Nucleophilic trifluoromethylation and difluorination of substituted aromatic aldehydes with Ruppert's and Deoxofluor? reagents

Article abstract of DOI:10.1016/S0022-1139(01)00447-X

Efficient, high yield syntheses of 2,2,2-trifluoro-1-(N,N-dialkylaminophenyl)-ethanols (3a, b) and 2,2,2-trifluoro-1-(hydroxyaryl)ethanols (6c-g) by reacting Ruppert's reagent, (trifluoromethyl)trimethylsilane (TMSCF₃), with appropriate substra

Full text of DOI:10.1016/S0022-1139(01)00447-X

Journal of Fluorine Chemistry 111 02001) 153±160
Nucleophilic tri¯uoromethylation and di¯uorination of substituted
aromatic aldehydes with Ruppert's and Deoxo¯uorTM reagents
Rajendra P. Singh, Debashis Chakraborty, Jean'ne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
Received 6 March 2001; accepted 13 June 2001
Abstract
Ef®cient, high yield syntheses of 2,2,2-tri¯uoro-1-0N,N-dialkylaminophenyl)-ethanols 03a, b) and 2,2,2-tri¯uoro-1-0hydroxyaryl)ethanols
06c±g) by reacting Ruppert's reagent, 0tri¯uoromethyl)trimethylsilane 0TMSCF3), with appropriate substrates in the presence of a catalytic
amount of cesium ¯uoride are described. A versatile route to the synthesis of substituted aryl di¯uoromethane derivatives 08h±l, 10m, 12n,
o, 14p) and the reactivity of substituted aromatic aldehydes towards bis02-methoxyethyl)aminosulfur tri¯uoride 0Deoxo¯uorTM) were also
investigated. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: 0Tri¯uoromethyl)trimethylsilane; 2,2,2-Tri¯uoro-1-0N,N-dialkylaminophenyl)-ethanols; 2,2,2-Tri¯uoro-1-0hydroxyaryl)ethanols; Bis02-methox-
yethyl)aminosulfur tri¯uoride; Aryldi¯uoromethane derivatives; Deoxo¯uorTM
1. Introduction
methanes involve the use of sulfur tetra¯uoride, [18±21]
amino¯uorosulfuranes [22±24] and di¯uorocarbenes [25].
Very recently bis02-methoxyethyl)-aminosulfur tri¯uoride
has been used to convert benzaldehyde into the corres-
ponding di¯uorotoluene [26,27] but no study has been
reported on substituted aromatic aldehydes. Also, the effect
of substituents in the aromatic ring towards the reactivity
with bis02-methoxyethyl)-aminosulfur tri¯uoride is not
described. It has been found that there exists a profound
difference in the reactivity of the aldehyde chosen based
upon substituents in the aromatic ring. In general, the
pattern of reactivity of the aldehydes corroborates the
nucleophilic mode of reaction behavior of bis02-methox-
yethyl)-aminosulfur tri¯uoride. Recently, we and others
have reported several novel tri¯uoro [28±36] and di¯uor-
omethylation reactions [37,38]. In this paper, we present
very ef®cient procedures for the syntheses of 2,2,2-tri¯uoro-
1-0N,N-dialkylaminophenyl)-ethanols and 2,2,2-tri¯uoro-
1-0hydroxyaryl)ethanol derivatives, and substituted
aryldi¯uoro-methane compounds in very good yield through
the use of TMSCF3 and bis02-methoxyethyl)aminosulfur
tri¯uor-ide, respectively.
The incorporation of a ¯uorine-containing group into an
organic molecule alters dramatically its physical, chemical
and biological properties [1,2]. The concomitant changes in
properties make these compounds suitable for diverse appli-
cations in material sciences, and agrochemistry, as well as in
the pharmaceutical industry [3±6]. The biological activity
[7,8] and numerous commercial applications [9±12] of orga-
no¯uorine compounds have encouraged interest in develop-
ing synthetic methods for selective and ef®cient incorporation
of ¯uorine or ¯uorinated groups into organic compounds
under mild reaction conditions. Although many practical
applications of hydroxy and amino-containing aryl com-
pounds have been reported [13], their synthetic routes tend
to be cumbersome. For example, an earlier synthesis of 06e)
was accomplished by the reaction of p-anislmagnesium bro-
mide and tri¯uoroacetic acid, followed by demethylation and
reduction 0Scheme 1) [14±16]. While Kimoto et al. reported
an alternative route to 06e) from simple phenol and tri¯uor-
oacetaldehyde ethyl hemiacetal, the products obtained after
heating at1208C for6 h were foundas isomeric mixtures[17].
Also starting from aromatic aldehydes, the general
reported routes to the synthesis of alkyl or aryl di¯uoro-
2. Results and discussion
* Corresponding author. Tel.: ‡1-208-885-6215;
Fax: ‡1-208-885-9146.
The syntheses of 2,2,2-tri¯uoro-1-0N,N-dimethylamino-
phenyl)ethanols 03a) were reported earlier [17] in good yield
E-mail address: jshreeve@uidaho.edu 0J.M. Shreeve).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 0 0 1 ) 0 0 4 4 7 - X

154
R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
Scheme 1.
Scheme 3.
hydrocarbon solvents like ethyl ether and diglyme can also
be used as alternative solvent systems. The reactions were
carried out with 0.7 eqv. excess of bis02-methoxyethyl)ami-
nosulfur tri¯uoride. [26,27] The aryldi¯uoromethane pro-
ducts were obtained as colorless oils. The aldehyde reactants
utilized in this study can be broadly classi®ed into two
classes, namely those with high to moderate electron
donor0s) with their in¯uence on the ±CHO functionality
and those with electron withdrawing substituents.
Scheme 2.
but the reaction also produced another isomer in trace
amounts which required puri®cation. In the present synth-
esis, the reaction of dialkylamino-anisaldehyde 01a, b) in
monoglyme with TMSCF3 in the presence of a catalytic
amount of CsF led to the formation of the corresponding
tri¯uoromethylated silyl ethers 02a, b) in essentially quan-
titative yields. Hydrolysis of the silyl ethers with 6N HCl
for 2 h furnished the 2,2,2-tri¯uoro-1-0N,N-dialkylamino-
phenyl)ethanols 03a, b) in 95% isolated yield 0Scheme 2).
No side products were observed.
Earlier, the syntheses of 4-methoxy-2,2,2,-tri¯uoro-1-
0hydroxyaryl)ethanol was mentioned [36], but the yield
and characterization data of the compounds were not given.
In the present work, the reactions of several anisaldehyde
derivatives 04c±g) with TMSCF3 in the presence of catalytic
amounts of CsF were carried out at room temperature in
monoglyme. The corresponding tri¯uoromethylated silyl
ethers 05c±g) were obtained in almost quantitative yield.
Treatment of 05c±g) with boron tribromide at À788C in
dichloromethane, followed by hydrolysis, resulted in 2,2,2-
tri¯uoro-1-0hydroxyaryl)ethanols 06c±g) in more than 92%
isolated yields 0Scheme 3, Table 1).
A variety of aromatic aldehydes 07h±l, 9m, 11n, o, 13p)
with variations in substituents and position with respect to
the aldehyde functionality were studied 0Scheme 4). Bis02-
methoxyethyl)aminosulfur tri¯uoride was chosen as the
¯uorinating agent because of its enhanced thermal stability
compared to DASTand its analogues. [26,27] As a result, the
reaction system could be subjected to 60±808C as required.
The reactions were conducted in CH2Cl2 as solvent. In cases
where both starting materials were liquids, the reactions
were accomplished under neat conditions. However, other
A critical analysis of the reaction conditions 0Table 2)
reveals that an electron donating substituent, such as OMe at
the meta-position of the aromatic ring has no in¯uence on
the reactivity and consequently 100% conversion of the
aldehyde moiety to di¯uoromethyl is achieved. The same
substituent at the ortho- or para-position reduces the elec-
trophilic character of the ±CHO functionality. As a result,
the presence of catalyst, such as HF and higher temperatures
are necessary to drive such reactions in the required direc-
tion. HF could be considered most convenient as it can be
generated in situ by adding EtOH. [26,27] In the case of 8h,
even drastic temperatures could not drive the reaction
beyond 57% conversion. Reactants 7j and 7k that are
isomers differing in the position of a ±OMe group have
comparable reactivity under identical reaction conditions.
The electrophilic character of the ±CHO moiety is greatly
enhanced when an electron withdrawing substituent is pre-
sent in the aromatic ring. For example, with 11n and 13p, the
reactions occur in very short periods of time under ambient
conditions without any catalyst. Substrate 11o is intermedi-
ate between the extreme cases of substituent in¯uence
described. Its reaction with bis02-methoxyethyl)aminosulfur
tri¯uoride is quite facile and complete conversion is
achieved 0Scheme 4, Table 2).
In conclusion, a simple procedure for the preparation of
2,2,2-tri¯uoro-1-0N,N-dialkylaminophenyl)ethanols, 2,2,2-
tri¯uoro-1-0hydroxyphenyl)ethanols and substituted di¯uoro
toluene using 0tri¯uoromethyl)trimethylsilane and bis02-
methoxyethyl)aminosulfur tri¯uoride has been described.
Yields are good to excellent. The pattern of reactivity of the
substituted aldehydes chosen is consistent with a nucleo-
philic mode of behavior for Deoxo¯uorTM
.

R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
155
Table 1
Preparation of 2,2,2-trifluoro-1-0N,N-dialkylaminophenyl)ethanols and 2,2,2-trifluoro-1-0hydroxyaryl)ethanols using 0trifluoromethyl)trimethylsilanea
Substrate
Intermediateb
Product
Yield 0%)c
95
95
92
94
92
93
92
a All the reactions were carried out with 5.0 mmol of substrate, 5.25 mmol of TMSCF3 and 0.1 mmol of CsF in 5.0 ml of monoglyme.
b Formed in quantitative yield.
c Isolated yield.
Scheme 4.

156
R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
Table 2
Fluorination of aromatic aldehydes with bis02-methoxyethyl)aminosulfur trifluoridea
Substrate
Reaction conditions
Products
Conversionb
100
Yieldc
94
Neat, RT, 16 h
Neat, 758C, 18 h
Ch2Cl2, 458C, 16 h
Ch2Cl2, 458C, 16 h
57
83
80
44
70
68
>
Ch2Cl2, 458C, 12 h
90
62
Ch2Cl2, 458C, 16 h
Ch2Cl2, RT, 3 h
Ch2Cl2, RT, 8 h
Neat, RT, 8 h
80
100
100
100
65
90
85
80
a All the reactions were carried out with 5 mmol of substrate, 8.5 mmol of bis02-methoxy-ethyl)aminosulfur trifluoride in 4 ml of dichloromethane.
b Based on GC/MS.
c Isolated yield.
3. Experimental
Chemical shifts are reported in ppm relative to the appro-
1
priate standard, CFCl3 for 19F and TMSfor H and 13C NMR
3.1. General
spectra. Infrared spectra were recorded as liquid ®lms
between KBr discs using a BIO-RAD FT spectrometer.
KBr pellets were prepared for solid samples. The melting
points were obtained by using a Mel-Temp II apparatus.
Electron impact mass spectra and HRMSwere measured at
70 eV using a JEOL JMSAX505HF spectrometer.
All the reactions were performed under a dry nitrogen
atmosphere. 0Tri¯uoromethyl)trimethylsilane was prepared
by literature procedures [39,40]. Cesium ¯uoride was placed
in an oven at 2008C and repeatedly ground until it remained
as a ®nely divided powder. Once this stage is reached, it may
be used in the reactions. Storing in the oven at 2008C retains
the compound in its ®nely divided state inde®nitely. The
aldehydes were purchased from Aldrich. Deoxo¯uorTM was
3.2. General procedure for synthesis of 2,2,2-trifluoro-
1--dialkylaminophenyl)ethanols
obtained from Air Products and Chemicals. 1H, 19F, and 13
NMR spectra were recorded in CDCl3 on a Bruker spectro-
meter operating at 200, 188, and 50 MHz, respectively.
C
The 4-0dialkylamino)benzaldehyde 05 mmol) and
TMSCF3 05.25 mmol) were dissolved in monoglyme
010 ml) and the mixture was cooled with cold water 0about

R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
157
‡
‡
108C). To the stirred solution, powdered cesium ¯uoride
00.1 mmol) was added. Heat was generated as the reaction
began. After 15 min, the water bath was removed and the
reaction mixture was stirred for 3 h. Volatile materials were
removed and dry pentane 020 ml) was added. The mixture
was ®ltered under nitrogen and washed. Removal of pentane
under reduced pressure gave the trimethylsilyl ether inter-
mediates 02a, b) in essentially quantitative yields. Hydro-
lysis of 02a, b) was carried out with 6N HCl in THF 05 ml)
for 2 h at room temperature, and the solution was neutralized
with sodium bicarbonate. Products were extracted with ethyl
acetate. The ethyl acetate solution was dried over anhydrous
MgSO4 and ®ltered. Removal of solvent furnished the
products 03a, b) which were further puri®ed by crystal-
lization from diethyl ether and pentane mixtures.
51), 202 0M Ð OH, 4), 120 0M Ð CF3CHOH, 41), 150
‡
‡
0M Ð CF3, 100), 69 0CF3 , 14). HRMS: calcd. for
‡
C10H12F3NO 0M ): 219.0871. Found: 219.0879. Anal.
calcd. for C10H12F3ON: C, 54.77; H, 5.52; N, 6.39. Found:
C, 54.89; H, 5.63; N, 6.35%.
3.6. 2,2,2-Trifluoro-1--4-N,N-diethylaminophenyl)
ethanol -3b)
Yield: 95%; mp 35±368C; IR 0KBr pellet): 3170 0broad),
2965, 1610, 1513, 1360, 1260, 1166, 880 cmÀ1; H NMR
1
0CDCl3): d 1.20 0t, 3H, J ˆ 7 Hz), 2.50 0b, s, 1H), 3.35 0q,
2H, J ˆ 7 Hz), 4.80 0q, 1H, J ˆ 6:7 Hz), 6.62 0d, 2H,
J ˆ 8:5 Hz), 7.27 0d, 2H, J ˆ 8:5 Hz). 19F NMR 0CDCl3):
d À78.75 0d, J ˆ 6 Hz); 13C NMR 0CDCl3): d À12.50,
44.25, 73.18 0q, JCÀCÀF ˆ 31:7 Hz), 111.10, 121.51,
124.62 0q, JCÀF ˆ 280:3 Hz), 128.60, 148.31; MS0EI) m/
3.3. 2,2,2-Trifluoro-1--4-N,N-
dimethylaminophenyl)trimethylsilyl ether -2a)
‡ ‡
z 0species, rel. int.): 247 0M , 40), 230 0M Ð OH, 3), 232
‡
‡
0M Ð CF3, 100), 69 0CF3 , 7). HRMS: calcd. for
‡
Yield: ꢀ100%; mp 54±558C; IR 0KBr pellet): 2950, 1618,
C12H16F3NO 0M ): 247.2600. Found: 247.2597.
1531, 1359, 1253, 1125, 881 cmÀ1; H NMR 0CDCl3): d
1
0.10 0s, 9H), 2.95 0s, 6H), 4.81 0q, 1H, J ˆ 6 Hz), 6.68 0d,
2H, J ˆ 8:5 Hz), 7.28 0d, 2H, J ˆ 8:5 Hz); 19F NMR
0CDCl3): d À78.86 0d, J ˆ 6 Hz). 13C NMR 0CDCl3):
d ˆ À0:23, 40.30, 73.09 0q, JCÀCÀF ˆ 13:8 Hz), 111.77,
122.70, 124.49 0q, JCÀF ˆ 280:2 Hz), 128.43, 150.91; MS
3.7. General procedure for synthesis of 2,2,2-trifluoro-
1--hydroxyphenyl)ethanols
Anisaldehyde or its derivatives 05 mmol) and TMSCF3
05.25 mmol) were dissolved under dry nitrogen in mono-
glyme and cooled to about 108C. Cesium ¯uoride
00.1 mmol) was added directly. After stirring for 15 min,
the cold bath was removed and stirring was continued for
3 h. Volatile materials were removed and the residue
obtained was dissolved in dry pentane 020 ml). It was ®ltered
under nitrogen and washed. Removal of pentane gave the
trimethylsilyl ether intermediates 05c±f) in nearly quantita-
tive yields. These intermediates were further dissolved in
dichloromethane and cooled to À788C. Boron tribromide
015 mmol, 1 M solution in dichloromethane) was added
dropwise. The reaction mixture was stirred at À788C for
15 h. It was quenched with brine solution and stirred for an
additional 1 h. The solution was neutralized with sodium
bicarbonate and products were extracted with ethyl acetate.
Further puri®cation of the products 06c±f) was carried out by
crystallization with ether and pentane mixtures.
‡
‡
0EI) m/z 0species, rel. int.): 292 0M ‡1, 11), 291 0M , 38),
‡
222 0M Ð CF3, 100); Anal. calcd. for C13H20F3ONSi: C,
53.58; H, 6.92; N, 4.81; Si, 9.61. Found: C, 53.67; H, 6.82;
N, 4.83; Si, 9.97%.
3.4. 2,2,2-Trifluoro-1--4-N,N-
diethylaminophenyl)trimethylsilyl ether -2b)
Yield: ꢀ100%; viscous liquid; IR 0KBr disc): 2970, 1614,
1523, 1357, 1263, 1166, 1129, 883 cmÀ1
;
1H NMR
0CDCl3): d 0.13 0s, 9H), 1.19 0t, 3H, J ˆ 7 Hz), 3.37 0q,
2H, J ˆ 7 Hz), 4.84 0q, 1H, J ˆ 6:7 Hz), 6.65 0d, 2H,
J ˆ 8:5 Hz), 7.26 0d, 2H, J ˆ 8:5 Hz); 19F NMR 0CDCl3):
d À78.77 0d, J ˆ 6 Hz); 13C NMR 0CDCl3): d À0.22, 12.51,
44.25, 73.17 0q, JCÀCÀF ˆ 31:7 Hz), 111.00, 121.54, 124.60
0q, JCÀF ˆ 280:3 Hz), 128.65, 148.31; MS0EI) m/z 0species,
‡
‡
‡
rel. int.): 319 0M , 42), 304 0M Ð CH3, 96), 250 0M
Ð
‡
CF3, 100), 73 0SiMe3 , 15).
3.8. 2,2,2-Trifluoro-1--2-methoxyphenyl)trimethylsilyl
ether -5c)
3.5. 2,2,2-Trifluoro-1--4-N,N-
dimethylaminophenyl)ethanol -3a)
Yield: 99%; viscous liquid; IR 0KBr disc): 2965, 1612,
1480, 1455, 1366, 1254, 1170, 1129, 1048, 868 cmÀ1; H
1
Yield: 95%; mp 98±998C; IR 0KBr pellet): 3359 0broad),
2894,1615, 1526, 1448, 1355, 1263, 1166, 1117, 1063, 907,
805 cmÀ1 1H NMR 0CDCl3): d 2.54 0b, s, 1H), 2.95 0s, 6H),
4.86 0q, 1H, J ˆ 6:5 Hz), 6.71 0d, 2H, J ˆ 8:6 Hz), 7.29 0d,
2H, J ˆ 8:7 Hz). 19F NMR 0CDCl3): d À78.58 0d,
J ˆ 6:5 Hz); 13C NMR 0CDCl3): d 40.38, 72.69 0q,
JCÀCÀF ˆ 31:5 Hz), 112.31, 124.25 0q, JCÀF ˆ 280:4 Hz),
NMR 0CDCl3): d 0.12 0s, 9H), 3.80 0s, 3H), 4.85 0q, 1H,
J ˆ 6:5 Hz), 6.78 0m, 1H), 7.00 0s ‡ d, 2H), 7.24 0d, 1H,
J ˆ 5:5 Hz); 19F NMR 0CDCl3): d À78.40 0d, J ˆ 6:5 Hz);
13C NMR 0CDCl3):
d
À0.29, 55.10, 73.25 0q,
JCÀCÀF ˆ 31:8 Hz), 111.12, 113.50, 119.81, 124.48 0q,
JCÀF ˆ 280:4 Hz), 129.36, 136.92, 159.05; MS0EI) m/z
‡
‡
0species, rel. int.): 278 0M , 20), 209 0M Ð CF3, 100),
73 0SiMe3 , 14).
‡
‡
128.39, 151.27; MS0EI) m/z 0species, rel. int.): 219 0M ,

158
R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
3.9. 2,2,2-Trifluoro-1--3-methoxyphenyl)trimethylsilyl
ether -5d)
3.13. 2,2,2-Trifluoro-1--2-hydroxyphenyl)ethanol -6c)
Yield: 92%; mp 111±1128C; IR 0KBr pellet): 3336 0br),
Yield: 99%; viscous liquid; IR 0KBr disc): 2960, 1604,
1490, 1457, 1367, 1257, 1171, 1130, 1047, 879 cmÀ1; H
1597, 1492, 1458, 1355, 1245, 1169, 1130, 1049, 873 cmÀ1
;
1H NMR 0CDCl3): d 3.76 0b, s, 2H), 5.16 0q, 1H,
J ˆ 6:5 Hz), 6.91 0m, 2H), 7.21 0m, 2H); 19F NMR 0CDCl3):
d À78.68 0d, J ˆ 6:5 Hz). 13C NMR 0CDCl3): d À0.34,
55.13, 72.89 0q, JCÀCÀF ˆ 31:9 Hz), 113.68, 124.53 0q,
JCÀF ˆ 28:0 Hz) 127.54, 128.81, 160.21; MS0EI) m/z 0spe-
1
NMR 0CDCl3): d 0.13 0s, 9H), 3.80 0s, 3H), 4.90 0q, 1H,
J ˆ 6:5 Hz), 6.95 0m, 1H), 7.00 0s ‡ d, 2H), 7.25 0d, 1H,
J ˆ 5:8 Hz); 19F NMR 0CDCl3): d À78.55 0d, J ˆ 6:5 Hz);
13C NMR 0CDCl3):
d
À0.38, 55.13, 73.15 0q,
‡
‡
‡
JCÀCÀF ˆ 31:9 Hz), 113.12, 114.51, 119.91, 124.50 0q,
cies, rel. int.): 192 0M , 48), 123 0M Ð CF3, 80), 95 0M Ð
CF3CO, 100); Anal. calcd. for C8H7F3O2: C, 49.99; H, 3.67.
Found: C, 50.24; H, 3.75%.
JCÀF ˆ 280:2 Hz), 129.24, 136.95, 159.56; MS0EI) m/z
‡
‡
0species, rel. int.): 278 0M , 24), 209 0M Ð CF3, 100),
73 0SiMe3 , 23).
‡
3.14. 2,2,2-Trifluoro-1--3-hydroxyphenyl)ethanol -6d)
3.10. 2,2,2-Trifluoro-1--4-methoxyphenyl)trimethylsilyl
ether -5e)
Yield: 94%; mp 103±1048C; IR 0KBr pellet): 3192
0broad), 1593, 1483, 1352, 1263, 1166, 1078, 1128,
937 cmÀ1; H NMR 0CDCl3): d 1.58 0b, s, 1H), 2.52 0b,
1
Yield: 100%; viscous liquid; IR 0KBr disc): 2960, 1614,
1514, 1463, 1365, 1254, 1168, 1130, 1033, 879, 845 cmÀ1
;
s, 1H), 4.96 0q, 1H, J ˆ 6:6 Hz), 6.87 0m, 1H), 7.02 0s ‡ d,
2H), 7.26 0d, 1H, J ˆ 5:6 Hz); 19F NMR 0CDCl3): d À78.46
0d, J ˆ 6:6 Hz); 13C NMR 050 MHz, CDCl3): d À0.34,
55.13, 72.89 0q, JCÀCÀF ˆ 31:9 Hz), 113.68, 124.53 0q,
JCÀF ˆ 28:0 Hz), 127.54, 128.81, 160.21; MS0EI) m/z
1H NMR 0CDCl3): d 0.12 0s, 9H), 3.69 0s, 3H), 4.86 0q, 1H,
J ˆ 6:5 Hz), 6.89 0d, 2H, J ˆ 8:7 Hz), 7.37 0d, 2H,
J ˆ 8:7 Hz); 19F NMR 0CDCl3):
d
À78.95 0d,
J ˆ 6:5 Hz); 13C NMR 0CDCl3): d À0.34, 55.13, 72.89
0q, JCÀCÀF ˆ 31:9 Hz), 113.68, 124.53 0q, JCÀF ˆ 28:0
Hz), 127.54, 128.81, 160.21; MS0EI) m/z 0species, rel.
‡
‡
0species, rel. int.): 192 0M , 49), 123 0M Ð CF3, 89),
‡
‡
95 0M Ð CF3CO, 100). HRMS: calcd. for C8H7F3O2 0M ):
192.0398. Found: 192.0408.
‡
‡
‡
int.): 278 0M , 24), 209 0M Ð CF3, 100), 73 0SiMe3 , 23).
Anal. calcd. for C12H17F3O2Si: C, 51.78; H, 6.16; Si, 10.06.
Found: C, 51.58; H, 6.20; Si, 9.87%.
3.15. 2,2,2-Trifluoro-1--4-hydroxyphenyl)ethanol -6e)
3.11. 2,2,2-Trifluoro-1--3-methyl-4-
methoxyphenyl)trimethylsilyl ether -5f)
Yield: 92%; colorless crystals; mp 125±1268C; IR 0KBr
pellet): 3200 0broad), 1601, 1510, 1443, 1244, 1160, 1126,
1066, 817 cmÀ1; 1H NMR 0CDCl3): d 1.20 0b, s, 1H), 2.76
0b, s, 1H), 3.69 0s, 3H), 4.94 0q, 1H, J ˆ 6:6 Hz), 6.84 0d, 2H,
J ˆ 8:3 Hz), 7.33 0d, 2H, J ˆ 8:7 Hz). 19F NMR 0CDCl3): d
À78.80 0d, J ˆ 6:6 Hz); 13C NMR 0CDCl3): d À0.34, 55.13,
72.89 0q, JCÀCÀF ˆ 31:9 Hz), 113.68, 124.53 0q,
JCÀF ˆ 28:0 Hz) 127.54, 128.81, 160.21; MS0EI) m/z 0spe-
Yield: 99%; viscous liquid; IR 0KBr disc): 2959, 1614,
1506, 1254, 1170, 1132, 1035, 881, 843 cmÀ1; H NMR
1
0CDCl3): d 0.10 0s, 9H), 2.22 0s, 3H), 3.81 0s, 3H), 4.90 0q,
1H, J ˆ 6:5 Hz), 6.80 0d, 1H, 8.0 Hz), 7.20 0s, 1H), 7.24 0d,
1H, J ˆ 8:0 Hz);19F NMR 0CDCl3):
d
À78.80 0d,
‡ ‡
cies, rel. int.): 192 0M , 30), 123 0M Ð CF3, 100),
J ˆ 6:0 Hz); 13C NMR 0CDCl3): d À0.29, 16.22, 55.20,
72.93 0q, JCÀCÀF ˆ 31:8 Hz), 109.4, 113.12, 124.480 0q,
JCÀF ˆ 280:7 Hz), 126.15, 126.50, 126.93, 129.72, 158.28;
‡
‡
690CF3
192.0398. Found: 192.0804.
, 2). HRMS: calcd. for C8H7F3O2 0M ):
‡
‡
Ð
MS0EI) m/z 0species, rel. int.): 292 0M , 10), 223 0M
‡
CF3, 100), 73 0SiMe3 , 8).
3.16. 2,2,2-Trifluoro-1--3-methyl-4-hydroxyphenyl)
ethanol -6f)
3.12. 2,2,2-Trifluoro-1--2,5-dimethyl-4-
methoxyphenyl)trimethylsilyl ether -5g)
Yield: 93%; mp 107±1088C; IR 0KBr pellet): 3205
0broad), 1611, 1508, 1440, 1248, 1155, 1129, 1061,
815 cmÀ1; H NMR 0CDCl3): d 2.40 0b, s, 1H), 3.69 0s,
1
Yield: 99%; viscous liquid; IR 0KBr disc): 3200 0broad),
2960, 1607, 1512, 1260, 1168, 1038, 885 cmÀ1; H NMR
1
3H), 4.94 0q, 1H, J ˆ 6:7 Hz), 5.12 0b, s, 1H), 6.74 0d, 1H,
J ˆ 8:1 Hz), 7.16 0d, 1H, J ˆ 8:1 Hz), 7.23 0s, 1H); 19F
NMR 0CDCl3): d À78.68 0d, J ˆ 6:7 Hz); 13C NMR
0CDCl3): d 15.70, 72.52, 0q, JCÀCÀF ˆ 31:20, Hz),
114.98, 124.17, 124.50 0q, JCÀF ˆ 280:5 Hz), 124.70,
126.41, 130.16, 154.77; MS0EI) m/z 0species, rel. int.):
0CDCl3): d 0.12 0s, 9H), 2.21 0s, 3H), 2.35 0s, 3H), 3.82 0s,
3H), 5.12 0q, 1H, J ˆ 6:5 Hz), 6.59 0s, 1H), 7.35 0s, 1H); 19
F
NMR 0CDCl3): d À78.37 0d, J ˆ 6:5 Hz); 13C NMR
0CDCl3):
d
À0.13, 16.35, 19.69, 55.54, 69.66 0q,
JCÀCÀF ˆ 31:0 Hz), 111,90, 124.50, 0q, JCÀF ˆ 281:0 Hz),
‡
‡
‡
124.68, 125.10, 130.76, 134.56, 158.55; MS0EI) m/z 0spe-
cies, rel. int.): 306 0M, 29), 237 0M Ð CF3, 100), 217 0M
206 0M , 56), 137 0M Ð CF3, 100), 69 0CF3 , 2); Anal.
calcd. for C9H9F3O2: C, 52.41; H, 4.40. Found: C, 52.17; H,
4.30%.
‡
‡
‡
Ð OSiMe3, 10), 73 0SiMe3 , 6).

R.P. Singh et al. / Journal of Fluorine Chemistry 111 -2001) 153±160
159
646 cmÀ1; H NMR d 7.03±7.01 0m, 2H), 6.88±6.86 0m,
1H), 6.59 0t, 1H, J ˆ 56:7 Hz), 3.88 0s, 6H); 19F NMR d
À108.2 0d, J ˆ 56:9 Hz); 13C NMR d 150.9, 149.3, 126.9,
118.8, 116.8 0t, J ˆ 237:4 Hz), 110.6, 108.0, 56.0, 55.9; MS
1
3.17. 2,2,2-Trifluoro-1--2,5-dimethyl-4-
hydroxyphenyl)ethanol -6g)
Yield: 92%; mp 114±1158C; IR 0KBr pellet): 3200
0broad), 2964, 1612, 1510, 1255, 1165, 1035, 888 cmÀ1
;
0EI) m/z 0species, rel. int.): 188 0M , 100), 173 0M Ð Me,
‡
‡
‡
1H NMR 0CDCl3): d 2.19 0s, 3H), 2.24 0s, 3H), 3.26 0b,
s, 2H), 3.82 0s, 3H), 5.17 0q, 1H, J ˆ 6:6 Hz), 6.56 0s, 1H),
7.29 0s, 1H); 19F NMR 0CDCl3): d À78.13 0d, J ˆ 6:6 Hz);
70), 169 0M Ð F, 15), 51 0CHF2, 65); HRMS: calcd for
‡
C9H10F2O2 0M ): 188.0649. Found: 188.0658.
13C NMR 0CDCl3):
d
15.64, 19.13, 68.89, 0q,
3.22. 1,10-Dimethyl-4-methoxy difluorotoluene -8l)
JCÀCÀF ˆ 31:5 Hz), 117.11, 122.11, 124.92, 129.93,
136.03, 154.65; MS0EI) m/z 0species, rel. int.): 220
Yield: 62%; liquid; IR 0KBr disc): 2963, 2837, 1512,
1463, 1317, 1265, 1113, 1072, 1007, 896, 848, 785, 692,
‡
‡
‡
0M , 19), 151 0M Ð CF3, 100), 69 0CF3 , 9); Anal. calcd.
for C10H11F3O2: C, 54.53; H, 5.05. Found: C, 54.77; H,
5.07%.
619 cmÀ1
,
1H NMR d 7.24 0s, 1H), 6.69 0t, 1H,
J ˆ 55:3 Hz), 6.65 0s, 1H), 3.84 0s, 3H) 2.40 0s, 3H),
2.20 0s, 3H); 19F NMR d À110.5 0d, J ˆ 55:7 Hz); 13C
NMR d 159.1, 135.3, 128.2, 124.1, 123.9, 114.8 0t,
J ˆ 234:9 Hz), 57.3, 18.4, 15.7; MS0EI) m/z 0species,
3.18. General procedure for difluoromethylation of
substituted aromatic aldehydes
‡
‡
‡
rel. int.): 186 0M , 100), 171 0M Ð Me, 35), 167 0M
‡
A solution of aromatic aldehyde 05 mmol) in dichloro-
methane 02 ml) was reacted with a solution of of Deoxo-
¯uorTM 01.88 g, 8.5 mmol) in dichloromethane 02 ml).
Ethanol 046 mg, 1 mmol) was added, and the reaction
was monitored by GC/MS. On completion, the reaction
was worked up by slow addition of sodium bicarbonate
solution followed by washing with water. The pure product
was isolated by ¯ash chromatography on silica gel in
hexane/ether mixture.
Ð F, 15), 51 0CHF2, 20); HRMS: calcd for C10H12F2O 0M ):
186.0856. Found: 186.0852.
3.23. 3,4-Methylenedioxy difluorotoluene -10m)
Yield: 65%; liquid; IR 0KBr disc): 2981, 2907, 1502,
1452, 1408, 1352, 1251, 1105, 1040, 931, 813, 869, 792,
632 cmÀ1; H NMR d 6.96À6.93 0m, 2H), 6.82±6.80 0m,
1
1H), 6.51 0t, 1H, J ˆ 56:1 Hz), 5.98 0s, 2H); 19F NMR d
À108.1 0d, J ˆ 55:9 Hz); 13C NMR d 149.6, 148.0, 128.3,
120.1, 114.6 0t, J ˆ 238:1 Hz), 108.2, 105.8, 101.6; MS0EI)
3.19. 2-Methoxy-difluorotoluene -8h)
‡
‡
‡
m/z 0species, rel. int.): 172 0M , 100), 153 0M Ð F, 25), 51
Yield: 94%; liquid; IR 0KBr disc): 2964, 2841, 1492,
1461, 1372, 1269, 1195, 1170, 1039, 861, 760, 695,
0CHF2, 35); HRMS: calcd. for C8H6F2O2 0M ): 172.0336.
Found: 172.0337.
663 cmÀ1; H NMR d 7.37±7.33 0m, 1H), 7.08À6.98 0m,
1
3H), 6.60 0t, 1H, J ˆ 57:2 Hz), 3.82 0s, 3H); 19F NMR d
À110.8 0d, J ˆ 57:4 Hz); 13C NMR d 159.8, 135.7, 129.8,
117.9, 116.6, 114.6 0t, J ˆ 237:5 Hz), 110.5, 55.3; MS0EI)
Acknowledgements
‡
‡
m/z 0species, rel. int.): 158 0M , 100), 143 0M Ð F, 10), 127
This work was supported by the National Science Foun-
dation 0Grant no. CHE-9720365) and donors of the Amer-
ican Chemical Society Petroleum Research Fund. We are
grateful to Dr. G.S. Lal 0Air Products and Chemicals) for a
generous supply of Deoxo¯uorTM reagent. We thank Dr. G.
Knerr for obtaining high resolution mass spectra and Dr.
Alex Blumenfeld for NMR measurements.
‡
0M Ð OMe, 80), 51 0CHF2, 20); HRMS: calcd. for
‡
C8H8F2O 0M ): 158.0543. Found: 158.0535.
3.20. 1,2-Dimethoxy difluorotoluene -8j)
Yield: 70%; liquid; IR 0KBr disc): 2944, 2841, 1488,
1376, 1275, 1230, 1045, 1027, 911, 791, 758, 653 cmÀ1; 1H
NMR d 7.19±7.15 0m, 2H), 7.01±6.99 0m, 1H), 6.92 0t, 1H,
J ˆ 55:8 Hz), 3.86 0s, 6H); 19F NMR d À114.1 0d,
J ˆ 55:3 Hz); 13C NMR d 152.6, 147.4, 128.2, 124.4,
117.4, 114.6 0t, J ˆ 236:5 Hz), 113.5, 55.8; MS0EI) m/z
References
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‡
‡
0species, rel. int.) 188 0M , 100), 173 0M Ð Me, 65), 169
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‡
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