Substituent Effects on the [N-I-N]+ Halogen Bond

Article abstract of DOI:10.1021/jacs.6b03842

We have investigated the influence of electron density on the three-center [N-I-N]⁺ halogen bond. A series of [bis(pyridine)iodine]⁺ and [1,2-bis((pyridine-2-ylethynyl)benzene)iodine]⁺ BF₄^- complexes substituted with electron withdrawing and donating functionalities in the para-position of their pyridine nitrogen were synthesized and studied by spectroscopic and computational methods. The systematic change of electron density of the pyridine nitrogens upon alteration of the para-substituent (NO₂, CF₃, H, F, Me, OMe, NMe₂) was confirmed by ¹⁵N NMR and by computation of the natural atomic population and the π electron population of the nitrogen atoms. Formation of the [N-I-N]⁺ halogen bond resulted in >100 ppm ¹⁵N NMR coordination shifts. Substituent effects on the ¹⁵N NMR chemical shift are governed by the π population rather than the total electron population at the nitrogens. Isotopic perturbation of equilibrium NMR studies along with computation on the DFT level indicate that all studied systems possess static, symmetric [N-I-N]⁺ halogen bonds, independent of their electron density. This was further confirmed by single crystal X-ray diffraction data of 4-substituted [bis(pyridine)iodine]⁺ complexes. An increased electron density of the halogen bond acceptor stabilizes the [N···I···N]⁺ bond, whereas electron deficiency reduces the stability of the complexes, as demonstrated by UV-kinetics and computation. In contrast, the N-I bond length is virtually unaffected by changes of the electron density. The understanding of electronic effects on the [N-X-N]⁺ halogen bond is expected to provide a useful handle for the modulation of the reactivity of [bis(pyridine)halogen]⁺-type synthetic reagents.

Full text of DOI:10.1021/jacs.6b03842

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Article
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Substituent Effects on the [N–I–N] Halogen Bond
Anna-Carin C Carlsson, Krenare Mehmeti, Martin Uhrbom, Alavi Karim,
Michele Bedin, Rakesh Puttreddy, Roland Kleinmaier, Alexei A. Neverov,
Bijan Nekoueishahraki, Jurgen Grafenstein, Kari Rissanen, and Mate Erdelyi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b03842 • Publication Date (Web): 06 Jun 2016
Downloaded from http://pubs.acs.org on June 11, 2016
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Substituent Effects on the [NIN]+ Halogen Bond
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Anna-Carin C. Carlsson,†,║ Krenare Mehmeti,† Martin Uhrbom,†, Alavi Karim,† Michele Bedin,†,
Rakesh Puttreddy,§ Roland Kleinmaier,†,¶ Alexei A. Neverov,‡, Bijan Nekoueishahraki,† Jürgen Gräf-
enstein,† Kari Rissanen,§ Máté Erdélyi†,#,*
† Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
‡ Department of Chemistry, Queen’s University, Kingston, Ontario, Canada K7L 3N6.
§ University of Jyvaskyla, Department of Chemistry, Nanoscience Center, P.O. Box. 35, FI-40014 University of Jyvaskyla,
Finland
# The Swedish NMR Centre, Medicinaregatan 5, SE-413 90 Gothenburg, Sweden
ABSTRACT: We have investigated the influence of electron density on the three-center [NIN]+ halogen bond. A series of
-
[bis(pyridine)iodine]+ and [1,2-bis((pyridine-2-ylethynyl)benzene)iodine]+ BF4 complexes substituted with electron withdrawing
and donating functionalities in the para-position of their pyridine nitrogen were synthesized and studied by spectroscopic and com-
putational methods. The systematic change of electron density of the pyridine nitrogens upon alteration of the para-substituent
(NO2, CF3, H, F, Me, OMe, NMe2) was confirmed by 15N NMR and by computation of the natural atomic population and the π
electron population of the nitrogen atoms. Formation of the [NIN]+ halogen bond resulted in >100 ppm 15N NMR coordination
shifts. Substituent effects on the 15N NMR chemical shift are governed by the π population rather than the total electron population
at the nitrogens. Isotopic perturbation of equilibrium NMR studies along with computation on the DFT level indicate that all stud-
ied systems possess static, symmetric [NIN]+ halogen bonds, independent of their electron density. This was further confirmed
by single crystal X-ray diffraction data of 4-substituted [bis(pyridine)iodine]+ complexes. An increased electron density of the halo-
gen bond acceptor stabilizes the [NIN]+ bond, whereas electron deficiency reduces the stability of the complexes, as demon-
strated by UV-kinetics and computation. In contrast, the NI bond length is virtually unaffected by changes of the electron density.
The understanding of electronic effects on the [NXN]+ halogen bond is expected to provide a useful handle for the modulation of
the reactivity of [bis(pyridine)halogen]+-type synthetic reagents.
INTRODUCTION
reagents in organic synthesis, for example for electrophilic
halogenation of alkenes, alkynes and aromatics, and for oxida-
tions.27-41 In three-center-four-electron [NXN]+ halogen
bonds,42,43 the halogen is stabilized by simultaneous coordina-
tion to two nitrogen electron donors. The three atoms of the
[NXN]+ system may either form a static, symmetric geome-
try, [NXN]+, or two asymmetric structures in a rapid equi-
A halogen bond (XB) is the close to linear, noncovalent in-
teraction between an electron poor region of a halogen and an
electron donor.1 The chemical nature of the interaction was
first rationalized by introduction of the -hole concept,2 fol-
lowed by description of the impact of charge-transfer, disper-
sion, polarization, and electrostatic forces.3-9 Over the past
decade, halogen bonds have been increasingly applied in a
variety of research disciplines including material sciences,
crystal engineering, structural biology, anion recognition and
transportation, medicinal chemistry, organic synthesis, and
organocatalysis.6,10-13 Halogen bonding was recently utilized in
the development of ionic liquid crystals,14 in multidentate
anion receptors,15-18 and in the enantioselective recognition of
chiral anions.19 It was demonstrated to be applicable as non-
covalent activator in organocatalysis,20 and as a new tool in
drug discovery. 11,21 It found application in the development of
luminescent22,23 and phosphorescent24 optoelectronic, and of
functional materials.25,26 Halogen bonding has the potential to
become a chemical tool as widely applicable as hydrogen
bonding.
librium, [NXN]+
[NXN]+,44,45 the latter being
analogous to the tautomeric exchange typical of related
[NHN]+ complexes.46 In the symmetric [NXN]+ geome-
try, the halogen forms two equally long and strong NX
bonds, and its motion between the two nitrogens is described
by a single-well energy potential. In contrast, in the asymmet-
ric, dynamic system, in each asymmetric isomer the halogen
forms one shorter and stronger covalent NX bond, and one
longer and weaker NX halogen bond. As the halogen jumps
between the two nitrogens, its motion is described by a dou-
ble-well energy potential.42,45 The centrosymmetric [NXN]+
halogen bonds are particularly strong,42,43,45,47 their strength
being similar to that of the halogen bond of the isoelectronic
[III]-.48 We have previously shown that the [NIN]+ halo-
gen bonds of [bis(pyridine)iodine]+ (1a, Figure 1) and [1,2-
bis((pyridine-2-ylethynyl)benzene)iodine]+ (2a) complexes are
exceptionally strong, and that their geometry is static symmet-
[Bis(pyridine)halogen]+ complexes and their substituted ana-
logues encompass a reactive halogen(I) species that is stabi-
lized by two electron donors in an [NXN]+ halogen bond.
Both bromine(I) and iodine(I) containing complexes are useful
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ric in solution,45,49 independent of the nature of the counterion
present.50
substituents, resulting in complexes with an increasing electron
density in the order NO2 < CF3 < H < F < Me < OMe < NMe2.
Complex 1 permits free rotation and adjustment of NI distances
for the most favorable interaction, whereas the 1,2-
diethynylbenzene backbone of 2 inhibits rotation around the
NIN axis and imposes some strain in the NI bonds to reach a
geometrically optimal [NIN]+ interaction. A mixture of 2a-d
and their mono-deuterated isotopologs 2a-d-d were used in IPE
NMR experiments for determining the geometry of their
[NIN]+ halogen bonds.
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7
8
The influence of electron density alteration on the strength
and geometry of the three-center-four-electron [NXN]+
halogen bond has so far not been assessed. A decreased elec-
tron donating ability of the nitrogens, as induced by electron
withdrawing substituents, can be expected to destabilize the
symmetric [NIN]+ halogen bond, and increase the reactivity
of the complex. If the central iodine(I) is unable to efficiently
accept electrons into its empty p-orbital from two electron
poor nitrogens simultaneously, it may prefer to compensate its
electron depletion by forming a covalent bond to one of the
nitrogens, instead of forming halogen bonds to both. Hence,
electron depletion might induce an asymmetric [NIN]+
geometry. In contrast, an increased electron density, induced
by electron donating substituents, is expected to stabilize the
symmetric [NIN]+ geometry by strengthening the two NI
halogen bonds. This is expected to decrease the reactivity of
the complex.
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Synthesis. The 4-substituted electron rich [bis(pyridine)io-
dine]+ BF4 complexes 1b (4-Me), 1c (4-OMe), and 1d (4-
-
NMe2) as well as their electron poor analogue 1f (4-CF3),
(Figure 1) were synthesized from their corresponding Ag+
complexes by addition of molecular I2, following our previ-
ously reported protocol50 towards 1a. Complex 1b (4-Me)
rapidly decomposed upon isolation.52
The 4-substituted [1,2-bis((pyridine-2-ylethynyl)benzene)-
iodine]+ BF4 complexes 2a (4-H), 2b (4-Me), 2c (4-OMe), 2d
-
(4-NMe2), 2e (4-F), 2f (4-CF3), and 2g (4-NO2), and their
selectively mono-deuterated, electron rich analogues 2a-d-d
were prepared from their corresponding 1,2-bis(pyridine-2-
ylethynyl)benzene ligands 3a to 3g, and 3b-d to 3d-d, via their
corresponding Ag+ complexes,50 as shown in Scheme 1. The
electron poor [NIN]+ complexes 2e (4-F) and 2f (4-CF3)
In this study, we report our findings, from systematic solu-
tion NMR, X-ray diffraction, reaction kinetics, and computa-
tional investigations on the influence of electron density al-
terations on [NIN]+ halogen bond strength and geometry.
An understanding of electronic effects is, above all, expected
to provide a useful handle for the modulation of the reactivity
of [bis(pyridine)halogen]+-type reagents.
1
were observed by H NMR to be significantly less stable in
CD2Cl2 solution as compared to their electron rich analogues.
Consequently, 2e and 2f could only be detected in a mixture
with their decomposition product, the analogous [NHN]+
complex. Our attempts to generate the electron poor complex
2g (4-NO2) yielded the corresponding [NHN]+ complex
only, due to the rapid decomposition of the targeted [NIN]+
complex in solution.
RESULTS AND DISCUSSION
[Bis(pyridine)halogen]+ complexes and their geometrically
restrained
[1,2-bis((pyridin-2-ylethynyl)benzene)halogen]+
analogs are the model systems typically used to gain under-
standing of the [NXN]+ halogen bond.42,43,45,49-51 In this
study, we introduce substituents of varying electronic proper-
ties in the para-positions relative to the pyridine nitrogens
(Figure 1), to study the influence of electron density alteration
on the strength and geometry of their [NIN]+ halogen bond.
The 4-substituted 1,2-bis(pyridine-2-ylethynyl)benzene lig-
ands 3a-c,e,f were synthesized using microwave-assisted
Sonogashira coupling (Scheme 1),53 following previously
optimized conditions.45 Compounds 3a (4-H),45 3b (4-Me),54
and 3c (4-OMe) were prepared from 1,2-diiodobenzene and
two equivalents of terminal alkyne 4a-c. Ligands 3e (4-F) and
3f (4-CF3) were obtained from 1,2-diethynylbenzene and 2-
bromo-4-fluoropyridine (7e) or 2-chloro-4-trifluoromethylpy-
ridine (7f).54 The electron poor ligand 3g (4-NO2) was pre-
pared from 1,2-diiodobenzene and 2 equiv. 4g using Sonoga-
shira coupling with Et3N as base, instead of Et2NH, and with-
out microwave heating to avoid side-reactions. The most elec-
tron rich ligand 3d (4-NMe2) was prepared from 3g (Scheme
2) via Béchamp reduction,55,56 followed by reductive amina-
tion of paraformaldehyde with sodium cyanoborohydride.57
R
R
4
4
5
6
3
5
3
2
2
N
I
6 N
I
-
-
BF4
BF4
2´
3´
N
H
N 2´H(D)
6´
5´
6´
5´
3´
4´
4´
R
R
The mono-deuterated ligands 3a-d to 3c-d were prepared in
accordance with our reported procedure,45 including two con-
secutive microwave-assisted Sonogashira couplings; coupling
of 1,2-diiodobenzene with one equivalent of 4a-c, generating
5a-c, was followed by coupling of the corresponding deuterat-
ed terminal alkyne 4a-d to 4c-d (Scheme 1). The 4-NO2-
substituted analogue 3g-d was prepared similarly from 5g and
4g-d, and was then converted to the 4-NMe2-subsituted 3d-d
via Béchamp reduction and subsequent reductive amination, as
described above (Scheme 2) for the conversion of 3g to 3d.
The terminal alkynes 4a-d and 4b-d were synthesized follow-
ing our published procedure45 via regioselective deuteration at
C6 of either 2-chloropyridine (7a) or 2-chloro-4-
methylpyridine (7b) using BuLi-LiDMAE, subsequent
1
2(2-d)
EDG
b: R = Me
a: R = H c:
EWG
e: R = F
f:
R = OMe
d: R = NMe2
R = CF3
g: R = NO2
-
Figure 1. [Bis(4-R-pyridine)iodine]+ BF4 (1a-g), and geometri-
cally restrained [1,2-bis((4-R-pyridine-2-ylethynyl)benzene)-
iodine]+ BF4- (2a-g) were used as model systems for evaluation of
the influence of electron density alteration on the [NIN]+ halo-
gen bond. A systematic alteration of the electron density of the
[NIN]+ halogen bond was achieved by variation of the R-
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R
5
+
6
7
N
X
e:
f:
R = F; X = Br
R = CF3; X = Cl
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Sonogashira
coupling
R
R
N
1. Ag+-Complexation
2. Halogenation
N
I
Sonogashira
di-coupling
-
BF4
a:
R = H
N
N
R
b: R = Me
c: R = OMe
d: R = NMe2
e:
f:
g:
2
3
R
I
I
R = F
R = CF3
R = NO2
R
+
N
4
R
N
TMS
a:
b:
c:
R = H
R = Me
R = OMe
R
R
N
Sonogashira
mono-
coupling
1. Sonogashira
coupling
2. TMS-Deprotection
g: R = NO2
+
D
N
D
X
4-d
I 5
7-d
1. Sonogashira
coupling
2. TMS-Deprotection
TMS
a: R = H; X = Cl
b: R = Me; X = Cl
g: R = NO2; X = Br
a: R = H
b:
c:
g:
R = Me
R = OMe
R = NO2
Sonogashira
coupling
R
R
R
N
N
R
N
X
N
1. Ag+-Complexation
2. Halogenation
-
7
BF4
I
a:
b:
g:
R = H; X = Cl
R = Me; X = Cl
R = NO2; X = Br
a:
b:
c:
d:
g:
R = H
R = Me
R = OMe
R = NMe2
R = NO2
N
D
D
2-d
3-d
R
Scheme 1. General synthetic route for the synthesis of 4-substituted [1,2-bis((pyridine-2-ylethynyl)benzene)iodine]+ BF4- complexes 2a (4-
H), 2b (4-Me), 2c (4-OMe), 2d (4-NMe2), 2e (4-F), 2f (4-CF3), and 2g (4-NO2) and their selectively mono-deuterated analogues 2a-d,g-d.
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NO2
NMe2
N
NO2
N
NMe2
N
N
4g
a
I
I
-
b, c
d, e
BF4
I
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(60%)
(85%, 66%)
(91%)
N
N
N
NO2
3g
2d
3d
(44%)
f
NMe2
NO2
NO2
NMe2
N
4g
NO2
NMe2
N
NMe2
NO2
N
N
D
4g-d
N
N
g
b, c
d, e
-
BF4
I
(86%)
D
(54%)
(85%, 55%)
N
N
D
D
N
I
5g
3g-d
3d-d
2d-d
NMe2
NO2
NMe2
Scheme 2. aReagents and Conditions: (a) 4g (2.2 equiv.), Pd(PPh3)2Cl2, CuI, Et3N, 75 C, 5 h, then rt, 18 h; (b) Fe, AcOH, 55 C, 1.5 h; (c)
CH2O, NaBH3CN, AcOH, rt, 24 h; (d) AgBF4, CH2Cl2, rt, 20 min; (e) I2, CH2Cl2, rt, 30 min; (f) 4g (0.8 equiv.), Pd(PPh3)2Cl2, CuI, Et3N,
75 C, 3 h; (g) 4g-d (2.1 equiv.), Pd(PPh3)2Cl2, CuI, Et3N, 75 C, 20 h.
Scheme 3. aReagents and Conditions: (a) 1. nBuLi (1 eqiuv.), THF, -78 C; 2. MeOD (5 equiv.), -78 C, 1 h, then rt, 24 h; (b) mCPBA,
CHCl3, rt, 24 h; (c) HNO3/H2SO4 2:1, 110 C, 3 h; (d) PBr3, CH2Cl2, 60 C 3 h; (e) TMS-acetylene, Pd(PPh3)2Cl2, CuI, Et3N, 5 C, 1 h,
then rt, 2 h; (f) KF, MeOH, rt, 2h; (g) K2CO3, THF/MeOH 1:1, rt, 1 h.
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microwave mediated Sonogashira coupling of TMS-acetylene,
and TMS-deprotection with KF in MeOH (Scheme 1).
(2a–g) between R and Δnπ(N) are found. Thus, the correlations
are indeed distinct, but not perfect. We therefore used Δn(N)
and Δnπ(N) directly to quantify the electron withdraw-
ing/donating properties of substituents.
The synthetic routes to the 4-MeO- and 4-NO2-substituted
terminal alkynes 4c and 4g (Scheme 3) both started from the
commercially available 2-bromo-4-nitropyridine (7g), whereas
those of their selectively mono-deuterated analogues 4c-d and
4g-d started from 2-bromo-4-nitropyridine-6-d (7g-d, Scheme
3). For selective monolithiation of 2,6-dibromopyridine at C-6
with n-BuLi, a method developed by Cai and co-workers was
followed.58 Successive electrophilic trapping with MeOD
furnished 2-bromo-6-deuteropyridine (8-d) in nearly quantita-
tive yield. For introducing the 4-NO2-group, 8-d was first
converted by mCPBA oxidation59 into its N-oxide 9-d, which
was then nitrated with H2SO4/HNO3 to provide 10-d. Subse-
quent reduction of 10-d with PBr3 generated the desired start-
ing material 7g-d in high yield.60 Sonogashira coupling of
either 7g or 7g-d with TMS-acetylene at room temperature
yielded the TMS-protected alkyne 6g or 6g-d, following the
procedure described by Sagitullina et al.61 In subsequent TMS-
deprotection, the 4-MeO- and 4-NO2-substituted terminal
alkynes 4c/4c-d and 4g/4g-d were selectively generated by the
choice of reaction conditions. Deprotection with KF in MeOH
at ambient temperature furnished 4-NO2-substituted 4g/4g-d,
whereas basic conditions using K2CO3 in THF/MeOH (1:1) at
ambient temperature provided 4-MeO-substituted 4c/4c-d as a
result of simultaneous TMS-removal and nucleophilic re-
placement of the 4-NO2-substituent. Further details regarding
the syntheses described above are given in the Supporting
Information.
Table 1. Calculated Changes Upon Substitution for Natu-
ral Atomic Populations Δn(N) and π Orbital Populations
Δnπ(N) for the N atoms of Iodine(I) Complexes 1a-g and
2a-g, versus Hammett and Resonance Substituent Con-
stants.
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Structure
4-R
103 ×
Δn(N)
R
103 ×
Δnπ(N)
para
H
Me
OMe
NMe2
F
CF3
NO2
H
0
0
3.0
5.9
18.5
-7.9
-17.7
-30.7
0
2.7
5.9
17.1
-6.3
-15.1
-26.7
0
0
1a
1b
1c
1d
1e
1f
1g
2a
2b
2c
2d
2e
2f
-0.17
-0.27
-0.83
0.06
0.54
0.78
0
-0.17
-0.27
-0.83
0.06
0.54
0.78
-0.18
-0.56
-0.98
-0.39
0.16
0.13
0
-0.18
-0.56
-0.98
-0.39
0.16
0.13
12.7
42.6
73.2
16.7
-15.5
-25.9
0
11.6
39.8
69.2
16.9
-11.4
-19.1
Me
OMe
NMe2
F
CF3
NO2
2g
The 15N NMR chemical shift, 15N, is recognized to be a sensi-
tive tool for the assessment of the coordinative bonds of nitro-
gen heterocycles.54,69 It has previously been used for the char-
acterization of halogen bonded complexes.45,49,50,70,71 Upon
formation of pyridine-based [NIN]+ complexes, analogous
to non-substituted 1a and 2a, ~100 ppm 15N chemical shift
changes, 15Ncoord, are induced.45 This chemical shift alteration
is the consequence of the establishment of a strong halogen
bond, in which the pyridine nitrogen acts as Lewis base, and
the introduction of a positive charge into the molecular sys-
tem. The bond strength of nitrogen heterocycles is commonly
assessed by the 15N NMR coordination shift, δ15Ncoord. It is
defined as the 15N chemical shift difference of a complex and
of its corresponding free nitrogen base (ligand), i.e.
δ15Ncoord=complex – ligand. A stronger coordinative bond
is commonly seen to be reflected by a larger |δ15Ncoord|.45,49 To
evaluate the influence of substituents on the electron density
of the pyridine nitrogen involved in the formation of
[NIN]+ complexes, we acquired the 15N NMR chemical
shift for 1a-d,f and 2a-f (Figure 1), δ15Ncomplex, and for their
corresponding free nitrogen bases (4-substituted pyridines and
3a-f), δ15Nligand. The δ15N values were detected for CD2Cl2
Alteration of electron density. A common approach to in-
crease XB strength is to enhance the electrophilicity of the
halogen bond donor using strongly electron withdrawing sub-
stituents.62 Accordingly, perfluoroaryl and -alkyl halides are
frequently applied halogen bond donors in model studies. The
alternative approach is to increase the electron density of the
halogen bond acceptor by the introduction of electron donating
substituents.63 A stronger halogen bond is often presumed to
be reflected by a shorter distance between the halogen bond
donor and the acceptor.48,64,65 Computational studies revealed
that the Hammett substituent constants of pyridine-based
halogen bond acceptors correlate to the strength of their halo-
gen bond.66,67 Strategic tuning of halogen bond strength is
expected to facilitate the development of halogen transfer
reagents and of supramolecular systems,12,20 for example.
The Hammett substituent constants, and the corresponding
induction and resonance constants F and R, are reported for
benzene derivatives and are not calibrated for pyridine rings.
To assess how well they describe electron donation/withdraw-
al in pyridine rings, we calculated the natural atomic popula-
tion (NAP68) n(N) as well as the π electron population nπ(N)
for the nitrogen atoms of 1a–g and 2a–g. The calculations
were performed with the computational protocol described
below for the investigation of equilibrium geometries and
bond energies. The changes of these populations, Δn(N) and
Δnπ(N), relative to 1a and 2a, respectively, are listed in Table
1, together with the corresponding Hammett and resonance
constants. Regression coefficients of 0.969 (1a–g) and 0.973
(2a–g) between para and Δn(N), and 0.965 (1a–g) and 0.975
1
solutions using indirect detection by H,15N HMBC experi-
ments. A single 15N NMR signal was observed for each com-
plex (Table 2). Electron donating substituents in the para-
position of the pyridine nitrogen increase the shielding of the
nitrogen, whereas electron withdrawing substituents have an
opposite effect. The influence of the substituents on the δ15N is
comparable for the ligands and complexes applied in this
study. We determined the regression coefficients r2 for the
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2
3
Table 2. 15N NMR Chemical Shift (ppm) of Iodine(I) Com-
primarily controlled by the paramagnetic ring currents of the
4
5
6
7
8
9
plexes 1a-d,f and 2a-f, and of the Corresponding Nitrogen
Bases. The 15N NMR Coordination Shifts Represent the
Chemical Shift Change Upon Complex Formation.
pyridine rings rather than by diamagnetic shielding or
deshielding. Consequently, the δ15N change is a specific
measure for the π donating or withdrawing property of substit-
uents. In particular, we find that fluorine, in contrast to com-
mon beliefs, dominantly acts as an electron donor, via reso-
nance, which is reflected by the comparable δ15Nof the fluo-
rine substituted 2e and 3e to those of the methyl substituted
analogues 2b and 3b (Table 2). This observation is corroborat-
ed by the literature.72 The δ15Ncoord of the iodine(I) complexes
do not vary to a significant extent, which is in excellent
agreement with previous observations of δ15Ncoord for analo-
gous silver(I) complexes, when detected in a noncoordinating
solvent and in the absence of a strongly coordinating counteri-
on.50,54 Overall, the observed large δ15Ncoord of 1a-d,f and 2a-f
confirms formation of [NIN]+ complexes; however, its
magnitude does not reflect interaction strength.
Structure
4-R



15
15
15
N
N
ligand
N
coord
complex
H
Me
OMe
NMe2
CF3
H
-175.1
-180.2
-195.0
-214.2
-164.1
-165.5
-170.2
-183.5
-202.9
-170.9
-156.7
-67.0
-108.1
-108.6
-109.0
-109.4
-112.5
-101.0
-101.0
-100.0
-100.7
-101.4
-106.0
1a
1b
1c
1d
1f
2a
2b
2c
2d
2e
2f
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
-71.6
-86.0
-104.8
-51.6
-64.5
-69.2
-83.5
-102.2
-69.5
-50.7
Me
OMe
NMe2
F
Halogen Bond Symmetry in Solution. Understanding the
factors governing the geometry of the three-center-four-
electron [NXN]+ halogen bond is a key for the description
of its nature.42,43,45,51 The solution NMR spectroscopic tech-
nique isotopic perturbation of equilibrium (IPE) has previous-
ly been proven to be a unique tool for distinguishing a rapidly
equilibrating mixture from a static, symmetric structure in
solution, and was successfully applied for symmetry determi-
nations of hydrogen and halogen bonds, of carbocations, and
of metal chelates.45,46,73,74 IPE relies on the detection of vibra-
tional energy changes in a molecule upon selective isotope
labeling, commonly a hydrogen to deuterium substitution
close to the interaction site of interest. When analyzing the
mixture of the labeled and the unlabeled isotopologs of a com-
pound, two sets of signals are detected; one set originates from
the nondeuterated compound, whereas the other set stems
from the deuterated analogue. The small shift difference be-
tween the signals of the isotopologs is called the isotope shift,
nobs, where n denotes the number of bonds between the ob-
served nucleus, commonly 13C, and the position of the isotopic
substitution. The observed chemical shift difference is the sum
CF3
Figure 2. The 15N NMR chemical shift changes (relative to 1a or
2a, respectively), Δδ15N of substituted pyridines (●), of the corre-
sponding 1,2-bis((pyridine-2-ylethynyl)benzene) ligands 3a-f (○),
and of their [NIN]+ complexes, 1a-d,f (▼) and 2a-f (∆), re-
spectively, strongly correlate to the corresponding changes in the
π(N) orbital population. This indicates that the variation in δ15Nis
dominatingly governed by the paramagnetic ring currents in the
pyridine moieties.
n
of the intrinsic isotope shift, 0, and the equilibrium isotope
shift, neq, according to eq 1:
nobs= C(D)  C(H) = n0 + neq
(1)
n
The intrinsic isotope effect, 0, which is present in all sys-
1
tems, is usually small and attenuates as n increases. The 0
and 20 isotope shifts, observed for the reporter atoms one and
two bonds from the isotopic substitution site, are negative,
often in the order of -0.3 ppm and -0.1 ppm, whereas the sign
of n0 observed for reporter atoms further away may vary. The
correlation of δ15N with both Δn(N) and Δnπ(N), as well as
σpara and R, both for the series of complexes 1a-d,f and 2a–f
and for the corresponding series of ligands (see SI for the
complete results). For the correlation with Δnπ(N), the r2 val-
ues are in the interval between 0.984 (ligands for 1a–d,f) and
0.995 (complexes 1a–d,f) (Figure 2), whereas for the correla-
tion with Δn(N) considerably lower r2 values, in the interval
between 0.824 (complexes 2a–f) and 0.920 (ligands 3a–f),
were calculated. Likewise, the regression coefficients with
respect to σpara and R were lower than the r2 with respect to
Δnπ(N). This finding indicates that the substituent effects on
the δ15Nare governed by the π population rather than the total
electron population at the nitrogen atoms. Thus, the δ15Nis
n
equilibrium isotope effect, eq, in contrast, is present only for
systems involved in a dynamic equilibrium process, and is
zero for static systems. Its magnitude depends on the equilib-
rium constant K of the exchange process:
neq = D(K1)/[2(K+1)]
(2)
where D denotes the chemical shift difference between the
signals of the isomeric forms, i.e. halogenated N+X and non-
halogenated N, in this particular case. The equilibrium con-
stant, K, is temperature dependent according to the van’t Hoff
n
equation,75 and so is the equilibrium isotope effect, eq. We
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have shown that the magnitude of the observed isotope shift,
nobs, does not allow straightforward differentiation between a
static [NXN]+ geometry and a dynamic [NXN]+
deuterium substitution site (n), but also on their distance to the
nitrogen that is directly involved in the fast equilibrium pro-
cess.45 Consequently, the temperature coefficients of the iso-
tope effects of carbons further away from the point of isotope
substitution, yet close to the nitrogen are large for dynamic,
but small for static systems.
[NXN]+ system in rapid equilibrium, but the temperature
dependence of nobs is a reliable measure for distinguishing the
two systems from each other.45 The symmetry of the [NIN]+
halogen bond of 2a-d was studied in solution with the IPE
technique using isotopolog mixtures and 13C {1H,2H} NMR
detection, as described in detail earlier.45 Similar to previous
studies of halogen bond symmetry,45,49,50 isotopolog mixtures
of the free ligands 3a-d were used as references for static
systems in the evaluation of the temperature dependence of the
isotope effects (Table 3). Due to their low stability, in combi-
nation with their poor solubility, the symmetry of the electron
poor complexes 3e-g could not be studied experimentally.
Table 4. Computationally Predicted NI and N–N Distanc-
es, NIN Angles, and Stabilization Energies for Complex-
es 1a-g and 2a-g and N–N distances for the Ligands 3a–ga.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Struc-
ture
4-R
r(NI)b r(NN)c r(NN)d
Estab
(kJ/mol)
∠(NIN)
(°)
(Å)
(Å)
(Å)
H
Me
2.3036 4.6072
2.3013 4.6026
180
180
180
180
180
180
180
0
1a
1b
1c
1d
1e
1f
1g
2a
2b
2c
2d
2e
2f
12.7
42.6
73.2
16.7
-15.5
-25.9
0
11.6
39.8
69.2
16.9
-11.4
-19.1
OMe 2.2980 4.5960
NMe2 2.2921 4.5841
F
CF3
NO2
H
Table 3. Temperature Coefficients (ppm × K) of the 13C
Isotope Shifts of Complexes 2a-d, and the Corresponding
References 3a-d for a Static Geometry.
2.3032 4.6063
2.3055 4.6109
2.3065 4.6131
2.3034 4.5934 4.6854 175.7
2.3011 4.5875 4.7166 175.4
Struc
-ture
4-R
C2
C3
C4
C5
C6
Σ
1obs
2obs 3obs 4obs 3obs |obs
|
Me
2aa,c
3aa,d
2ba
H
H
Me
Me
-8.9
-8.1
-10.8 +0.7
-9.1 -1.5
0
+3.4
0
-2.0
-4.5
-2.5
22.4
26.6
OMe 2.2982 4.5832 4.6586 175.7
NMe2 2.2930 4.5715 4.7700 175.4
F
-11.2 -11.3 +1.3
-8.8
26.3
(20.
4)
22.3
17.1
(19.
2)
16.1
2.3027 4.5921 4.6756 175.7
2.3041 4.5939 4.6624 175.5
2.3043 4.5952 4.5880 175.7
3bb
-8.6
n.d.e +3.0 n.d.e
CF3
NO2
2g
2cb
3cb
2db
OMe
OMe
NMe2
-5.4
-5.9
-5.8
-11.5 +2.3
-8.9 +2.3
-10.2 +3.2
0
0
0
-3.1
0
n.d.e
aAll calculations were done for CD2Cl2 solution with the
b
computational protocol described below. For all compounds,
r(NI)1 = r(NI)2. [N–I–N]+ complexes 1a-g and 2a-g. dLigands
c
3a-g.
3db
NMe2 -4.1.c
-9.2
+0.9 +1.1
-4.9
For a more detailed analysis of the halogen bonds and their
symmetry, we calculated equilibrium geometries and energies
of 1a-g and 2a-g. All calculations were performed using densi-
ty functional theory (DFT), employing the B3LYP exchange
and correlation functional.77-79 The LANL08 basis set80 in
conjunction with LANL2DZ effective core potential81-83 were
used for I, whereas Pople´s 6-311+G(d,p)84-86 basis set was
used for N, and Pople´s 6-311G(d,p)84,85 basis set for the re-
maining atoms. Solvent effects were accounted for by the
Polarizable Continuum Model (PCM)87,88 with dichloro-
methane as solvent. Calculations predict symmetric equilibri-
um geometries for compounds 1a-g and 2a-g (Table 4), with
NI distances that are 18% (~0.41 Å) longer than that of the
corresponding NI covalent bond (2.077-2.094 Å, Table S31,
Supporting Information), and considerably shorter than the
sum of the van der Waals radii of the participating atoms (3.53
Å, RXB= 0.6550,64,89). The bond lengths for the geometrically
restrained (2) and the corresponding non-restrained analogues
(1) differ by less than 0.01 Å, indicating that the strain energy
required to distort the 1,2-ethynylbenzene backbone is small
as compared to the energetic gain upon forming a symmetric
three-center [NIN]+ halogen bond.45 Upon formation of the
[NIN]+ complexes 2a–f, the N–N distance decreases by
0.07 to 0.2 Å, whereas for 2g, it slightly increases by 0.007 Å.
The NIN angle is linear (180°) for the [bis(pyridine)iodine]+
complexes 1a–g, and is approximately 175.5° for the [1,2-
bis((pyridine-2-ylethynyl)benzene)iodine]+ complexes 2a-g,
aThe 13C{1H,2H} experiments were run at 125.71 MHz. bThe
c
13C{1H,2H} experiments were run at 201.20 MHz. Temperature
interval -20 to 25 C. dTemperature interval -10 to 25 C. eDue to
minor temperature dependence and to limited solubility, this
coefficient could not be reliably determined.
n
The temperature coefficients obs for complexes 2a-d (Table
3) are small and comparable to those of the corresponding
reference molecules 3a-d, in both magnitude and sign. The
sum of the absolute value of the observed isotope effects,
Σ|obs|, is comparable for the free ligands and their correspond-
ing [NIN]+ halogen bonded complexes. The overall temper-
ature dependence of the isotope effect of systems involved in
rapid equilibrium, such as [NHN]+ complexes, were previ-
ously reported to be significantly higher than those of their
corresponding free ligands.45 In agreement with previous
2
studies,45,49,50,76 the obs’s of C3 were largest for both the free
ligands 3a-d and their iodine(I) complexes 2a-d. A static,
symmetric geometry of 2a-d, independent of the electron
density of their [NIN]+ bond, was further indicated by the
relative magnitude of the temperature coefficients. Thus, a
larger temperature dependence was detected for the carbons
1
1
2
closest to the position of H-to-2H substitution, obs and obs
.
For dynamic systems, such as the corresponding [NHN]+
complexes, the magnitude of the temperature coefficients
depends not only on the distance of the reporter 13C’s to the
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2
3
4
5
6
7
8
9
+
R
N
N
R
R
+
N
I
N
N
N
I
+
+
1a–g
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
R
R
N
N
R
R
+
+
N
I
N
I
N
N
+
+
2a–g
N
N
R
Scheme 4. The formal reactions used to define the stabilization energies of complexes 1a–g and 2a–g.
in excellent agreement with previous reports on the geometry
of halogen bonds.6,10,42,48 The N–I bond length shows only
minor dependence on the electronic properties of the substitu-
ent, with a less than 0.02 Å difference observed between the
shortest and longest bonds. The N–I bond length correlates
with the π electron population, Δnπ(N), with r2 of 0.953 (1a–g)
and 0.935 (2a–g), (Figure 3). Significantly lower correlation
was found between r(N–I) and the total electron population
Δn(N), as reflected by the r2 0.800 for 1a–g, and 0.700 for 2a–
g. This indicates that the slight variation in the N–I bond
length of the studied complexes is governed by the π popula-
tion at the nitrogen atoms. To assess the stability of complexes
1a–g and 2a–g, we calculated their stabilization energies
according to the formal reactions shown in Scheme 4. Since
we are interested in the strength of the electronic bond rather
than wish to make a comparison to experimental thermochem-
ical data, the electronic energies are considered here and not
the Gibbs free energies. Whereas the geometry, i.e. the bond
lengths and bond angles, of the complexes is virtually
Figure 4. The correlation of the stabilization energy (Estab) and
the change of the natural atom population at the N atoms of the
iodine(I) complexes of substituted pyridines (1a-g) (○) and of the
corresponding 1,2-bis((pyridine-2-ylethynyl)benzene) ligands
(2a-g) (●).
Figure 3. The correlation of the NI bond distance with the
change in the π(N) population of iodine(I) complexes of substitut-
ed pyridines (1a-g) (●) and of the corresponding 1,2-
bis((pyridine-2-ylethynyl)benzene) ligands (2a-g) (○).
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3
independent of electron density, their stability varies by nearly
4
5
6
7
8
9
100 kJ/mol, depending on the electronic nature of the substitu-
ents (Table 4, Figure 4). An increased electron density stabi-
lizes the [NIN]+ bond (1b-d and 2b-d), whereas electron
deficiency reduces the stability of the complexes (1e-g and 2e-
g). The correlation coefficients between the stabilization ener-
gy, Estab, and the natural atomic population, Δn(N), are 0.991
for 1a–g and 0.989 for 2a–g, whereas the corresponding r2
values for the π electron population, Δnπ(N), are significantly
lower, 0.851 for 1a–g, and 0.828 for 2a–g. Thus, whereas the
NI bond length proved to correlate strongly with Δnπ(N), the
stabilization energy correlates nearly perfectly with the total
natural atomic population (NAP) at the nitrogen atoms. This
can be rationalized from the mechanism of the three-center-
four-electron [NIN]+ bond: the larger the natural atomic
population, Δn(N), the higher the energies of the occupied
orbitals at the nitrogen, which facilitates the charge transfer to
iodine(I). This is in line with the findings of Ebrahimi et al.,
who investigated the nature of the [NXN]+ bond with a
variety of theoretical methods.90 The computationally predict-
ed variation of the [NIN]+ bond strength agrees excellently
with the experimentally observed higher stability of electron
rich complexes 2b-d as compared to the unsubstituted 2a, and
the instability of 2e in solution that prevented their IPE study.
It should be noted that the rapid decomposition of 2g prevent-
ed its experimental investigation completely, in line with its
computationally predicted instability.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 5. The solid state geometries of complexes 1c (top,
CCDC-1452897), and 1f (bottom, CCDC-1452897), obtained
-
by single crystal X-ray crystallography. The BF4 counterion is
omitted from the figure for clarity. The crystal of compound
1c was obtained as a solvate and thus each molecular unit
contains one molecule dichloroethane. Both complexes pos-
sess coplanar pyridine rings and nearly centrosymmetric ge-
ometries.
Table 5. X-ray Crystallographically Determined NI Bond
Distances and NIN Bond Angles for 1a, c, d, and f.
Structure
4-R
H
r(N-X)1
(Å)
r(N-X)2
(Å)
σ (N-X-N)
(°)
1a91
2.260(3)
2.259(3)
2.255(3)
2.260(3)
2.259(3)
2.260(3)
2.262(3)
2.239
180.0
180.0
177.7(1)
178.0(1)
179.4
We emphasize that the correlations found above must not be
misinterpreted as causal relationships. For instance, the close
correlation between Δn(N) and Estab does not indicate that the
halogen bond strength is governed solely by electrostatic
interactions between the partial charges of the N and I atoms.
Rather, as has been discussed e.g. in reference 10, halogen
bonding is caused by an interplay between electrostatic,
charge-transfer and not the least polarization and dispersion
effects. The Δn(N) and Δnπ(N) values are to be considered just
as indicators for the properties of the substituents, in lieu of
properly calibrated Hammett, induction, and resonance con-
stants.
1c
OMe
NMe2
2.252(3)
2.232
1d92,a
2.247
2.252
177.7
1f
CF3
2.251(5)
2.256(5)
2.272(5)
2.271(5)
176.2(2)
175.2(2)
a
-
-
The counterion of 1d is NO3 instead of BF4 . This does not
influence the geometry of [bis(pyridine)iodine]+ complexes.
and monitored the reaction proceeding in dry dichloroethane
solution at 25 C at the wavelength of maximum change (1a,f:
230 nm, 1c, 257 nm, and 1d, 300 nm). The reactions of 1a,c,d
were monitored using a Cary 100 UV-vis spectrophotometer,
whereas an Applied Photophysics SX-17MV stopped-flow
reaction analyzer was used for the fast reactions with 1f (4-
CF3). The observed rate constants (kobs) were obtained by
NLLSQ fitting of the absorbance versus time traces for the
disappearance of the iodine(I) complex to the standard expo-
nential model:
Geometry in the solid state. Single crystals were obtained via
slow diffusion of hexane into dichloroethane solutions of 1c
and 1f under cooling from 24°C to -20°C over two days. Crys-
tallographic data for 1a and 1d were taken from the
literature.91,92 The X-ray crystallographic analysis confirmed
that the NIN angle is linear (Figure 5) and that the iodine-
centered complexes are symmetric, even in the solid state
(Table 5), independent of their electron density. The small
difference between the NI bond lengths within a complex,
lower than <0.4%, is likely due to crystal packing forces, and
does not reflect a real asymmetry. Supporting the DFT predic-
tions above, the X-ray crystallographic data corroborate that
alteration of the electron density of the pyridine nitrogen caus-
es only very minor, < 2%, change in the NI bond length.
At = A∞+(A0–A∞)e-kobst
(3)
The saturation profile obtained when plotting kobs of 1a,c,f
against the alkene concentration implies that the mechanism
for the iodonium transfer is similar to that previously proposed
for bromocyclization with 4-penten-1-ol.39 Saturation was not
reached in the corresponding experiment with the electron rich
and slowly reacting 1d, suggesting a different rate limiting
step. However, in the lower alkene concentration range the kobs
versus [4-penten-1-ol] profile was linear permitting determina-
tion of the second-order rate constant (k2), even for this reac-
tion. The logarithm of the second-order rate constants, (k2 =
9.21 M-1s-1 (1a, H), k2 = 1.92 M-1s-1 (1c, OCH3), k2 = 0.00195
M-1s-1 (1d, N(Me)2), and k2 =126.9 M-1s-1 (1f, CF3)), normal-
Halogen bond strength in solution established by UV-Vis
kinetics. For experimental evaluation of the electron density
dependence of the halogen bond strength of [NIN]+ com-
plexes, we have monitored the rate of disappearance of the UV
absorbance of [bis(pyridine)iodine)]+ upon iodonium transfer
from complexes 1a,c,d,f to 4-penten-1-ol, using a procedure
described by Neverov and Brown.39,93 The mechanistic detail-
sof halonium transfer from bis(pyridine)-type complexes to
alkenes are well understood.39,93-97 We have used pseudo first-
order conditions, with a large excess of olefin (3.9-77 mM),
9
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ized to 1 mM concentration of added 4-sustituted pyridine, as
a function of the change of natural atomic population, Δn(N),
is shown in Figure 6.
Table 6. Dissociation of [Bis(4-R-pyridine)iodine]+ Com-
plexes 1a,c,f (7.68×10-5 M) in Presence of an Excess DMAP
(0.15 mM) in Dry Dichloroethane. Observed kobs Dissocia-
tion Rate Constants at 298 K, and the Enthalpy and En-
tropy of Activation.a
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Figure 6. The second-order rate constants (M-1 × s-1) of
1a,c,d,f in iodocyclization reactions with 4-penten-1-ol in the
presence of 4-R-pyridine (R = H, OMe, NMe2 or CF3), nor-
malized to 1 mM, obtained in dry dichloroethane, are shown
as a function of the change of natural atomic population,
Δn(N). A linear correlation is seen for all but the most electron
rich complex 1d.
b
H‡c
S‡c
Struc-
ture
4-R
kobs
( s-1)
(J mol-1K-1)
(kJ mol-1 )
H
0.392
0.333
3.322
70.97
+/- 1.07
72.83
+/- 0.80
39.16
-14.45
+/- 3.49
-13.23
+/- 2.60
-105.47
+/- 6.15
1a
1c
1f
OCH3
CF3
The magnitude of the second-order rate constants of com-
plexes 1a,c,d,f follows the inverse order of substituent elec-
tronegativity, i.e. k2(1f, CF3) >> k2(1a, H) > k2(1c, OCH3) >>
k2(1d, NMe2). Whereas the log(k2) of complexes 1a,c,f corre-
lates linearly to the change of natural atomic population,
Δn(N), which corresponds to the Hammett para, the corre-
sponding logk2 of 1d is an evident outlier (Figure 6), corrobo-
rating the hypothesis that the iodonium transfer mechanism for
1d is different from that of its less electron rich analogues.
+/- 1.87
aExperiments run under stopped-flow with 7.68 × 10-5M iodine(I)
complex 1a,c,f, and 0.15 mM DMAP in the reaction cell. Ob-
b
c
served rate constants kobs determined at 298 K. Activation pa-
rameters, H‡ and S‡, determined from Eyring plots.
CONCLUSIONS
Electron density changes do not disturb the symmetric ge-
ometry of the [NIN]+ halogen bond of bis(pyridine)-type
systems, neither in solution nor in the solid state. Despite
having a strong influence on the strength of the halogen bond,
the electron density of the pyridine nitrogens does not signifi-
cantly affect the NI bond lengths. The slight change (< 0.7%)
correlates only weakly to the variation in total electron popula-
tion, Δn(N), but much more strongly to that in the π popula-
tion Δn(N). This observation is important to stress, as shorten-
ing of the halogen bond donor-acceptor distance is one of the
most commonly used characteristics for categorizing halogen
bond strength.
The 15N NMR chemical shift of halogen bonded complexes
is a good measure for the  electron population of the involved
nitrogen. The 15N NMR coordination shift of the studied io-
dine(I) complexes reflects the formation of the [NIN]+
halogen bond; however, its magnitude does not directly reflect
the strength of the halogen bond. Analogous lack of correla-
tion between bond energy and chemical shift was recently
reported for analogous tetrel bonds.98
Due to the difficulties in identifying appropriate wave-
lengths for reaction monitoring, no kinetics experiments were
undertaken for the analogous 4-substituted 1,2-bis((pyridine-
2-ylethynyl)benzene)iodine(I) complexes 2a-f.
We studied the kinetics of the dissociation of complexes
1a,c,e-f in the presence of the strong XB acceptor 4-
dimethylaminopyridine (DMAP), the free base of 1d. This
ligand exchange reaction is rapid due to the significantly high-
er stability of complex 1d as compared to the less electron rich
complexes. Moreover, the reaction is easy to follow as 1d has
high absorbance. The dissociation rate constants (kobs) at 25 C
(Table 6) were determined from stopped-flow experiments by
addition of DMAP (0.15 mM; concentration at which rate of
the reaction was independent of [DMAP]) to 1a, 1c, or 1e
(7.68 × 10-5M) in dry dichloroethane at 272 nm. We measured
the initial rate kinetics for the formation of the DMAP coordi-
nated complex 1d. In addition, the thermodynamic activation
parameters H‡ and S‡, shown in Table 6, for the reactions
were determined from the same experiments performed at
different temperatures (Table 6) by Eyring plots of the ob-
tained kobs rate constants. The obtained activation parameters
indicate that the lower the electron density of an [NIN]+
complex, the lower the activation barrier for iodine(I) transfer.
This observation indicates, in excellent agreement with the
DFT computations, that a decrease in electron density of the
[NIN]+ halogen bond decreases its strength.
The stability of the [NIN]+ halogen bond correlates to the
electron density of the nitrogen halogen bond acceptors. A
linear correlation to the natural atomic population, Δn(N) of
the para-substituted pyridines was seen for most substituents.
However, reaction kinetics indicate that the iodine(I) complex
bearing the strongly resonance donating N,N-
dimethylamino substituent has a different iodonium trans-10
fer mechanism as compared to the other analogous com-
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(9) Pinter, B.; Nagels, N.; Herrebout, W. A.; De Proft, F. Chem.
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Eur. J. 2013, 19, 519.
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may be helpful for providing a tool for thorough control of
electrophilic halogenation reactions. As [bis(pyridine)iodine]+
complexes are common synthetic reagents, this may be of
significance for the development of new, stereoselective halo-
genating agents in the future.
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ASSOCIATED CONTENT
(14) Catalano, L.; Cavallo, G.; Metrangolo, P.; Resnati, G.;
Terraneo, G. Top.
Curr.
Chem.
2016,
DOI:
Supporting Information. Details on the synthesis, spectroscopic
data for compound identification, and details on the NMR, com-
putational, X-ray diffractometric, and kinetic investigations. This
material is available free of charge via the Internet at
http://pubs.acs.org.s.
10.1007/128_2015_666 .
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AUTHOR INFORMATION
Corresponding Author
* mate@chem.gu.se.
Present Addresses
║Department of Biochemistry and Molecular Biology, Colorado
State University, Fort Collins, CO 80523-1870, USA. Astra-
Zeneca, CVMD iMED, Pepparedsleden 1, Mölndal, 43183, Swe-
den.Department of Chemistry, Ångström Laboratory, Uppsala
University, S-751 20 Uppsala, Sweden. ¶ Chemtura Organometal-
lics GmbH, Bergkamen, 59192 Germany. &Afton Chemical,
Richmond, Virginia, 23219, USA
Funding Sources
European Union Seventh Framework Programme (ME,
FP7/2007-2013) grant agreement n˚ 259638. The Swedish Re-
search Council (ME, 2012:3819), and the Academy of Finland
(KR, 263256 and 265328).
ACKNOWLEDGMENT
The research leading to these results has received funding from
the European Research Council under the European Union's
Seventh Framework Programme (FP7/2007-2013) / ERC grant
agreement n° 259638. We thank the Swedish Research Council
(ME 2007:4407; 621-2008-3562) and the Academy of Finland
(KR: 263256 and 265328) for financial support, and Professor
Stan Brown (Department of Chemistry, Queen’s University) for
giving us access to equipment for the UV/Vis kinetic experi-
ments.
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ABBREVIATIONS
XB, Halogen bond; DMAP, dimethylaminopyridine.
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