J ¼ 7.5, MeCH2Ar); 1.22 – 1.44 (m, 4 CH2); 1.50 – 1.64 (m, CH2CH2Ar); 2.60 – 2.68 (m,
CH2CH2Ar); 2.73 (q, J ¼ 7.5, MeCH2Ar); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR
(63 MHz): 13.5 (MeCH2); 14.0 (MeCH2); 19.5 (CH2); 22.6 (CH2); 29.1 (CH2); 29.6 (CH2); 30.9 (CH2);
3
1
31.7 (CH2); 33.3 (CH2Ar); 52.6 (MeO); 107.8 (CCOOMe); 120.0 (q, J ¼ 6.7, CHCCF3); 123.6 (q, J ¼
272.7, CF3); 127.0 (q, J ¼ 31.7, CCF3); 135.1 (CC2H5); 146.9 (CC7H15); 160.2 (COH); 170.3 (CO). 19F-
2
NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 346 (25, Mþ), 314 (70), 285 (11), 243 (100), 230 (19).
HR-EI-MS (70 eV): 346.1751 (Mþ, C18H25F3Oþ3 ; calc. 346.1756).
Methyl 4-Heptyl-2-hydroxy-3-propyl-6-(trifluoromethyl)benzoate (5t). Starting with 3b (0.489 g,
1.58 mmol), 4r (0.499 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5t was isolated as a
yellow oil (0.321 g, 57%). IR (ATR): 2957w, 2927m, 2872m, 2857w, 1671m, 1610m, 1573m, 1456w, 1439w,
1399w, 1334w, 1302m, 1283s, 1222s, 1193m, 1135s, 1091m. 1H-NMR (300 MHz): 0.89 (t, J ¼ 7.0,
MeC6H12); 1.01 (t, J ¼ 7.4, MeCH2CH2Ar); 1.24 – 1.41 (m, 4 CH2); 1.50 – 1.62 (m, 2 H2CH2Ar); 2.59 – 2.71
(m, 2 CH2Ar); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 14.5
(MeCH2); 22.5 (CH2); 22.6 (CH2); 28.3 (CH2); 29.1 (CH2); 29.6 (CH2); 30.9 (CH2); 31.7 (CH2); 33.4
(CH2); 52.6 (MeO); 107.7 (CCOOMe); 119.9 (q, 3J ¼ 6.7, CHCCF3); 123.6 (q, 1J ¼ 272.7, CF3); 127.0 (q,
2J ¼ 31.6, CCF3); 133.8 (CC3H7); 147.2 (CC7H15); 160.4 (COH); 170.4 (CO). 19F-NMR (282 MHz): ꢀ
58.6 (CF3). EI-MS (70 eV): 360 (25, Mþ), 328 (78), 285 (8), 257 (100), 229 (18). HR-EI-MS (70 eV):
360.1908 (Mþ, C19H27F3Oþ3 ; calc. 360.1912). Anal. calc. for C19H27F3O3 (360.41): C 63.32, H 7.55; found: C
63.40, H 7.52.
1-[4-Heptyl-2-hydroxy-6-(trifluoromethyl)phenyl]ethanone (5u). Starting with 3b (0.478 g,
1.54 mmol), 4p (0.403 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5u was isolated
as a pale red solid (0.371 g, 80%). M.p. 82 – 838. IR (ATR): 3331w, 2958w, 2927m, 2857w, 1688w, 1615m,
1586m, 1464w, 1435w, 1356w, 1323w, 1280w, 1265w, 1234w, 1191w, 1158m, 1143m, 1120s, 1023m. 1H-NMR
(300 MHz): 0.88 (t, J ¼ 6.9, MeC6H12); 1.21 – 1.38 (m, 4 CH2); 1.55 – 1.68 (m, CH2CH2Ar); 2.57 – 2.65 (m,
CH2Ar, COMe); 6.98 (s, 1 arom. H); 7.07 (s, 1 arom. H); 10.04 (s, OH). 13C-NMR (75 MHz): 14.0
5
(MeCH2); 22.6 (CH2); 29.0 (CH2); 29.1 (CH2); 30.5 (CH2); 31.4 (q, J ¼ 5.4, COMe); 31.7 (CH2); 35.8
(CH2); 119.1 (CCOMe); 119.3 (q, 3J ¼ 5.8, CHCCF3); 121.5 (COHCH); 123.8 (q, 1J ¼ 273.6, CF3); 128.7
(q, 2J ¼ 31.1, CCF3); 149.3 (CC7H15); 158.7 (COH); 204.8 (CO). 19F-NMR (282 MHz): ꢀ 55.4 (CF3). EI-
MS (70 eV): 302 (13, Mþ), 287 (100), 218 (10). HR-EI-MS (70 eV): 302.1488 (Mþ, C16H21F3Oþ2 ; calc.
302.1494). Anal. calc. for C16H21F3O2 (302.33): C 63.56, H 7.00; found: C 63.30, H 7.20.
Methyl 4-Heptyl-2-hydroxy-3-methoxy-6-(trifluoromethyl)benzoate (5v). Starting with 3b (0.441 g,
1.42 mmol), 4s (0.479 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5v was isolated as a
red oil (0.297 g, 60%). IR (ATR): 2956w, 2927m, 2857m, 1746w, 1673m, 1609m, 1574w, 1441w, 1412w,
1363w, 1328w, 1274w, 1262w, 1197w, 1178m, 1133s, 1063m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7,
MeC6H12); 1.20 – 1.40 (m, 4 CH2); 1.50 – 1.67 (m, CH2CH2Ar); 2.65 (t, J ¼ 7.8, CH2Ar); 3.91 (s, MeO);
3.97 (s, MeO); 7.12 (s, 1 arom. H); 10.63 (s, OH). 13C-NMR (75 MHz): 14.0 (MeCH2); 22.6 (CH2); 29.1
(CH2); 29.4 (CH2); 30.1 (CH2); 30.2 (CH2); 31.7 (CH2); 52.8 (MeO); 60.6 (MeO); 110.4 (CCOOMe);
120.1 (q, 3J ¼ 6.7, CHCCF3); 123.4 (q, 1J ¼ 272.7, CF3); 124.3 (q, 2J ¼ 32.0, CCF3); 140.9 (COMe); 149.2
(CC7H15); 155.0 (COH); 169.6 (CO). 19F-NMR (282 MHz): ꢀ 58.4 (CF3). EI-MS (70 eV): 348 (28, Mþ),
316 (100), 245 (89), 225 (180), 204 (14). HR-EI-MS (70 eV): 348.1543 (Mþ, C17H23F3O4þ ; calc. 348.1548).
Anal. calc. for C17H23F3O4 (348.36): C 58.61, H 6.65; found: C 58.55, H 6.76.
Ethyl 4-(7-Chloroheptyl)-2-hydroxy-6-(trifluoromethyl)benzoate (5w). Starting with 3c (0.650 g,
1.88 mmol), 4m (1.035 g, 3.77 mmol), and TiCl4 (0.21 ml, 1.88 mmol) in CH2Cl2 (4 ml), 5w was isolated as
a colorless solid (0.303 g, 44%). IR (Nujol): 1689w, 1621m, 1577w, 1488w, 1402w, 1326w, 1310w, 1287w,
1215m, 1173m, 1142m, 1128s, 1020s, 1010s, 1001m. 1H-NMR (300 MHz): 1.29 – 1.50 (m, Me, 3 CH2);
1.57 – 1.69 (m, CH2); 1.70 – 1.83 (m, CH2); 2.62 (t, J ¼ 7.7, CH2); 3.53 (t, J ¼ 6.7, CH2); 4.43 (q, J ¼ 7.2,
CH2O); 7.00 (d, 4J ¼ 1.2, 1 arom. H); 7.12 (d, 4J ¼ 1.2, 1 arom. H); 10.89 (s, OH). 13C-NMR (125 MHz):
13.5 (Me); 26.7 (CH2); 28.6 (CH2); 28.9 (CH2); 30.3 (CH2); 32.5 (CH2); 35.8 (CH2); 45.0 (CH2); 62.4
3
1
2
(CH2O); 108.7 (C); 119.7 (q, J ¼ 6.7, CHCCF3); 121.2 (CH); 123.4 (q, J ¼ 273.6, CF3); 130.1 (q, J ¼
31.8, CCF3); 149.6 (C); 162.2 (COH); 169.2 (CO). 19F-NMR (282 MHz): ꢀ 58.0 (CF3). EI-MS

Helvetica Chimica Acta – Vol. 96 (2013)
55
(70 eV): 366 (18, Mþ), 320 (29), 285 (12), 215 (13), 202 (100), 173 (16). HR-EI-MS (70 eV): 366.1200
(Mþ, C17H22ClF3Oþ3 ; calc. 366.1210).
Methyl 2-Hydroxy-4-nonyl-6-(trifluoromethyl)benzoate (5x). Starting with 3d (0.322 g, 0.95 mmol),
4a (0.287 g, 1.10 mmol), and TiCl4 (0.12 ml, 1.10 mmol) in CH2Cl2 (2 ml), 5x was isolated as a colorless
solid (0.107 g, 32%). M.p. 46 – 478. IR (ATR): 2957w, 2918m, 2851w, 1678m, 1620m, 1579m, 1487m,
1461w, 1441w, 1362w, 1339w, 1285m, 1261m, 1220m, 1206w, 1170m, 1126s, 1092s, 1024s, 1002m. 1H-NMR
(300 MHz): 0.88 (t, J ¼ 6.8, MeC8H16); 1.21 – 1.36 (m, 6 CH2); 1.55 – 1.67 (m, CH2CH2Ar); 2.61 (t, J ¼ 7.7,
CH2Ar); 3.96 (s, MeO); 7.01 (s, 1 arom. H); 7.13 (s, 1 arom. H); 10.76 (s, OH). 13C-NMR (75 MHz): 14.1
(MeCH2); 22.7 (CH2); 29.1 (CH2); 29.2 (CH2); 29.3 (CH2); 29.5 (CH2); 30.4 (CH2); 31.9 (CH2); 35.9
(CH2Ar); 52.7 (MeO); 108.4 (CCOOMe); 119.7 (q, 3J ¼ 6.7, CHCCF3); 121.3 (CHCOH); 123.4 (q, 1J ¼
273.1, CF3); 130.1 (q, 2J ¼ 31.7, CCF3); 150.1 (CC9H19); 162.0 (COH); 169.7 (CO). 19F-NMR (282 MHz):
ꢀ 58.8 (CF3). EI-MS (70 eV): 346 (34, Mþ), 314 (57), 234 (19), 215 (58), 202 (100), 173 (14). HR-EI-MS
(70 eV): 346.1757 (Mþ, C18H25F3O3þ ; calc. 346.1756). Anal. calc. for C18H25F3O3 (346.38): C 62.41, H 7.27;
found: C 62.28, H 7.28.
Methyl 2-Hydroxy-3-methyl-4-nonyl-6-(trifluoromethyl)benzoate (5y). Starting with 3d (0.328 g,
0.97 mmol), 4b (0.302 g, 1.10 mmol), and TiCl4 (0.12 ml, 1.10 mmol) in CH2Cl2 (2 ml), 5y was isolated as
a colorless solid (0.230 g, 66%). M.p. 43 – 448. IR (ATR): 2920m, 2851w, 1663m, 1612m, 1581m, 1462m,
1437w, 1401w, 1346w, 1286w, 1257w, 1237m, 1204w, 1190w, 1165w, 1144w, 1127w, 1114m, 1055w. 1H-NMR
(300 MHz): 0.88 (t, J ¼ 6.7, MeC8H16); 1.22 – 1.40 (m, 6 CH2); 1.49 – 1.61 (m, CH2CH2Ar); 2.24 (s, Me);
2.64 (t, J ¼ 7.9, CH2Ar); 3.96 (s, MeO); 7.10 (s, 1 arom. H); 11.10 (s, OH). 13C-NMR (125 MHz): 11.7
(MeAr); 14.1 (MeCH2); 22.7 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 30.0 (CH2); 31.9
(CH2); 34.1 (CH2Ar); 52.7 (MeO); 107.5 (CCOOMe); 119.7 (q, 3J ¼ 6.7, CHCCF3); 123.6 (q, 1J ¼ 272.7,
CF3); 126.9 (q, 2J ¼ 31.7, CCF3); 129.2 (CMe); 147.5 (CC9H19); 160.4 (COH); 170.3 (CO). 19F-NMR
(282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 360 (37, Mþ), 328 (100), 229 (80), 216 (82), 187 (18). HR-EI-
MS (70 eV): 360.1908 (Mþ, C19H27F3O3þ ; calc. 360.1912). Anal. calc. for C19H27F3O3 (360.41): C 63.32, H
7.55; found: C 63.24, H 7.84.
Methyl 3-Ethyl-2-hydroxy-4-nonyl-6-(trifluoromethyl)benzoate (5z). Starting with 3d (0.340 g,
1.00 mmol), 4q (0.317 g, 1.10 mmol), and TiCl4 (0.12 ml, 1.10 mmol) in CH2Cl2 (2 ml), 5z was isolated
as a colorless oil (0.224 g, 60%). IR (ATR): 2956w, 2925m, 2855w, 1671m, 1611, 1574w, 1439, 1399, 1336m,
1291s, 1248, 1232, 1193m, 1135s, 1062m. 1H-NMR (300 MHz): 0.89 (t, J ¼ 6.7, MeC8H16); 1.16 (t, J ¼ 7.5,
MeCH2Ar); 1.22 – 1.44 (m, 6 CH2); 1.51 – 1.63 (m, CH2CH2Ar); 2.64 (t, J ¼ 7.9, CH2CH2Ar); 2.73 (q, J ¼
7.5, MeCH2Ar); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.06 (s, OH). 13C-NMR (125 MHz): 13.5 (MeCH2);
14.0 (MeCH2); 19.5 (CH2); 22.6 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.7 (CH2); 30.9 (CH2); 31.9
(CH2); 33.3 (CH2Ar); 52.6 (MeO); 107.9 (CCOOMe); 120.0 (q, 3J ¼ 6.6, CHCCF3); 123.7 (q, 1J ¼ 272.9,
2
CF3); 126.9 (q, J ¼ 31.6, CCF3); 135.1 (CC2H5); 146.9 (CC9H19); 160.2 (COH); 170.3 (CO). 19F-NMR
(282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 374 (26, Mþ), 342 (75), 313 (13), 243 (100), 230 (23). HR-EI-
MS (70 eV): 374.2063 (Mþ, C20H29F3O3þ ; calc. 374.2069). Anal. calc. for C20H29F3O3 (374.44): C 64.15, H
7.81; found: C 64.06, H 7.96.
1-[2-Hydroxy-4-nonyl-6-(trifluoromethyl)phenyl]ethanone (5aa). Starting with 3d (0.326 g,
0.96 mmol), 4p (0.269 g, 1.10 mmol), and TiCl4 (0.12 ml, 1.10 mmol) in CH2Cl2 (2 ml), 5aa was isolated
as a pale orange solid (0.197 g, 62%). M.p. 67 – 688. IR (ATR): 3325w, 2923w, 2853w, 1688w, 1615m,
1
1586m, 1466w, 1435w, 1355w, 1322w, 1268w, 1235w, 1191w, 1158m, 1120s, 1022m. H-NMR (300 MHz):
0.88 (t, J ¼ 6.7, MeC8H16); 1.20 – 1.38 (m, 6 CH2); 1.55 – 1.69 (m, CH2CH2Ar); 2.57 – 2.65 (m, CH2Ar,
COMe); 6.98 (s, 1 arom. H); 7.08 (s, 1 arom. H); 10.07 (s, OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 22.6
(CH2); 29.1 (CH2); 29.3 (CH2); 29.4 (CH2); 29.4 (CH2); 30.5 (CH2); 31.4 (q, 5J ¼ 5.5, COMe); 31.8 (CH2);
3
1
35.8 (CH2); 119.0 (q, J ¼ 1.6, CCOMe); 119.3 (q, J ¼ 5.9, CHCCF3); 121.6 (COHCH); 123.8 (q, J ¼
273.6, CF3); 128.7 (q, 2J ¼ 31.2, CCF3); 149.3 (CC9H19); 158.9 (COH); 204.8 (CO). 19F-NMR
(282 MHz): ꢀ 55.4 (CF3). EI-MS (70 eV): 330 (15, Mþ), 315 (100), 218 (14). HR-EI-MS (70 eV):
330.1800 (Mþ, C18H25F3Oþ2 ; calc. 330.1807). Anal. calc. for C18H25F3O2 (330.39): C 65.44, H 7.63; found:
C 65.42, H 7.60.
Methyl 2-Hydroxy-6-(trifluoromethyl)-4-undecylbenzoate (5ab). Starting with 3e (0.580 g,
1.58 mmol), 4a (0.430 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ab was isolated
as a pale yellow solid (0.230 g, 39%). M.p. 53 – 548. IR (ATR): 2957w, 2917w, 2849w, 1680m, 1620m,

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Helvetica Chimica Acta – Vol. 96 (2013)
1579m, 1487w, 1460w, 1441w, 1362w, 1337w, 1302w, 1286m, 1240w, 1216w, 1205m, 1167m, 1127s, 1092m,
1
1023w, 1003m. H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC10H20); 1.21 – 1.36 (m, 8 CH2); 1.54 – 1.68 (m,
CH2CH2Ar); 2.61 (t, J ¼ 7.7, CH2Ar); 3.97 (s, MeO); 7.01 (s, 1 arom. H); 7.13 (s, 1 arom. H); 10.76 (s,
OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 22.7 (CH2); 29.1 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2);
29.6 (CH2); 29.6 (CH2); 30.4 (CH2); 31.9 (CH2); 35.9 (CH2Ar); 52.7 (MeO); 108.4 (CCOOMe); 119.7 (q,
3J ¼ 6.7, CHCCF3); 121.3 (CHCOH); 123.4 (q, 1J ¼ 273.3, CF3); 130.1 (q, 2J ¼ 31.7, CCF3); 150.1
(CC11H23); 162.0 (COH); 169.7 (CO). 19F-NMR (282 MHz): ꢀ 58.8 (CF3). EI-MS (70 eV): 374 (46,
Mþ), 342 (46), 234 (32), 215 (90), 202 (100), 189 (14), 173 (20). HR-EI-MS (70 eV): 374.2060 (Mþ,
C20H29F3Oþ3 ; calc. 374.2069). Anal. calc. for C20H29F3O3 (374.44): C 64.15, H 7.81; found: C 64.51, H 7.83.
Methyl 2-Hydroxy-3-methyl-6-(trifluoromethyl)-4-undecylbenzoate (5ac). Starting with 3e (0.559 g,
1.53 mmol), 4b (0.453 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ac was isolated as
a colorless solid (0.303 g, 51%). M.p. 49 – 508. IR (ATR): 2918w, 2850w, 1663m, 1612m, 1580w, 1461w,
1437w, 1401w, 1346w, 1285w, 1245w, 1229w, 1205w, 1190w, 1165w, 1143m, 1128s, 1114s, 1062s, 1012m.
1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC10H20); 1.21 – 1.39 (m, 8 CH2); 1.48 – 1.62 (m, CH2CH2Ar); 2.24
(s, Me); 2.64 (t, J ¼ 7.9, CH2Ar); 3.96 (s, MeO); 7.10 (s, 1 arom. H); 11.11 (s, OH). 13C-NMR (125 MHz):
11.7 (MeAr); 14.1 (MeCH2); 22.7 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 29.6 (CH2);
3
29.6 (CH2); 30.0 (CH2); 31.9 (CH2); 34.1 (CH2Ar); 52.6 (MeO); 107.6 (CCOOMe); 119.7 (q, J ¼ 6.7,
1
2
CHCCF3); 123.6 (q, J ¼ 272.8, CF3); 126.9 (q, J ¼ 31.7, CCF3); 129.2 (CMe); 147.5 (CC11H23); 160.4
(COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 388 (50, Mþ), 356 (71), 33
(12), 287 (13), 229 (100), 216 (66), 203 (18), 187 (25). HR-EI-MS (70 eV): 388.2219 (Mþ, C21H31F3O3þ ;
calc. 388.2225). Anal. calc. for C21H31F3O3 (388.46): C 64.93, H 8.04; found: C 64.87, H 8.40.
Methyl 3-Ethyl-2-hydroxy-6-(trifluoromethyl)-4-undecylbenzoate (5ad). Starting with 3e (0.529 g,
1.44 mmol), 4q (0.476 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ad was isolated as
a colorless oil (0.274 g, 47%). IR (ATR): 2924w, 2854w, 1671m, 1611m, 1574w, 1439w, 1399w, 1336m,
1292s, 1247s, 1231s, 1193m, 1136s, 1062m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC10H20); 1.15 (t, J ¼
7.5, MeCH2Ar); 1.21 – 1.43 (m, 8 CH2); 1.51 – 1.63 (m, CH2CH2Ar); 2.64 (t, J ¼ 7.9, CH2CH2Ar); 2.73
(q, J ¼ 7.5, MeCH2Ar); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR (63 MHz): 13.5
(MeCH2); 14.1 (MeCH2); 19.5 (CH2); 22.7 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 29.6
(CH2); 29.7 (CH2); 30.9 (CH2); 31.9 (CH2); 33.3 (CH2Ar); 52.6 (MeO); 107.8 (CCOOMe); 120.0 (q, 3J ¼
6.7, CHCCF3); 123.6 (q, 1J ¼ 272.7, CF3); 127.0 (q, 2J ¼ 31.7, CCF3); 135.1 (CC2H5); 146.9 (CC11H23); 160.2
(COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 402 (27, Mþ), 370 (59), 341
(13), 243 (100), 230 (26). HR-EI-MS (70 eV): 402.2374 (Mþ, C22H33F3O3þ ; calc. 402.2382). Anal. calc. for
C22H33F3O3 (402.49): C 65.65, H 8.26; found: C 65.63, H 8.58.
Methyl 2-Hydroxy-3-propyl-6-(trifluoromethyl)-4-undecylbenzoate (5ae). Starting with 3e (0.537 g,
1.47 mmol), 4r (0.499 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ae was isolated as
a pale yellow solid (0.297 g, 49%). M.p. 38 – 398. IR (ATR): 2949w, 2914w, 2864w, 2847w, 1661m, 1611m,
1578m, 1484w, 1464w, 1440w, 1398w, 1355w, 1306w, 1284w, 1263w, 1243w, 1226w, 1206w, 1193w, 1167w,
1145m, 1131s, 1117s, 1092m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC10H20); 1.01 (t, J ¼ 7.4,
MeCH2CH2Ar); 1.22 – 1.42 (m, 8 CH2); 1.49 – 1.63 (m, 2 CH2CH2Ar); 2.59 – 2.71 (m, 2 CH2Ar); 3.96 (s,
MeO); 7.11 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 14.5 (MeCH2); 22.5
(CH2); 22.7 (CH2); 28.3 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 29.6 (CH2); 29.7 (CH2);
30.9 (CH2); 31.9 (CH2); 33.4 (CH2); 52.6 (MeO); 107.7 (CCOOMe); 119.9 (q, 3J ¼ 6.7, CHCCF3); 123.6
(q, 1J ¼ 272.6, CF3); 127.0 (q, 2J ¼ 31.7, CCF3); 133.8 (CC3H7); 147.2 (CC11H23); 160.4 (COH); 170.4
(CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 416 (31, Mþ), 384 (100), 341 (11), 257 (100),
229 (21). HR-EI-MS (70 eV): 416.2535 (Mþ, C23H35F3O3þ ; calc. 416.2538). Anal. calc. for C23H35F3O3
(416.52): C 66.32, H 8.47; found: C 66.40, H 8.77.
1-[2-Hydroxy-6-(trifluoromethyl)-4-undecylphenyl]ethanone (5af). Starting with 3e (0.541 g,
1.48 mmol), 4p (0.403 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5af was isolated
as a orange solid (0.353 g, 67%). M.p. 57 – 588. IR (ATR): 3306w, 2921w, 2852w, 1691m, 1651w, 1615m,
1586m, 1504m, 1464w, 1435w, 1355w, 1326w, 1269w, 1236w, 1191m, 1142m, 1120s, 1022m. 1H-NMR
(300 MHz): 0.88 (t, J ¼ 6.7, MeC10H20); 1.21 – 1.36 (m, 8 CH2); 1.56 – 1.68 (m, CH2CH2Ar); 2.57 – 2.65 (m,
ArCH2, COMe); 6.98 (s, 1 arom. H); 7.08 (s, 1 arom. H); 10.09 (s, OH). 13C-NMR (75 MHz): 14.1
(MeCH2); 22.7 (CH2); 29.2 (CH2); 29.3 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 29.6 (CH2); 30.5

Helvetica Chimica Acta – Vol. 96 (2013)
57
(CH2); 31.4 (q, 5J ¼ 5.2, COMe); 31.9 (CH2); 35.7 (CH2); 119.1 (q, 3J ¼ 5.8, CHCCF3); 119.5 (q, 3J ¼ 1.6,
CCOMe); 121.4 (COHCH); 123.8 (q, 1J ¼ 273.5, CF3); 128.6 (q, 2J ¼ 31.2, CCF3); 149.1 (CC11H23); 158.4
(COH); 204.9 (CO). 19F-NMR (282 MHz): ꢀ 55.4 (CF3). EI-MS (70 eV): 358 (48, Mþ), 343 (100), 218
(56). HR-EI-MS (70 eV): 358.2118 (Mþ, C20H29F3O2þ ; calc. 358.2114).
Methyl 2-Hydroxy-4-tridecyl-6-(trifluoromethyl)benzoate (5ag). Starting with 3f (0.582 g,
1.47 mmol), 4a (0.430 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ag was isolated
as a orange solid (0.202 g, 34%). M.p. 58 – 598. IR (ATR): 2957w, 2917s, 2877s, 2849s, 1680s, 1619m,
1580m, 1487w, 1461w, 1441w, 1428w, 1365m, 1338s, 1307s, 1288m, 1281s, 1218s, 1206m, 1170m, 1138m,
1
1126s, 1093m, 1035m, 1021w, 1004m. H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC12H24); 1.18 – 1.38 (m,
10 CH2); 1.55 – 1.69 (m, CH2CH2Ar); 2.61 (t, J ¼ 7.7, CH2Ar); 3.97 (s, MeO); 7.01 (s, 1 arom. H); 7.13 (s, 1
arom. H); 10.76 (s, OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 22.7 (CH2); 29.1 (CH2); 29.3 (CH2); 29.4
(CH2); 29.5 (CH2); 29.6 (CH2); 29.6 (CH2); 29.6 (CH2); 29.7 (CH2); 30.4 (CH2); 31.9 (CH2); 35.9
(CH2Ar); 52.7 (MeO); 108.4 (CCOOMe); 119.7 (q, 3J ¼ 6.7, CHCCF3); 121.3 (CHCOH); 123.4 (q, 1J ¼
273.5, CF3); 130.1 (q, 2J ¼ 31.8, CCF3); 150.1 (CC13H27); 162.0 (COH); 169.7 (CO). 19F-NMR
(282 MHz): ꢀ 58.8 (CF3). EI-MS (70 eV): 402 (59, Mþ), 370 (35), 234 (42), 215 (88), 202 (100), 189
(17), 173 (24). HR-EI-MS (70 eV): 402.2378 (Mþ, C22H33F3O3þ ; calc. 402.2382). Anal. calc. for
C22H33F3O3 (402.49): C 65.65, H 8.26; found: C 65.88, H 8.59.
Methyl 2-Hydroxy-3-methyl-4-tridecyl-6-(trifluoromethyl)benzoate (5ah). Starting with 3f (0.596 g,
1.51 mmol), 4b (0.453 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ah was isolated as
a colorless solid (0.220 g, 35%). M.p. 57 – 588. IR (ATR): 2917w, 2849w, 1663m, 1612m, 1580m, 1486w,
1461w, 1437w, 1401w, 1346m, 1311w, 1285w, 1252w, 1237w, 1219w, 1204w, 1190w, 1165w, 1144w, 1128w,
1115w, 1063m, 1030w, 1011m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC12H24); 1.19 – 1.42 (m, 10 CH2);
1.49 – 1.61 (m, CH2CH2Ar); 2.24 (s, Me); 2.64 (t, J ¼ 7.9, CH2Ar); 3.96 (s, MeO); 7.10 (s, 1 arom. H); 11.11
(s, OH). 13C-NMR (75 MHz): 11.7 (MeAr); 14.1 (MeCH2); 22.7 (CH2); 29.4 (CH2); 29.4 (CH2); 29.5
(CH2); 29.6 (CH2); 29.6 (CH2); 29.6 (CH2); 29.6 (CH2); 29.7 (CH2); 30.0 (CH2); 31.9 (CH2); 34.1
(CH2Ar); 52.6 (MeO); 107.6 (CCOOMe); 119.7 (q, 3J ¼ 6.8, CHCCF3); 123.6 (q, 1J ¼ 273.0, CF3); 126.9
(q, 2J ¼ 31.6, CCF3); 129.2 (CMe); 147.5 (CC13H27); 160.4 (COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ
58.6 (CF3). EI-MS (70 eV): 416 (63, Mþ), 384 (59), 366 (21), 315 (12), 229 (100), 216 (66), 203 (20), 187
(28). HR-EI-MS (70 eV): 416.2531 (Mþ, C23H35F3O3þ ; calc. 416.2538). Anal. calc. for C23H35F3O3
(416.52): C 66.32, H 8.47; found: C 66.23, H 8.56.
Methyl 3-Ethyl-2-hydroxy-4-tridecyl-6-(trifluoromethyl)benzoate (5ai). Starting with 3f (0.599 g,
1.52 mmol), 4q (0.476 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ai was isolated as
a colorless solid (0.284 g, 43%). M.p. 34 – 358. IR (ATR): 2987w, 2957w, 2916w, 2849w, 1663m, 1610m,
1575m, 1465m, 1453w, 1436w, 1398w, 1345w, 1294w, 1251w, 1235m, 1216m, 1203w, 1190w, 1163w, 1144w,
1132w, 1076w, 1063m. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC12H24); 1.15 (t, J ¼ 7.5, MeCH2Ar);
1.22 – 1.43 (m, 10 CH2); 1.51 – 1.63 (m, CH2CH2Ar); 2.64 (t, J ¼ 8.0, CH2CH2Ar); 2.73 (q, J ¼ 7.5,
MeCH2Ar); 3.96 (s, MeO); 7.11 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR (75 MHz): 13.5 (MeCH2); 14.1
(MeCH2); 19.5 (CH2); 22.7 (CH2); 29.4 (CH2); 29.4 (CH2); 29.5 (CH2); 29.6 (CH2); 29.6 (CH2); 29.6
(CH2); 29.7 (CH2); 29.7 (CH2); 31.0 (CH2); 31.9 (CH2); 33.3 (CH2Ar); 52.6 (MeO); 107.8 (CCOOMe);
3
1
2
120.0 (q, J ¼ 6.7, CHCCF3); 123.6 (q, J ¼ 272.7, CF3); 127.0 (q, J ¼ 31.6, CCF3); 135.1 (CC2H5); 146.9
(CC13H27); 160.2 (COH); 170.3 (CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 430 (35,
Mþ), 398 (49), 369 (12), 243 (100), 230 (28). HR-EI-MS (70 eV): 430.2688 (Mþ, C24H37F3Oþ3 ; calc.
430.2695).
Methyl 2-Hydroxy-3-propyl-4-tridecyl-6-(trifluoromethyl)benzoate (5aj). Starting with 3f (0.593 g,
1.50 mmol), 4r (0.499 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5aj was isolated as
a colorless solid (0.298 g, 45%). M.p. 46 – 478. IR (ATR): 2949w, 2914w, 2864w, 2846w, 1661m, 1611m,
1579m, 1484w, 1464w, 1441w, 1399w, 1356w, 1307w, 1285w, 1250w, 1232w, 1218w, 1194w, 1168w, 1145m,
1
1131s, 1118s, 1093m, 1080m, 1038w. H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC12H24); 1.01 (t, J ¼ 7.4,
MeCH2CH2Ar); 1.22 – 1.42 (m, 10 CH2); 1.48 – 1.63 (m, 2 CH2CH2Ar); 2.58 – 2.71 (m, 2 CH2Ar); 3.96 (s,
MeO); 7.10 (s, 1 arom. H); 11.05 (s, OH). 13C-NMR (75 MHz): 14.1 (MeCH2); 14.5 (MeCH2); 22.5
(CH2); 22.7 (CH2); 28.3 (CH2); 29.4 (CH2); 29.4 (CH2); 29.5 (CH2); 29.7 (CH2); 29.7 (CH2); 29.7 (CH2);
29.7 (CH2); 29.7 (CH2); 30.9 (CH2); 31.9 (CH2); 33.4 (CH2); 52.6 (MeO); 107.7 (CCOOMe); 119.9 (q,
3J ¼ 6.7, CHCCF3); 123.7 (q, 1J ¼ 272.2, CF3); 127.0 (q, 2J ¼ 31.8, CCF3); 133.8 (CC3H7); 147.3 (CC13H27);

58
Helvetica Chimica Acta – Vol. 96 (2013)
160.4 (COH); 170.4 (CO). 19F-NMR (282 MHz): ꢀ 58.6 (CF3). EI-MS (70 eV): 444 (Mþ, 32), 412 (88),
257 (100), 229 (22). HR-EI-MS (70 eV): 444.2844 (Mþ, C25H39F3O3þ ; calc. 444.2851). Anal. calc. for
C25H39F3O3 (444.57): C 67.54, H 8.84, found: C 67.84, H 9.31.
[2-Hydroxy-4-tridecyl-6-(trifluoromethyl)phenyl](phenyl)methanone (5ak). Starting with 3f
(0.596 g, 1.51 mmol), 4u (0.506 g, 1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5ak
was isolated as a yellow solid (0.445 g, 66%). M.p. 62 – 638. IR (ATR): 3185w, 2920w, 2850w, 1654w,
1614w, 1596w, 1580w, 1467w, 1448w, 1433w, 1352w, 1326w, 1318w, 1276w, 1250w, 1190w, 1172w, 1153m,
1124s, 1073s, 1025w. 1H-NMR (300 MHz): 0.88 (t, J ¼ 6.7, MeC12H24); 1.19 – 1.41 (m, 10 CH2); 1.57 – 1.71
(m, CH2CH2Ar); 2.64 (t, J ¼ 7.4, CH2Ar); 6.50 (s, OH); 6.95 (s, 1 arom. H); 7.11 (s, 1 arom. H); 7.41 – 7.48
(m, 2 arom. H); 7.59 (tt, J ¼ 7.4, 4J ¼ 1.7, 1 arom. H); 7.72 – 7.79 (m, 2 arom. H). 13C-NMR (75 MHz): 14.1
(MeCH2); 22.7 (CH2); 29.2 (CH2); 29.4 (CH2); 29.4 (CH2); 29.5 (CH2); 29.7 (CH2); 29.7 (CH2); 29.7
(CH2); 29.7 (CH2); 30.9 (CH2); 31.9 (CH2); 35.7 (CH2); 118.9 (q, 3J ¼ 4.5, CHCCF3); 120.1 (CH); 121.4
1
2
(CCOMe); 123.4 (q, J ¼ 274.8, CF3); 128.5 (CH); 129.2 (q, J ¼ 31.6, CCF3); 129.6 (CH); 133.9 (CH);
137.7 (C); 147.4 (CC13H27); 154.5 (COH); 196.8 (CO). 19F-NMR (282 MHz): ꢀ 56.7 (CF3). EI-MS
(70 eV): 448 (100, Mþ), 427 (61), 280 (28), 260 (23), 105 (97). HR-EI-MS (70 eV): 448.2580 (Mþ,
C27H35F3Oþ2 ; calc. 448.2589). Anal. calc. for C27H35F3O2 (448.56): C 72.30, H 7.86; found: C 72.37, H 7.79.
1-[2-Hydroxy-4,6-bis(trifluoromethyl)phenyl]ethanone (5al). Starting with 3g (1.5 mmol), 4p
(1.65 mmol), and TiCl4 (0.18 ml, 1.65 mmol) in CH2Cl2 (3 ml), 5al was isolated as a yellow oil (35%).
IR (KBr): 3379m, 3020m, 2927m, 2855w, 1703s, 1628s, 1601s, 1513w, 1445m, 1388s, 1365m, 1274s, 1241m,
1184m, 1155s, 1107s, 952s, 880m. 1H-NMR (300 MHz): 2.64 (s, Me); 7.38 (s, CHCꢀOH); 7.47 (s,
CF3CCHCCF3); 8.69 (br s, OH). 13C-NMR (75.5 MHz): 31.7 (q, 5J ¼ 3.7, Me); 115.1 (m, CF3CCHCCF3);
118.1 (q, 5J ¼ 3.7, CHCꢀOH); 122.6 (q, 1J ¼ 273.0, CF3); 122.9 (q, 1J ¼ 274.0, CF3); 127.9 (CCOMe); 129.3
(q, 2J ¼ 33.0, CF3CC); 133.8 (q, 2J ¼ 33.9, CF3CCH); 155.6 (COH); 204.1 (COMe). 19F-NMR
(235.4 MHz): ꢀ 56.9 (s, CF3), ꢀ 63.6 (s, CF3). EI-MS (70 eV): 272 (17, Mþ), 257 (100), 209 (37), 181
(23), 131 (18), 69 (32). Anal. calc. for C10H6F6O2 (272.14): C 44.13, H 2.22; found: C 44.00, H 2.41.
REFERENCES
[1] P. Langer, Synthesis 2002, 441.
[2] C. Mamat, T. Pundt, A. Schmidt, P. Langer, Tetrahedron Lett. 2006, 47, 2183.
[3] S. Bꢀttner, A. Riahi, I. Hussain, M. A.Yawer, M. Lubbe, A. Villinger, H. Reinke, C. Fischer, P.
Langer, Tetrahedron 2009, 65, 2124.
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2008, 6, 3542.
[5] S. Bꢀttner, M. Lubbe, H. Reinke, C. Fischer, P. Langer, Tetrahedron 2008, 64, 7968.
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[7] T.-H. Chan, P. Brownbridge, J. Am. Chem. Soc. 1980, 102, 3534; G. A. Molander, K. O. Cameron, J.
Am. Chem. Soc. 1993, 115, 830.
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Received February 2, 2012