Efficient synthesis of chlorohydrins using ClCH2MgCl·LiCl

Article abstract of DOI:10.1016/j.tetlet.2012.10.132

The mixed lithium-magnesium carbenoid ClCH₂MgCl·LiCl was easily generated in THF through the reaction of chloroiodomethane with i-PrMgCl·LiCl at -78 °C. This reagent reacts well with a number of aldehydes to give the corresponding chlorohydrins in good yields.

Full text of DOI:10.1016/j.tetlet.2012.10.132

Tetrahedron Letters 54 (2013) 287–290
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Tetrahedron Letters
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Efficient synthesis of chlorohydrins using ClCH2MgClÁLiCl
Rodolfo H. V. Nishimura, Fabiano T. Toledo, João L. C. Lopes, Giuliano C. Clososki
⇑
Research Center for Natural and Synthetic Products, University of São Paulo, Av. do Café S/N, Ribeirão Preto—SP 14.040-903, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The mixed lithium–magnesium carbenoid ClCH2MgClÁLiCl was easily generated in THF through the
reaction of chloroiodomethane with i-PrMgClÁLiCl at À78 °C. This reagent reacts well with a number of
aldehydes to give the corresponding chlorohydrins in good yields.
Received 24 September 2012
Revised 26 October 2012
Accepted 30 October 2012
Available online 20 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Carbenoids
Chlorohydrins
Organomagnesium
Turbo Grignard
Lithium chloride
Lithium carbenoids have been recognized as valuable organo-
metallic intermediates, however, their low thermal stability has
precluded their application in organic synthesis.1 In contrast,
magnesium carbenoids are less prone to thermal decomposition
and therefore better suited for synthetic applications.2 These re-
agents are frequently prepared from the iodine–magnesium or
sulfoxide-magnesium exchange reaction of the corresponding
iodides and sulfoxides.3 Due to its special reactivity, the ‘turbo
Grignard’ i-PrMgClÁLiCl (2) has emerged as the reagent of choice
for halogen-magnesium exchange reactions.4 In this study, we
have investigated the preparation of the mixed lithium–magne-
sium carbenoid ClCH2MgClÁLiCl through the iodine–magnesium
exchange reaction of chloroiodomethane (1) with i-PrMgClÁLiCl.
We also investigated the application of this in-situ generated
reagent to the synthesis of chlorohydrins, which are important
intermediates in organic synthesis.5
We initiated our study by screening some conditions for the
iodine–magnesium exchange reaction of 1 with i-PrMgClÁLiCl. First,
we performed the reaction of 1 mmol of chloroiodomethane with
1 equiv of i-PrMgClÁLiCl for 10 min at À78 °C. Further addition of
benzaldehyde (1 equiv) followed by stirring at the same tempera-
ture for 30 min yielded the corresponding 2-chloro-1-phenyletha-
nol (4a) with 78% conversion (Table 1, entry 1). In contrast, when
the same reaction was performed at À40 °C, the desired product
was not detected by GC analysis, and the starting material was
recovered to a large extent (Table 1, entry 2). When the reaction
was performed under ‘‘Barbier-like conditions’’ at À78 °C (i-PrMg
ClÁLiCl was added dropwise to a mixture of chloroiodomethane
and benzaldehyde in THF) the alcohol formed due to the 1,
2-addition of i-PrMgClÁLiCl to benzaldehyde was the major
product. Therefore, the chlorohydrin 4a was obtained in only 38%
Table 1
Screening for the preparation of 2-chloro-1-phenylethanol 4a
.
2
1) i-PrMgCl LiCl ( )
OH
THF, T ºC, 10 min
Cl
Cl
I
Ph
3a
2) PhCHO ( ), THF
1
4a
T ºC, 30 min
Entry
1 (mmol)
2 (mmol)
3a (mmol)
Temp (°C)
4aa (% conv.)
1
2
3c
4
5
6
7
1.0
1.0
1.0
1.5
2.0
2.0
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
À78
À40
À78
À78
À78
À60
À40
78
NDb
38
87
99
95
37
a
b
c
Conversions determined by GC analysis.
ND = not detected.
Using barbier-like conditions.
1. i-PrMgCl.LiCl (2)
THF, −78 ºC, 10 min
2. RCHO (3), 30 min
OH
Cl
Cl
I
R
1
4
R = aryl, heteroaryl, alkyl
⇑
Corresponding author. Tel.: +55 16 3602 4252; fax: +55 16 3602 4243.
E-mail address: gclososki@fcfrp.usp.br (G.C. Clososki).
Scheme 1. Preparation of the mixed lithium–magnesium carbenoid and its
reaction with aldehydes.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.132

288
R. H. V. Nishimura et al. / Tetrahedron Letters 54 (2013) 287–290
conversion (Table 1, entry 3). Interestingly, the use of excess of the
iodide favors the reaction. Thus, the reaction of benzaldehyde
(1 mmol) with the magnesium carbenoid prepared through the
reaction of 1.5 mmol of chloroiodomethane with 1 equiv of 2 at
À78 °C for 10 min led to 2-chloro-1-phenylethanol 4a in 87% con-
version (Table 1, entry 4). Moreover, when 2 equiv of 1 were used
the desired product was obtained in 99% conversion (Table 1, entry
5). Hoffmann and co-workers already detected the formation of
long-lived iodine ate-complexes in iodine–magnesium exchange
reactions of 1,1-dihaloalkanes with Grignard reagents.6 Moreover,
the conversion of these intermediates into the corresponding
magnesium carbenoids appeared to be catalyzed by diverse
Table 2
Chlorohydrins produced via Scheme 1
Entry
1
ClCH2MgClÁLiCl
Aldehydea (3)
Condition
Product (4)
Yieldb (%)
90
CHO
OH
Cl
1.2 equiv
À78 °C, 30 min
3a
4a
Me
CHO
OH
Cl
Cl
Me
2
3
1.2 equiv
1.2 equiv
À78 °C, 30 min
À78 °C, 30 min
92
92
3b
4b
OH
CHO
3c
Me
4c
Me
OH
CHO
Me
Cl
4
5
6
1.5 equiv
1.5 equiv
1.2 equiv
À78 °C, 30 min
À78 °C, 30 min
À78 °C, 30 min
93
74
93
3d
4d
Me
MeO
MeO
MeO
CHO
3e
CHO
3f
OH
Cl
4e
OH
MeO
Cl
F
4f
F
CHO
OH
Cl
7
8
1.2 equiv
1.5 equiv
À78 °C to rt, 30 min
À78 °C, 30 min
86
85
3g
O2N
4g
O2N
Cl
N
O
CHO
CHO
N
OH
4h
3h
3i
Cl
9
1.5 equiv
1.5 equiv
À78 °C, 30 min
À78 °C, 30 min
90
94
O
S
OH
4i
Cl
CHO
10
S
3j
OH
4j
CHO
OH
Cl
11
12
13
1.5 equiv
2.0 equiv
2.0 equiv
À78 °C, 30 min
81
82
91
3k
4k
CHO
OH
Cl
À78 °C to rt, 30 min
À78 °C to rt, 30 min
3l
4l
OH
CHO
7
3m
Cl
7
4m
CHO
OH
9
Cl
Cl
14
15
2.0 equiv
2.0 equiv
À78 °C to rt, 30 min
À78 °C to rt, 30 min
74
90
3n
CHO
3o
9
4n
OH
4o
a
1 mmol Of the aldehyde.
Isolated yields.
b

R. H. V. Nishimura et al. / Tetrahedron Letters 54 (2013) 287–290
289
electrophiles.6b Thus, in our system, the use of excess of chloroi-
odomethane could contribute with the reaction by favoring the
formation of an iodine ate-complex of type [ClCH2–I–CH2Cl]
ÀMgCl+ÁLiCl.7 In the presence of aldehydes, this symmetric
intermediate could be converted into the reactive carbenoid
ClCH2MgClÁLiCl.
In summary, we have described the preparation of the mixed
lithium–magnesium carbenoid ClCH2MgClÁLiCl and investigated
its application in the synthesis of chlorohydrins. This reagent can
be easily generated in THF at temperatures between À60 °C to
À78 °C through the iodine–magnesium exchange reaction of the
‘turbo Grignard’ i-PrMgClÁLiCl with chloroiodomethane. ClCH2
MgClÁLiCl reacts well with a number of aldehydes to give the cor-
responding chlorohydrins in good yields. The scope of this method-
ology and its applicability toward the synthesis of biologically
active molecules are currently being investigated in our
laboratories.
The iodine–magnesium exchange reaction of 1 with i-PrMg
ClÁLiCl was also accomplished at À60 °C in THF. Further reaction
with benzaldehyde at the same temperature led to the formation
of 2-chloro-1-phenylethanol 4a with 95% conversion (Table 1, en-
try 6). In contrast, attempts to perform the reaction at higher
temperatures did not give good results. For example, when both
the iodine–magnesium exchange reaction and the reaction with
benzaldehyde were performed at À40 °C, the desired 2-chloro-1-
phenylethanol 4a was obtained in only 37% conversion (Table 1,
entry 7).
As observed in Table 1, conditions used in entry 5 appeared to be
the best for this reaction. Thus, a number of chlorohydrins were syn-
thesized in good yields through the reaction of ClCH2MgClÁLiCl with
different aldehydes at À78 °C (Scheme 1 and Table 2). Best product
yields were mostly obtained when 1.2–1.5 equiv of the carbenoid
were used. Similar to the results obtained by Villieras and cowork-
ers,8 which used a ClCH2Li-LiBr combination for the synthesis of
chlorohydrins (reactions were performed at À110 °C), no oxirane
formation was observed in our reactions and, consequently, purifi-
cation was easily achieved by column chromatography.9
Representative procedure: synthesis of 4a
i-PrMgClÁLiCl (0.95 mol/L, 1.3 mL, 1.2 mmol) was added to a
solution of chloroiodomethane (0.17 mL, 2.4 mmol) in THF (2 mL)
under nitrogen atmosphere at À78 °C, and the reaction mixture
was stirred for 10 min. After this time a solution of benzaldehyde
(0.11 g, 1 mmol) in THF (1 mL) was added to the reaction, and
the mixture was stirred for 30 min. After that, NH4Cl was added
(30 mL) and the reaction products were subjected to ethyl acetate
extraction (3 Â 30 mL). The combined organic extracts were dried
over anhydrous MgSO4 and the solvent was evaporated under re-
duced pressure. The residue was purified by column chromatogra-
phy on silica gel using hexane/ethyl acetate (4:1) as eluent,
affording the desired product 4a in 90% yield (light yellow oil).
Thus, the reaction of 1.2 equiv of ClCH2MgClÁLiCl with benzalde-
hyde led to the full conversion of the substrate within 30 min at
À78 °C. After purification, the 2-chloro-1-phenylethanol 4a was
isolated in 90% yield (Table 2, entry 1). Ring-substituted aromatic
aldehydes are also excellent substrates, thus the reaction of
1.2 equiv of ClCH2MgClÁLiCl with m- and p-tolualdehyde afforded
both 2-chloro-1-(m-tolyl)ethanol (4b) and 2-chloro-1-(p-tolyl)eth-
anol (4c) in 92% yields (Table 2, entries 2 and 3). In addition, full
conversion of o-tolualdehyde was achieved with 1.5 equiv of
ClCH2MgClÁLiCl and afforded the 2-chloro-1-(o-tolyl)ethanol (4d)
in 93% yield (Table 2, entry 4). The methodology employed herein
appears to be applicable for other electron-rich substrates such as
3,4-dimethoxybenzaldehyde, which gave 2-chloro-1-(3,4-dime-
thoxyphenyl)ethanol (4e) in 74% yield (Table 2, entry 5). Aromatic
aldehydes containing withdrawing groups such as 4-fluorobenzal-
dehyde and 4-nitrobenzaldehyde are also suitable substrates and
were fully converted into the corresponding chlorohydrins by
using 1.2 equiv of the reagent. After the purification step, 2-
chloro-1-(4-fluorophenyl)ethanol (4f) and 2-chloro-1-(4-nitro-
phenyl)-ethanol (4g) were isolated with yields of 93% and 86%,
respectively (Table 2, entries 6 and 7). Also of importance is the
fact that the methodology is compatible with heterocyclic alde-
hydes. In this context, the reaction of ClCH2MgClÁLiCl with piconil-
aldehyde (3h), furfural (3i) and 2-thiophenecarbaldehyde (3j) gave
the corresponding 2-chloro-1-(pyridin-2-yl)ethanol (4h) 2-chloro-
1-(furan-2-yl)ethanol (4i) and 2-chloro-1-(thiophen-2-yl)ethanol
(4j) with yields of 85%, 90% and 94%, respectively (Table 2, entries
8–10). Additionally, using the same reaction conditions, we found
that cinnamaldehyde (3k) was converted into the desired (E)-1-
chloro-4-phenylbut-3-en-2-ol (4k) in 81% yield (Table 2, entry
11). Alkyl aldehydes are also interesting substrates, thus the reac-
tion of heptanal (3l) with 1.5 equiv of ClCH2MgClÁLiCl gave the ex-
pected 1-chloro-2-octanol (4l) with 51% yield. In contrast, when
2 equiv of the carbenoid were used the desired alkyl chorohydrin
was isolated in 82% yield (Table 2, entry12). Similarly, reactions
of decanal (3m), dodecanal (3n) and cyclohexanecarboxaldehyde
(3o) with 2 equiv of ClCH2MgClÁLiCl allowed the isolation of the
corresponding 1-chloroundecan-2-ol (4m), 1-chlorotridecan-2-ol
(4n), and 2-chloro-1-cyclohexylethanol (4o) in 91%, 74%, and 90%
yields, respectively (Table 2, entries 13–15).
Acknowledgments
We are grateful to the Brazilian foundations FAPESP, CAPES and
CNPq for financial support.
References and notes
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5310; (d) Schulze, V.; Brönstrup, M.; Böhm, V. P. W.; Schwerdtfeger, P.;
146.9, 127.0, 123.8, 73.0, 50.3; LRMS (m/z,%): 201 (1), 252 (100), 106 (13), 77
(20); 2-chloro-1-(pyridin-2-yl)ethanol (4h): light yellow oil; 1H NMR (CDCl3,
300 MHz) d: 8.45–8.43 (m, 1H), 7.63 (td, J = 7.8 Hz, J = 1.8 Hz, 1H), 7.37 (d,
J = 8.0 Hz, 1H), 7.17–7.13 (m, 1H), 4.90 (dd, J = 6.0 Hz, J = 4.8 Hz, 1H), 3.79 (dd,
J = 11.0 Hz, J = 4.8 Hz, 1H), 3.69 (dd, J = 11.0 Hz, J = 6.0 Hz, 1H); 13C NMR (CDCl3,
75 MHz) d: 158.5, 148.4, 136.8, 122.9, 121.1, 72.9, 49.2; LRMS (m/z,%): 122 (39),
108 (100), 80 (17), 78 (47); 2-chloro-1-(furan-2-yl)ethanol (4i): light yellow oil;
1H NMR (CDCl3, 300 MHz) d: 7.30 (t, J = 1.5 Hz, 1H), 6.28–6.27 (m, 2H), 4.82 (dd,
J = 6.5 Hz, J = 5.0 Hz, 1H), 3.75 (dd, J = 11.4 Hz, J = 5.0 Hz, 1H), 3.70 (dd,
J = 11.4 Hz, J = 6.5 Hz, 1H), 3.11 (s, 1H); 13C NMR (CDCl3, 75 Hz) d: 152.6,
142.4, 110.3, 107.5, 65.9, 47.3; LRMS (m/z,%): 146 (11), 97 (100), 69 (14); 2-
chloro-1-(thiophen-2-yl)ethanol (4j): light yellow oil; 1H NMR (CDCl3, 400 MHz)
d: 7.30 (dd, J = 5.0 Hz, J = 1.8 Hz, 1H), 7.06–7.04 (m, 1H), 7.00 (dd, J = 5.2 Hz,
J = 3.6 Hz, 1H), 5.16 (ddd, J = 8.1 Hz, J = 4.0 Hz, J = 0.4 Hz, 1H), 3.81 (dd,
J = 11.2 Hz, J = 4.0 Hz, 1H), 3.75 (dd, J = 11.2 Hz, J = 8.1 Hz, 1H), 2.90 (br, 1H);
13C NMR (CDCl3, 100 MHz) d: 143.2, 126.9, 125.4, 124.7, 70.2, 50.4; LRMS (m/
z,%): 162 (7), 113 (100), 85 (48). (E)-1-chloro-4-phenylbut-3-en-2-ol (4k): light
yellow oil; 1H NMR (CDCl3, 500 MHz) d: 7.25–7.12 (m, 5H), 6.56 (d, J = 16.0 Hz,
1H), 6.06 (dd, J = 16.0 Hz, J = 6.0 Hz, 1H), 4.37 (dd, J = 7.0 Hz, J = 4.0 Hz, 1H), 3.54
(dd, J = 11.0 Hz, J = 4.0 Hz, 1H), 3.45 (dd, J = 11.0 Hz, J = 7.0 Hz, 1H), 2.98, (br,
1H); 13C NMR (CDCl3, 125 MHz) d: 136.0, 132.5, 128.5, 127.9, 127.3, 126.5, 72.1,
49.3; LRMS (m/z,%): 182 (12), 133 (100), 115 (40), 91 (23), 77 (27); 1-
chlorooctan-2-ol (4l): 1H NMR (CDCl3, 400 MHz) d: 3.84–3.78 (m, 1H), 3.64 (dd,
J = 11.2 Hz, J = 3.2 Hz, 1H), 3.48 (dd, J = 11.2 Hz, J = 7.2 Hz, 1H), 1.57–1.42 (m,
3H), 1.40–129 (m, 8H), 0.90–0.87 (m, 3H); 13C (CDCl3, 100 MHz) d: 71.4, 50.6,
34.2, 31.7, 29.1, 25.5, 22.5, 14.0. LRMS (m/z,%): 115 (19), 97 (81), 69 (22), 55
(100); 1-chlorotridecan-2-ol (4m): white solid; mp = 43.8 °C; 1H NMR (CDCl3,
400 MHz) d: 3.83–3.77 (m, 1H), 3.64 (dd, J = 11.2 Hz, J = 3.2 Hz, 1H), 3.48 (dd,
J = 11.2 Hz, J = 7.2 Hz, 1H), 2.10 (br, 1H), 1.56–1.49 (m, 2H), 1.32–1.26 (m, 18H),
0.88 (t, J = 7.2 Hz, 3H); 13C (CDCl3, 100 MHz) d: 71.4, 50.6, 34.2, 31.9, 29.7, 29.6,
29.5, 29.4 (2 C), 29.3, 25.5, 22.7, 14.1; LRMS (m/z,%): 185 (20), 140 (3), 125 (9),
111 (51), 97 (81), 83 (71), 69 (94), 55 (100); 1-chloroundecan-2-ol (4n): light
yellow oil; 1H NMR (CDCl3, 400 MHz) d: 3.76–3.70 (m, 1H), 3.56 (dd, J = 11.2 Hz,
J = 3.2 Hz, 1H), 3.40 (dd, J = 11.2 Hz, J = 7.2 Hz, 1H), 2.20 (br, 1H), 1.49–1.25 (m,
3H), 1.35–1.19 (m, 13H), 0.81 (t, J = 7.2 Hz, 3H); 13C (CDCl3, 100 MHz) d: 71.4,
50.5, 34.2, 31.8, 29.5 (3C), 29.3, 25.5, 22.6, 14.1; LRMS (m/z,%): 157 (20), 112 (3),
97 (41), 83 (100), 69 (60), 55 (76); 2-chloro-1-cyclohexylethanol (4o): light
yellow oil; 1H NMR (CDCl3, 400 MHz) d: 3.65–3.62 (m, 1H), 3.53–3.45 (m, 2H),
2.10 (br, 1H), 1.86–1.80 (m, 1H), 1.73–1.57 (m, 4H), 1.50–1.40 (m, 1H), 1.26–
0.93 (m, 6H); 13C (CDCl3, 100 MHz) d: 75.6, 49.0, 41.2, 28.9, 28.3, 26.2, 26.0, 25.8.
LRMS (m/z,%): 113 (34), 95 (100), 82 (17), 67 (34), 55 (59).
Schimeczek, M.; Hoffmann, H. W. Angew. Chem., Int. Ed. 1998, 37, 824.
7. The nature of the species involved in the reaction is currently being investigated
in our laboratories. A symmetric iodine-ate complex was already detected by
Hoffmann et al. in the iodine–magnesium exchange reaction of iodoform with i-
PrMgCl (see Ref. 6c).
8. Tzarhouni, R.; Kirschleger, B.; Rambaud, M.; Villieras, J. Tetrahedron Lett. 1984,
25, 835.
9. NMR and MS data: 2-chloro-1-phenylethanol (4a): light yellow oil; 1H NMR
(CDCl3, 500 MHz) d: 7.30–7.25 (m, 5H), 4.81 (dd, J = 9.0 Hz, J = 3.0 Hz, 1H), 3.66
(dd, J = 11.0 Hz, J = 3.0 Hz, 1H), 3.57 (dd, J = 11.0 Hz, J = 9.0 Hz, 1H), 2.68 (br, 1H);
13C NMR (CDCl3, 125 MHz) d: 139.9, 128.6, 128.4, 126.0, 74.0, 50.8; LRMS (m/
z,%): 156 (5), 107 (100), 79 (70), 77 (46); 2-chloro-1-(m-tolyl)ethanol (4b): light
yellow oil; 1H NMR (CDCl3, 300 MHz) d: 7.20–7.04 (m, 4H), 4.76 (dd, J = 8.4 Hz,
J = 3.0 Hz, 1H), 3.64 (dd, J = 11.1 Hz, J = 3.0 Hz, 1H), 3.54 (dd, J = 11.1 Hz,
J = 8.4 Hz, 1H), 2.68 (br, 1H), 2.28 (s, 3H); 13C NMR (CDCl3, 75 Hz) d: 139.8,
138.3, 129.1, 128.5, 126.6, 123.1, 74.1, 50.8, 21.4; LRMS (m/z,%): 170 (7), 121
(100), 93 (65), 91 (50), 77 (34); 2-chloro-1-(p-tolyl)ethanol (4c): light yellow oil;
1H NMR (CDCl3, 400 MHz) d: 7.16–7.06 (m, 4H), 4.71 (dd, J = 8.4 Hz, J = 3.9 Hz,
1H), 3.58 (dd, J = 11.1 Hz, J = 3.9 Hz, 1H), 3.50 (dd, J = 11.1 Hz, J = 8.4 Hz, 1H),
2.65 (br, 1H), 2.25 (s, 3H); 13C NMR (CDCl3, 100 MHz) d: 138.1, 136.9, 129.2,
125.9, 73.8, 50.7, 21.1; LRMS (m/z,%): 170 (5), 121 (100), 93 (41), 91 (42), 77
(30); 2-chloro-1-(o-tolyl)ethanol (4d): light yellow oil; 1H NMR (CDCl3, 500 MHz)
d: 7.28–7.25 (m, 1H), 7.02–7.00 (m, 2H), 6.95 (m, 1H), 4.84 (dd, J = 9.0 Hz,
J = 3.5 Hz, 1H), 3.43 (dd, J = 11.5 Hz, J = 3.5 Hz, 1H), 3.34 (dd, J = 11.5 Hz,
J = 9.0 Hz, 1H), 2.90 (br, 1H), 2.10 (s, 3H); 13C NMR (CDCl3, 125 MHz) d: 138.0,
134.6, 130.4, 128.0, 126.2, 125.4, 70.7, 49.5, 18.8; LRMS (m/z,%): 170 (5), 121
(100), 93 (52), 91 (47), 77 (34); 2-chloro-1-(3,4-dimethoxyphenyl)ethanol (4e):
light yellow oil; 1H NMR (CDCl3, 300 MHz) d: 6.95–6.84 (m, 3H), 4.85 (dd,
J = 8.7 Hz, J = 3.6 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.72 (dd, J = 11.4 Hz,
J = 3.6 Hz, 1H), 3.64 (dd, J = 11.4 Hz, J = 8.7 Hz, 1H); 13C NMR (CDCl3, 75 Hz) d:
165.3, 149.2, 132.5, 118.5, 111.1, 109.1, 73.9, 56.0, 55.9, 50.9; LRMS (m/z,%): 216
(22), 167 (100), 139 (72), 124 (25), 77 (16); 2-chloro-1-(4-fluorophenyl)ethanol
(4f): 1H NMR (CDCl3, 500 MHz) d: 7.24 (dd, J = 9.0 Hz, J = 5.5 Hz, 2H), 6.95 (t,
J = 9.0 Hz, 2H), 4.76 (dd, J = 8.5 Hz, J = 3.5 Hz, 1H), 3.59 (dd, J = 11.5 Hz, J = 3.5 Hz,
1H), 3.50 (dd, J = 11.5 Hz, J = 8.5 Hz, 1H), 2.98 (br, 1H); 13C NMR (CDCl3,
125 MHz) d: 162.5 (d, J = 245.2 Hz), 135.7 (d, J = 3.1 Hz), 127.7 (d, J = 8.1 Hz),
115.4 (d, J = 21.4 Hz), 73.3, 50.5; LRMS (m/z,%): 174 (3), 125 (100), 97 (50), 95
(15), 77 (23); 2-chloro-1-(4-nitrophenyl)ethanol (4g): reddish solid; 1H NMR
(CDCl3, 500 MHz) d: 8.17 (d, J = 9.0 Hz, 2H), 7.52 (d, J = 8.5 Hz, 2 H), 4.97 (dd,
J = 7.5 Hz, J = 3.0 Hz, 1H), 3.72 (dd, J = 11.0 Hz, J = 3.3 Hz, 1H), 3.58 (dd,
J = 11.0 Hz, J = 7.5 Hz, 1H), 2.85 (br, 1H); 13C NMR (CDCl3, 125 Hz) d: 147.9,