Effects of hydrogen bonding on the gas-phase reactivity of didehydroisoquinolinium cation isomers

Article abstract of DOI:10.1039/c8cp03350a

Two previously unreported isomeric biradicals with a 1,4-radical topology, the 1,5-didehydroisoquinolinium cation and the 4,8-didehydroisoquinolinium cation, and an additional, previously reported isomer, the 4,5-didehydroisoquinolinium cation, were studied to examine the importance of the exact location of the radical sites on their reactivities in the gas phase. The experimental results suggest that hydrogen bonding in the transition state enhances the reactivity of the 1,5-didehydroisoquinolinium cation towards tetrahydrofuran but not towards allyl iodide, dimethyl disulfide or tert-butyl isocyanide. The observation of no such enhancement of reactivity towards tetrahydrofuran for the 4,8-didehydroisoquinolinium and 4,5-didehydroisoquinolinium cations supports this hypothesis as these two biradicals are not able to engage in hydrogen bonding in their transition states for hydrogen atom abstraction from tetrahydrofuran. Quantum chemical transition state calculations indicate that abstraction of a hydrogen atom from tetrahydrofuran by the 1,5-didehydroisoquinolinium cation occurs at the C-1 radical site and that the transition state is stabilized by hydrogen bonding.

Full text of DOI:10.1039/c8cp03350a

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Effects of hydrogen bonding on the gas-phase
reactivity of didehydroisoquinolinium cation
isomers†
Cite this:DOI: 10.1039/c8cp03350a
Nelson R. Vinueza, ‡ Bartłomiej J. Jankiewicz, § Vanessa A. Gallardo,
John J. Nash and Hilkka I. Kenttamaa
*
¨
Two previously unreported isomeric biradicals with a 1,4-radical topology, the 1,5-didehydroisoquinolinium
cation and the 4,8-didehydroisoquinolinium cation, and an additional, previously reported isomer, the
4,5-didehydroisoquinolinium cation, were studied to examine the importance of the exact location of the
radical sites on their reactivities in the gas phase. The experimental results suggest that hydrogen bonding
in the transition state enhances the reactivity of the 1,5-didehydroisoquinolinium cation towards
tetrahydrofuran but not towards allyl iodide, dimethyl disulfide or tert-butyl isocyanide. The observation
of no such enhancement of reactivity towards tetrahydrofuran for the 4,8-didehydroisoquinolinium and
4,5-didehydroisoquinolinium cations supports this hypothesis as these two biradicals are not able to
engage in hydrogen bonding in their transition states for hydrogen atom abstraction from tetrahydrofuran.
Quantum chemical transition state calculations indicate that abstraction of a hydrogen atom from
tetrahydrofuran by the 1,5-didehydroisoquinolinium cation occurs at the C-1 radical site and that the
transition state is stabilized by hydrogen bonding.
Received 26th May 2018,
Accepted 1st August 2018
DOI: 10.1039/c8cp03350a
rsc.li/pccp
Introduction
Didehydroarenes, aromatic carbon-centered s,s-biradicals,
have received intense attention since the discovery that
1
,4-didehydroarenes and analogs are the biologically active
1–3
intermediates of the enediyne class of antitumor antibiotics.
Gas-phase studies on related charged molecules (that can be
studied using mass spectrometers) have offered valuable insights
4–9
into the reactivities of these elusive species. These studies have
suggested that the reactivity of the biradicals depends on the
magnitude of the (calculated) vertical electron affinity (EA) of their
radical sites, their (calculated) singlet–triplet splitting (DES–T), and
their (calculated) distortion energy if they are meta-benzyne
analogs. However, the importance of the exact location of the
radical sites in isomers with the same radical topology has not
been explored.
Fig. 1 The dehydro- and didehydroisoquinolinium cations studied.
Herein we report a study on the reactivities of two previously
unreported, isomeric biradicals with a 1,4-radical topology, the
7
–9
1,5-didehydroisoquinolinium cation 6 and the 4,8-didehydro-
isoquinolinium cation 7, and compare their behavior to that of
1
0
an earlier reported isomer, the 4,5-didehydroisoquinolinium
cation 5, as well as related monoradicals (Fig. 1).
Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette,
IN, 47907, USA. E-mail: hilkka@purdue.edu
†
Electronic supplementary information (ESI) available: Cartesian coordinates,
Results and discussion
electronic energies, zero-point vibrational energies, 298 K thermal contributions,
an X-ray structure. CCDC 1844327. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c8cp03350a
The three isomeric biradicals and their monoradical analogs
were generated from iodo- and/or nitroprecursors in a dual-cell
Fourier-transform ion cyclotron resonance mass spectrometer
via protonation followed by cleavage of the iodine atoms and/or
nitro groups via collision-activated dissociation, as described
‡
Current address: Department of Textile Engineering, Chemistry and Science,
College of Textiles, North Carolina State University, Raleigh, NC, 27695, USA.
Current address: Institute of Optoelectronics, Military University of Technology,
§
Kaliskiego 2, 00-908 Warsaw, Poland.
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4
–6,9
previously.
The radicals were isolated and transferred into a
The reactivity of a given monoradical toward different
clean cell for reactivity studies. The reactivities of the different reagents depends on several variables, including the ionization
1
6,17
radicals toward each reagent are compared below.
energy of the reagent and the reaction mechanism.
Based on
Based on the literature, organic singlet ground-state biradicals of the literature, the efficiencies of reactions of the monoradicals
the type of interest here may be expected to display similar reactivity studied here with THF are expected to be lower than with allyl
1
6
if they have similar EAs and S–T splittings (with the exception of iodide, DMDS, and t-BuNC. This was observed for 2, 3 and 4.
4,8,9,11
meta-benzyne analogs).
However, in this study, biradical 6 was However, monoradical 1 exhibits comparable reactivity toward
found to abstract a hydrogen atom from tetrahydrofuran (THF) THF as toward the other reagents (reaction efficiencies: THF:
substantially faster than biradical 7 (reaction efficiencies: 68% and 83%; allyl iodide: 73%; DMDS: 87%; t-BuNC: 100%; Table 1).
12,13
10%, respectively) despite having a similar (calculated)
EA and This observation can be rationalized by a stabilizing hydrogen
S–T splitting. In sharp contrast, both biradicals abstract an iodine bonding interaction in the transition state for hydrogen atom
1
8
atom from allyl iodide at a similar efficiency (54% and 41%, respec- abstraction from THF, as reported earlier. This effect is only
tively). To rationalize these findings, the reactivities of biradicals 5–7 possible for 1 since only this radical has a radical site on the
and related monoradicals 1–4 are discussed in detail below.
carbon atom adjacent to the protonated nitrogen atom, which
+
The reactivity of the monoradicals is straightforward. The enables THF to engage in hydrogen bonding with the NH
1
-dehydroisoquinolinium cation (1), 4-dehydroisoquinolinium proton in the transition state.
1
0
cation (2), 8-dehydroisoquinolinium cation (3) and 5-dehydro-
isoquinolinium cation (4) react predominantly by abstraction mostly yield primary product ions analogous to those of the
The reactions of biradicals 6 and 7 with all studied reagents
1
0
of a hydrogen atom from THF, an iodine atom from allyl iodide, four related monoradicals. They also yield secondary product
an SCH group from dimethyl disulfide (DMDS) and CN and ions not observed for the monoradicals (Tables 1 and 2) due to
3
4
,14
HCN groups from tert-butyl isocyanide (t-BuNC), as expected
radical reactions at the second radical site. These reactions are
(
(
Table 1). The reactivities of the monoradicals reflect their analogous to those occurring at the most reactive radical site of
calculated) EAs, also as expected. Monoradical 1 is the most the biradicals and to those observed for the monoradicals. For
1
5
reactive, followed by 2, 3 and 4 (calculated EAs are as follows: example, two consecutive hydrogen atom abstractions from THF,
: 6.45 eV; 2: 5.76 eV; 3: 5.16 eV; 4: 4.98 eV; Table 1). two consecutive iodine atom abstractions from allyl iodide,
1
a
b,c
Table 1 Reaction efficiencies and product branching ratios for reactions of monoradicals 1–4 with various reagents, and the calculated vertical
d
electron affinities (EA) of the radicals
Reagents
Radical
c
H abs 100%
I abs 94%
abs 6%
SCH
3
abs 100%
CN abs 96%
HCN abs 4%
3 5
C H
EA = 6.45 eV
Efficiency = 83%
H abs 100%
Efficiency = 73%
I abs 94%
Efficiency = 87%
SCH abs 100%
Efficiency = 100%
3
CN abs 96%
HCN abs 4%
3 5
C H abs 6%
EA = 5.76 eV
EA = 5.16 eV
Efficiency = 39%
H abs 100%
Efficiency = 71%
I abs 100%
Efficiency = 73%
SCH abs 100%
Efficiency = 84%
3
CN abs 94%
HCN abs 6%
Efficiency = 25%
H abs 100%
Efficiency = 43%
I abs 98%
Efficiency = 34%
SCH abs 100%
Efficiency = 68%
3
CN abs 94%
HCN abs 6%
3 5
C H abs 2%
EA = 4.98 eV
Efficiency = 8%
Efficiency = 36%
Efficiency = 48%
Efficiency = 63%
a
b
c
d
Reaction efficiencies (efficiency) are reported as kreaction/kcollision  100. Branching ratios for primary products. abs = abstraction. Calculated
at the CASPT2/CASSCF(12,11)/cc-pVTZ//CASPT2/CASSCF(11,11)/cc-pVTZ level of theory.
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a
b,c
Table 2 Reaction efficiencies and product branching ratios for reactions of biradicals 5–7 with various reagents, and calculated vertical electron
d
e
affinities (EA) and singlet–triplet splittings (DEST
)
Reagents
Radical
e
2
 H abs 40%
I abs 58%
SCH
(21) SCH
SCH abs 31%
HSCH 18%
3
abs 51%
HCN abs 70%
CN abs 30%
(21) CN abs
(21) HCN abs
(21) Addition
H abs 14%
21) H abs
CH O abs 25%
O abs 6%
abs 6%
abs 5%
(21) I abs
3
abs
(
(21) C
3
H
5
abs
2
2
C
3
H
4
abs 42%
3
H
C
H
2
2 4
H
À
EA = 5.77 eV
DEST = À1.1 kcal molÀ1
C
C
C
H
H
H
abs 2%
O abs 1%
abs 1%
3
3
4
6
2
3
f
g
h
i
Efficiency = 27%
Efficiency = 42%
Efficiency = 62%
Efficiency = 55%
H abs 50%
SCH
(21) SCH
3
abs 89%
abs
HCN abs 39%
CN abs 32%
(21) CN abs
(
21) H abs
2
3
CH O abs 13%
SSCH
HSCH
SCH
3
6%
4%
2
H
 H abs 9%
3
(21) HCN abs
(21) Addition
À
abs 8%
2
abs 1%
+
EA = 6.22 eV
C
2
H
4
abs 7%
H transfer 29%
DEST = À8.9 kcal molÀ1
H
O abs 4%
2
H +CH
H + CH
Addition 1%
2
O abs 3%
2
2
abs 2%
C
C
C
3
2
3
H
H
H
6
4
3
abs 1%
O abs 1%
abs 1%
j
k
l
m
Efficiency = 68%
Efficiency = 54%
Efficiency = 75%
Efficiency = 96%
H abs 35%
SCH
(21) SCH
SCH abs 7%
HSCH abs 5%
3
abs 88%
HCN abs 62%
(21) HCN abs
(21) C H N abs
5 9
CN abs 38%
(21) CN abs
(21) HCN abs
(
2
C
H
21) H abs
 H abs 33%
abs 10%
abs 6%
3
abs
2
2
H
4
3
À
C
3
H
3
abs 4%
EA = 5.69 eV
CH
2
O abs 4%
5 9
(21) C H N abs
(21) Addition
DEST = À7.6 kcal molÀ1
H + CH
abs 2%
H + CH abs1%
abs 1%
Efficiency = 10%
abs 4%
2
3 6
C H
2
2
3 5
C H
n
o
Efficiency = 41%
Efficiency = 48%
Efficiency = 41%
a
b
Reaction efficiencies (efficiency) are reported as kreaction/kcollision  100. The precision of the measured efficiencies is Æ10%. Primary products’
c
d
branching ratios; secondary products are noted as (21) and are listed under the primary products that produce them. abs = abstraction. Vertical
electron affinities calculated at the CASPT2/CASSCF(13,12)/cc-pVTZ//CASPT2/CASSCF(12,12)/cc-pVTZ level of theory. Singlet–triplet splittings
e
calculated at the CASPT2/CASSCF(12,12)/cc-pVTZ//CASPT2/CASSCF(12,12)/cc-pVTZ level of theory. Note that a negative value means that the singlet
state lies energetically below the triplet state. Zero-point energies and 298 K thermal contributions were derived from the (unscaled) UB3LYP/
f
cc-pVTZ//UB3LYP/cc-pVTZ frequencies. From non-linear curve fit (least squares non-linear fit of the pseudo-first order plot), 25% of the reactant
g
h
i
j
k
l
ion population is unreactive. Same as f but 47%. Same as f but 43%. Same as f but 13%. Same as f but 13%. Same as f but 16%. Same as
m
n
o
f but 15%. Same as f but 20%. Same as f but 63%. Same as f but 64%.
two consecutive SCH
consecutive CN group abstractions from t-BuNC were observed of 6 and slightly greater than those of 7 toward these three
Table 2). The proposed mechanisms for the dominant reac- reagents (with the exception of t-BuNC because this reagent
tions of biradical 7 with allyl iodide are shown in Scheme 1. is basic enough to rapidly deprotonate 6 but not 5 or 7).
3
group abstractions from DMDS and two biradical 5. The reaction efficiencies of 5 are smaller than those
(
Biradical 6 has a greater (calculated) EA than 7 (6: 6.22 eV; 7: Biradical 5 has a relatively small (calculated) S–T splitting
À1
5
(
.69 eV), while their (calculated) S–T splittings are similar (À1.1 kcal mol ; Table 2), which is expected to make it more
À1
À1
6: À8.9 kcal mol ; 7: À7.6 kcal mol ; Table 2), which suggests reactive than 6 and 7, but it has a lower EA than 6 and an EA
greater reactivity for 6 than 7. This was observed for all four of comparable to that for 7. The reaction efficiencies measured for
the neutral reagents studied here: THF, DMDS, t-BuNC and allyl 5, 6 and 7 (for allyl iodide: 42%, 54%, and 41%; for DMDS: 62%,
iodide (Table 2).
75%, and 48%, respectively; Table 2) suggest that the greater EA
Most of the reactions of 6 and 7 with DMDS, t-BuNC and of 6 counteracts the rate enhancing effect of the small S–T
1
0
allyl iodide were also observed for a previously reported
splitting of 5.
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To the best of our knowledge, this is the first time that hydrogen
bonding has been observed to influence the reactivity of a
biradical.
Conclusions
The isomeric biradicals 5, 6 and 7 studied here were found to
undergo two radical reactions with all reagents, as expected.
Their product distributions and reaction efficiencies are similar,
with the exception of one reagent – THF. The much higher
efficiency of reactions of 6 with THF, compared to the efficien-
cies of 5 and 7, is likely due to a stabilizing hydrogen bonding
interaction that 6 can have with THF in the transition state for
Scheme 1 Proposed stepwise mechanisms for iodine atom abstraction
followed by iodine atom or allyl group abstraction from two allyl iodide
molecules by biradical 7.
A deviation from above reactivity trends was revealed by the hydrogen atom abstraction. This result indicates that the possi-
high efficiency at which 6 reacts with THF (efficiencies of 6, bility of stabilizing hydrogen bonding in a transition state must
7
and 5 are 68%, 10%, and 27%, respectively; Table 2). This may be taken into account when considering reactivities of biradicals
be explained by a stabilizing hydrogen bonding interaction in capable of forming a hydrogen bond. When hydrogen bonding is
the transition state for reaction of 6 with THF. Biradical 6 is the not the reactivity controlling factor, the EA and S–T splitting
only biradical among the ones studied here that is capable appear to be the principal factors affecting the reactivity of
of hydrogen bonding in the transition state, due to the isomeric biradicals. Finally, the reaction efficiencies of the
short distance between the C-1 radical site and the protonated 1- and 4-dehydroisoquinolinium cations (i.e., monoradicals 1
nitrogen atom, the only site capable of hydrogen bonding with and 2) are systematically greater than those of the biradicals
the oxygen atom of THF (Scheme 2). Similar behavior was dis- with a radical site at C-1 or C-4 in spite of the fact that the
cussed above for monoradical 1. As observed for monoradical 1, biradicals have equal or greater calculated EAs. This is true even for
biradical 6 reacts with THF at a comparable efficiency as with 5 with a relatively small calculated S–T splitting (À1.1 kcal/mol).
the other reagents (Table 2), which is not the case for mono- Therefore, coupling between the radical sites, even when
radicals 2–4 or biradicals 5 and 7. Furthermore, transition state very weak, lowers the reactivity of the biradicals compared to
calculations carried out for 6 support the hypothesis that monoradicals.
hydrogen bonding stabilizes the transition state for the abstraction
As the dependence of the reactivity on the exact location
of the first hydrogen atom from THF by the C-1 radical site (Fig. 2). of the radical sites in isomeric biradicals with the same radical
The activation enthalpy and the enthalpy of reaction were calcu- topology has not been explored until now, the findings described
À1
À1
lated to be À15.0 kcal mol and À21.9 kcal mol , respectively. above greatly improve the understanding of the chemical proper-
ties of organic biradicals. Further, the finding of the importance
of hydrogen bonding capability for the hydrogen atom abstrac-
tion efficiency of a biradical implies that biradical intermediates
that are capable of forming a hydrogen bond near one or both of
the radical sites are likely to cleave DNA more efficiently than
biradicals without this capability.
Experimental
Materials and methods
Scheme 2 Proposed stepwise mechanisms for hydrogen atom abstrac-
tion reactions from two THF molecules by biradical 6.
All experiments were carried out in a Finnigan FTMS 2001 dual-
cell FT-ICR mass spectrometer. The mono- and biradicals 1–4
and 6–7 (Table 1) were generated in one cell by using previously
1
4,19
reported methods.
Briefly, the nitro- and/or iodoprecursors
of the radicals were introduced into one side of the dual-cell ion
trap of the mass spectrometer via a heated solids probe, ionized
by protonation, and isolated by ejecting all other ions from the
ion trap. The ionized precursors were then transferred into the
other, clean cell, followed by sustained off-resonance irradiated
2
0
collision-activated dissociation (SORI-CAD) to homolytically
cleave C–I and/or C–NO bonds of the protonated precursors.
The (bi)radicals were isolated and allowed to react with tetra-
hydrofuran (THF), allyl iodide (AI), dimethyl disulfide (DMDS)
2
Fig. 2 Transition state calculated for hydrogen atom abstraction from
THF by the C-1 radical site in 6 (UB3LYP/cc-pVTZ//UB3LYP/cc-pVTZ level
of theory).
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and tert-butyl isocyanide (t-BuNC) for varying periods of time. Computational methods
The second-order reaction rate constants (kexp) and reaction
Molecular geometries for all species were optimized at the
multiconfigurational self-consistent field (MCSCF) and density
functional (DFT) levels of theory by using the correlation-
efficiencies (k
the literature.
/kcollision) were determined as described in
The absolute values are estimated to be
reaction
,21–24
4
accurate only within Æ50% but the relative values are much
more accurate (Æ10%). The product branching ratios were
determined by dividing the abundance of each primary reac-
tion product ion by the sum of all primary reaction product
abundances.
28
consistent polarized valence-triple-z (cc-pVTZ) basis set. The
MCSCF calculations were of the complete active space (CASSCF)
29
variety and included (in the active space) the full p-space
for each molecule and, for each of the mono- and biradicals,
the nonbonding s orbital(s). The DFT calculations used the
3
0
gradient-corrected exchange functional of Becke, which was
combined with the gradient-corrected correlation functional
Synthetic procedures
The precursor for monoradical 4, 5-nitroisoquinoline, was pur-
chased from Sigma-Aldrich and used without further purifica-
tion. The precursors for monoradical 1, 1-iodoisoquinoline,
and monoradical 2, 4-iodoisoquinoline, were synthesized
by known methods. The precursors for biradical 5, 4-iodo-5-
nitroisoquinoline, and biradical 7, 4-iodo-8-nitroisoquinoline,
were also synthesized by known methods.
The precursor for monoradical 3, 8-iodoisoquinoline,
was synthesized by dissolving (0.5 g, 3.36 mmol) 8-aminoiso-
quinoline (Carbocore) in a mixture of concentrated HCl (3 mL)
31
of Lee, Yang and Parr (B3LYP). All DFT geometries were
verified to be local minima by computation of analytic vibra-
tional frequencies, and these (unscaled) frequencies were used
to compute zero-point vibrational energies (ZPVE) and 298 K
2
5
2
6
thermal contributions (H298–E ) for all species. DFT calcula-
0
10
27
tions for the mono- and biradicals employed an unrestricted
formalism.
To improve the molecular orbital calculations, dynamic
electron correlation was also accounted for by using multi-
32,33
reference second-order perturbation theory
(CASPT2) for
and H
solution of NaNO
solution. This solution was stirred for 15 min, and a solution of
KI (1.12 g, 6.73 mmol) in H O (3 mL) was added to it. The mixture
2
O (3 mL) cooled in an ice/salt bath and slowly adding a
multi-configurational self-consistent field (MCSCF) reference
wave functions; these calculations were carried out for the
MCSCF optimized geometries. Some caution must be applied
in interpreting the CASPT2 results since this level of theory is
known to suffer from a systematic error proportional to the
2
(0.28 g, 4.03 mmol) in H O (2 mL), to give a red
2
2
was heated for 3 h at 100 1C, and then cooled and basified with
aqueous NH . The product was extracted with dichloromethane
34
3
number of unpaired electrons. Thus, the electronic energies
and the organic layer washed with 5% sodium metabisulfide
followed by a brine solution, then dried and chromatographed
are of the CASPT2/CASSCF(m,n)/cc-pVTZ//CASSCF(m,n)/cc-pVTZ
variety (where m is the number of active electrons and n is the
number of active orbitals), and estimates of the thermodynamic
on silica gel, eluting with CH
2
Cl
2
: MeOH (95 : 5), to give
-iodoisoquinoline (0.52 g, 60%). H NMR (400 MHz, CDCl
d 7.30 (t, J = 7.9 Hz, 1H), 7.44 (d, J = 5.6 Hz, 1H), 7.71 (d, J = 7.1 Hz,
H), 8.05 (d, J = 7.7 Hz, 1H), 8.54 (d, J = 5.7 Hz, 1H), 9.35 (s, 1H).
1
8
3
)
quantities, E and H298, are derived by adding to these electro-
0
nic energies ZPVE and the sum of ZPVE and (H298–E ), respec-
0
1
tively, where the latter are derived from the DFT calculations.
+
ESI MS: [M + H] m/z 256.
The precursor for biradical 6, 1-iodo-5-nitroisoquinoline, was
synthesized by dissolving (1.50 g, 9.65 mmol) 1-chloroisoquinoline
v
In order to compute vertical electron affinities (EA ) for
the mono- and biradicals, single-point calculations (CASPT2/
CASSCF(m,n)/cc-pVTZ), using the CASSCF(m,n)/cc-pVTZ optimized
geometry for each radical, were also carried out for the states that
are produced when a single electron is added to the nonbonding
(Carbocore) in cooled (0 1C) concentrated H SO (20 mL), which
2 4
3
turned the solution yellow. An excess of concentrated HNO (2 mL)
was added to the stirred solution and a change of color to orange
was observed. The solution was stirred at 0 1C for 5 min, then
allowed to warm up to room temperature and stirred for 30 min
more. The solution was poured onto ice, turning the mixture to
a creamy yellow color. The solution was basified to pH 8,
filtered and dried to give yellow crystals. The products were
separated by chromatography. Two products were obtained,
35
s orbital (or one of the two such orbitals) of each molecule.
Thus, for the monoradicals (doublet ground states), these calcula-
tions were carried out for (zwitterionic) singlet states, whereas for
the biradicals (singlet ground states), calculations were carried out
36
for (zwitterionic) doublet states.
All CASPT2/MCSCF and DFT calculations were carried out
37
38
with the MOLCAS 8.0 and Gaussian 09 electronic structure
program suites, respectively.
1
-chloro-5-nitroisoquinoline (70% yield) and 1-chloro-8-nitro-
isoquinoline (10% yield).
-Iodo-5-nitroisoquinoline 6 was synthesized for the first time
1
from 1-chloro-5-nitroisoquinoline by following the procedure Conflicts of interest
25
described by Wolf, in which the chlorine atom was exchanged
with an iodine atom (yield 80%). The halogen exchange was verified
by mass spectrometry that revealed the absence of 1-chloro-5-
There are no conflicts to declare.
+
1
nitroisoquinoline ([M + H] m/z 209). H NMR (400 MHz, CDCl ) d
3
Acknowledgements
7
.81 (t, J = 8.0 Hz, 1H), 8.38 (d, J = 6.1 Hz, 1H), 8.47 (d, J = 6.1 Hz, 1H),
+
8.56 (d, J = 2.4 Hz, 1H), 8.58 (d, J = 3.4 Hz, 1H). ESI MS: [M + H]
This material is based upon work supported by the National
Science Foundation under grant number CHE-1464712.
m/z 301. The structure was also verified by X-ray crystallography.
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Notes and references
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2
7 N. R. Vinueza, B. J. Jankiewicz, V. A. Gallardo, G. Z.
LaFavers, D. DeSutter, J. J. Nash and H. I. Kentt ¨a maa,
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