Extending the series of p-substituted tetrafluorobenzoic acids: synthesis, properties and structure

Article abstract of DOI:10.1016/j.jfluchem.2017.03.002

The synthesis of the derivatives of p-aminotetrafluorobenzoic acid, p-H₂NC₆F₄CO₂H (2b), by hydrolysis, acylation or interaction with aldehydes was developed giving H₂NC₆F₄CO₂K (2a), C₆F₅C(O)N(H)C₆F₄CO₂Et (3) and (E)-ArCH[dbnd]NC₆F₄CO₂Et (4–11). The chemical derivatization of tetrafluoroterephthalic acid, p-HO₂CC₆F₄CO₂H (12), by hydrolysis, etherification and reduction was performed giving a number of symmetrical X(O)CC₆F₄C(O)X (13–15; X?=?Cl, NEt₂, OMe) or unsymmetrical YC₆F₄CO₂Me (15a–b, 16, 18–21; Y?=?CO₂K, CO₂H, CH₂OH, C(O)Cl, C(O)C₆H₃(i-Pr)₂, CO₂CH₂C₆F₄CO₂Me, CO₂C₆H₄Bu-t), HOCH₂C₆F₄CO₂H (17), [MeO₂CC₆F₄]₂Y (22, 23; Y?=?OCH₂CH₂O, N(H)C₆H₄N(H)) compounds. All substances were thoroughly investigated by spectroscopic methods (multinuclear NMR and IR spectroscopy, mass-spectrometry). The molecular structures of p-H₂NC₆F₄CO₂Et (2) and p-HO₂CC₆F₄CO₂Me (15b) have been determined by X-ray diffraction analysis.

Full text of DOI:10.1016/j.jfluchem.2017.03.002

Accepted Manuscript
Title: Extending the series of p-substituted tetrafluorobenzoic
acids: Synthesis, properties and structure
Author: Kirill V. Zaitsev Yuri F. Oprunenko Elmira Kh.
Lermontova Andrei V. Churakov
PII:
S0022-1139(17)30044-1
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2017.03.002
FLUOR 8952
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
30-1-2017
3-3-2017
4-3-2017
Please cite this article as: K.V. Zaitsev, Y.F. Oprunenko, E.Kh. Lermontova,
A.V. Churakov, Extending the series of p-substituted tetrafluorobenzoic acids:
synthesis, properties and structure, Journal of Fluorine Chemistry (2017),
http://dx.doi.org/10.1016/j.jfluchem.2017.03.002
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Extending the series of p-substituted tetrafluorobenzoic acids: synthesis, properties
and structure
Kirill V. Zaitsev,a, * Yuri F. Oprunenko,a Elmira Kh. Lermontova,b Andrei V. Churakovb
aDepartment of Chemistry, M.V. Lomonosov Moscow State University, Leninskye Gory 1, 3,
Moscow 119991, Russia
bN.S. Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of
Sciences, Leninsky pr., 31, Moscow, Russia
∗Corresponding author. Tel.: +7-495-939-3887; fax: +7-495-939-0067
e-mail: zaitsev@org.chem.msu.ru
Abstract: The synthesis of the derivatives of p-aminotetrafluorobenzoic acid, p-
H2NC6F4CO2H (2b), by hydrolysis, acylation or interaction with aldehydes was developed
giving H2NC6F4CO2K (2a), C6F5C(O)N(H)C6F4CO2Et (3) and (E)-ArCH=NC6F4CO2Et (4-11).
The chemical derivatization of tetrafluoroterephthalic acid, p-HO2CC6F4CO2H (12), by
hydrolysis, etherification and reduction was performed giving a number of symmetrical
X(O)CC6F4C(O)X (13-15; X = Cl, NEt2, OMe) or unsymmetrical YC6F4CO2Me (15a-b, 16, 18-
21; Y = CO2K, CO2H, CH2OH, C(O)Cl, C(O)C6H3(i-Pr)2, CO2CH2C6F4CO2Me, CO2C6H4Bu-t),
HOCH2C6F4CO2H (17), [MeO2CC6F4]2Y (22, 23; Y = OCH2CH2O, N(H)C6H4N(H))
compounds. All substances were thoroughly investigated by spectroscopic methods
(multinuclear NMR and IR spectroscopy, mass-spectrometry). The molecular structures of p-
H2NC6F4CO2Et (2) and p-HO2CC6F4CO2Me (15b) have been determined by X-ray diffraction
analysis.
Keywords: tetrafluoroaromatics; p-aminotetrafluorobenzoic acid; tetrafluoroterephthalic
acid; perfluorobenzoates; X-ray diffraction analysis
1. Introduction
Application of derivatives of fluorine containing carboxylic acids is widely known in
modern organic [1], coordination [2] and inorganic [3] synthesis, bioorganic chemistry [4],
1
Page 1 of 26

surface chemistry [5], photoaffinity labeling [6], as potential drugs [7], semiconductors [8],
liquid crystals [9] and other materials with useful properties [10]. Thus, elaboration of synthetic
ways to modified para-substituted tetrafluorobenzoates may be regarded as an actual
fundamental and applied task. Elaboration of convenient ways to these derivatives containing
OH, NH, HO2C-groups suitable for subsequent introduction of peptides, sugars, metals etc. is
also an actual challenge. In this work in continuation of our research in organofluorine
compounds [11] and widening the series of tetrafluorobenzoates and their derivatives [12]
especially for carboxylate complexes [13], the related compounds containing substituted p-
aminotetrafluorobenzoic and tetrafluoroterephthalic acid cores are described.
2. Results and Discussion
2.1.
Derivatives of p-aminotetrafluorobenzoic acid
Examination of the literature indicated that very few convenient ways for substituted
aminotetrafluorobenzoic acids were available. In this work the key intermediate for subsequent
synthesis, known [14] ethyl ester 2, was obtained by reduction of the azido group in 1 by SnCl2
(for detailed procedure see Experimental part). Such way of reduction is very easy to perform
and utilizes the accessible and cheap reagent suitable for application in the presence of other
reductable [15] groups (compare with propylene dithiol [16] or H2/Pd [6b]). Subsequent alkaline
hydrolysis by KOH in dry EtOH allowed to isolate known potassium salt 2a [17] without
possible decarboxylation. Under acidic hydrolysis 2a gave free known [14, 18] acid 2b (Scheme
1). It should be noted that compounds 2a and 2b are obtained by the new ways and fully
characterized by NMR as well as 2. The synthetic scheme presented here may be used for the
synthesis of other substituted derivatives.
Scheme 1. Synthesis of p-aminotetrafluorobenzoic acid.
All these reactions proceed smoothly giving target compounds in high yields (88-92 %)
without possible additional F atoms substitution and may be regarded as a most convenient
synthesis of substituted aminoperfluoroaryl carboxylic acids (compare with action of hydrazine
with subsequent reduction [18a], metallation with subsequent interaction with CO2 [18b] or
possible [19] interaction with NH3 under high pressure).
2
Page 2 of 26

The structure of 2 in solid state was investigated by X-ray diffraction analysis (Figure S1,
Table S1, Supporting Information). In this molecule the ethoxycarbonyl group and arene ring are
nearly coplanar (torsion angle is 2.26(19)o). In 2 the adjacent molecules are combined in chains
by N-H···O hydrogen bonds (Figure S2). In a crystal π-π interaction between arene rings (parallel
displaced interaction) is observed with interplanar separation equal to 3.348(1) Å [20]. So in this
case the packing is formed by hydrogen bonds and stacking interactions.
For increasing the synthetic application of derivatives of p-aminotetrafluorobenzoic acid the
application of the reactivity of the amino group (cf. acylation, diazotisation) [6b, 6d, 16] in
several types of novel reactions were carried out. Using low nucleophilicity of this N atom the
interaction with C6F5COCl (Scheme 2) and MeI were done. In the first case the target compound
3 was obtained in high yield (87 %). This way may be regarded as alternative to interaction of
azides with aldehydes [1d, 21] or thioacids [1c], which also allows to obtain amides. On
contrary, attempts to alkylate nitrogen atom in 2 by MeI in the presence of K2CO3 resulted only
to the mixture of initial compounds without any signs of reaction even under harsh conditions
(reflux up to 40 h). It is interesting to note that the attempts to increase the number of acylated
derivatives of 2 using other approaches (Boc2O/DMAP or Hünig’s base, Ac2O/DMAP) are
unsuccessful what is correlates with low reactivity of the related p-H2NC6F4NH2 [6d].
Obviously, nitrogen atom in 2 is a very weak nucleophile.
At the same time the interaction of 2 with a number of aldehydes (Scheme 2) resulted to the
corresponding imines 4-11 in high yields (72-91 %). It was found that this interaction processed
under harsh conditions (reflux in toluene) with acid catalysis in the presence of reagents
(MgSO4), which are able to bind water, formed as a by-product. These conditions effectively
allow to shift the reaction equilibrium to the target products and significantly reduce the time of
the reaction (usually up to 35 h). It must be emphasized that the conditions found in this work for
interaction of aldehydes with substituted perfluoroamino compounds is differed significantly
from known ones (compare with activation of amino group by SOCl2 for related reagents) [22]
and allows to obtain the target derivatives in one stage in high yields.
3
Page 3 of 26

Scheme 2. Chemical properties of ethyl p-aminotetrafluorobenzoate 2.
It should be noted that the interaction of 2 with terephthalic aldehyde, p-OHCC6H4CHO,
gave mono- (10) or diimine (11) depending on the stoichiometry. Furthermore, the interaction
with alkyl (propanal), conjugated (crotonaldehyde) or aromatic aldehydes with typical electron
donating groups (p-MeC6H4CHO, vanillin) resulted only to the mixtures of initial compounds
under conditions studied. So it is evident the dependence of this interaction on the structure of
the carbonyl compound and the presence of electron withdrawing groups in aldehydes facilitates
the reaction.
The structure of compounds 2-11 was investigated by multinuclear NMR, IR spectroscopy
and mass-spectrometry (see Supporting Information, Figs. S5-S41 for further details) and
composition was confirmed by elemental analysis. There is only one set of the signals in NMR
spectra of 4-11, so a single species is present. Apparently, the CH=N fragment has a (E)-
configuration, what may be explained by thermodynamic stability of this diastereomer under
formation conditions of the reaction (thermodynamic control under prolonged heating). To
1
confirm this thesis additional NMR experiments (2D H-19F HOESY NMR) for the model
compound 4 was performed (Supporting Information, Fig. S42). According to the data obtained
(Scheme 3), very strong coupling between CH=N and b-F atoms is observed (8.59/-153.16 ppm),
unambiguously indicating the (E)-configuration. In comparison with this interaction four weak
interactions are also observed (8.59/-140.77; 7.98/-153.16; 4.45/-140.77; 1.42/-140.77 ppm). It
should be noted that the same (E)-configuration has been observed by X-ray analysis previously
in related C6F5N=CH-p-C6H4Me [22].
4
Page 4 of 26

Scheme 3. Determination of configuration of imine 4 by 2D 1H-19F HOESY NMR.
According to the data obtained it is evident that in 1-11 changing in a substituent nature at N
atom strongly effects on b fluorine and CH=N atoms (Table 1). At the same time such effect is
1
insignificant in the case of CO2Et (CO2H) group (usually δ = 4.25 – 4.45/1.28-1.41 ppm in H
and δ = 158.6-167.8/60.6-62.8/13.6-14.2 ppm in 13C NMR).
Table 1. Characteristic NMR chemical shifts for compounds 1-11 (CDCl3, rt).
compound
δ (CHN=), ppm
δ (CHN=), ppm
δ (F-a), ppm
δ (F-b), ppm
p-N3C6F4CO2Et (1)a
-
-
-139.13 to -139.22
-141.03 to -141.15
-139.07 br
-151.17 to -151.25
-162.39 to -162.51
-143.07 br
p-H2NC6F4CO2Et (2)
-
-
C6F5C(O)N(H)-p-C6F4CO2Et (3)b
PhCH=N-p-C6F4CO2Et (4)
p-FC6H4CH=N-p-C6F4CO2Et (5)
-
-
8.55
8.52
168.97
167.34
166.36
168.21
171.31
158.03
167.72
191.30
-140.25 to -140.35
-140.24 to -140.34
-139.81 to -139.91
-140.09 to -140.19
-139.67 to -139.77
-139.67 to -139.77
-139.94 to -140.01
-142.11 to -142.24
-152.97 to -153.07
-153.03 to -153.13
-152.36 to -152.44
-152.73 to -152.83
-151.15 to -151.65
-152.55 to -152.65
-152.48 to -152.56
-162.35 to -162.47
(m-O2NC6H4)CH=N-p-C6F4CO2Et (6) 8.69
(o-BrC6H4)CH=N-p-C6F4CO2Et (7)
(o-HOC6H4)CH=N-p-C6F4CO2Et (8)
C6F5CH=N-p-C6F4CO2Et (9)
8.97
8.82
8.72
p-OHCC6H4CH=N-p-C6F4CO2Et (10) 8.66
p-C6H4(CH=N-p-C6F4CO2Et)2 (11)b
10.08
a taken from [12]; b in CDCl3/DMSO-d6 (1:1)
In these cases the F atoms in hetero p-disubstituted C6F4 ring represent an AA’BB’ system
with full nonequivalence of fluorine atoms what results in spin-spin coupling of nonfirst order.
As one may see from Table 1, the difference in chemical shifts between a and b fluorine atoms is
significant (up to 21 ppm).
The vibration band of the C=O stretching in 3-11 is in the range of 1722-1734 cm−1 and is in
somewhat longer wavelength in comparison with corresponding amino derivatives 2, 2a and 2b
5
Page 5 of 26

(1692-1700 cm−1) reflecting the increasing of the electron withdrawing properties under imine
formation. The bands of C=N (1614-1650 cm−1) and C-F (1198-1234, 1302-1318 cm−1) may be
easily observed also.
2.2.
Derivatives of tetrafluoroterephthalic acid
Tetrafluoroterephthalic acid 12 may be regarded as a perspective fluorine containing linker,
for example to substituted amines (Scheme 4). The corresponding known [23] but not fully
characterized before this work bis acid chloride 13 may be easily obtained from free acid and
SOCl2 and used in the synthesis of the variety of symmetrically substituted derivatives, for
example 14 [24]. Application of this synthetic way using commercially available diacid 12
represents a convenient way for the symmetric derivatives.
Scheme 4. Synthesis of 13, 14, symmetrical derivatives of 12.
But presence of two chemically equivalent CO2H complicates the unsymmetrical
modification of 12 and to solve this problem the novel synthetic strategy should be developed.
Our synthetic strategy includes the synthesis of diester of tetrafluoroterephthalic acid 15
with its following modification by selective basic hydrolysis (to synthesize monoester 15b
through monopotassium salt 15a) and then by regioselective reduction of one carboxylic
function in the presence of another one (CO2H vs. CO2Me).
The diester 15 may be readily obtained by slow addition of SOCl2 to the solution of free acid
12 in MeOH [25]. So the selective hydrolysis of the excess of dimethylterephthalate 15 in the
presence of potassium hydroxide in methyl alcohol resulted in the formation of p-
(methoxycarbonyl)tetrafluorobenzoic acid (15a) (Scheme 5). Under acidic hydrolysis 15a gives
known [14] compound 15b not fully characterized before this investigation.
Scheme 5. Chemical properties of tetrafluoroterephthalic acid 12.
6
Page 6 of 26

The structure of compound 15b in the solid state was studied by single crystal X-ray
diffraction analysis (Figure S3, Table S1, Supporting Information). In a crystal, adjacent
molecules are combined in centrosymmetric dimers by strong hydrogen bonds forming typical
motif for related acids (Figure S4) [3b, 26].
In this work the conditions for the selective reduction of ester CO2Me or carboxylic CO2H
functional group in 15b in the presence of another one were found (Scheme 6). It should be
noted that for fluorinated compounds conditions of these alternative reactions have not yet
found. Compound 16 was obtained by action of NaBH4 on 15b activated by CDI. This approach
is easy to perform especially in comparison with other alternative methods known for
unfluorinated derivatives (compare with NaBH4/I2 mixture [27] or LiBH4 [28] and Zn(BH4)2
[27b]) and allows to obtain 15b in analytically pure form after isolation. It should be noted that
in our hands the performing the synthesis of 16 under conditions known from the patent
literature (action of NaBH4 on 15 in DME) [29] resulted only to inseparable mixture of 12, 16
and p-HOCH2C6F4CH2OH.
In difference of above mentioned reaction, action of NaBH4 in aq. dioxane resulted to
reduction of more active CO2Me group giving 17 (compare with nonofluorinated acid [30] or
action of LiBH4 [31]). Compound 17 is known [32] but not fully characterized and there is no
description of its synthesis in literature.
OH
O
OH
O
OH
F
F
F
F
F
F
F
F
NaBH4
NaBH4
H2O/dioxane
CDI/THF
F
F
F
F
MeO
O
MeO
O
HO
15b
17
16
Scheme 6. Synthesis of derivatives of tetrafluoroterephthalic acid. Synthesis of unsymmetrical
derivatives 16, 17.
Application of our desymmetrization procedure for the synthesis of 15b allows to obtain
a series of the unsymmetrical heterosubstituted tetrafluoroterephthalates 19-23. Derivatives of
various amines (19, 23), phenols (20) or alcohols (21, 22) may be obtained easily in high yields
(76-92 %). In this case the intermediate acid chloride 18 may be used (Scheme 7).
7
Page 7 of 26

Scheme 7. Chemical properties of 15b. Synthesis of unsymmetrical derivatives 19 - 23.
The composition and purity of the intermediate and final products were confirmed by
1
elemental analysis, IR spectroscopy and H, 13C and 19F NMR spectroscopy (Supporting
Information, Figs. S43-S85). In difference of compounds 1-11, in 15-23 the two types of fluorine
atoms have very close values (difference only up to 5 ppm).
Conclusions
The effective synthetic strategies for the modification of ethyl p-aminotetrafluorobenzoate
and tetrafluoroterephthalic acid were developed what allows to obtain symmetrical and
unsymmetrical derivatives which are suitable for further modification and attaching novel
fragments into the para position of the carboxyperfluorophenyl ring. A series of their novel
derivatives may be easily obtained by simple typical organic reactions. The composition of all
intermediates and final products was confirmed by elemental analysis and NMR spectroscopy. In
a crystal hydrogen bonds strongly effects on packing resulting in dimers (for carboxylic acid
15b) or infinite chains (for aminoester 2). It is evident that the synthetic methods developed in
this work for the synthesis of the substituted fluorine compounds (reduction, interaction with
aldehydes, amines, alcohols and phenols) and the carboxylates obtained (synthesis and
investigation of main group and transition metal derivatives) will be used for further
investigations in various fields.
8
Page 8 of 26

3. Experimental part
3.1.
General methods and remarks
1H (400.130 MHz), 13C (100.613 MHz) and 19F (376.498 MHz) NMR spectra were recorded
on Bruker 400 or Agilent 400MR spectrometers at 298 K. Chemical shifts are given in ppm
relative to internal reference, Me4Si (1H and 13C NMR spectra), or external reference, CFCl3 (19F
1
spectra). 2D H-19F HOESY NMR spectrum was registered on a Bruker Avance 400
spectrometer at 400.13 and 376.5 MHz, respectively, where avance-verison (12/01/11) of the
hoesyph program with phase sensitive 2D heteronuclear NOE was used. The spectral window
1
19
width on H and F is equal to 4400 and 14000 Hz, respectively. 8 scans were used for each of
the 64 increments [33]. Elemental analyses were carried out by the Microanalytical Laboratory
of the Chemistry Department of the Moscow State University using Heraeus Vario Elementar
instrument. IR spectra were recorded using Nicolet iS5 Fourier Transform IR spectrometer, with
resolution 4 cm-1, 32 scans. The samples were prepared as a slurry in nujol or as a mull after
acetone solution slow evaporation. The mull was examined as a thin film between flat ZnSe
plates. Mass spectra (EI-MS, 70 eV) were recorded on a quadropoule mass spectrometer
FINNIGAN MAT INCOS 50 with direct insertion; all assignments were made with reference to
the most abundant isotopes.
The solvents were dried using common procedures. Ethanol, CH2Cl2 and CDCl3 were
refluxed and distilled over CaH2 under argon atmosphere. MeOH was refluxed and distilled over
Mg. Et3N, toluene were refluxed and distilled over Na/benzophenone. THF and dioxane were
stored over KOH, and then refluxed and distilled over Na/benzophenone.
All aldehydes, SOCl2, p-HO2CC6F4CO2H (12) were commercially available (“Sigma-
Aldrich”) compounds and used without additional purification. Usually liquid aldehydes were
distilled before synthesis.
p-N3C6F4CO2Et (1) [12] was obtained using literature procedure. Novel compounds were
detected as n.c.
3.2. Synthesis of derivatives of ethyl 4-amino-2,3,5,6-tetrafluorobenzoate
3.2.1. Ethyl 4-amino-2,3,5,6-tetrafluorobenzoate (2)
Solid SnCl2*2H2O (11.20 g, 49.7 mmol) was added portionwise (Caution! N2 evolution) to
the solution of p-N3C6F4CO2Et (2.62 g, 9.9 mmol) in EtOAc (80 mL) and EtOH (30 mL). After
9
Page 9 of 26

10 min ice (50 g) was added and reaction mixture was neutralized by saturated aq. NaHCO3 until
pH 7-8. The mixture was extracted with EtOAc (3 x 20 mL), dried over MgSO4. All volatile
materials were removed under vacuum giving the target product (2.20 g, 94 %) as a white
powder, m.p. 83-84 oC, m.p. 80.5-81.5 oC [14]. 1H NMR (400.130 MHz, CDCl3): δ = 4.40 (br s,
2H, NH2), 4.38 (q, 3JH-H = 7.2 Hz, 2H, OCH2), 1.37 (t, 3JH-H = 7.2 Hz, 3H, CH3) ppm. 13C NMR
(100.613 MHz, CDCl3,): δ = 160.70 (C=O), 147.37-147.15, 144.84-144.62, 137.26-137.00,
2
134.88-134.62, 129.94-129.66 (5m), 99.35 (t, J13C-19F = 13.9 Hz) (aromatic carbons), 61.75
19
(OCH2), 14.07 (OCH2CH3) ppm. F NMR (376.498 MHz, CDCl3): δ = -141.03 to -141.15 (m,
2F), -162.39 to -162.51 (m, 2F) ppm. IR (mull): ν = 3494 (m), 3361 (s) (NH), 3215 (m), 2983
(w), 1700 (s) (C=O), 1662 (m), 1644 (s), 1498 (s), 1308 (s), 1226 (s) (C-F), 1020 (m), 945 (m)
cm-1. EIMS, 70 eV, m/z (rel. int.): 237 (40) [M]+, 209 (25) [M-Et]+, 192 (100) [M-OEt]+, 164
(18) [M-CO2Et]+, 145 (8) [M-CO2Et-F]+, 137 (15) [C5F4]+, 117 (7) [C5F3]+. Anal. Calcd for
С9H7F4NO2 (Mw 237.1510): С, 45.58; H, 2.98; N, 5.91 %. Found: C, 45.64; H, 3.11; N, 5.77 %.
The crystals suitable for X-ray analysis were obtained by slow evaporation of solution of p-
H2NC6F4CO2Et in CH2Cl2.
3.2.2. Potassium 4-amino-2,3,5,6-tetrafluorobenzoate (2a)
The solution of KOH (0.26 g, 4.2 mmol) in dry EtOH (20 mL) was added slowly to the
solution of p-H2NC6F4CO2Et (1.00 g, 4.2 mmol) in dry EtOH (20 mL). The mixture obtained
was stirred for 12 h, then the volume of the solution was decreased twice, the solid was filtered
13
off and washed with toluene (2 x 10 mL) giving 2a (0.97 g, 93%) as a yellowish powder. C
NMR (100.613 MHz, D2O): δ = 167.27 (C=O), 144.91-144.78, 138.03-137.82, 135.60-135.44,
127.48-127.28, 106.30-106.23 (5m, aromatic carbons) ppm. 19F NMR (376.498 MHz, D2O): δ =
-146.42 to –146.54 (m, 2F), -161.02 to -161.14 (m, 2F) ppm. 19F NMR data correspond to known
from literature [17]. IR (nujol): ν = 3320 (s) (NH), 1692 (m) (C=O), 1492 (m), 1311, 1222 (C-F)
cm-1.
4-Amino-2,3,5,6-tetrafluorobenzoic acid (2b)
The solution of KOH (0.32 g, 5.7 mmol) in dry EtOH (20 mL) was added slowly to the
solution of p-H2NC6F4CO2Et (1.00 g, 4.2 mmol) in dry EtOH (20 mL). The mixture obtained
was stirred for 12 h, then concentrated HCl was added to pH 1. The solution obtained was
extracted with CH2Cl2 (3 x 20 mL), dried over MgSO4, the all volatile materials were removed
o
under reduced pressure giving 2b (0.77 g, 88%) as a yellowish powder, m.p. 185-186 C, m.p.
o
o
o
o
1
176-177 C [18c], 178-180 C [18a], 182 C [14], 182-184 C [18b]. H NMR (400.130 MHz,
10
Page 10 of 26

DMSO-d6): δ = 6.82-6.73 (m, 1H, CO2H), 6.03 (br s, 2H, NH2) ppm. 13C NMR (100.613 MHz,
D2O): δ = 167.18 (C=O), 144.98-144.79, 142.74-142.28, 137.97-137.80, 135.59-135.50, 127.45-
13
127.13, 110.28-109.98 (6m, aromatic carbons) ppm. C NMR (100.613 MHz, DMSO-d6): δ =
164.58 (C =O), 147.10-147.01, 144.73-144.60, 136.67-136.56, 134.36-134.16, 128.98-128.69
(5m, aromatic carbons), 90.36 (t, 2J13C-19F = 23.8 Hz) ppm. 19F NMR (376.498 MHz, D2O): δ = -
19
145.95 to –146.06 (m, 2F), -160.73 to -160.84 (m, 2F) ppm. F NMR (376.498 MHz, DMSO-
d6): δ = -142.72 to –142.77 (m, 2F), -161.55 to -161.59 (m, 2F) ppm. IR (nujol): ν = 3326 (m)
(NH), 2920 (s), 1696 (s) (C=O), 1488 (m), 1318 (s), 1226 (s) (C-F) cm-1.
3.2.4. Ethyl-2,3,5,6-tetrafluoro-4-{[(pentafluorophenyl)carbonyl]amino}benzoate (3) (n.c.)
a) Synthesis of C6F5C(O)Cl. At 0 oC C6F5CO2H (3.00 g, 14.2 mmol) was added portionwise
to SOCl2 (5.20 mL, 70.7 mmol) (Attention! HCl and SO2 evolution!) and the mixture obtained
was refluxed for 3 h, then all volatile materials were removed under reduced pressure. The
C6F5C(O)Cl obtained (3.20 g, >99%) as a gray powder was used further without additional
purification.
b) Synthesis of 3. Crude C6F5C(O)Cl (0.22 g, 0.9 mmol) was added to the solution of
compound 2 (0.20 g, 0.8 mmol) and Et3N (0.14 mL, 1.0 mmol) in CH2Cl2 (20 mL). The mixture
obtained was stirred overnight, then washed with saturated aq. NaHCO3 (3x20 mL), water (20
mL) and dried over MgSO4. All volatile materials were removed under reduced pressure giving
the target compound as a grayish powder (0.32 g, 87 %), recrystallized from EtOH, m.p. 169-170
1
3
oC. H NMR (400.130 MHz, CDCl3): δ = 7.71 (br s, 1H, NH), 4.44 (q, JH-H = 7.1 Hz, 2H,
3
OCH2), 1.40 (t, JH-H = 7.1 Hz, 3H, OCH2CH3) ppm. 13C NMR (100.613 MHz, DMSO-
d6/CDCl3: 1/1): δ = 158.60 (br s, CO2Et), 155.28 (br s, C(O)N), 145.49-145.27, 144.81-144.61,
142.99-142.71, 142.30-142.09, 140.57-140.21, 138.64-138.54, 138.14-137.99, 135.48-135.32,
118.27-118.06, 110.39-110.16 (10m, C6F5, C6F4), 62.12 (OCH2CH3), 13.42 (OCH2CH3) ppm.
19F NMR (376.498 MHz, DMSO-d6/CDCl3: 1/1): δ = -139.07, -143.07 (2 br s, each 2F) (C6F4), -
138.80 to -138.85 (m, 2F), -147.37 to -147.49 (m, 1F), -158.91 to 159.07 (m, 2F) (C6F5) ppm. IR
(mull): ν = 3201 (w), 2995 (w) (NH), 1738 (s) (C=O), 1689 (s) (C=O), 1651 (m), 1473 (s), 1417
(m), 1321 (s), 1232 (s) (C-F), 997 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 431 (6) [M]+, 386 (3)
[M-OEt]+, 359 (1) [M-CO2Et]+, 195 (100) [C6F5CO]+, 191 (3) [NC6F4CO]+, 167 (18) [C6F5]+,
148 (2) [C6F4]+. Anal. Calcd. for C16H6F9NO3 (Mw 431.2094): C, 44.57; H, 1.40; N, 3.25%.
Found: C, 44.46; H 1.52; N, 3.07%.
3.2.5. General procedure for aldimines 4-10 synthesis
11
Page 11 of 26

The corresponding aldehyde (0.97 mmol, 1.15 eq.) was added to the mixture of compound 2
(0.84 mmol, 1.0 eq.), MgSO4 (0.50 g) and catalytic quantities of TosOH (0.0080 g, 0.04 mmol, 5
mol %) in absolute toluene (20 mL). The mixture obtained was refluxed (TLC control; usually
30-35 h), then all volatile materials were removed under reduced pressure and the residue was
purified by chromatography and then recrystallized.
3.2.5.1.
(E)-Ethyl-2,3,5,6-tetrafluoro-4-[(phenylmethylidene)amino]benzoate,
(E)-
PhCH=N-p-C6F4CO2Et (4) (n.c.)
Rf 0.2 (silicagel; EtOAc/petroleum ether 1:20), white powder from n-hexane (0.22 g, 82 %),
o
1
m.p. 78-79 C. H NMR (400.130 MHz, CDCl3): δ = 8.55 (br s, 1H, CH=N), 7.95-7.91, 7.53-
3
7.47 (2m, each 2H, aromatic protons), 7.59-7.54 (m, 1H, aromatic proton), 4.44 (q, JH-H = 7.1
3
Hz, OCH2), 1.40 (t, JH-H = 7.1 Hz, OCH2CH3) ppm. 13C NMR (100.613 MHz, CDCl3): δ =
4
3
168.97 (t, J13C-19F = 3.0 Hz, CH=N), 159.83 (t, J13C-19F = 3.2 Hz, CO2Et), 158.09 – 157.94,
146.57 – 146.35, 144.02 – 143.84, 140.78 – 140.49, 138.26 – 138.03, 107.89 – 107.64 (6m,
19
C6F4), 134.84, 133.15, 129.55, 128.93 (C6H5), 62.47 (OCH2CH3), 14.06 (OCH2CH3) ppm. F
NMR (376.498 MHz, CDCl3): δ = -140.25 to -140.35 (m, 2F), -152.97 to -153.07 (m, 2F) ppm.
IR (mull): ν = 2964 (w), 1726 (s) (C=O), 1626 (m) (C=N), 1481 (s), 1471 (s), 1367 (m), 1311
(s), 1207 (s) (C-F), 1003 (m), 968 (s), 756 (m), 686 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 325
(100) [M]+, 296 (32) [M-Et]+, 280 (62) [M-OEt]+, 252 (16) [M-CO2Et]+, 202 (3) [M-OEt-Ph]+,
176 (1) [C6F4CO]+, 148 (4) [C6F4]+, 77 (8) [C6H5]+. Anal. Calcd. for C16H11F4NO2 (Mw
325.2577): C, 59.08; H, 3.41; N, 4.31%. Found: C, 59.16; H, 3.35; N, 4.29%.
3.2.5.2.
(E)-Ethyl-2,3,5,6-tetrafluoro-4-[{(4-fluorophenyl)methylidene}amino]benzoate,
(E)-(p-FC6H4)CH=N-p-C6F4CO2Et (5) (n.c.)
Rf 0.3 (silicagel; toluene/petroleum ether 1:1), white powder from n-hexane (0.22 g, 76 %),
m.p. 74-75oC. 1H NMR (400.130 MHz, CDCl3): δ = 8.52 (br s, 1H, CH=N), 7.98-7.93, 7.22-7.16
(2m, each 2H, aromatic protons), 4.44 (q, 3JH-H = 7.1 Hz, 2H, OCH2), 1.40 (t, 3JH-H = 7.1 Hz, 3H,
13
4
OCH2CH3) ppm. C NMR (100.613 MHz, CDCl3): δ = 167.34 (t, J13C-19F = 2.8 Hz, CH=N),
159.84 (br s, CO2Et), 146.54 – 146.21, 143.98 – 143.89, 140.73 – 140.59, 138.30 – 138.08,
1
3
108.02 – 107.86 (5m, C6F4), 165.77 (d, J13C-19F = 255.6 Hz), 131.82 (d, J13C-19F = 9.2 Hz),
4
2
131.26 (d, J13C-19F = 3.1 Hz), 116.29 (d, J13C-19F = 22.1 Hz) (C6H4), 62.51 (OCH2CH3), 14.09
19
(OCH2CH3) ppm. F NMR (376.498 MHz, CDCl3): δ = -104.63 to -104.70 (m, 1F, FC6H4), -
140.24 to -140.34 (m, 2F, C6F4), -153.03 to -153.13 (m, 2F, C6F4) ppm. IR (mull): ν = 2987 (w),
1734 (s) (C=O), 1615 (m) (C=N), 1483 (s), 1367 (m), 1306 (s), 1225 (s) (C-F), 1209 (s), 993
(m), 756 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 343 (100) [M]+, 314 (38) [M-Et]+, 298 (70) [M-
12
Page 12 of 26

OEt]+, 270 (22) [M-CO2Et]+, 176 (1) [C6F4CO]+, 148 (6) [C6F4]+, 108 (1) [CHC6H4F]+. Anal.
Calcd. for C16H10F5NO2 (Mw 343.2481): C,55.99; H 2.94; N, 4.08%. Found: C, 55.78; H, 3.12;
N, 4.18%.
3.2.5.3.
(E)-Ethyl-2,3,5,6-tetrafluoro-4-[{(3-nitrophenyl)methylidene}amino]benzoate,
(E)-(m-O2NC6H4)CH=N-p-C6F4CO2Et (6) (n.c.)
Rf 0.4 (silicagel; toluene/petroleum ether 2:1), yellow powder from n-hexane (0.24 g, 77 %),
1
m.p. 102-103oC. H NMR (400.130 MHz, CDCl3): δ = 8.69 (br s, 1H, CH=N), 8.78-8.73, 8.43-
8.39, 8.33-8.27, 7.75-7.69 (4m, each 1H) (aromatic protons), 4.44 (q, 3JH-H = 7.2 Hz, 2H, OCH2),
3
1.40 (t, JH-H = 7.2 Hz, OCH2CH3) ppm. 13C NMR (100.613 MHz, CDCl3): δ = 166.36 (t, 4J13C-
19F = 3.1 Hz, CH=N), 159.58 (br s, CO2Et), 146.45 – 146.29, 143.94 – 143.69, 140.61 – 140.46,
138.12 – 137.96, 132.79 – 132.68, 108.85-108.65 (6m, C6F4), 148.65, 136.34, 134.68, 127.19,
19
124.14 (C6H4), 62.63 (OCH2CH3), 14.05 (OCH2CH3) ppm. F NMR (376.498 MHz, CDCl3): δ
= -139.81 to -139.91 (m, 2F), -152.36 to -152.44 (m, 2F) ppm. IR (mull): ν = 3093 (w), 2848
(w), 1722 (s) (C=O), 1616 (m) (C=N), 1533 (s) (NO2), 1487 (m), 1475 (s), 1350 (s) (NO2), 1313
(s) (C-F), 1201 (s) (C-F), 1007 (m), 980 (m), 816 (m), 733 (m), 671 (m) cm-1. EIMS, 70 eV, m/z
(rel. int.): 370 (51) [M]+, 341 (15) [M-Et]+, 325 (33) [M-OEt]+, 309 (9) [M-OEt-O]+, 298 (13)
[M-CO2Et]+, 279 (11) [M-OEt-NO2]+, 251 (7) [M-CO2Et-NO2]+, 220 (8) [M-Et-C6H4NO2]+, 176
(6) [C6F4CO]+, 148 (10) [C6F4]+. Anal. Calcd. for C16H10F4N2O4 (Mw 370.2552): C, 51.90; H,
2.72; N, 7.57%. Found: C, 51.68; H, 2.76; N, 7.43%.
3.2.5.4.
(E)-Ethyl-2,3,5,6-tetrafluoro-4-[{(2-bromophenyl)methylidene}amino]benzoate,
(E)-(o-BrC6H4)CH=N-p-C6F4CO2Et (7) (n.c.)
Rf 0.3 (silicagel; toluene/petroleum ether 1:1), white crystals from n-hexane (0.25 g, 74 %),
1
m.p. 108-109oC. H NMR (400.130 MHz, CDCl3): δ = 8.97 (br s, 1H, CH=N), 8.27 (dd,3JH-H
=
4
3
4
7.8 Hz, JH-H = 2.0 Hz, 1H), 8.65 (dd, JH-H = 7.4 Hz, JH-H = 1.6 Hz, 1H), 7.46-7.37 (m, 2H)
3
3
(aromatic protons), 4.45 (q, JH-H = 7.1 Hz, 2H, OCH2), 1.40 (t, JH-H = 7.1 Hz, 3H, OCH2CH3)
13
4
ppm. C NMR (100.613 MHz, CDCl3): δ = 168.21 (t, J13C-19F = 3.1 Hz, CH=N), 159.78 (br s,
CO2Et), 134.11, 133.45, 133.42, 129.40, 127.92, 126.98 (C6H4), 62.55 (OCH2), 14.10
(OCH2CH3) ppm. The signals of carbons bound with F atoms were not found due to low
solubility. 19F NMR (376.498 MHz, CDCl3): δ = -140.09 to -140.19 (m, 2F), -152.73 to -152.83
(m, 2F) ppm. IR (mull): ν = 2987 (w), 1726 (s) (C=O), 1628 (m) (C=N), 1593 (s), 1487 (s), 1369
(m), 1311 (s) (C-F), 1223 (s) (C-F), 1009 (m), 982 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 403
(19), 405 (19) [M]+, 374 (4), 376 (4) [M-Et]+, 358 (10), 360 (10) [M-OEt]+, 330 (3), 332 (3) [M-
CO2Et]+, 252 (15) [M-CO2Et-Br]+, 176 (13) [C6F4CO]+, 148 (22) [C6F4]+, 102 (15) [NCHC6H4]+.
13
Page 13 of 26

Anal. Calcd. for C16H10BrF4NO2 (Mw 404.1537): C, 47.55; H, 2.49; N, 3.47%. Found: C, 47.72;
H, 2.56; N, 3.43%.
3.2.5.5.
(E)-Ethyl-2,3,5,6-tetrafluoro-4-[{(2-hydroxyphenyl)methylidene}amino]benzoate,
(E)-(o-HOC6H4)CH=N-p-C6F4CO2Et (8) (n.c.)
Rf 0.3 (silicagel; toluene/petroleum ether 1:1), yellow crystals from n-hexane (0.25 g, 86 %),
1
m.p. 102-103oC. H NMR (400.130 MHz, CDCl3): δ = 12.14 (s, 1H, OH), 8.82 (br s, 1H,
3
4
CH=N), 7.50-7.44 (m, 1H), 7.41 (dd, JH-H = 7.8 Hz, JH-H = 1.6 Hz, 1H), 7.06-7.02, 7.41-6.95
3
3
(2m, each 1H) (aromatic protons), 4.45 (q, JH-H = 7.2 Hz, 2H, OCH2), 1.41 (t, JH-H = 7.2 Hz,
4
3H, OCH2CH3) ppm. 13C NMR (100.613 MHz, CDCl3): δ = 171.31 (t, J13C-19F = 4.3 Hz,
CH=N), 159.54 (br s, CO2Et), 146.52-146.40, 144.15-143.81, 141.68-141.48, 139.21-139.03
(4m, C6F4), 161.56, 135.37, 133.54, 119.63, 118.55, 117.82 (C6H4), 62.69 (OCH2), 14.08
(OCH2CH3) ppm. Two carbons bound to F atoms have been not found due to low solubility and
19
due to overlap with other signals. F NMR (376.498 MHz, CDCl3): δ = -139.67 to -139.77 (m,
2F), -151.15 to -151.65 (m, 2F) ppm. IR (mull): ν = 2983 (w), 1734 (C=O), 1614 (m) (C=N),
1574 (m), 1477 (s), 1367 (m), 1311 (s) (C-F), 1223 (m) (C-F), 1198 (m), 982 (m), 752 (m) cm-1.
EIMS, 70 eV, m/z (rel. int.): 341 (100) [M]+, 312 (13) [M-Et]+, 296 (29) [M-OEt]+, 268 (19) [M-
CO2Et]+, 240 (5) [M-CO2Et-CO]+, 221 (14) [C6F4CO2Et]+, 192 (6) [C6F4CO2]+, 176 (8)
[C6F4CO]+, 148 (10) [C6F4]+, 106 (4) [(HO)CHC6H4]+. Anal. Calcd. for C16H11F4NO3 (Mw
341.2571): C,56.31; H, 3.25; N, 4.10%. Found: C, 56.12; H, 3.41; N, 3.92%.
3.2.5.6.
Ethyl-2,3,5,6-tetrafluoro-4-[{(pentafluorophenyl)methylidene}amino]benzoate,
(E)-C6F5CH=N-p-C6F4CO2Et (9) (n.c.)
Rf 0.3 (silicagel; toluene/petroleum ether 1:1), white crystals from n-hexane (0.29 g, 82 %),
o
3
m.p. 103-104 C. 1H NMR (400.130 MHz, CDCl3): δ = 8.72 (br s, 1H, CH=N), 4.44 (q, JH-H
=
3
7.2 Hz, 2H, OCH2), 1.40 (t, JH-H = 7.2 Hz, 3H, OCH2CH3) ppm. 13C NMR (100.613 MHz,
CDCl3): δ = 158.03 (m, CH=N), 159.49 (br s, CO2Et), 148.06-147.83, 146.50-146.25, 145.40-
145.19, 143.88-143.65, 142.81-142.41, 140.25-140.07, 139.32-139.04, 137.70-137.53, 136.81-
136.42, 135.20-135.11, 133.06-132.61 (13m, C6F5, C6F4), 62.72 (OCH2CH3), 14.06 (OCH2CH3)
19
ppm. F NMR (376.498 MHz, CDCl3): δ = -139.67 to -139.77 (m, 2F), -139.87 to 139.98 (m,
2F), -145.83 to -145.98 (m, 1F), -152.55 to -152.65 (m, 2F), -160.56 to -160.71 (m, 2F) ppm. IR
(mull): ν = 2925 (w), 1728 (s) (C=O), 1643 (m) (C=N), 1502 (s), 1483 (s), 1475 (s), 1421 (m),
1369 (m), 1311 (s) (C-F), 1221 (s) (C-F), 1005 (m), 960 (m) cm-1. EIMS, 70 eV, m/z (rel. int.):
415 (66) [M]+, 386 (32) [M-Et]+, 370 (84) [M-OEt]+, 342 (22) [M-CO2Et]+, 323 (3) [M-CO2Et-
F]+, 221 (8) [C6F4CO2Et]+, 192 (11) [C6F4CO2]+, 176 (13) [C6F4CO]+, 167 (9) [C6F5]+, 148 (30)
14
Page 14 of 26

[C6F4]+. Anal. Calcd. for C16H6F9NO2 (Mw 415.2100): C, 46.28; H, 1.46; N, 3.37%. Found: C,
46.32; H, 1.41; N, 3.56%.
3.2.5.7.
Ethyl-2,3,5,6-tetrafluoro-4-[{(4-formylphenyl)methylidene}amino]benzoate, (E)-
(p-OHCC6H4)CH=N-p-C6F4CO2Et (10) (n.c.)
Rf 0.4 (silicagel; toluene/petroleum ether 2:1), yellowish crystals from n-hexane (0.21 g, 72
%), m.p. 112-114 oC. 1H NMR (400.130 MHz, CDCl3): δ = 10.11 (s, 1H, CHO), 8.66 (br s, 1H,
3
CH=N), 8.13-8.07, 8.05-8.00 (2m, each 2H, aromatic protons), 4.44 (q, JH-H = 7.1 Hz, 2H,
3
OCH2), 1.40 (t, JH-H = 7.1 Hz, 3H, OCH2CH3) ppm. 13C NMR (100.613 MHz, CDCl3): δ =
191.49 (CHO), 167.72 (t, 3J13C-19F = 3.1 Hz, CH=N), 159.70-159.67 (m, CO2Et), 146.53-146.35,
143.98-143.74, 140.67-140.47, 138.18-137.95, 132.68-132.61 (5m, C6F4), 139.57, 139.10,
130.01 (aromatic carbons), 62.62 (OCH2), 14.08 (OCH2CH3) ppm. Two carbons have been not
found due to low solubility and due to overlap with other signals. 19F NMR (376.498 MHz,
CDCl3): δ = -139.94 to -140.01 (m, 2F), -152.48 to -152.56 (m, 2F) ppm. IR (mull): ν = 2985
(w), 1728 (s) (C=O), 1689 (s) (C=O), 1650 (m) (C=N), 1483 (m), 1302 (m) (C-F), 1198 (s) (C-
F), 1003 (w), 769 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 353 (31) [M]+, 324 (25) [M-Et]+, 308
(100) [M-OEt]+, 280 (57) [M-CO2Et]+, 251 (6) [M-CO2Et-CHO]+, 192 (15) [C6F4CO2]+, 176 (2)
[C6F4CO]+, 148 (7) [C6F4]+, 105 (3) [C6H4CHO]+, 77 (13) [C6H5]+. Anal. Calcd. for
C17H11F4NO3 (Mw 353.2678): C, 57.80; H, 3.14; N, 3.96%. Found: C, 57.92; H, 2.88; N, 3.81%.
3.2.5.8.
p-C6H4((E)-CH=N-p-C6F4CO2Et)2 (11) (n.c.)
Obtained analogously to 10 using 0.5 eq. of p-C6H4(CHO)2. Rf 0.4 (silicagel; toluene),
o
1
yellowish crystals (0.22 g, 91 %), recrystallized from toluene, m.p. 212-213 C. H NMR
(400.130 MHz, DMSO-d6/CDCl3 (1:1)): δ = 10.08 (br s, 2H, 2CH=N), 8.02 (s, 4H, aromatic
3
3
13
protons), 4.25 (q, JH-H = 7.0 Hz, 2H, OCH2), 1.28 (t, JH-H = 7.0 Hz, 3H, OCH2CH3) ppm. C
NMR (100.613 MHz, DMSO-d6/CDCl3 (1:1)): δ = 191.30 (CH=N), 160.07 (CO2Et), 150.28-
150.16, 144.40-144.30, 143.15-142.23, 134.01-133.92, 131.43-131.32, 109.23-108.40 (6m,
C6F4), 160.07, 146.80, 139.37, 129.52 (aromatic carbons), 60.67 (OCH2), 13.67 (OCH2CH3)
ppm. 19F NMR (376.498 MHz, DMSO-d6/CDCl3 (1:1)): δ = -142.11 to -142.24 (m, 2F), -162.35
to -162.47 (m, 2F) ppm. IR (mull): ν = 3733 (w), 2989 (w), 1726 (s) (C=O), 1618 (m) (C=N),
1483 (s), 1315 (s) (C-F), 1234 (s) (C-F), 1005 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 572 (100)
[M]+, 543 (12) [M-Et]+, 527 (17) [M-OEt]+, 516 (3) [M-2Et]+, 499 (8) [M-CO2Et]+, 470 (3) [M-
CO2Et-Et]+, 454 (1) [M-CO2Et-OEt]+, 426 (2) [M-2CO2Et]+, 353 (1) [M-C6F4CO2Et]+, 305 (2)
[M-C6F4CO2Et-OEt]+, 221 (3) [C6F4CO2Et]+, 176 (3) [C6F4CO]+, 148 (2) [C6F4]+. Anal. Calcd.
15
Page 15 of 26

for C26H16F8N2O4 (Mw 572.4035): C, 54.56; H 2.82; N, 4.89%. Found: C, 54.72; H, 2.92; N,
4.73%.
3.3. Synthesis of derivatives of p-HO2CC6F4CO2H
3.3.1. 2,3,5,6-Tetrafluorobenzene-1,4-dicarboxylic acid, p-HO2CC6F4CO2H (12)
13C NMR (100.613 MHz, MeOH-d4): δ = 161.66 (CO2H), 146.99-146.81, 144.41-144.29,
19
117.33-117.05 (3m, C6F4) ppm. F NMR (376.498 MHz, MeOH-d4): δ = -141.83 (s, 4F) ppm.
19F NMR (376.498 MHz, D2O): δ = -140.83 (s, 4F) ppm.
3.3.2. 2,3,5,6-Tetrafluorobenzene-1,4-dicarbonyl dichloride, p-ClC(O)C6F4C(O)Cl (13)
o
At 0 C HO2CC6F4CO2H (12) (1.90 g, 8.0 mmol) was added portionwise to SOCl2 (20.00
mL, 274.0 mmol) and the mixture obtained was refluxed for 5 h, then all volatile materials were
removed under reduced pressure. The C6F5C(O)Cl obtained (2.16 g, 98%) as a grayish powder
13
was used further without additional purification. C NMR (100.613 MHz, CDCl3): δ = 158.02
(CO2H), 144.58-144.46, 141.95-141.68, 120.24-119.95 (3m, C6F4) ppm. 19F NMR (376.498
MHz, CDCl3): δ = -136.32 (s, 4F) ppm.
3.3.3. N,N,N’N’-Tetraethyl-2,3,5,6-tetrafluorobenzene-1,4-dicarboxamide,
p-
Et2NC(O)C6F4C(O)NEt2 (14)
At 0 oC the solution of HNEt2 (1.18 mL, 11.4 mmol, 4.4 eq.) in CH2Cl2 (20 mL) was added
dropwise to the solution of 13 (0.71 g, 2.6 mmol) in CH2Cl2 (20 mL). The mixture obtained was
stirred at room temperature overnight, then washed with saturated aq. NaHCO3 (3x20 mL), by
water (20 mL), dried over MgSO4 and then all volatile materials were removed under reduced
pressure. Compound 14 (0.81 g, 89%) was isolated as yellowish crystals after recrystallization
from toluene, m.p. 134-135 oC. 1H NMR (400.130 MHz, CDCl3): δ = 3.57, 3.21 (2q, 3JH-H = 7.0
3
Hz, each 2H, NCH2), 1.24, 1.10 (2t, JH-H = 7.0 Hz, each 3H, NCH2CH3) ppm. 13C NMR
(100.613 MHz, CDCl3): δ = 158.18 (CON), 143.59-143.38, 141.13-140.89, 117.71-117.26 (3m,
C6F4), 43.20, 39.72 (NCH2), 13.93, 12.64 (NCH2CH3) ppm. 19F NMR (376.498 MHz, CDCl3): δ
= -140.54 (s, 4F) ppm. IR (nujol): ν = 2967 (w), 1703 (s) (C=O), 1483 (s), 1318 (s) (C-F), 1234
(s) (C-F), 994 (m) cm-1. EIMS, 70 eV, m/z (rel. int.): 348 (100) [M]+, 276 (7) [M-NEt2]+, 176 (3)
[C6F4CO]+, 148 (2) [C6F4]+.
3.3.4. Dimethyl tetrafluoroterephthalate, p-MeO2CC6F4CO2Me (15)
16
Page 16 of 26

o
At 0 C SOCl2 (91.30 mL, 767.2 mmol) was added dropwise to the solution of p-
HO2CC6F4CO2H (12) (15.00 g, 63.0 mmol) in methanol (260 mL). The mixture was warmed to
room temperature and refluxed for 10 h, then all volatile materials were removed under reduced
pressure and the residue obtained was extracted with Et2O (3 x 20 mL). The ether extracts were
washed with saturated aq. NaHCO3 (Attention! CO2 evolution) and then with water (20 mL). The
organic layer was dried over MgSO4, and the solvent was evaporated. The residue obtained was
recrystallized from petroleum ether/toluene (10:1) mixture. The target compound 15 (11.90 g, 71
o
o
o
1
%) was isolated as a white powder, m.p. 79-80 C, m.p. 79-79.5 C [14], m.p. 80 C [25]. H
1
NMR (400.130 MHz, DMSO-d6): δ = 3.96 (s, 6H, OCH3) ppm. H NMR (400.130 MHz,
13
CDCl3): δ = 3.98 (s, 6H, OCH3). C NMR (100.613 MHz, DMSO-d6): δ = 162.13 (CO2Me),
53.91 (OCH3) ppm. The signals of C6F4 were not found due to low intensity and high value of
nuclear coupling. 13C NMR (100.613 MHz, CDCl3): δ = 159.35 (CO2Me), 145.85-145.58,
19
143.26-142.99, 115.19-114.95 (3m, aromatic carbons), 53.54 (OCH3) ppm. F NMR (376.498
19
MHz, DMSO-d6): δ = -138.90 (s, 4F) ppm. F NMR (376.498 MHz, CDCl3): δ = -138.30 (s,
4F) ppm. IR (nujol): ν = 2960 (s), 1735 (s) (C=O), 1480 (s), 1342 (s) (C-F), 1219 (s) (C-F), 1009
(m) cm-1. EIMS, 70 eV, m/z (rel. int.): 266 (100) [M]+, 251 (2) [M-Me]+, 235 (7) [M-OMe]+, 176
(3) [C6F4CO]+, 148 (2) [C6F4]+.
3.3.5. Potassium 2,3,5,6-tetrafluoro-4-(methoxycarbonyl)benzoate, p-KO2CC6F4CO2Me (15a)
(n.c.)
Analogously to 2a from 15 (0.48 g, 1.8 mmol) and KOH (0.10 g, 1.8 mmol). Yield 0.46 g,
1
13
88 %. White powder. H NMR (400.130 MHz, D2O): δ = 3.97 (s, 3H, OCH3) ppm. C NMR
(100.613 MHz, D2O): δ = 164.81, 162.01 (CO2, CO2Me), 145.23-146.07, 143.67-143.40,
141.22-141.02, 110.77-110.49 (4m, aromatic carbons), 53.69 (OCH3) ppm. The 2 signals of C6F4
were not found due to low solubility, low intensity and high value of nuclear coupling. 19F NMR
(376.498 MHz, D2O): δ = -140.28 to -140.38 (m, 2F), -144.63 to -144.74 (m, 2F) ppm. IR
(nujol): ν = 3130 (w), 1694 (s) (C=O), 1477 (s), 1316 (s) (C-F), 1212 (s) (C-F), 1023 (m) cm-1.
3.3.6. 2,3,5,6-Tetrafluoro-4-(methoxycarbonyl)benzoic acid, p-HO2CC6F4CO2Me (15b)
At 0oC solution of KOH (1.74 g, 31.0 mmol) in MeOH (55 mL) was added dropwise to the
solution of p-MeO2CC6F4CO2Me (6) (8.66 g, 32.5 mmol) in MeOH (53.5 mL). The mixture was
warmed slowly to room temperature and refluxed for 8 hours, then all volatile materials were
removed under reduced pressure, and then water (30 mL) was added. The solution obtained was
extracted with CH2Cl2 (3x50 mL). The aqueous layer was acidified to pH 1 with 1 M aq. HCl
and extracted with Et2O (3x30 mL). The organic layer was dried over MgSO4, and the all
17
Page 17 of 26

volatile materials were removed under reduced pressure. The material obtained was
recrystallized from the minimum amount of hot chloroform giving 15b (4.82 g, 59%) as white
crystals. M.p. 111-112 oC, m.p. 110-111 oC [14]. 1H NMR (400.130 MHz, DMSO-d6): δ = 12.80
1
(s, 1H, COOH), 3.95 (s, 3H, OCH3) ppm. H NMR (400.130 MHz, CDCl3): δ = 11.06 (s, 1H,
1
COOH), 4.01 (s, 3H, CH3) ppm. H NMR (400.130 MHz, D2O): δ = 4.75 (s, 1H, COOH), 3.91
(s, 3H, CH3) ppm. 13C NMR (100.613 MHz, DMSO-d6): δ = 169.32, 162.14 (C=O), 55.93
(OCH3) ppm. The signals of C6F4 were not found due to low intensity and high value of nuclear
13
coupling. C NMR (100.613 MHz, CDCl3): δ = 163.91, 159.39 (C=O), 146.52-146.28, 145.93-
145.69, 143.92-143.69, 143.37-143.13, 116.24-115.91, 113.70-113.41 (6m, C6F4), 53.78 (OCH3)
ppm. 13C NMR (100.613 MHz, D2O): δ = 178.32, 157.40 (C=O), 146.18-145.96, 145.02-144.92,
144.37-144.22, 143.66-143.42, 141.93-141.71, 112.29-112.21 (6m, C6F4), 53.72 (OCH3) ppm.
19F NMR (376.498 MHz, DMSO-d6): δ = -138.92 to -139.07 (m, 2F), -139.96 to -140.12 (m, 2F)
ppm. 19F NMR (376.498 MHz, D2O): δ = -141.96 to -142.10 (m, 2F), -138.85 to -138.94 (m, 2F)
19
ppm. F NMR (376.498 MHz, CDCl3): δ = -136.44 to -136.56 (m, 2F), -137.72 to -137.84 (m,
2F) ppm. IR (mull): ν = 3265 (w), 1700 (s) (C=O), 1742 (s) (C=O), 1477 (s), 1311 (s) (C-F),
1221 (s) (C-F) cm-1. IR (nujol): ν = 2960 (s), 1745 (s) (C=O), 1715 (s) (C=O), 1480 (s), 1318 (s)
(C-F), 1228 (s) (C-F) cm-1. EIMS, 70 eV, m/z (rel. int.): 252 (1) [M]+, 235 (100) [M-OH]+, 220
(24) [M-OH-Me]+, 204 (43) [M-OH-OMe]+, 176 (78) [C6F4CO]+, 148 (52) [C6F4]+. Anal. Calcd.
for С9H4F4O4 (Mw 252.1193): C, 42.88; H, 1.60 %. Found: C, 42.65; H, 1.56 %.
The crystals suitable for X-ray analysis were obtained by slow evaporation of solution of
15b in CH2Cl2.
3.3.7. Methyl-2,3,5,6-tetrafluoro-4(hydroxymethyl)benzoate, p-HOCH2C6F4CO2Me (16)
At 0 oC carbodiimidazole (0.4180 g, 2.58 mmol) was added to the solution of 15b (0.5000 g,
1.98 mmol) in THF (20 mL), the solution obtained was stirred for 30 min at the same
temperature and then NaBH4 (0.0450 g, 1.19 mmol) was added. Reaction mixture was stirred at
room temperature overnight, then all volatile materials were removed under reduced pressure,
EtOAc (40 mL) and aq. saturated NaCl (40 mL) were added. Organic phase was washed with
saturated aq. NaHCO3, water, dried over MgSO4, the solvent was evaporated and the residue
obtained was purified by flash chromatography (silicagel, EtOAc/petroleum ether 2:5, Rf 0.40).
Compound 16 (0.25 g, 54 %) was isolated as a white powder after recrystallization form MeOH,
o
1
m.p. 69-70 C. H NMR (400.130 MHz, CDCl3): δ = 5.32 (s, 2H, OCH2), 3.98 (s, 3H, OCH3)
ppm. The signal of OH proton was not found. 13C NMR (100.613 MHz, CDCl3): δ = 159.22 (br
s, CO2Me), 145.61-145.58, 143.45-143.24, 138.43-137.72, 120.42-120.01, 116.12-115.72 (5m,
18
Page 18 of 26

C6F4), 57.09 (HOCH2), 53.40 (OCH3) ppm. One signal of C6F4 was not found due to low
intensity and high value of nuclear coupling. 19F NMR (376.498 MHz, CDCl3): δ = -139.89 to -
138.99 (m, 2F), -140.69 to -140.77 (m, 2F) ppm. IR (mull): ν = 3473 (w), 2962 (w), 1739 (s)
(C=O), 1481 (s), 1313 (s) (C-F), 1171 (s) (C-F), 1001 (w), 964 (w), 756 (m) cm-1. EIMS, 70 eV,
m/z (rel. int.): 238 (2) [M]+, 223 (2) [M-Me]+, 220 (100) [M-H2O]+, 208 (62) [M-CHO]+, 193
(11) [M-CHO-Me]+, 176 (86) [C6F4CO]+, 148 (59) [C6F4]+. Anal. Calcd. for C9H6F4O3 (Mw
238.1358): C, 45.39; H, 2.54 %. Found: C, 45.12; H, 2.4 2%.
3.3.8. 2,3,5,6-Tetrafluoro-4-(hydroxymethyl)benzoic acid, p-HOCH2C6F4CO2H (17)
At 0 oC NaBH4 (1.05 g, 27.8 mmol) was added portionwise (Caution! Hydrogen evolution!)
to the solution of 6b (1.00 g, 4.0 mmol) in H2O/dioxane (40 mL, 1:1). The mixture was stirred at
o
room temperature for 15 hours, and then was acidified at 0 C to pH 1 by 2 M aq. HCl, and
extracted with EtOAc (3x20 mL). The organic layer was dried over MgSO4, and all volatile
materials were removed under reduced pressure. The material obtained was recrystallized from
n-hexane with the minimum amount of ethyl acetate giving 7 (0.74 g, 84%) as white crystals.
o
1
M.p. 102-103 C. H NMR (400.130 MHz, DMSO-d6): δ = 3.94 (s, 2H, CH2OH) ppm. The
protons of CO2H and OH groups were not found. 13C NMR (100.613 MHz, DMSO-d6): δ =
159.65 (C = O), 145.49 – 145.37, 144.90 – 144.75, 142.94 – 142.78, 142.73 – 142.23, 116.91 –
116.63, 113.40 – 113.16 (6m, aromatic carbons), 53.69 (CH2OH) ppm. 19F NMR (376.498 MHz,
DMSO-d6): δ = -138.97 to -139.22 (m, 2F), -140.10 to -140.25 (m, 2F) ppm. IR (mull): ν = 3382
(w), 2954 (w), 1725 (s) (C=O), 1464 (s), 1321 (s) (C-F), 1192 (s) (C-F), 984 (m) cm-1. EIMS, 70
eV, m/z (rel. int.): 224 (1) [M]+, 207 (1) [M-OH]+, 189 (63) [M-H2O-OH]+, 176 (100)
[C6F4CO]+, 148 (42) [C6F4]+. Anal. Calcd. for C8H4F4O3 (Mw 224.1092): C, 42.87; H, 1.80 %.
Found: C, 43.33; H, 2.06 %.
3.3.9. Methyl 4-(chlorocarbonyl)-2,3,5,6-tetrafluorobenzoate, p-Cl(O)CC6F4CO2Me (18)
(n.c.)
Analogously to 13 from HO2CC6F4CO2Me (16) (0.73 g, 2.9 mmol) and SOCl2 (10.00 mL,
137.0 mmol). Recrystallized from n-hexane/toluene. Yellowish powder (0.66 g, 84 %). 1H NMR
13
(400.130 MHz, CDCl3): δ = 4.01 (s, 3H, OCH3) ppm. C NMR (100.613 MHz, CDCl3): δ =
163.51, 159.39 (2C=O), 146.45-146.23, 145.87-146.67, 143.82-143.62, 143.29-143.10, 116.10-
19
115.78, 113.89-113.57 (6m, C6F4), 53.75 (OCH3) ppm. F NMR (376.498 MHz, CDCl3): δ = -
136.64 to -136.73 (m, 2F), -137.83 to -137.93 (m, 2F) ppm.
3.3.10. General procedure for the synthesis of derivatives 19-22
19
Page 19 of 26

o
At 0 C solution of p-Cl(O)CC6F4CO2Me (18) (0.1100 g, 0.41 mmol) in CH2Cl2 (10 mL)
was added dropwise to the solution of the corresponding reagent (0.37 mmol), Et3N (0.06 mL,
0.44 mmol) in CH2Cl2 (20 mL). The solution obtained was stirred overnight, then washed with
saturated aq. NaHCO3 (3x20 mL) and water (20 mL), dried over MgSO4. All volatile materials
were removed under reduced pressure giving the target compound.
3.3.10.1. Methyl 4-{[2,6-bis(1-methylethyl)phenyl]carbamoyl}-2,3,5,6-tetrafluorobenzoate,
DippNH(O)CC6F4CO2Me (19) (n.c.)
1
3
White powder (0.12 g, 82 %). H NMR (400.130 MHz, CDCl3): δ = 7.03 (d, JH-H 7.6 Hz,
3
3
2H), 6.79 (t, JH-H 7.6 Hz, 1H) (aromatic protons), 3.94 (s, 3H, OCH3), 2.92 (sept, JH-H 6.8 Hz,
2H, CH), 1.27 (d, 3JH-H 6.8 Hz, 12H) ppm. 13C NMR (100.613 MHz, CDCl3): δ = 162.84, 159.72
(2C=O), 145.77-145.58, 144.97-144.84, 143.21-143.02, 142.50-142.30, 118.85-118.37, 113.41-
113.09 (6m, C6F4), 137.82, 131.82, 124.42, 123.60 (aromatic carbons), 53.31 (OCH3), 28.03
19
(CH), 23.01 (CH3) ppm. F NMR (376.498 MHz, CDCl3): δ = -139.75 to -139.84 (m, 2F), -
142.32 to -142.42 (m, 2F) ppm. IR (mull): ν = 3477 (w), 3012 (w), 1738 (s) (C=O), 1672 (s)
(C=O), 1523 (m), 1474 (s), 1322 (s) (C-F), 1219 (s) (C-F), 984 (m) cm-1. EIMS, 70 eV, m/z (rel.
int.): 411 (2) [M]+, 380 (1) [M-OMe]+, 352 (18) [M-CO2Me]+, 176 (100) [C6F4CO]+, 148 (11)
[C6F4]+. Anal. Calcd. for C21H21F4NO3 (Mw 411.3900): C, 61.31; H, 5.15; N, 3.40 %. Found: C,
60.84; H, 4.87; N, 3.42 %.
3.3.10.2. 4-tert-Butylphenyl-methyl-2,3,5,6-tetrafluorobenzene-1,4-dicarboxylate,
p-(t-
BuC6H4)O2CC6F4CO2Me (20) (n.c.)
1
White powder (0.13 g, 92 %), m.p. 78-79oC. H NMR (400.130 MHz, CDCl3): δ = 7.47-
7.44, 7.19-7.16 (2m, each 2H, aromatic protons), 4.01 (s, 3H, OCH3), 1.34 (s, 9H, C(CH3)3)
ppm. 13C NMR (100.613 MHz, CDCl3): δ = 159.35-159.26, 157.55-157.48 (2m, 2CO2), 149.81,
147.66, 126.59, 120.47 (C6H4), 145.88-145.70, 143.42-143.21, 114.79-114.63 (3m, C6F4), 53.60
(OCH3), 34.55 (C(CH3)3), 31.31 (C(CH3)3) ppm. Several carbon signals of C6F4 were not found
due to low intensity and high value of nuclear coupling. 19F NMR (376.498 MHz, CDCl3): δ = -
137.39 to -137.50 (m, 2F), -137.71 to -137.82 (m, 2F) ppm. IR (mull): ν = 2962 (w), 1745 (s)
(C=O), 1481 (s), 1323 (s) (C-F), 1198 (s) (C-F), 1171 (s), 997 (m) cm-1. EIMS, 70 eV, m/z (rel.
int.): 384 (23) [M]+, 369 (77) [M-Me]+, 353 (6) [M-OMe]+, 325 (2) [M-CO2Me]+, 310 (1) [M-
CO2Me-Me]+, 268 (1) [M-CO2Me-Bu-t]+, 235 (100) [M-OC6H4Bu-t]+, 207 (3) [M-CO-
OC6H4Bu-t]+, 192 (3) [M-CO-Me-OC6H4Bu-t]+, 176 (8) [C6F4CO]+, 148 (5) [C6F4]+, 91 (4)
[OC6H4]+. Anal. Calcd. for C19H16F4O4 (Mw 384.3216): C, 59.38; H, 4.20 %. Found, C, 59.52; H,
4.12 %.
20
Page 20 of 26

3.3.10.3. p-MeO2CC6F4CO2CH2-p-C6F4CO2Me (21) (n.c.)
Colorless crystals (0.15 g, 86 %). 1H NMR (400.130 MHz, CDCl3): δ = 5.53 (s, 2H, OCH2),
13
3.98 (s, 6H, OCH3) ppm. C NMR (100.613 MHz, CDCl3): δ = 159.65, 159.22 (br s, C=O),
158.20-158.15 (m, C=O), 146.70-146.65, 145.83-145.61, 144.02-143.92, 143.24-143.04, 116.07-
115.91, 114.01-113.70 (6m, 2C6F4), 55.35 (HOCH2), 53.61, 53.43 (2OCH3) ppm. 19F NMR
(376.498 MHz, CDCl3): δ = -137.29 to -137.40 (m, 2F), -137.71 to -137.83 (m, 2F), -138.73 to -
138.83 (m, 2F), -140.69 to -140.79 (m, 2F) ppm. IR (mull): ν = 3260 (w), 1728 (s) (C=O), 1478
(s), 1312 (s) (C-F), 1182 (s) (C-F) cm-1. EIMS, 70 eV, m/z (rel. int.): 472 (7) [M]+, 457 (1) [M-
Me]+, 441 (44) [M-OMe]+, 410 (1) [M-2OMe]+, 382 (2) [M-OMe-CO2Me]+, 354 (1) [M-
2CO2Me]+, 236 (10) [O2CC6F4CO2]+, 220 (100) [O2CC6F4CO]+, 205 (12) [OCC6F4CO]+, 176
(45) [C6F4CO]+, 148 (23) [C6F4]+. Anal. Calcd. for C18H8F8O6 (Mw 472.2397): C, 45.78; H, 1.71
%. Found, C, 45.93; H, 1.87 %.
3.3.10.4. 4,4’-Ethane-1,2-diyl-dimethyl-bis(2,3,5,6-tetrafluorobenzene-1,4-dicarboxylate),
[p-MeO2CC6F4CO2CH2]2 (22) (n.c.)
1
White powder (0.09 g, 88 %), m.p. 96-97oC. H NMR (400.130 MHz, CDCl3): δ = 4.72 (s,
13
4H, 2OCH2), 3.98 (s, 6H, 2OCH3) ppm. C NMR (100.613 MHz, CDCl3): δ = 159.29-159.26,
157.66-158.62 (2m, CO2), 146.02-145.56, 143.46-142.97, 115.56-115.33 (3m, C6F4), 63.69
(OCH2), 53.63 (OCH3) ppm. Three carbon signals of C6F4 were not found due to low intensity
and high value of nuclear coupling. 19F NMR (376.498 MHz, CDCl3): δ = -137.60 to -137.70 (m,
2F), -137.82 to -137.92 (m, 2F) ppm. IR (mull): ν = 1738 (s) (C=O), 1477 (s), 1437 (m), 1319 (s)
(C-F), 1261 (m), 1198 (m) (C-F), 1171 (s), 935 (m), 740 (m) cm-1. EIMS, 70 eV, m/z (rel. int.):
530 (42) [M]+, 499 (22) [M-OMe]+, 471 (2) [M-CO2Me]+, 279 (11) [M-OCC6F4CO2Me]+, 251
(2) [O2CC6F4CO2Me]+, 235 (100) [OCC6F4CO2Me]+, 220 (3) [OCC6F4CO2]+, 204 (2)
[OCC6F4CO]+, 176 (9) [C6F4CO]+, 148 (4) [C6F4]+. Anal. Calcd. for C20H10F8O8 (Mw 530.2758):
C, 45.30; H, 1.90 %. Found, C, 45.08; H, 2.14 %.
3.3.11. o-C6H4[NHC(O)-p-C6F4CO2Me]2 (23) (n.c.)
Analogously to 19 using 18 (0.89 g, 3.3 mmol), Et3N (0.46 mL, 3.3 mmol) and o-
phenylenediamine (0.18 g, 1.6 mmol). Brownish powder (0.72 g, 76 %), recrystallized from
1
CHCl3, m.p. 164-165oC. H NMR (400.130 MHz, CDCl3): δ = 8.93 (br s, 2H, 2NH), 7.48, 7.31
(2br s, each 2H, aromatic carbons), 4.00 (br s, 6H, 2OCH3) ppm. 13C NMR (100.613 MHz,
CDCl3): δ = 159.59-159.43, 156.78-156.71 (2m, CO2), 145.82-145.65, 144.94-144.82, 143.19-
143.04, 142.40-142.20, 123.30-122.93, 114.20-113.88 (6m, C6F4), 129.41, 127.81, 125.99
21
Page 21 of 26

(aromatic carbons), 53.65 (OCH3) ppm. 19F NMR (376.498 MHz, CDCl3): δ = -137.20 to -
137.59 (br m, 4F), -139.43 to -139.84 (br m, 4F) ppm. IR (mull): ν = 3523 (w), 3023 (w), 1741
(s) (C=O), 1667 (s) (C(O)N), 1527 (m), 1477 (s), 1325 (s) (C-F), 1225 (s) (C-F), 995 (m), 750
(m) cm-1. EIMS, 70 eV, m/z (rel. int.): 576 (2) [M]+, 545 (1) [M-OMe]+, 325 (19) [M-
OCNHC6F4CO2Me]+, 176 (8) [C6F4CO]+, 148 (9) [C6F4]+. Anal. Calcd. for C24H12F8N2O6 (Mw
576.3491): C, 50.01; H, 2.10; N, 4.86%. Found: C, 49.83; H, 1.92; N, 4.76%.
3.4.
X-ray diffraction studies
Intensity data for 2 and 15b were measured on a Bruker SMART APEX II diffractometer
(graphite monochromatized MoKα radiation, λ= 0.71073 Å) using ω-scan mode. The structures
were solved by direct methods and refined by full matrix least-squares on F2 with anisotropic
thermal parameters for all non-hydrogen atoms. In 2, all H atoms were found from difference
Fourier synthesis and refined isotropically. As for 15b, methyl H atoms were placed in
calculated positions and refined using a riding model. Carboxylic atom H1 (common to both
disorder components) was found from difference Fourier map and refined isotropically.
Experimental details are given in Table 1.
Crystallographic data have been deposited at the Cambridge Crystallographic Data Center as
supplementary publications (CCDC-1529963 and 1529964) containing the supplementary
crystallographic
data.
The
data
can
be
obtained
free
of
charge
via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail:
deposit@ccdc.cam.ac.uk.
Acknowledgments
This work was supported in part by M.V. Lomonosov Moscow State University Program of
Development. X-ray diffraction studies were performed at the Centre of Shared Equipment of
IGIC RAS. We thank Dr. A.S. Peregudov (INEOS RAS, Moscow, Russia) for assistance in the
1H-19F HOESY NMR spectrum registration.
Supplementary Material
Supplementary data associated with this article (X-ray structures of 2 and 15b, Figs. S1-S4;
crystallographic data for 2 and 15b, Table S1; NMR spectra for compounds 2-23, Figs. S5-S85)
may be found in the online version.
22
Page 22 of 26

References
a) J. E. Redman, M. R. Ghadiri, Org. Lett. 4 (2002) 4467-4469;
[1]
b) J. Leroy, B. Schöllhorn, J.-L. Syssa-Magalé, K. Boubekeur, P. Palvadeau, J. Fluorine
Chem. 125 (2004) 1379-1382;
c) S. Xie, R. Fukumoto, O. Ramström, M. Yan, J. Org. Chem. 80 (2015) 4392-4397;
d) S. Xie, Y. Zhang, O. Ramstrom, M. Yan, Chem. Sci. 7 (2016) 713-718.
R. S. Pandurangi, K. V. Katti, R. R. Kuntz, C. L. Barnes, W. A. Volkert, Inorg. Chem. 35
(1996) 3716-3718.
[2]
[3]
a) A.-A. Al-Terkawi, G. Scholz, F. Emmerling, E. Kemnitz, Cryst. Growth Des. 16
(2016) 1923-1933;
b) A. Orthaber, C. Seidel, F. Belaj, J. H. Albering, R. Pietschnig, U. Ruschewitz, Inorg.
Chem. 49 (2010) 9350-9357.
[4]
a) R. S. Pandurangi, S. R. Karra, K. V. Katti, R. R. Kuntz, W. A. Volkert, J. Org. Chem.
62 (1997) 2798-2807;
b) R. S. Pandurangi, P. Lusiak, R. R. Kuntz, W. A. Volkert, J. Rogowski, M. S. Platz, J.
Org. Chem. 63 (1998) 9019-9030;
c) C. Chambon, D. Bennat, F. Delolme, G. Dessalces, T. Blachère, M. Rolland de Ravel,
E. Mappus, C. Grenot, C. Y. Cuilleron, Biochemistry 40 (2001) 15424-15435.
O. El Zubir, I. Barlow, E. Ul-Haq, H. A. Tajuddin, N. H. Williams, G. J. Leggett,
Langmuir 29 (2013) 1083-1092.
[5]
[6]
a) J. F. W. Keana, S. X. Cai, J. Org. Chem. 55 (1990) 3640-3647;
b) K. G. Pinney, J. A. Katzenellenbogen, J. Org. Chem. 56 (1991) 3125;
c) S. X. Cai, D. J. Glenn, J. F. W. Keana, J. Org. Chem. 57 (1992) 1299-1304;
d) K. A. H. Chehade, H. P. Spielmann, J. Org. Chem. 65 (2000) 4949-4953;
e) C. Cismaş, T. Gimisis, Tetrahedron Lett. 49 (2008) 1336-1339.
a) T. P. Tran, E. L. Ellsworth, J. P. Sanchez, B. M. Watson, M. A. Stier, H. D. H.
Showalter, J. M. Domagala, M. A. Shapiro, E. T. Joannides, S. J. Gracheck, D. Q.
Nguyen, P. Bird, J. Yip, A. Sharadendu, C. Ha, S. Ramezani, X. Wu, R. Singh, Bioorg.
Med. Chem. Lett. 17 (2007) 1312-1320;
[7]
b) L. C. Davies, F. Friedlos, D. Hedley, J. Martin, L. M. Ogilvie, I. J. Scanlon, C. J.
Springer, J. Med. Chem. 48 (2005) 5321-5328.
[8]
a) B. Schüpbach, M. Bolte, M. Zharnikov, A. Terfort, Eur. J. Org. Chem. (2010) 3041-
3048;
b) F. C. Krebs, T. Jensen, J. Fluorine Chem. 120 (2003) 77-84.
23
Page 23 of 26

[9]
D. W. Bruce, P. Metrangolo, F. Meyer, T. Pilati, C. Präsang, G. Resnati, G. Terraneo, S.
G. Wainwright, A. C. Whitwood, Chem. – Eur. J. 16 (2010) 9511-9524.
[10] a) S. J. Lord, H.-l. D. Lee, R. Samuel, R. Weber, N. Liu, N. R. Conley, M. A. Thompson,
R. J. Twieg, W. E. Moerner, J. Phys. Chem. B 114 (2010) 14157-14167;
b) J. D. Azoulay, Z. A. Koretz, B. M. Wong, G. C. Bazan, Macromolecules 46 (2013)
1337-1342;
c) L.-H. Liu, M. Yan, Acc. Chem. Res. 43 (2010) 1434-1443;
d) Y. Ren, A. Orthaber, R. Pietschnig, T. Baumgartner, Dalton Trans. 42 (2013) 5314-
5321;
e) Y. Ren, Y. Dienes, S. Hettel, M. Parvez, B. Hoge, T. Baumgartner, Organometallics 28
(2009) 734-740.
[11] a) K. V. Zaitsev, A. A. Kapranov, Y. F. Oprunenko, A. V. Churakov, J. A. K. Howard, B.
N. Tarasevich, S. S. Karlov, G. S. Zaitseva, J. Organomet. Chem. 700 (2012) 207-213;
b) K. V. Zaitsev, A. A. Kapranov, A. V. Churakov, O. K. Poleshchuk, Y. F. Oprunenko,
B. N. Tarasevich, G. S. Zaitseva, S. S. Karlov, Organometallics 32 (2013) 6500-6510;
c) K. V. Zaitsev, K. Lam, Z. Zhanabil, Y. Suleimen, A. V. Kharcheva, V. A. Tafeenko,
Y. F. Oprunenko, O. K. Poleshchuk, E. K. Lermontova, A. V. Churakov,
Organometallics 36 (2017) 298-309;
d) M. Huang, M. M. Kireenko, K. V. Zaitsev, Y. F. Oprunenko, A. V. Churakov, J. A. K.
Howard, E. K. Lermontova, D. Sorokin, T. Linder, J. Sundermeyer, S. S. Karlov, G. S.
Zaitseva, Eur. J. Inorg. Chem. (2012) 3712-3724;
e) M. Huang, M. M. Kireenko, E. K. Lermontova, A. V. Churakov, Y. F. Oprunenko, K.
V. Zaitsev, D. Sorokin, K. Harms, J. Sundermeyer, G. S. Zaitseva, S. S. Karlov, Z.
Anorg. Allg. Chem. 639 (2013) 502-511;
f) M. M. Kireenko, K. V. Zaitsev, A. V. Churakov, G. S. Zaitseva, S. S. Karlov, Acta
Crystallogr., Sect. E 68 (2012) m1385-m1386;
g) K. V. Zaitsev, Y. F. Oprunenko, A. V. Churakov, G. S. Zaitseva, S. S. Karlov, Main
Group Met. Chem. 37 (2014) 67-74.
[12] N. N. Solodukhin, N. E. Borisova, A. V. Churakov, K. V. Zaitsev, J. Fluorine Chem. 187
(2016) 15-23.
[13] a) R. C. Leif, L. M. Vallarino, M. C. Becker, S. Yang, Cytometry, Part A 69A (2006)
767-778;
b) C. Seidel, C. Lorbeer, J. Cybińska, A.-V. Mudring, U. Ruschewitz, Inorg. Chem. 51
(2012) 4679-4688;
24
Page 24 of 26

c) M. Sobieray, J. Gode, C. Seidel, Po, C. Feldmann, U. Ruschewitz, Dalton Trans. 44
(2015) 6249-6259.
[14] G. G. Yakobson, V.N. Odinokov, T. D. Petrova, N. N. Vorozhtsov, Zh. Obsh. Khim. (in
Russ.) 39 (1964) 2953; Chem. Abstr. 62 (1965) 470.
[15] K. R. Gee, J. F. W. Keana, Synth. Commun. 23 (1993) 357-360.
[16] L. Qin, C. Sheridan, J. Gao, Org. Lett. 14 (2012) 528-531.
[17] R. Shang, Q. Xu, Y.-Y. Jiang, Y. Wang, L. Liu, Org. Lett. 12 (2010) 1000-1003.
[18] a) J. Burdon, W. B. Hollyhead, J. C. Tatlow, J. Chem. Soc. (1965) 6336-6342;
b) C. Tamborski, E. J. Soloski, J. Org. Chem. 31 (1966) 746-749;
c) J. A. Castellano, J. Green, J. M. Kauffman, J. Org. Chem. 31 (1966) 821-824.
[19] L. V. Politanskaya, V. D. Shteingarts, E. V. Tretyakov, J. Fluorine Chem. 188 (2016) 85-
98.
[20] C. Janiak, J. Chem. Soc., Dalton Trans. (2000) 3885-3896.
[21] S. Xie, O. Ramström, M. Yan, Org. Lett. 17 (2015) 636-639.
[22] A. Li, X. Bin, S.-Z. Zhu, Q.-C. Huang, J.-S. Liu, J. Fluorine Chem. 68 (1994) 145-148.
[23] a) A. Orthaber, R. Pietschnig, Phosphorus, Sulfur, Silicon, Relat. Elem. 188 (2013) 128-
131;
b) M. I. Bruce, J. Chem. Soc. A (1968) 1459-1464.
[24] J. Burdon, P. Dodman, J. Fluorine Chem. 4 (1974) 249-259.
[25] C. Pérez Medina, C. López, R. M. Claramunt, J. Elguero, Eur. J. Org. Chem. (2010) 890-
899.
[26] T. M. Klapötke, B. Krumm, P. Mayer, H. Piotrowski, Z. Anorg. Allg. Chem. 627 (2001)
1983-1989.
[27] a) J. V. B. Kanth, M. Periasamy, J. Org. Chem. 56 (1991) 5964-5965;
b) D. Zhang, Z. Chen, H. Cai, X. Zou, J. Fluorine Chem. 130 (2009) 938-941.
[28] F.-C. Huang, L. F. H. Lee, R. S. D. Mittal, P. R. Ravikumar, J. A. Chan, C. J. Sih, E.
Caspi, C. R. Eck, J. Am. Chem. Soc. 97 (1975) 4144-4145.
[29] Y. Jiang, D. Wang, US Patent (2007) 20070055075.
[30] a) A. Saeed, Z. Ashraf, J. Chem. Sci. 118 (2006) 419-423;
b) A. Bianco, P. Passacantilli, G. Righi, Synth. Commun. 18 (1988) 1765-1771.
[31] H. C. Brown, E. J. Mead, B. C. Subba Rao, J. Am. Chem. Soc. 77 (1955) 6209-6213.
[32] J. Abe, H. Nagahori, R. Omori, K. Mikata, M. Kurosawa, Y. Tomigahara, N. Isobe, J.
Agric. Food Chem. 63 (2015) 8651-8661.
[33] C. Yu, G. Levy, J. Am. Chem. Soc. 106 (1984) 6533-6537.
25
Page 25 of 26

-a series of imines was obtained under interaction of p-H2NC6F4CO2Et with aldehydes
-symmetrical and unsymmetrical derivatives of p-HO2CC6F4CO2H were obtained
-molecular structures of p-H2NC6F4CO2Et and p-HO2CC6F4CO2Me were investigated
Page 26 of 26