Mass spectrometrical and quantum-chemical study of pentafluorophenylhydrazones

Article abstract of DOI:10.1002/jms.4540

Twenty-one pentafluorphenylhydrazones have been analyzed by means of tandem mass spectrometry (ESI MS/MS) conditions to compare their fragmentations with those ones obtained from quantum-chemical calculations of the hydrazone moiety depending on the substitution from the aldehyde site. The hydrazone N–N bond is disrupted under such conditions, and these results are in accordance with the facts that an electron-rich particle, such as an anion and or radical in a solution, can cause this disruption and simultaneous defluorination in para-position of the hydrazone part of the molecule.

Full text of DOI:10.1002/jms.4540

Milata Viktor (Orcid ID: 0000-0001-8986-1752)
Mass spectrometrical and quantum-chemical study of
pentafluorophenylhydrazones.
Dušan Bortňáka, Daniel Pecherd, Daniel Végha, Martin Brezab, Peter Mikušc, Viktor Milataa
aDepartment of Organic Chemistry; bDepartment of Physical Chemistry, Faculty of Chemical and
Food Technology, Slovak Technical University, Radlinského 9, SK-812 37 Bratislava, Slovakia
cDepartment of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius
University in Bratislava, Odbojárov 10, SK-832 32 Bratislava, Slovakia
dToxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava,
Odbojárov 10, SK-832 32 Bratislava, Slovakia
DEDICATION: This publication is dedicated to 200 years cumulated anniversary of Heterocyclic
chemistry at Technical University Vienna on the occasion of Prof. Fritz Sauter (90), Prof. J. Fröhlich
(60) and Prof. M. Mihovilovic (50).
ABSTRACT
Twenty-one pentafluorphenylhydrazones have been analyzed by means of tandem mass
spectrometry (ESI MS/MS) conditions to compare their fragmentations with those ones obtained
from quantum-chemical calculations of the hydrazone moiety depending on the substitution from
the aldehyde site. The hydrazone N – N bond of is disrupted under such conditions and therefore
these results are in accordance with the facts that an electron rich particle, such as an anion and or
radical in a solution, can cause this disruption and simultaneous defluorination in para-position of
the hydrazone part of the molecule.
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/jms.4540
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1 INTRODUCTION
Hydrazones are very useful intermediates in organic synthesis [1] for their possible broad
application[2]. In continuation of our previous work (synthetic exploitation of
pentafluorophenylhydrazine), where we demonstrated its different reactivity in comparison to
phenylhydrazine with 3-oxo-2-ethoxymethylenebutanenitrile [3] or its reactions with various ,-
activated enolethers [4] or in Clauson-Kaas Reaction [5], we decided to study nucleophilic
substitution of the azide anion with various pentafluorophenylhydrazones 1 listed in Table 1 (Fig. 1):
Poly/perfluorinated aromatics are very frequently used substrates for numerous nucleophiles like
azides ([5-8], nitromethane [9-11], cyanide anion ([12], or other nucleophiles [13]. They are
employed as a principal step in the building of selective substituted (hetero)aromatics. We have
prepared a set of pentafluorophenylhydrazones and started to study the planned reaction with the
azide anion. Because preliminary results were very repugnant, we decided to extend the set of the
studied compounds to twenty-one derivatives. Our set included the sterically hindered alkyl-
substituted derivative 1u, variously substituted phenylderivatives with electron-withdrawing (1i, 1j),
activated (1a, 1b) or strongly activated (1c-1h) derivatives and electron-rich five-membered
heterocycles with diene (furane derivatives 1r-1t) with less (1k) or more aromatic character
(thiophene derivatives 1l – 1q) bearing different substituents in positions 5-, but also 4- (1q, 1m) and
finally bithiophene derivatives 1n, 1p where we have prepared also the corresponding hydrazone
from the deuterated aldehyde 1o for special study.
2 MATERIALS AND METHODS
All NMR spectra were obtained using an INOVA NMR 300 MHz spectrometer (operating frequencies
of 300 MHz (1H), 75 MHz (13C) and 282 MHz (19F) ) equipped by an inverse triple resonance probe
and a standard tuneable X/H probe with the possibility to tune the high frequency channel to the
1
resonance frequency of 19F. Tetramethylsilane was used for the calculation of the H and 13C
chemical shift scales and correctly referenced using the (residual) solvent signals (2.50 and 39.52
19
ppm for DMSO, 7.26 and 77.00 ppm for chloroform). CFCl3 was used for the calculation of the F
chemical shift scale; in order to correctly reference the 19F chemical shift scale an automatic
referencing mechanism exploiting the 2H signal of the deuterated solvent was used.
2.1 Synthesis
The synthesis of the pentafluorophenylhydrazones 1, published previously in ref. [17], was properly
modified (Scheme 1). The synthesis is based on the condensation of the ethanolic solution of
pentafluorophenylhydrazine with an ethanolic solution of appropriate aldehyde and with a catalytic
amount of hydrochloric acid according to the following scheme:
Particular products were sufficiently pure for the synthesis, but before the mass spectra analysis the
samples were purified by recrystallisation or column chromatography (the yield of 1r is low due to its
lower stability in acidic media while other furane derivatives have stabilizing substituents; the given
result is obtained after chromatography). Majority of used aldehydes were obtained from Merck /
Sigma-Aldrich® and pentafluorophenylhydrazine has been obtained from Flurochem®. New
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compounds are presented with their physico-chemical properties, for known compounds only
unpublished characteristics are presented (Table 2).
General procedure for the preparation of pentafluorophenylhydrazones 1
To the solution of the corresponding aldehyde in ethanol we have added the ethanolic solution of
the pentafluorophenylhydrazine according to the amounts given in Table 2. To this mixture a
catalytic amount of concentrated hydrochloric acid was added (approximately 3-5 drops). The
reaction mixture has been refluxed for 8 hours (under TLC + UV control). The solvent was evaporated
under reduced pressure and the residue has been crystallized from ethanol to obtain the
pentafluorophenylhydrazone 1.
1-Benzylidene-2-(perfluorophenyl)hydrazine (1a)
White crystalline matter.
1-(2-methylbenzylidene)-2-(perfluorophenyl)hydrazine (1b)
White crystalline matter. 1H NMR (300 MHz, dmso) δ 10.27 (s, 1H), 8.41 (s, 1H), 7.68 (m, 1H), 7.22
(m, 3H), 2.41 (s, 3H). 13C NMR (75 MHz, dmso) δ 141.3, 137.8 (d,tt, J= 244, 14, 5 Hz) 137.1 (dm, J=
244H) 135.7, 133.5 (dtt J=242, 20, 5 Hz) 132.6, 130.8, 128.6, 126.0, 125.4, 121 (t J=11Hz) 19.2.
1-((4-bromo-5-methylthiophen-2-yl)methylene)-2-(perfluorophenyl)hydrazine (1m)
Brown crystalline matter. 1H NMR (300 MHz, dmso) δ 10.37 (s, 1H), 8.17 (s, 1H), 7.23 (s, 1H), 2.34 (s,
3H). 13C NMR (75 MHz, dmso) δ 137.7 (dm J=245 Hz), 137.3 (dm J=246 Hz) 137.2, 136.0, 135.0, 133,9
(dm J= 247Hz) 129.9, 120.8 (m) 108.7, 14.6.
(E)-1-((5-nitrofuran-2-yl)methylene)-2-(perfluorophenyl)hydrazine (1s)
Orange crystalline matter. 1H NMR (300 MHz, dmso) δ 10.95 (s, 1H), 8.03 (s, 1H), 7.75 (d, J = 3.9 Hz,
1H), 7.03 (d, J = 4.0 Hz, 1H). 13C NMR (75 MHz, dmso) δ 152.7, 151.3, 138.2 (dm J= 245 Hz) 137.7 (dm
J=247 Hz) 135,1 (dm J= 245 Hz) 129.4, 119,8 (m) 115.2, 112.5.
2.2 LC-Q-TOF MS/MS conditions
Liquid chromatography high-resolution tandem mass spectrometry (LC-MS/MS) analyses were
performed on an LC Agilent Infinity System (Agilent Technologies, Santa Clara, CA, USA) equipped
with a gradient pump (1260 Bin Pump VL), an automatic injector (1260 HiPals), and a column
thermostat (1290 TCC). The LC was performed using the Zorbax Extend-C18 column, 2.1x50 mm,
1.7µm (Agilent Technologies, Santa Clara, CA, USA) column with a mixture of acetonitrile and 0.1%
aqueous solution of formic acid as mobile phases. Gradient elution was used with the linear gradient
from 5 to 95% of acetonitrile in 10 minutes. The flow rate was of 400 μL/min.
The LC system was coupled with a quadrupole time-of-flight mass spectrometer (6520 Accurate Mass
Q-TOF LC/MS - Agilent Technologies, Santa Clara, CA, USA) which was equipped with an electrospray
ionization source operated in positive ionization mode. All measurements were performed with the
following MS parameters: drying gas temperature 360°C, drying gas flow 12 L.min−1, nebulizing gas
pressure 60 psi, ESI source voltage 3500 V, fragmentor voltage 100 V, skimmer voltage 65 V,
collision gas N2. The system was calibrated before analysis to an external standard and internal
calibration during the analysis using a reference solution was used as well. The data were scanned
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over the mass range m/z = 50 - 1000. MS/MS fragmentation was done applying collision energy of
10, 20, and 40 eV, respectively.
All compounds were dissolved in the acetonitrile-water mixture (1:1, V/V) resulting in solutions with
concentrations of 1 mg/mL, which were used for the LC-MS/MS analysis (injection volume 1.0 µL).
The obtained m/z of [M+H]+ adducts of the analyzed compounds were compared to the theoretical
m/z values of these adducts calculated by MassHunter software and the mass deviations in ppm were
calculated [(m/ztheor.-m/zobtained)/m/ztheor. x 106]. All mass deviations were lower than 5 ppm. The
fragmentation spectra of each compound obtained by applying all of the above-mentioned collision
energies were also recorded, and the tentative molecular formulas were calculated for the most
abundant fragments (MassHunter Workstation Software Version B.06.00).
2.3 Computational methods
Geometries of the neutral compounds A under study and of their AH+ cations protonated at
heteroatom sites in their singlet ground states were optimized at the DFT level of theory using the
B3LYP hybrid functional [21]. Dunning’s correlation consistent cc-pVDZ basis sets were used for all
atoms [22]. Stability of the optimized structures was tested by vibrational analysis (no imaginary
vibrations). All calculations were performed using Gaussian16 software [23]. MOLDRAW software
was used for geometry manipulation and visualisation purposes. [24]. If the conformational changes
due to protonation cause sufficient bond elongation, these bonds are weakened and hence are more
likely to cleave. [25]. Therefore the bond elongation after protonation
Δd = d(AH+) – d(A)
(1)
where A and AH+ are the neutral molecule and its protonated cation, respectively, seem to be a good
prediction parameter for MS fragmentation. However, quantum chemistry alone cannot predict the
collision energies appropriate for fragmentation[26].
3 RESULTS AND DISSCUSION
In this structure-fragmentation correlation study, we have used mass spectrometry for both
confirming molecular mass and elemental composition of investigated ions (due to complications
with elemental analysis of fluorinated compounds), as well as for the study of the title compounds in
deep vacuum. Mass spectrometry can be a versatile tool for study of energies of the bonds in the
molecule under deep vacuum conditions, e.g. without any stabilizing influences like solvatation,
dipole-dipole interaction etc., and, of course, without the influence of any anion/nucleophile. [27]
From this point of view, we can consider the influence of the strong electron-withdrawing effect of
the pentafluorophenyl nucleus onto -NH-N=CH- fragment substituted from the opposite side with
alkyl, aryl, electron-rich five-membered heteroaryl nuclei bearing various substituents in different
positions. Such hydrazones 1 were prepared from logical components, but their chemical reaction
with azide or cyanide anion, respectively gave surprisingly unexpected products, 2,3,5,6-
tetrafluorophenylaniline and corresponding nitrile [17]. Thus, breaking of the NH-N= is the crucial
moment to study the behaviour of the title molecules. For this reason we have used tandem mass
spectrometry technique applied to the molecular ion: even though we have recorded
fragmentations of this molecular ion applying multiple collision energies, for comparison we
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considered only the lowest one, e.g. 10 eV to gently influence studied molecules and thus finding the
softest bond(s) in the molecule. A representative MS/MS spectrum (collision energy of 10 eV) of one
of the studied compounds is presented in Fig. 2. Abundancies of the individual fragments obtained
by MS/MS analysis are summarized in the Table 3. The relative abundancies were calculated as the
ratio of absolute abundance of the fragment and the sum of abundancies of all observed masses
with abundance >1.00% of the most abundant mass). (Fig. 2):
Fig. 2: ESI MS/MS spectrum of 1r
Strong electron-withdrawing effect of the penta/tetrafluorophenyl substituent is causing
polarization of N-N bond. The nitrogen of this bond, which is bounded by the stronger double bond
with the carbon atom is in conjugation with (hetero)aromatic nucleus. Therefore, the fragmentation
of most of the derivatives 1 results in Ar-CH(D)N ion and ion C6F5NH with m/z 182,0026 (path B,
Scheme 2):
At the same time a parallel fragmentation (Table 3) based on the dehydrofluorination (path A) or
double dehydrofluorination (path AA) of the protonated species during ionization occurs. This
scheme is applied for unsubstituted phenyl derivative 1a and slightly activated (2-methylphenyl)
derivatives 1b. Other mesomerically strongly activated arylderivatives (1c-1h) have common feature
that ion m/z 182 is observed only in low abundancies and only one dehydrofluorination occurrs –
path A (with the exception of 2,4-dihydroxyderivative 1e displaying follow-up dehydrocyanation of
the ion m/z 182 and the presence of path AA). For 1d, 1h the ion M – 182 (Ar-CH(D)=N) undergoes
dehydrocyanation less (1d) or more (1h) intensively. In the trimethoxyderivative 1g the
demethylation of the M – 182 ion m/z 180 and following demethoxylation to ion m/z 149 (relative
abundance 2.57%) is present.
Deactivated arylderivatives (1i, 1j) produce the ion m/z 182 with parallel (dehydro)fluorination and
following denitration (m/z 266; relative abundance 6.96 %) or demethoxycarbonylation (m/z 267;
relative abundance 7.91 %).
Arylsubstituted pentafluorophenylhydrazones were supplemented with electron-rich five-
membered heterocycles with various substituents (1k-1t). 1-Methylpyrrol-2-yl derivative 1k does
not produced the ion m/z 182, but M – 182 = 108 is sufficiently intensive (relative abundance 32.13
%). Besides the path A the dehydrocyanation of the parent ion (m/z 263; relative abundance 15.73
%) parallelly occurs. Thiophene derivative 1l fragments through both path A and B, while its 5-
methyl-4-bromo analogue 1m does not displayed ion m/z 182. Dithiophene derivatives 1n – 1p
display only the ion M – 182. In the case of deuterated analogue 1o the fragmentation confirms the
fact that no deuterium is migrated between the fragments. The 5-Nitrothienyl derivative 1q behaves
differently: besides the fragmentation path B, the typical fragmentation for the nitrocompounds,
e.g. M – 16 (deoxygenation; relative abundance 7.01 %), followed by (M – 16) – 30 (removal NO;
relative abundance ) and final defluorination to the ion m/z 272 (relative abundance 1.54 %) occurs
parallelly. Interesting is also the third fragmentation path to m/z 272 (relative abundance 3.47 %)
which represents the elimination of H2ONS fragment from the molecular ion. Unlike the aromatic
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thiophene derivatives, the furane ones have higher diene character. The parent furane derivative 1r
displays paths B, A and AA with following decarbonylation or denitrogenation of ions m/z 257 (path
A) or 237 (path AA), respectively. The 5-Nitrofurane derivative 1s undergoes path B and
also produces the ion m/z 247 (after the release of O2N-CH=O fragment similar to thiophene; relative
abundance 10.73 %). This ion is defluorinated or should eliminate C4H3N to m/z 182 by the path
parallel to the path B. The 5-(4-Bromophenyl)furane derivative 1t undergoes fragmentation similar
to activating arylderivatives and does not produce the ion m/z 182, but produces an ion M – 182 =
251. Alternatively, it undergoes decyanation (m/z 405; relative abundance 2.12 %) followed by
debromination to the ion m/z 325 (relative abundance 0.46 %).
The aromatic nucleus from aldehyde part of the title pentafluorophenylhydrazones derivatives 1a-1t
produces the Ar-CH(D)N ion and the C6F5NH ion with m/z 182,0026 (path B). This is supported by the
fact that non-aromatic aldehyde derivative of 2,2-dimethylpropanal 1u produces the ion with m/z
197 (C6H2F5N2; relative abundance 11.97 %) which gives the ion m/z 182 after elimination of NH. In
this case, also an elimination of HCN is occurring with the resulting ion m/z 155 (C5F5; relative
abundance 0.42 %). Path A displays no ion, but path AA gives the ion m/z 227.
Studied aromatic and heteroaromatic derivatives of pentafluorophenylhydrazones 1 present one
principal fragmentation occurring after breaking the N – N bond of the hydrazone bridge, which is
not typical for aliphatic analogues. This fact confirms our experimental results of the reaction of the
title pentafluorophenylhydrazones with anions which give us similar products and also parallel
nucleophilic substitution of the fluorine atom in position 4 [17].
To confirm the presence of fluorine atoms in the molecules we also measured 19F NMR spectra and
performed HRMS instead of elemental analysis. Because some compounds prepared previously by
us have not been yet published with 19F NMR spectra, they are displayed in Table 4.
3.2 Quantum chemical calculations-fragmentation correlation
The protonation at F atoms in meta- and para- positions leads usually to C-F bond breaking and a
simple HF removal. This is connected with up to 0.05 Å changes in bridge bonds. Protonated F atoms
in ortho- positions can be moreover replaced by H atoms and for the realated HF splitting is taken
the H atom from the -NH- bridge site. The protonation of other heteroatoms is connected with
lower bridge bonds changes than of the F atoms. Nitro group N atoms are not protonated and the H
atom is shifted to the neighboring aromatic C atoms. Analogously for the Br atom in 1m the proton
is shifted to the bridge –N= site.
The greatest N-N bond elongation is connected with the protonation at the bridge –NH- site (Table
5) whereas the neighboring –N= site protonation has much lower bond-length consequences (Table
6). Our results indicate that the N-N bond splitting is more probable than of the neigboring NH-CPhF
bond to the fluorinated benzene ring (maybe except 1g). An alternative C(H)-N bridge bond break is
even much less probable and breaking the C(H) bond to an aromatic carbon atom of the R
substituent is highly improbable.
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4 CONCLUSIONS
Twenty-one pentafluorophenylhydrazones have been prepared to study their reaction with the
azide anion which provided an unexpected decay to nitrile and 2,3,5,6-tetrafluoroaniline. Therefore,
we studied energies and bond dissociation of these molecules in the gaseous phase under strong
dilution (ESI MS/MS). We have found that the N – N bond of the hydrazone is disrupted under such
conditions (fragment C6F5NH = 182.0026 and corresponding (protonated) nitrile = M – 182.0026 are
produced). These results are in accordance with the facts that electron-rich particles, such as
an anion or a radical in a solution, can cause this disruption and simultaneous mono/double
de(hydro)fluorination in para-position of the hydrazone residuum of the molecule.
ACKNOWLEDGEMENTS
This work has been supported by the Research and Development Agency under the contracts No.
APVV-17-0513 and is also the result of the project: Research Center for Industrial Synthesis of Drugs,
ITMS 26240220061, supported by the Research & Development Operational Program funded by the
ERDF.
We thank the HPC center at the Slovak University of Technology in Bratislava, which is a part of the
Slovak Infrastructure of High Performance Computing (SIVVP Project ITMS 26230120002 funded by
the European Region Development Funds) for computing facilities. M.B. thanks the Ministry of
Education, Science, Research and Sport of the Slovak Republic for funding within the scheme
‘Excellent research teams’.
ORCID
Viktor Milata 0000-0001-8986-1752
Martin Breza 0000-009-5995-0279
Daniel Pecher 0000-0002-9284-1493
Dušan Bortňák 0000-0003-4140-9163
Daniel Végh 0000-0003-3945-7107
Peter Mikuš 0000-0001-5755-9970
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Table 1: List of prepared and studied compounds
Entry
1a
Substituent R
Ref.
[14]
phenyl
1b
1c
2-methylphenyl
2-hydroxyphenyl
[15]
[16]
1d
1e
4-methoxyphenyl
2,4-dihydroxyphenyl
[17]
[16]
1f
benzo[d][1,3]dioxol-5-yl
[17]
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1g
3,4,5-trimethoxyphenyl
[16]
1h
1i
4-(N,N-dimethylamino)phenyl
4-(methoxycarbonyl)phenyl
4-nitrophenyl
[17]
[17]
[16]
[18]
1j
1k
1-methylpyrrol-2-yl
1l
thiophene-2-yl
[19]
1m
4-bromo-5-methylthiophene-2-yl
1n
2,2´-bithiophene-5-yl
[19]
1o
1p
2,2´-bithiophene-5-yl
5´-bromo-2,2´-bithiophene-5-yl
* like above
[17]
[17]
1q
1r
1s
1t
5-nitrothiophene-2-yl
fur-2-yl
[17]
[20]
5-nitrofuran-2-yl
5-(4-bromophenyl)furan-2-yl
[17]
[17]
1u
tert-butyl
* appropriate deuterated aldehyde has been used
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Table 2: Reaction conditions of the pentafluorophenylhydrazine with the corresponding aldehyde
Compd.
C6F5NHNH2
(g/mmol/ml of EtOH)
Adehyde
(g/mmol/ml of EtOH)
Yield
(%)
Note
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
1.866/9.42/20
1.649/8.32/20
1.622/8.19/20
1.455/7.34/20
1.434/7.24/20
1.319/6.66/15
1.010/5.10/10
1.328/6.70/15
1.207/6.09/15
1.311/6.62/15
1.815/9.17/20
1.766/8.91/20
0.966/4.88/10
1.020/5.15/10
0.202/1.0/5
1.000/9.42/5
1.000/8.32/5
1.000/8.19/5
1.000/7.34/5
1.000/7.24/30
1.000/6.66/45
1.000/5.10/20
1.000/6.70/35
1.000/6.09/25
1.000/6.62/20
1.000/9.17/5
1.000/8.91/5
1.000/4.88/20
1.000/5.15/20
0.200/1.0/5
42
72
92
40
35
74
89
81
98
71
27
64
60
88
91
73
85
a
a
a
a
a
a
a
a
a
a
b
a
a
a
a
a
a
b
a
a
c
0.725/3.66/10
1.260/6.36/15
2.062/10.41/20
1.404/7.09/15
0.789/3.98/10
0.500/2.52
1.000/3.66/20
1.000/6.36/15
1.000/10.41/5
1.000/7.09/15
1.000/3.98/20
0.197/2.29
8
63
quant.
quant.
s
t
u
a – crystallized from ethanol, b – chromatographed (silicagel 60 m/toluene), c – use of BF3.Et2O
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Table 3: Reaction conditions of the pentafluorophenylhydrazine with corresponding aldehyde
Parent ion
[M + H]+
Path B
Ar - CH(D)N
Rel.
Path A
M - HF
Path AA
C6F5NH
Rel.
M - 2H2F
Compou
nd
Rel.
Rel.
Rel.
abun
d.
abun
d.
abun
d.
abun Abun abun
Abund.
Abund.
Abund.
Abund.
d.
d.
d.
(%)
(%)
(%)
(%)
(%)
20833.0
6
15404.
27
1807.
99
1a
1b
1c
1d
1e
1f
38.74 5900.51 10.97 5806.4 10.80
28.65
22.95
13.34
6.70
3.36
2.51
<1.00
<1.00
<1.00
<1.00
-
51635.2
6
18821.7
6
8127.5
4
29787.
80
3259.
04
39.78
14.50
6.26
12843.7
6
4060.5
8
124.1
7
42.20 4161.70 13.67 635.31 2.09
87434.1
5
47257.2
9
1613.3
5
12518.
16
1256.
99
46.83
46.07
34.67
25.31
43.03
<1.00
<1.00
342298.
83
319676.
31
2170.8
2
32142.
01
2508.
32
4.33
26053.2
0
41399.3
9
1766.2
5
183.7
8
55.09 298.98 <1.00
2.35
15339.2
2
1g
1h
4438.53 19.91
118604 48.57
68.81
32.26
6.13
-
-
-
-
35.34 <1.00
472.66 <1.00
-
-
78782.4
1
-
73120.4
43.61
2
10276.0
4
19689.
77
25255.
15.06
53
1600.
34
1i
1j
11.74
<1.00
-
624.26 30.90
23.69
1.17 924.87 45.79 138.41 6.85
-
23685.2
33.02
8
23048.7
1
1174.8
299.1
4
1k
32.13
11.47
-
-
1.64
<1.00
2
43715.8
39.40
7
12732.1
4
10763.
67
30654.
95
3503.
35
1l
1m
1n
1o
1p
1q
9.70
27.63
3.16
33104.1
1477.2
7
3616.3
7
238.5
4
59.05 5690.99 10.15
2.64
6.45
<1.00
2
12540.2
5102.1 21.80
29229 27.48
53.58
71.52
77.00
1.20
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
76064.9
6
15776.7
16.77
8
72453.6
3
4718.9
2
3194.46 29.46 130.21
43.51 559.41 5.16
66408.0
9
23735.2
4
17662.
57
29901.
2324.
50
1r
1s
1t
38.37
13.71
10.20
17.28
1.97
1.34
7
409.88 20.40
17.85
<1.00 948.61 47.22 39.63
-
-
-
22088.2
34.50
2
29777.6
9
2052.9
46.51
3.21 875.35 <1.00
-
6
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131484.
93
53404.2
0
36698.
1
15670.
14
7697.
99
1u
34.34
13.95
9.58
4.09
2.01
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Table 4. 19F NMR spectra of selected compounds 1
 (19F NMR)
 (19F NMR)
Compound
Compound
1b
-156.20 (d, J = 24.9 Hz, 2F), - 1j
164.47 (td, J = 23.9, 4.0 Hz,
2F), -170.75 (tt, J = 23.3, 6.0
Hz, 1F)
-155.23 (m, 2F), -164.04 (td, J = 22.3,
3.3 Hz, 2F), -168.55 (tt, J = 23.3, 4.9 Hz,
1F)
1c
-156,84 (m, 2F), -164.16 (m, 1m
2F), -170.50 (tt, J = 23.3, 5.9
Hz, 1F)
-155.75 (m, 2F), -164.33 (m, 2F), -169.73
(m, 1F).
1d
δ -156.00 (dd, J = 19.9, 4.6
Hz,2F), -164.53 (td, J = 23.2,
4.1 Hz, 2F), -170.81 (tt, J =
23.3, 6.1 Hz, 1F)
1r
-155.48 (dd, J = 19.0, 4.0 Hz, 2F), -
164.36 (td, J = 21.8, 2.8 Hz, 2F), -169.68
(tt, J = 23.3, 5.6 Hz 1F)
1g
-155.61 (m, 2F), -164.32 (m, 1s
2F), -170.05 (m, 1F)
-154.48 (d, J = 23.4 Hz, 2F), -163.80 (td, J
= 22.5, 3.7 Hz, 2F), -167.08 (t, J = 23.1
Hz, 1F)
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Table 5. Relevant bond-length changes, Δd [Å] (Eq. (1)), for the protonation at the bridge –NH- site
Entry
1a
1b
1c
CR-CH
CH-N
N-NH
NH-CPhF
0.076
0.077
0.075
0.055
0.079
0.128
0.082
0.073
0.078
0.075
0.073
0.073
-0.015
-0.016
-0.025
-0.032
-0.023
-0.027
-0.030
-0.006
-0.021
-0.021
-0.011
-0.012
0.007
0.009
0.016
0.022
0.013
0.015
0.020
0.002
0.011
0.012
0.004
0.004
0.131
0.132
0.109
0.064
0.126
0.126
0.120
0.139
0.128
0.133
0.138
0.138
1d
1f
1g
1h
1j
1l
1m
1q
1s
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Table 6. Relevant bond-length changes, Δd [Å] (Eq. (1)), for the protonation at the bridge –N= site
Entry
1a
1b
1c
CR-CH
CH-N
N-NH
NH-CPhF
0.037
0.040
0.033
0.022
0.041
0.091
0.044
0.032
0.039
0.038
0.031
0.030
-0.027
-0.028
-0.021
-0.062
-0.038
-0.045
-0.050
-0.020
-0.035
-0.033
-0.025
-0.024
0.019
0.019
0.015
0.044
0.026
0.030
0.036
0.016
0.023
0.023
0.018
0.018
0.038
0.038
0.024
0.012
0.044
0.048
0.047
0.037
0.041
0.042
0.041
0.040
1d
1f
1g
1h
1j
1l
1m
1q
1s
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Fig. 1: Title pentafluorophenylhydrazones 1
Fig. 2: ESI MS/MS spectrum of 1r
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Scheme 1
1
Scheme 1: Preparation of the pentafluorophenylhydrazones 1
Scheme 2
1
Scheme 2: Fragmentation scheme of pentafluorophenylhydrazones 1
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