Convenient fluorination of nitro and nitrile compounds with Selectfluor

Article abstract of DOI:10.1016/j.tetlet.2005.05.056

A variety of nitro and nitrile compounds were fluorinated in good yields by Selectfluor under mild conditions. For these transformations to be successful, it is crucial to select proper amounts of an appropriate base as a function of the properties of the substrate and also to use Selectfluor only as required.

Full text of DOI:10.1016/j.tetlet.2005.05.056

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4905–4909
Convenient fluorination of nitro and nitrile compounds
with Selectfluor
Weimin Peng and JeanÕne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
Received 19 April 2005; revised 4 May 2005; accepted 6 May 2005
Available online 3 June 2005
Abstract—A variety of nitro and nitrile compounds were fluorinated in good yields by Selectfluor under mild conditions. For these
transformations to be successful, it is crucial to select proper amounts of an appropriate base as a function of the properties of the
substrate and also to use Selectfluor only as required.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The remarkable synthetic importance of nitro com-
pounds is based on two facts: (1) nitro compounds, espe-
cially aromatic nitro compounds, are valuable
precursors for azo dyes and explosives; and (2) their easy
availability and transformation into a variety of other
diverse functionalities makes them important reagents
for syntheses of complex target molecules.1 The wide-
spread interest in halogenated nitro compounds also
stems from their pronounced antimicrobial and insecti-
cidal activity.2 Although halogenation of nitroalkanes
is especially well known and simple,3 there are few satis-
factory methods for introducing fluorine or fluorine-
containing groups into nitro compounds.4 The usual
method is reaction of nitronate salts with fluorine5 or
perchloryl fluoride.6 However, these reagents are not
as readily used as off-the-shelf reagents, and their high
reactivities while offering little or no selectivity has cur-
tailed their use. In a rather novel process, fluorination of
nitro compounds with acetyl hypofluorite was reported.7
However, this requires the preparation of a rather unsta-
ble fluorinating reagent, which must be utilized
immediately.
amides,9 and N-fluoroquinuclidinium fluoride10 for fluo-
rination of nitro compounds was studied, but each of
these methods was examined with only a small number
of nitro compounds. Currently, 1-chloromethyl-4-flu-
oro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluorobo-
rate) (SelectfluorTM, F-TEDA-BF4) is a commercially
available, powerful electrophilic fluorinating agent,
which is effective for site-selective fluorination of a vari-
ety of organic molecules.11 In order to develop a conve-
nient method for introducing fluorine into nitro
compounds with the potential for modifying the proper-
ties of some traditional high energy nitro compounds,
the base mediated reactions of nitro compounds with
Selectfluor were investigated.
The reaction of phenyl nitromethane 1a with Selectfluor
did not proceed under neutral conditions even when
subjected to heat or microwave radiation. It was clear
that in order to carry out this transformation an anionic
center would have to be formed initially. Potassium
hydroxide was an adequate base to cause the reaction
to occur. A mixture of acetonitrile and water (1:1) was
the best choice of solvent in which Selectfluor, KOH,
and 1a were dissolved. This reaction was carried out in
a stepwise process. After stirring the base and 1a for
2–3 hours in order to form the corresponding potassium
nitronate salt, Selectfluor was added in one portion, and
stirring was continued for 12 h to complete the reaction.
In most cases, a mixture of monofluorinated 2a, difluo-
rinated 3a, and starting material 1a was found. The nat-
ure of the base and amounts of base and Selectfluor were
controlled to guide the outcome of the reaction. After a
series of runs (Table 1), undertaken by balancing the
More convenient, more efficient, and more straightfor-
ward methods for introduction of fluorine into nitro
compounds are highly desired. The use of a variety of
N–F-containing electrophilic fluorinating reagents
including perfluoropiperidine,8 N-fluoro-N-alkyl-sulfon-
Keywords: Fluorination; Nitro compounds; Nitrile; Selectfluor.
*
Corresponding author. Tel.: +1 208 885 6215; fax: +1 208 885
9146; e-mail: jshreeve@uidaho.edu
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.056

4906
W. Peng, J. M. Shreeve / Tetrahedron Letters 46 (2005) 4905–4909
Table 1. Optimization of the reaction conditions between 1a and Selectfluor
F
F F
Ph NO2
Solvent
1a
+
1a
+
Selectfluor
+
Base
Ph NO2
2a
3a
1
1
1
1
1
1
1
1
1
None
CH3CNa
No reaction
0
1
KOH (1)
KOH (1)
KOH (2)
KOH (2)
KOH (1.5)
TBAH (2)
TBAH (2)
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN
10 (72%)b
10
:
:
:
:
:
:
:
:
:
:
:
:
:
:
1
2
0
1.1
1.6
0
1
10
10 (70%)b
13 (81%)b
2
2
2.5
1
1.5
1
0.1
0c
0
0
1
1
2
CH3CN
2
a Reflux or irradiation by microwave.
b Isolated yield.
c Complicated reaction.
yield of the intended product 2a, the chemoselectivity
(ratio of 2a to 3a) and conversion of 1a, the optimized
reaction conditions (highlighted in Table 1) using
1.5 equiv of KOH and Selectfluor was found, which
led to the monofluorinated product 2a in high yield,
although minor amounts of the difluorinated species
3a and a trace amount of starting material 1a was
observed in the crude product mixture prior to column
separation.
required for complete conversion of the starting material
resulting in the monofluorinated compound as the major
product. However, when the same amounts of KOH
and Selectfluor were used in the reaction with 4-nitro-
phenyl nitromethane 1d, the reaction exhibited poor
chemoselectivity for both monofluorinated and difluori-
nated products in a ratio of 2:1. Under similar condi-
tions with benzoyl nitromethane 1e, the mono-
fluorinated product 2e was obtained in very low yield
although most of the starting material had been con-
sumed. This reaction did not give the difluorinated
product but rather benzoic acid was found as a low yield
by-product. If 1 equiv of each KOH and Selectfluor
were used (Table 2), 2e was obtained in 40% yield
accompanied by a 20% yield of benzoic acid. Since diflu-
oronitromethane, which would be the expected hydro-
lyzed product of the difluorinated compound, was not
detected by 19F NMR spectra in the reaction mixture,
the following decarboxylation14 and oxidation process
is proposed (Scheme 1) in order to rationalize the forma-
Further experiments led to the conclusion that there
were no general reaction conditions that would work
well for all substrates.12 Depending on the substrate, a
different base, solvent system, and quantity of base
and Selectfluor were required for the intended transfor-
mation to occur. The optimized reaction results for each
substrate are given in Table 2.13
For most of the aryl substituted nitromethane com-
pounds (1a–c), 1.5 equiv of KOH and Selectfluor were
Table 2. Monofluorination of nitro compound 1 with Selectfluor
F
F F
1) Base/Solvent
+
+
R
NO2
R
NO2
R
NO2
R
NO2
2) Selectfluor
1
2
3
1
R
Basea
S–Fb
Solvent
2:3:1
2c
19F NMRd
1a Ph
KOH (1.5)
KOH (1.5)
KOH (1.5)
KOH (1.0)
KOH (1.0)
TBAHf (1.5)
TBAH (1.5)
TBAH (1.5)
NaH (1.1)
1.5
1.5
1.5
1
CH3CN/H2Oe
CH3CN/H2Oe
CH3CN/H2Oe
CH3CN/H2Oe
CH3CN/H2Oe
CH3CN/H2Og
CH3CN/H2Og
CH3CN/H2Og
DMF
13:1:0.1
12.4:1:0
5.2:1:0
7:1:0
81
79
64
83
40
89
98
88
70
30
À139.9
À137.3
À140.9
À142.9
À144.8
À145.8
À146.7
À147.5
À148.0
À153.9h
À163.1h
1b 4-MeOC6H4–
1c 4-BrC6H4–
1d 4-O2NC6H4–
1e PhCO–
1
1:0:0
33:1:1
1:0:0
1f PhCH2–
1.5
1.5
1.5
1.1
1.5
1g C11H23
–
1h CH3CO(CH2)2–
1i n-BuO2C(CH2)2–
1j PhC(OH)–
37:1:0.5
6:0:1
20:0:1
KOH (1.5)
CH3CN/H2Og
a Equivalents.
b Selectfluor, equivalents.
c Yield, %. All compounds were confirmed by NMR.
d d (ppm).
e 1:1 ratio.
f Tetrabutylammonium hydroxide.
g 2:1 ratio.
h Two diastereomers were produced in a ratio of 10:8.

W. Peng, J. M. Shreeve / Tetrahedron Letters 46 (2005) 4905–4909
4907
O
O
O
Selectfluor
NO2
Selectfluor
[O]
OH
CO2H
Decarboxylation
[O]
1e
Scheme 1.
tion of benzoic acid. Selectfluor can also behave as an
oxidizing agent, and nitro compounds are labile to oxi-
dation to aldehydes or acids by some moderately strong
oxidizers.1 It has been reported that some secondary and
primary nitro compounds could be oxidized to ketones
and aldehydes, respectively, by using FClO3.6d The pro-
posed ketoacid intermediate was not detected.
chemistry. Some direct fluorination methods by treat-
ment of the corresponding carbanion species of nitrile
compounds with electrophilic fluorinating agents such
as FClO3,16 N-fluorobenzene disulfonimide,17 and fluo-
rine18 have been investigated. However, we looked for
a general method to fluorinate a variety of nitrile com-
pounds with Selectfluor.
For alkyl substituted nitromethanes 1f–h, tetrabutylam-
monium hydroxide (TBAH), was used. When the ratio
of acetonitrile and water was changed to 2:1, the reac-
tions gave the monofluorinated products 2f–h in high
yields and only traces of unreacted starting material
and difluorinated products were observed. In the case
of the nitro ester 1i, since the ester moiety, whether in
the starting material or in the product, underwent vigor-
ous hydrolysis when either KOH or TBAH was used as
base, this reaction was carried out using anhydrous
DMF as solvent with NaH as base. Perhaps due to the
hydroxyl functionality, the reaction of nitro alcohol 1j
was very complicated and gave the desired product only
in low yield.
Since protons alpha to the nitrile group have lower acid-
ity than those in nitro compounds, bases such as KOH
and TBAH did not promote the reaction of a nitrile
compound with Selectfluor. Although sodium hydride
did work in the reaction of a-benzoyl acetonitrile (4),19
it was a surprise to find that the reaction gave a mixture
of difluorinated (19F d À92.04 ppm), and monofluori-
nated products (19F d À191.70 ppm) and starting mate-
rial in a ratio of 10:4:7 with difluorinated product (5) as
the major product even when 1 equiv each of NaH and
Selectfluor were used in the reaction (Scheme 2). The
second fluorination step from monofluorinated product
to difluorinated product occurs more readily than the
first step fluorination of the starting material. Thus,
the monofluorinated product was not obtained. Finally,
4 reacted with 2.2 equiv each of NaH and Selectfluor to
furnish the difluorinated product 5 exclusively in 60%
yield (Scheme 2). Only a very strong base such as BuLi
Under the same conditions using KOH as base, we
found that the monofluorinated compound 2a could un-
dergo further fluorination to give the difluorinated prod-
uct 3a in 73% yield. Thus, if another portion of base and
Selectfluor was added to the same reaction mixture after
the first monofluorination step of 1a was completed, the
difluorinated product 3a could be directly obtained in
one pot through two stages. This two-stage process15
gave the difluorinated products of 1a–d as expected in
a straightforward manner although in a moderate yield
(Table 3).
O
O
1) NaH (2.2 eq.)/THF, r.t.
2) Selectfluor (2.2 eq.), r.t.
CN
CN
F F
5
4
60%
F
O
1) BuLi (1 eq.)/THF, -78 C
CN
CN
O
2) Selectfluor (1 eq.), -78 C to r.t.
Given the success of fluorinating nitro compounds, we
attempted, by using the same method, to introduce fluo-
rine into some nitrile compounds since these materials
also play a very important role in synthetic organic
6
7
35%
Scheme 2.
Table 3. Two-stage difluorination of nitro compound 1 with Selectfluor
F F
NO2
F
1) two aliquots base
NO2
+
NO2
2) two aliquots Selectfluor
R
CH3CN/H2O (1:1)
R
R
1a-d
3a-d
2a-d
Entry
1
Basea
S–Fb
3:2
3c
19F NMRd
1
2
3
4
1a H
1.5
1.5
1.5
1
1.5
1.5
1.5
1
1:0
5:1
1:0
10:1
47
41
28
66
À86.8
À85.9
À86.8
À86.8
1b MeO–
1c Br
1d NO2
a KOH, equivalents.
b Selectfluor, equivalents.
c Isolated yield, %.
d d (ppm).

4908
W. Peng, J. M. Shreeve / Tetrahedron Letters 46 (2005) 4905–4909
Burkart, M. D.; Vincent, S. P.; Wong, C.-H. Angew.
Chem., Int. Ed. 2005, 44, 192; (c) Banks, R. E. J. Fluorine
Chem. 1998, 87, 1; (d) Stavber, S.; Zupan, M. Acta Chim.
Slov. 2005, 52, 13.
promoted the fluorination of 4-methylbenzyl cyanide
(6). When 1 equiv of BuLi was used, the reaction gave
only the corresponding monofluorinated product 7
(19F d À164.38 ppm) in 30% yield (Scheme 2) along with
other by-products. About 50% of the starting material
was recovered. Increasing the quantity of BuLi resulted
in lower starting material conversion and more by-prod-
uct formation. Efforts to find the conditions to fully con-
vert the starting material and improve the reaction yield
are still in progress.
12. Compounds 1a, 1c, 1f, and 1g were prepared according to:
(a) Kornblum, N.; Larson, H. O.; Blackwood, R. K.;
Mooberry, D. D.; Oliveto, E. P.; Graham, G. E. J. Am.
Chem. Soc. 1956, 78, 1497; 1a could also be prepared
according to: (b) Ballini, R.; Barboni, L.; Giarlo, G. J.
Org. Chem. 2004, 69, 6907; 1b was synthesized in low yield
according to: (c) Bose, D. S.; Vanajatha, G. Synth.
Commun. 1998, 28, 4531; 1d: (d) Kornblum, N.; Smiley,
R. A.; Blackwood, R. K.; Iffland, D. C. J. Am. Chem. Soc.
1955, 77, 6269; 1e: (e) Long, L. M.; Troutman, H. D. J.
Am. Chem. Soc. 1949, 71, 2469; 1h and 1i: (f) Grossman,
R. B.; Comesse, S.; Rasne, R. M.; Hattori, K.; Delong, M.
N. J. Org. Chem. 2003, 68, 871; 1j: (g) Beebe, X.; Schore,
N. E.; Kurth, M. J. J. Org. Chem. 1995, 60, 4196.
13. General procedure for monofluorination of nitro com-
pound 1 (1d as an example): 1.1 mL of aqueous 0.5 N
KOH solution was added to the mixture of nitrophenyl-
nitromethane 1d (0.55 mmol, 100 mg) in acetonitrile
(5 mL) and water (5 mL). The reaction mixture was
stirred at 25 ꢁC for 2 h. Selectfluor (0.55 mmol, 205 mg)
was added to the reaction mixture in one portion, and
stirring was continued for 12 h. The resulting mixture was
poured into 20 mL water and extracted with methylene
chloride (3 · 15 mL). The extracts were washed with
20 mL brine, dried (Na2SO4), and filtered. The solvent
was evaporated and the resulting residue was chromato-
graphed with n-hexane/ethyl acetate/CH2Cl2 (5:1:1) as
eluent to give the monofluorinated nitro compound 2d.
Compound 2b: 4-methoxyphenylfluoronitromethane. Pale
yellow oil (n-hexane/AcOEt (5/1), Rf 0.3). 1H NMR
(300 MHz, CDCl3) d 7.56 (d, J = 8.7 Hz, 2H), 6.99 (d,
J = 8.7 Hz, 2H), 6.56 (d, J = 48.4 Hz, 2H), 3.86 (s, 3H).
19F NMR (282.5 MHz, CDCl3) d À137.32. 13C NMR
(75.5 MHz, CDCl3) d 163.3, 129.2 (d, J = 5.9 Hz), 123.3
(d, J = 21.8 Hz), 115.4, 111.1 (d, J = 238.4 Hz), 56.3. GC–
MS (EI) 154 (M+ÀMeO), 140, 139, 124, 109, 96, 91, 70,
63, 50, 39. IR (KBr) 2939, 2843, 1612, 1574, 1516, 1373,
1305, 1257, 1207, 1177, 1095, 1028, 867, 835, 795, 751, 710,
584, 525 cmÀ1. Anal. Calcd for C8H8FNO3: C, 51.90; H,
4.36; N, 7.56. Found: C, 52.00; H, 4.45; N, 7.54.
In conclusion, the reactions of a variety of nitro com-
pounds with Selectfluor were investigated. By choosing
an appropriate base as a function of the properties of
the substrate and using proper quantities of the base
and Selectfluor, these compounds could be monofluori-
nated or difluorinated in good to high yield with nearly
complete conversion. The study for efficient fluorination
of nitrile compounds is continuing.
Acknowledgments
We gratefully acknowledge the support of the National
Science Foundation (Grant CHE-0315275), AFOSR
(Grant F49620-03-1-0209), and ONR (Grant N00014-
02-1-0600).
References and notes
1. Ono, N. The Nitro Group in Organic Synthesis; Wiley-
VCH: New York, 2001.
2. (a) Metcalf, R. L. Organic Insecticides: Their Chemistry
and Mode of Action; Interscience: New York, 1955; p 134;
(b) Ivanov, Y. Y.; Brell, B. K.; Postnova, L. B.; Martinov,
Y. B. Khim. Pharm. J. 1986, 968; (c) Cartwright, D.
Recent Developments in Fluorine-Containing Agrochem-
icals. In Organofluorine Chemistry—Principles and Com-
mercial Applications; Banks, R. E., Smart, B. E., Tatlow, J.
C., Eds.; Plenum Press: New York, 1996; pp 237–262; (d)
Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
New York, 2004; pp 271–275.
Compound 2h: 5-fluoro-5-nitro-2-pentanone. Clear liquid
(n-hexane/AcOEt (3/1), Rf 0.3). 1H NMR (300 MHz,
CDCl3) d 5.96 (ddd, J = 50.5, 6.0, 4.9 Hz, 1H), 2.73–2.36
(m, 4H), 2.22 (s, 3H). 19F NMR (282.5 MHz, CDCl3) d
À147.46 (dt, J = 50.5, 22.6 Hz). 13C NMR (75.5 MHz,
3. Noble, P., Jr.; Borgardt, F. G.; Reed, W. L. Chem. Rev.
1964, 61, 19.
4. For a review, see: Adolph, H. G.; Koppers, W. M.
Aliphatic Fluoronitro Compounds. In Nitro Compounds;
Feuer, H., Nielsen, A. T., Eds.; VCH: New York, 1990.
5. (a) Baum, K. J. Org. Chem. 1970, 35, 846; (b) Grakauskas,
V.; Baum, K. J. Org. Chem. 1968, 33, 3080.
CDCl3)
d 206.1, 110.8 (d, J = 238.8 Hz), 36.8 (d,
J = 4.0 Hz), 30.7, 27.9 (d, J = 20.1 Hz). GC–MS (EI) 134
(M+ÀO+1), 103, 87, 73, 59, 43, 39. IR (KBr) 2925, 2360,
2341, 1719, 1573, 1427, 1370, 1359, 1170, 1130 cmÀ1
.
Anal. Calcd for C5H8FNO3: C, 40.27; H, 5.41; N, 9.39.
Found: C, 40.62; H, 5.30; N, 9.31.
14. Wang, J.; Scott, A. I. J. Chem. Soc., Chem. Commun.
1995, 2399.
6. (a) Takeuchi, Y.; Ogura, H.; Kanada, A.; Koizumi, T. J.
Org. Chem. 1992, 57, 2196; (b) Lorand, J. P.; Urban, J.;
Overs, J.; Ahmed, Q. A. J. Org. Chem. 1969, 34, 4176; (c)
Takeuchi, Y.; Nagata, K.; Koizumi, T. J. Org. Chem.
1989, 54, 5453; (d) Shechter, H.; Roberson, E. B., Jr. J.
Org. Chem. 1960, 25, 175; (e) Kamlet, M. J.; Adolph, H.
G. J. Org. Chem. 1968, 33, 3073.
7. Rozen, S.; Bar-Haim, A.; Mishani, E. J. Org. Chem. 1994,
59, 6800.
8. Banks, R. E.; Williamson, O. E. Chem. Ind. (London)
1964, 1864.
9. Barnette, W. E. J. Am. Chem. Soc. 1984, 106, 452.
10. Banks, R. E.; DuBoisson, R. A.; Tsiliopoulos, E. J.
Fluorine Chem. 1986, 32, 461.
11. For reviews, see: (a) Singh, R. P.; Shreeve, J. M. Acc.
Chem. Res. 2004, 37, 31; (b) Nyffeler, P. T.; Duron, S. G.;
15. General procedure for two-stage difluorination of nitro
compound 1d (as a example): 1.1 mL aqueous 0.5 M KOH
was added to the mixture of nitrophenylnitromethane 1d
(0.55 mmol, 100 mg) in acetonitrile (5 mL) and water
(5 mL). The reaction mixture was stirred at 25 ꢁC for 2 h.
Selectfluor (0.55 mmol, 205 mg) was added in one portion,
and the mixture was stirred for 3 h. Another quantity of
1.1 mL of aqueous 0.5 M KOH and Selectfluor (0.55
mmol, 205 mg) were added to the reaction mixture again
with a 2 h interval. Stirring was continued overnight at
25 ꢁC. The resulting mixture was poured into 20 mL water
and extracted with methylene chloride (3 · 15 mL). The

W. Peng, J. M. Shreeve / Tetrahedron Letters 46 (2005) 4905–4909
4909
extracts were washed with 20 mL brine, dried (Na2SO4),
and filtered. The solvent was evaporated to dryness and
the resulting residue was chromatographed with n-hexane/
ethyl acetate/CH2Cl2 (10:1:1) as eluent to give the diflu-
orinated nitro compound 3d.
16. (a) Schaub, R. E.; Kissman, H. M.; Weiss, M. J. J. Org.
Chem. 1964, 29, 2775; (b) Ridge, D. N.; Hanifin, J. W.;
Harten, L. A.; Johnson, B. D.; Menschik, J.; Nicolau, G.;
Sloboda, A. E.; Watts, D. E. J. Med. Chem. 1979, 22,
1385; (c) Bardin, V. V.; Furin, G. G.; Yakobson, G. G.
Zh. Org. Khim. 1984, 20, 567.
17. (a) Davis, F. A.; Han, W.; Murphy, C. K. J. Org. Chem.
1996, 60, 4730; (b) Kotoris, C. C.; Chen, M.-J.; Taylor, S.
D. J. Org. Chem. 1998, 63, 8052; (c) Umemoto, T.;
Fukami, S.; Tomizawa, G.; Harasawa, K.; Kawada, K.;
Tomita, K. J. Am. Chem. Soc. 1990, 112, 8563.
18. Chambers, R. D.; Hutchinson, J. J. Fluorine Chem. 1998,
92, 45.
Compound 3d: 4-nitrophenyldifluoronitromethane. White
solid (mp 81–83 ꢁC, n-hexane/AcOEt/CH2Cl2 (5:1:1), Rf
1
0.3). H NMR (300 MHz, CDCl3) d 8.42 (d, J = 8.6 Hz,
2H), 8.01 (d, J = 8.6 Hz, 2H). 19F NMR (282.5 MHz,
CDCl3) d À86.78. 13C NMR (75.5 MHz, CDCl3) d 151.8,
133.9 (t, J = 25.8 Hz), 128.7 (t, J = 5.3 Hz), 125.2, 121.3 (t,
J = 286.1 Hz). GC–MS (EI) 172 (M+ÀNO2), 156, 142,
126, 114, 107, 88, 75, 63, 50, 38. IR (KBr) 3117, 2963,
1948, 1811, 1615, 1599, 1533, 1413, 1352, 1296, 1262, 1217,
1093, 1014, 954, 859, 819, 707, 462, cmÀ1. Anal. Calcd for
C7H4F2N2O4: C, 38.55; H, 1.85; N, 12.84. Found: C,
38.57; H, 2.07; N, 12.66.
19. Compound 4 was prepared according to the literature
method: Polivka, Z.; Holubek, J.; Svatek, E.; Metys, J.;
Protiva, M. Collect. Czech. Chem. Commun. 1984, 49,
621.