Willgerodt-Type Dichloro(aryl)-λ 3-Iodanes: A Structural Study

Article abstract of DOI:10.1055/s-0037-1611886

Crystallographic structural analysis of four electronically diverse Willgerodt-type reagents is disclosed together with a solution-phase NMR analysis. These data reveal a plethora of intermolecular non-covalent interactions and confirm the expected T-shape geometry of the reagents. In all cases the I-Cl bonds are orthogonal to the plane of the aryl ring. This study provides important structural insights into this venerable class of dichlorination reagent and has implications for crystal engineering.

Full text of DOI:10.1055/s-0037-1611886

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
special topic
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en
J. C. Sarie et al.
Special Topic
Synthesis
Willgerodt-Type Dichloro(aryl)-3-Iodanes: A Structural Study
Jérôme C. Sarie
Willgerodt-Type
Reagents
X-ray and solution-phase analysis
Jessica Neufeld
Constantin G. Daniliuc
Cl
I
θ1
δ+
Ryan Gilmour*
0
0
0
0-0
0
0
2-
3
1
5
3-6
0
6
5
θ2
I
Cl
I
Cl
Cl
θT
Organisch-Chemisches Institut, Westfälische Wilhelms-Univer-
sität Münster, Corrensstraße 40, 48149 Münster, Germany
ryan.gilmour@uni-muenster.de
= Ph, CO2Et, Br, CF3
Published as part of the Special Topic Halogenation methods
(with a view towards radioimaging applications)
Received: 04.06.2019
Accepted after revision: 25.06.2019
Published online: 09.07.2019
mented by its ability to engage in radical processes, as is ev-
ident from the dichlorinate rubber induced by thermal de-
composition.7 This free-radical character was elegantly har-
nessed by Breslow and co-workers to achieve the site-
selective C(sp3)–H chlorination in steroids triggered by light
irradiation.8
The Willgerodt reagent and derivatives thereof continue
to enjoy widespread appeal as both oxidants and chlorina-
tion agents.9 A prominent, contemporary application in-
cludes the vicinal difunctionalisation of -bonds. Employ-
ing the para-substituted analogue (p-PhC6H4ICl2), Nicolaou
and co-workers developed an enantioselective dichlorina-
tion of cinnamyl alcohols (Scheme 1, top).10
DOI: 10.1055/s-0037-1611886; Art ID: ss-2019-s0315-st
Abstract Crystallographic structural analysis of four electronically di-
verse Willgerodt-type reagents is disclosed together with a solution-
phase NMR analysis. These data reveal a plethora of intermolecular non-
covalent interactions and confirm the expected T-shape geometry of
the reagents. In all cases the I–Cl bonds are orthogonal to the plane of
the aryl ring. This study provides important structural insights into this
venerable class of dichlorination reagent and has implications for crystal
engineering.
Key words chlorination, hypervalency, iodine(III), X-ray crystallogra-
phy
Despite their venerable history, Willgerodt’s original re-
port cautions that a principal weakness of dichloro(aryl)-
3-iodanes is their lack of stability.1 This has led to the de-
velopment of innovative strategies to mitigate degradation.
Approaches including recycling strategies11 or in situ gener-
ation from iodosobenzene12 have been reported to address
this intrinsic limitation.
Willgerodt’s synthesis of dichloro(phenyl)-3-iodane in
1886 remains a defining innovation in main group structur-
al chemistry, and the genesis of hypervalent iodine.1 Gener-
ated by exposing iodobenzene to Cl2(g), the product was
named ‘Phenyljodidchlorid’ (1a → 2a) and attributed the
molecular formula PhI(III)Cl2 (Scheme 1). Historically, it is
pertinent to note that Kekule’s papers on the structure of
benzene were published only 20 years earlier.2 Over a cen-
tury of interest and sustained innovation exploring the re-
activity of the Willgerodt reagent has resulted in a powerful
legacy.3 This is a consequence of the reagent’s versatility in
serving as both a nucleophilic and electrophilic chlorine
source. Its synthetic value was demonstrated as early as
1937 in the vicinal dichlorination of chalcone, where the
practical advantages of 2a versus Cl2(g) were highlighted.4
Brønsted acid activation was later demonstrated through
kinetic interrogation leading to a putative mechanism to ac-
count for the formation of the anti-adducts.5 This latter de-
velopment continues to inform and inspire the design of
catalytic paradigms to generate ArIX2 species in situ via
I(I)/I(III) catalysis.6 The polar reactivity of 2a is comple-
The reactivity of dichloro(aryl)-3-iodanes is a conse-
quence of the linear three-centre, four-electron Cl–I–Cl
bond intrinsic to these reagents. The distorted T-shape ge-
ometry expected for these RICl2 species has been confirmed
by X-ray analysis on a number of derivatives.13,14 However,
despite their prominence as chlorination/oxidation re-
agents, structural studies of para-substituted ArICl2 species
in the solid state are underrepresented. Herein, a solid-state
analysis of selected para-substituted ArICl2 systems is dis-
closed to contribute to the current renaissance of hyperva-
lent iodine mediated halogenation (Figure 1, bottom).
Initially, a series of electronically diverse Willgerodt-
type reagents was prepared according to a modified proce-
dure reported by Zhang and Zhao (Table 1).15
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. C. Sarie et al.
Special Topic
Synthesis
The Willgerodt reagent
Cl
I
Cl2(g)
• 1886 Willgerodt
• Discovery
I
Cl
1a
2a
• 1937 Allen
• Chalcone
• 1958 Keefer • 1972 Breslow
• 2019 This
study
• Structural
analysis
• 2011 Nicolaou
• Enantioselective
• dichlorination
• Brønsted acid
• Steroids
• activation
X-ray: Hypervalent dichloro-λ3-iodane
Cl
I
Cl Cl
I
Cl
Cl
I
Cl
Cl
I
R
CF3
CF3
C6F12H
3
4
5
Cl
2
Cl
Cl
Ph
Br
I
EtO2C
F3C
I
This study:
Cl
Cl
I
Cl
Cl
I
• 4 unreported X-ray structures
• Solution-phase analysis
• Solid-state analysis
Cl
Cl
Scheme 1 Conceptual framework of this study
Table 1 Synthesis of Dichloroaryl-3-iodanes 2a–i
Entry Iodoarene
Product
Time (h) Yield (%)
Cl
I
Cl
I
aq NaOCl (15%), conc. HCl
6c,d
7d
8c
Br
2f
0.5
94
97
93
92
Br
I
R
R
I
H2O/CH3CN
r.t.a
Cl
Cl
2
1
Cl
I
EtO2C
F3C
O2N
2g 0.5
EtO2C
F3C
O2N
I
Entry Iodoarene
1
Product
Time (h) Yield (%)
Cl
Cl
I
Cl
I
2a
0.5
–
85
94
I
I
2h
2i
2
2
Cl
Cl
Cl
I
Cl
I
2b
MeO
Me
Ph
I
MeO
Me
Ph
2b
2c
9c
I
Cl
Cl
Cl
a According to a modified procedure reported by Zhang and Zhao:15 iodo-
arene (1 mmol), aq NaOCl (15%, 2 mL), conc. HCl (2 mL), H2O/MeCN (8 mL,
1:1 v/v).
3
I
I
0.5
83
88
83
Cl
b At 0 °C, filtered directly after addition of conc. HCl.
c Iodoarene (4 mmol scale).
Cl
I
d H2O/MeCN (2:1 v/v). All yields refer to isolated yields.
4
I
2d 0.5
Cl
Cl
I
Gratifyingly, all nine aryl iodides were successfully con-
5c
Cl
I
Cl
2e
0.5
verted into the corresponding hypervalent dichloro(aryl)-
3-iodanes in high yields (up to 97%). The synthesis of the
electron-rich p-methoxy-substituted analogue 2b was per-
formed at 0 °C and was filtered instantly after the addition
Cl
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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J. C. Sarie et al.
Special Topic
Synthesis
of concentrated HCl (Table 1, entry 2). Electron-deficient
substrates such as p-trifluoromethyl- and p-nitro-deriva-
tives required extended reaction times (Table 1, entries 8
and 9). Gratifyingly, several examples could be scaled-up to
4 mmol scale with no erosion of the yield (Table 1, entries 5,
6, 8 and 9).
the downfield region at  = 125.5, corresponding to a Δppm
of 31.0 and illustrating once more the expected, strong elec-
tron-withdrawing character of ICl2 (Figure 1, b).18
These observations are persistent throughout the series,
from the most electron-rich p-methoxy-substrate 2b to the
most electron-poor p-nitro 2i (see the experimental sec-
tion). The average deviation of the ipso-carbon C1 between
ArI and ArICl2 is 29.9 ppm and a linear shift correlation be-
tween the starting material and the product is observed
(Figure 2, a).
The structural evaluation began with a solution-phase
NMR analysis of this electronically diverse pool of ArICl2
species. Consistent with the findings reported by Wu and
1
Shafir with ArI(OAc)2,16 the H NMR spectrum of the Will-
gerodt reagent 2a shows consistent deshielding of all pro-
tons on the aromatic ring compared to iodobenzene. This
downfield shift is more pronounced for the ortho-proton
H2 (ΔH 0.48) than for the meta-H3 and para-H4 signals
(ΔH 0.37 and 0.26, respectively) (Figure 1, a).
Consistent with the observation from the 1H NMR spec-
tra of the Willgerodt reagent and of iodobenzene, the
I(I)/I(III) oxidation results in a downfield shift of the ortho-
and meta-protons, regardless of the para-substituent. This
difference remains a constant 0.49 ppm for H2 and 0.35
ppm for H3. Again, a linear correlation between the corre-
sponding proton signals from the starting materials and the
products can be observed (Figure 2, b).
Figure 2 (a) Correlation between the 13C NMR signals of C1 for ArI and
ArICl2. (b) Correlation between the 1H NMR signals of H2 and H3 for ArI
and ArICl2
Figure 1 (a) 1H NMR stack plot of iodobenzene (top, 400 MHz, CDCl3,
296 K) and 2a (bottom, 599 MHz, CDCl3, 299 K). (b) 13C NMR stack plot
of iodobenzene (top, 101 MHz, CDCl3, 296 K) and 2a (bottom, 151
MHz, CDCl3, 299 K).
From the test set, it was possible to isolate crystals of
four dichloro-3-iodanes that were suitable for X-ray analy-
sis (Table 2). The first of this quartet, p-PhC6H4ICl2 (2d)
(CCDC 1918404), was employed by Nicolaou and co-work-
ers in combination with catalytic (DHQ)2PHAL for the enan-
tioselective dichlorination of cinnamic alcohols.10 This spe-
In the 13C NMR spectra, the ipso-carbon (C1) of iodoben-
zene shows a characteristic upfield signal at  = 94.5 due to
normal halogen dependence (NHD).17 After oxidation to the
hypervalent species 2a, this signal is drastically shifted to
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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J. C. Sarie et al.
Special Topic
Synthesis
Table 2 Selected Intramolecular Bond Lengths and Angles
Cl
I
Cl
Cl
I
Cl
Cl
I
Cl
Cl
I
Cl
Structurea
O
O
CF3
Br
2d (CCDC 1918404)
2f (CCDC 1918405)
2g (CCDC 1918406)
2h (CCDC 1918407)
Distances (Å)
C1–I1
2.100(2)
2.503(1)
2.503(1)
2.5029
2.095(12)
2.471(3)
2.500(3)
2.486
2.110(2)
2.472(1)
2.521(1)
2.497
2.102(2)
2.485(1)
2.490(1)
2.488
I1–Cl1
I1–Cl2
I1–Clb
Angles θ (°)
θ1
87.0(1)
87.0(1)
174.0(1)
86.7(4)
89.6(4)
176.1(1)
87.8(1)
89.0(1)
176.6(1)
89.3(1)
88.7(1)
177.8(1)
θ2
θT
Dihedral angles ϕc (°)
ϕ1a
ϕ1b
ϕ2a
ϕ2b
–81.3
98.7
73.7
102.0
–75.0
–79.2
103.8
–76.0
104.0
105.0
–75.0
–103.1
–107.5
75.7
–81.3
98.7
a ORTEP: 2d and 2g, thermal ellipsoids are set at 50% probability; 2f, thermal ellipsoids are set at 30% probability; 2h, thermal ellipsoids are set at 15% probability.
b Average of I1–Cl1 and I1–Cl2 distances.
c ϕ1a: Cl1–I1–C1–C2. ϕ1b: Cl1–I1–C1–C6. ϕ2a: Cl2–I1–C1–C2. ϕ2b: Cl2–I1–C1–C6.
cies, together with the three remaining dichloro-3-io-
danes, allow the influence of the p-substituent on the
structure to be interrogated. Specifically, 2f contains a p-Br
group (CCDC 1918405), 2g an ester (CCDC 1918406) and 2h
a trifluoromethyl moiety (CCDC 1918407). For the purposes
of describing distances and angles in the solid-state study,
the solid line (–) corresponds to an intramolecular bond
whilst the broken lines (--) refer to intermolecular interac-
tions (Figure 3).
played this characteristic geometry. The C1–I1 bond lengths
of compounds 2d, 2f, 2g and 2h vary between 2.095(12) Å
and 2.110(2) Å, and are thus consistent with literature val-
ues ranging from 2.00 Å13a and 2.125 Å14a,b for di-
chloro(aryl)-3-iodanes and slightly shorter than the fluori-
nated aliphatic examples13c,14c (between 2.140 Å and 2.229
Å).
In addition, symmetrical compound 2d comprises a I1–
Cl1 bond length of 2.503(1) Å, where a θT angle of 174.0(1)°
was measured. Compounds 2f, 2g and 2h exhibit non-sym-
metrical angles and distances, which may be a consequence
of crystal packing effects.
Cl1 I1 Cl2
θ2
θ1
Cl
I
Cl
Cl
I
Cl
ö
C1
θT
Cl
I
Cl
C6
C2
Hypervalent p-BrC6H4ICl2 (2f) displays angles θ1 of
86.7(4)° and θ2 of 89.6(4)° and an overall θT angle of
176.1(1)° for distances of I1–Cl1 (2.471(3) Å) and I1–Cl2
(2.500(3) Å). The ester 2g has a θ1 angle of 87.8(1)°, and a θ2
of 89.0(1)° for a measured θT of 176.6(1)°. The three-centre
four-electron bond comprises an I1–Cl1 bond length of
2.472(1) Å and an I1–Cl2 bond of 2.521(1) Å. Comparably,
the structure of p-CF3 2h consists of two I1–Cl1 and I1–Cl2
bonds of 2.485(1) Å and 2.490(1) Å, respectively, as well as
bond angles θ1 of 89.3(1)°, θ2 of 88.7(1)° and a measured θT
of 177.8(1)°.
a)
b)
c)
Figure 3 (a) Atom labelling for this study. (b) Nomenclature to de-
scribe angles. (c) Representation of torsion angles.
A consistent feature of dichloro-3-iodanes that spans
the initial X-ray investigation of the Willgerodt reagent
from Archer and van Schalwyk13a to the most recent exam-
ple of ortho- and para-nitro-substituted reagents,14d is the
distorted T-shape geometry of the RICl2 unit. In line with
previous data (2d, 2f, 2g, 2h), the four new structures dis-
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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J. C. Sarie et al.
Special Topic
Synthesis
Interestingly, the four structures in this study display
representative dihedral angles that deviate from orthogo-
nality (ϕ1a of –81.3° for 2d, 73.7° for 2f, 102.0° for 2g and
–76.0° for 2h). The unsymmetrical compounds 2f, 2g and
2h exhibit non-equivalent torsion angles of –103.1° (ϕ1b),
–107.5° (ϕ2a) and 75.7° (ϕ2b) for 2f, –75.0° (ϕ1b), –79.2°
(ϕ2a) and 103.8° (ϕ2b) for 2g, and finally 104.0° (ϕ1b),
105.0° (ϕ2a) and –75.0° (ϕ2b) for 2h. Inspection of the ex-
panded solid-state structures reveals a plenum of intermo-
lecular interactions that are noteworthy.
2d. Secondary intermolecular C8–H8--Cl1 interactions
(3.715(2) Å with an angle C8–H8--Cl1 of 144.9°) allows for
the formation of a 2D network based upon halogen chains
(Figure 5).
Compounds with a symmetrical unit in the solid state
are organised as a polymeric structure with prominent in-
termolecular Cl1--Cl1 and Cl1--I1 interactions. In the case
of p-PhC6H4ICl2 (2d), two different Cl1--Cl1 interactions
with distances of 3.329(1) Å and 3.494(1) Å are observed,
while the Cl1--I1 distance measures 3.625(1) Å (Figure 4). It
is interesting to note that both Cl1--Cl1 distances are inferi-
or to the sum of the chlorine van der Waals radii (1.75 (Cl) +
1.75 (Cl) = 3.50 Å) and that the same phenomenon is ob-
served for the Cl1–I1 interactions, where the distance is less
than 3.71 Å (sum of the chlorine and iodine van der Waals
radii: 1.75 (Cl) + 1.96 (I)).19
Figure 5 Expansion of the polymeric chain into a 2D network through
C8–H8--Cl1 interactions in 2d
Figure 4 Formation of the halogen-based polymeric chain in 2d
Chlorine--chlorine and chlorine--iodine interactions are
also observed in p-BrC6H4ICl2 (2f) with lengths of 3.326(4)
Å for Cl1--Cl2 and 3.357(4) Å for Cl2--I1 having been mea-
sured (Figure 6, a). Intriguingly, this inter-halogen frame-
work seems to be influenced by a bridging Cl2--Br1 interac-
tion [3.418(4) Å; smaller than the sum of the chlorine and
bromine van der Waals radii (1.75 (Cl) + 1.85 (Br) = 3.60 Å)]
(Figure 6, b).19 Expansion of the structure into 3D space via
the involvement of a C2–H2--Cl1 interaction (3.797(1) Å for
a C2–H2--Cl1 angle of 157.1°) is observed. The chlorine
Structural analyses of the parent Willgerodt reagent 2a
reveal a polymeric zig-zag structure originating from the
chlorine atoms at the hypervalent iodine centres.13 In con-
trast, the polymeric structure for compound 2d is built
upon two bridging chlorine contacts for each iodine centre.
Closer inspection reveals an intermolecular Cl1--I1--Cl1 an-
gle of 54.7° and a torsion angle between the Cl1--I1--Cl1
plane and the T-shaped Cl1–I1(C1)–Cl1 plane of 14.8° for
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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J. C. Sarie et al.
Special Topic
Synthesis
atom Cl2 that is in contact with three different halogens
Cl1--Cl2, Cl2--I1 and Cl2--Br1 is also notably the closest to
orthogonality (C–I–Cl) with an angle θ2 of 89.6(3)° (Cl1: θ1
of 86.7(3)°). The angle between the planes, exemplified by
the atoms I1--Cl2--I1 and Br1--Cl2--Cl1, is only 15.3° lead-
ing to a quasi-planar orientation.
Figure 7 Packing diagram illustrating the expansion of 2f into a com-
plex 3D network
mers has a Cl--ArH distance of 3.77 Å. In addition, this scaf-
fold displays a -- interaction between juxtaposed dimers
of 3.384(1) Å (Figure 8). The overall architecture of the crys-
tal 2g is predicated on a polymer-type structure with alter-
nating halogen contacts.
Figure 6 (a) Presentation of the inter-halogen interaction observed in
2f. (b) Packing diagram representing the bromine–chlorine and hydro-
gen–chlorine interactions in 2f.
Figure 8 Packing diagram representing the polymer-type structure of
2g with alternating halogen contacts and -- interactions
It is pertinent to mention that dichloro(4-bromoben-
zene)-3-iodane (2f) is the only species in which a chlorine
atom engages in three discrete interactions with other hal-
ogen atoms, thereby allowing expansion to a complex net-
work (Figure 7).
Analogous to the crystal packing observed for the Will-
gerodt reagent,13 p-ethyl ester 2g is a dimer in the solid
state in which two intermolecular axial I1--Cl2 interactions
of 3.384(4) Å are noted: These are slightly longer than those
measured for 2f. Secondly, Cl1-- interactions with the es-
ters of the adjacent dimers are visible from the X-ray analy-
sis and contrast sharply with the chlorine--chlorine and
chlorine--iodine interactions observed in related systems
(the distance Cl1--C7(ester) is 3.301(3) Å). This result is in-
teresting when compared with Archer’s original report for
2a13a in which the comparable closest contact of the two di-
Structural analysis of dichloro(4-trifluoromethylben-
zene)-3-iodane (2h) again reveals a stair-like, polymeric
array based on halogen interactions akin to the Willgerodt
reagent. The axial Cl2--I1 interaction of 3.428(1) Å is com-
parable to the 3.40 Å for the parent molecule 2a.13 Despite
the initial similarity, closer inspection reveals that 2h dif-
fers from 2a by a significantly shorter intermolecular Cl2--
Cl2 distance (3.293(1) Å compared to 4.15 Å for 2a)13 (Fig-
ure 9, a).
Whereas crystallographic analysis of compound 2a re-
veals a 2D structure based on interlaced polymeric chains,
expansion of the 2h network shows clear interactions be-
tween the p-CF3 substituents of each monomer of every
polymeric chain. Specifically, a significant C5–H5--F2 inter-
action measuring 3.508(3) Å (C5–H5--F2 angle of 175.5°) is
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

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J. C. Sarie et al.
Special Topic
Synthesis
for extraction or purification were purchased as technical grade and
distilled on a rotary evaporator prior to use. Column chromatography
was performed using silica gel (40–63 m; VWR Chemicals) as the
stationary phase. Reaction monitoring was achieved by analytical
thin-layer chromatography (TLC) on aluminium foil pre-coated with
silica gel 60 F254 (Merck). Compounds were visualised with UV light
(254 nm) or by chemical staining using a solution of KMnO4 [KMnO4
(10 g), K2CO3 (65 g), NaOH (1 N, 15 mL) in water (1 L)] followed by
heating. Concentration in vacuo was performed at ~10 mbar at 40 °C
unless otherwise stated. Melting points were measured on a Büchi B
545 melting point apparatus in open capillaries (ramp 3 °C/min) and
are uncorrected. NMR spectra were measured by the NMR service at
the Organisch-Chemisches Institut, Westfälische Wilhelms-Universi-
tät Münster on a Bruker Avance II 400 or an Agilent DD2 600 spec-
trometer. 1H NMR chemical shifts are given relative to TMS and are
referenced to the residual solvent peak as internal standard. Spectra
of other nuclides as 13C and 19F are referenced according to the proton
resonance of TMS as the primary reference for the unified chemical
shift scale. 1H NMR spectra are reported as follows: chemical shift ()
in ppm (multiplicity, coupling constant JFH and JHH in Hz, number of
protons, assignment of proton). 13C NMR spectra are reported as fol-
lows: chemical shift () in ppm (multiplicity, coupling constant JFC in
Hz, number of carbons, assignment of carbon). 19F NMR spectra are
reported as follows: chemical shift () in ppm (multiplicity, coupling
constant JFH in Hz, number of fluorines, assignment of fluorine). Reso-
nance multiplicities are abbreviated as s (singlet), d (doublet), t (trip-
let), q (quartet), p (pentet) or m (multiplet). Assignments of unknown
compounds are based on COSY, HMBC and HSQC spectra. Mass spec-
tra were measured by the MS service of the Organisch-Chemisches
Institut, Westfälische Wilhelms-Universität on a Triplequad TSQ 7000
(MS EI) or a Trace 1310 with ISQ 7000 Single Quad Mass Spectrometer
(GC EI-MS).
Figure 9 (a) Formation of the halogen-based polymeric chain in 2h.
(b) Expansion of the polymeric chain into a 2D network through C5–
H5--F2 interactions
4-Iodo-1,1′-biphenyl (1d)
The title compound was prepared according to a modified procedure
from Yoon et al.20 4-Bromo-1,1′-biphenyl (1.2 g, 5.0 mmol, 1.0 equiv)
was dissolved in dry tetrahydrofuran (15 mL). The mixture was
cooled to –78 °C, n-butyllithium (4.7 mL, 1.6 M in hexane, 7.5 mmol,
1.5 equiv) was added dropwise and the reaction mixture was stirred
for 1 h. Iodine (252 mg, 7.5 mmol, 1.5 equiv) was dissolved in dry te-
trahydrofuran (10 mL) and was then added dropwise to the reaction
mixture. The mixture was slowly warmed to room temperature and
stirred for 24 h. The reaction was then quenched by addition of water
(20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted
with ethyl acetate (3 × 20 mL). The combined organic layers were
washed with brine (20 mL), dried over MgSO4 and filtered. The sol-
vent was removed in vacuo and the crude residue was purified by col-
umn chromatography using n-pentane (100%) to afford 4-iodo-1,1′-
biphenyl (1d) (1.20 g, 4.2 mmol, 86%) as a yellow solid.
supported by an intermolecular F1--F1 interaction of 2.930
Å: This is comparable to the sum of their van der Waals ra-
dii (1.47 (F) + 1.47 (F) = 2.94 Å) (Figure 9, b).19
Interestingly, when the intermolecular I1--Cl2 interac-
tion occurs with the axial position of the adjacent hyperva-
lent iodine centre, the angle between the planes Cl1–
I1(Cl2)–Cl2 and Cl1–I1(C1)–Cl2 is 20.0° for 2h, 15.6° for 2f
and only 1.7° for 2g.
In conclusion, a solution-phase NMR analysis has re-
vealed the influence of para substituents on an electroni-
cally diverse group of Willgerodt-type chlorination re-
agents based on the hypervalent dichloro(aryl)-3-iodane
scaffold. This is complemented by a crystallographic study
for the four novel systems, which demonstrate subtle differ-
ences in packing. In addition to providing information on
this venerable class of dichlorination reagents, it is envis-
aged that these data will have implications for crystal engi-
neering and structural chemistry in a broader sense.
Mp 105–106 °C; Rf = 0.45 (n-pentane).
1H NMR (400 MHz, CDCl3):  = 7.77 (m, 2 H), 7.56 (m, 2 H), 7.45 (m, 2
H), 7.40–7.30 (m, 3 H).
MS (EI): m/z (%) = 280.0 (84%) [M]•+, 153.1 (100) [M – I]•+, 77.0 (56)
[M – C6H4I]•+.
The analytical data are in agreement with the literature.21
Dichloro(aryl)-3-iodanes; General Procedure
Dichloro(aryl)-3-iodanes were prepared according to a modified pro-
cedure from Zhang and Zhao.15 The corresponding aryl iodide (1.0
mmol, 1.0 equiv) was dissolved in acetonitrile (4 mL). Then water (4
mL) and NaOCl (15% aq, 2 mL) were added slowly to the solution.
All chemicals were purchased as reagent grade and used as received.
Solvents were dried using a Grubbs purification system including col-
umns packed with molecular sieves and aluminium oxide. Solvents
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

H
J. C. Sarie et al.
Special Topic
Synthesis
Dropwise addition of conc. HCl (2 mL) led to a yellow precipitate. The
reaction mixture was stirred for the indicated time (see Table 1), then
filtered and washed with n-pentane to obtain the desired di-
chloro(aryl)-3-iodane.
ent temperature for 30 min to afford, after work-up, dichloro[(1,1′-bi-
phenyl)-4-yl]-3-iodane (2d) as a yellow solid (308 mg, 0.88 mmol,
88%).
Mp 80–81 °C.*
1H NMR (400 MHz, CDCl3):  = 8.23 (m, 2 H, H2), 7.66 (m, 2 H, H3), 7.57
Dichloro(phenyl)-3-iodane (2a)
(m, 2 H, H6), 7.49 (m, 2 H, H7), 7.43 (m, 1 H, H8).
According to the general procedure using iodobenzene (110 L, 1.0
mmol, 1.0 equiv), acetonitrile (4 mL), water (4 mL), NaOCl (2 mL) and
conc. HCl (2 mL). The reaction mixture was stirred at ambient tem-
perature for 30 min to afford, after work-up, dichloro(phenyl)-3-io-
dane (2a) as a yellow solid (234 mg, 0.85 mmol, 85%).
13C{1H} NMR (151 MHz, CDCl3):  = 145.7 (1 C, C4), 138.78 (1 C, C5),
134.4 (2 C, C2), 130.3 (2 C, C3), 129.3 (2 C, C7), 129.0 (1 C, C8), 127.6 (2
C, C6), 123.6 (1 C, C1).
MS (EI): m/z (%) = 347.9 (10) [M – H2]•+, 314 (82) [M – HCl]•+, 280.0
(22) [M – Cl2]•+, 153.2 (18) [M – ICl2]•+.
Mp 80–82 °C.
* In agreement with the literature.24
1H NMR (400 MHz, CDCl3):  = 8.19 (m, 2 H, H2), 7.60 (m, 1 H, H4), 7.48
(m, 2 H, H3).*
Dichloro(4-chlorophenyl)-3-iodane (2e)
13C{1H} NMR (151 MHz, CDCl3):  = 134.0 (2 C, C2), 132.2 (1 C, C4),
According to the general procedure using 1-chloro-4-iodobenzene
(953 mg, 4.0 mmol, 1.0 equiv), acetonitrile (8 mL), water (16 mL),
NaOCl (8 mL) and conc. HCl (8 mL). The reaction mixture was stirred
at ambient temperature for 30 min to afford, after work-up, di-
chloro(4-chlorophenyl)-3-iodane (2e) as a yellow solid (1.02 g, 3.3
mmol, 83%).
131.7 (2 C, C3), 125.5 (1 C, C1).*
MS (EI): m/z (%) = 272.0 (1) [M – H2]•+, 238.1 (8) [M – HCl]•+, 204.1
(100) [M – Cl2]•+, 77.0 (92) [M – ICl2]•+.
* In agreement with the literature.22
Dichloro(4-methoxyphenyl)-3-iodane (2b)
Mp 100–102 °C (Lit.15 113–114 °C).
1H NMR (400 MHz, CDCl3):  = 8.11 (m, 2 H, H2), 7.45 (m, 2 H, H3).
According to the general procedure using 1-iodo-4-methoxybenzene
(234 mg, 1.0 mmol, 1.0 equiv), acetonitrile (4 mL), water (4 mL),
NaOCl (2 mL) and conc. HCl (2 mL) at 0 °C. The reaction mixture was
directly filtered to afford dichloro(4-methoxyphenyl)-3-iodane (2b)
as a yellow solid (287 mg, 0.94 mmol, 94%).
13C{1H} NMR (151 MHz, CDCl3):  = 139.2 (1 C, C4), 135.2 (2 C, C2),
131.9 (2 C, C3), 121.9 (1 C, C1).
MS (EI): m/z (%) = 272.0 (1) [M – HCl]•+, 238.1 (100) [M – Cl2]•+, 111.1
(71) [M – ICl2]•+.
Mp 68–70 °C.*
1H NMR (400 MHz, CDCl3):  = 8.06 (m, 2 H, H2), 6.94 (m, 2 H, H3), 3.87
Dichloro(4-bromophenyl)-3-iodane (2f)
(s, 3 H, H5).
According to the general procedure using 1-chloro-4-iodobenzene
(1.13 g, 4.0 mmol, 1.0 equiv), acetonitrile (8 mL), water (16 mL),
NaOCl (8 mL) and conc. HCl (8 mL). The reaction mixture was stirred
at ambient temperature for 30 min to afford, after work-up, di-
chloro(4-bromophenyl)-3-iodane (2f) as a yellow solid (1.34 g, 3.8
mmol, 94%).
13C{1H} NMR (101 MHz, CDCl3):  = 162.6 (1 C, C4), 136.3 (2 C, C2),
117.3 (2 C, C3), 114.4 (1 C, C1), 55.9 (1 C, C5).
MS (EI): m/z (%) = 302.0 (1) [M – H2]•+, 268.1 (36) [M – HCl]•+, 234.0
(100) [M – Cl2]•+, 107.0 (8) [M – ICl2]•+.
* In agreement with the literature.15
Mp 112–114 °C (Lit.15 121–122 °C).
Dichloro(p-tolyl)-3-iodane (2c)
1H NMR (400 MHz, CDCl3):  = 8.04 (m, 2 H, H2), 7.61 (m, 2 H, H3).
13C{1H} NMR (151 MHz, CDCl3):  = 135.3 (2 C, C2), 134.8 (2 C, C3),
According to the general procedure using p-iodotoluene (219 mg, 1.0
mmol, 1.0 equiv), acetonitrile (4 mL), water (4 mL), NaOCl (2 mL) and
conc. HCl (2 mL). The reaction mixture was stirred at ambient tem-
perature for 30 min to afford, after work-up, dichloro(p-tolyl)-3-
iodane (2c) as a yellow solid (248 mg, 0.83 mmol, 83%).
127.4 (1 C, C4), 122.9 (1 C, C1).
MS (EI): m/z (%) = 281.9 (100) [M – Cl2]•+, 155.0 (60) [M – ICl2]•+.
Ethyl 4-(Dichloro-3-iodaneyl)benzoate (2g)
Mp 65 °C (dec.).
The general procedure was modified using ethyl 4-iodobenzoate (276
mg, 1.0 mmol, 1.0 equiv), acetonitrile (2 mL), water (4 mL), NaOCl (2
mL) and conc. HCl (2 mL). The reaction mixture was stirred at ambi-
ent temperature for 30 min to afford, after work-up, ethyl 4-(di-
chloro-3-iodaneyl)benzoate (2g) as a yellow solid (335 mg, 0.97
mmol, 97%).
1H NMR (400 MHz, CDCl3):  = 8.04 (m, 2 H, H2), 7.27 (m, 2 H, H3), 2.46
(s, 3 H, H5).
13C{1H} NMR (151 MHz, CDCl3):  = 143.4 (1 C, C4), 134.0 (2 C, C2),
132.5 (2 C, C3), 122.1 (1 C, C1), 21.5 (1 C, C5).
MS (EI): m/z (%) = 285.9 (18) [M – H2]•+, 252.0 (34) [M – HCl]•+, 218.1
(100) [M – Cl2]•+, 91.0 (75) [M – ICl2]•+.
Mp 93–94 °C.
The analytical data are in agreement with the literature.23
1H NMR (400 MHz, CDCl3):  = 8.27 (m, 2 H, H2), 8.11 (m, 2 H, H3), 4.42
(q, 3JHH =7.1 Hz, 2 H, H6), 1.41 (t, 3JHH =7.1 Hz, 3 H, H7).
Dichloro[(1,1′-biphenyl)-4-yl]-3-iodane (2d)
13C{1H} NMR (151 MHz, CDCl3):  = 164.7 (1 C, C5), 134.0 (1 C, C4),
133.9 (2 C, C2), 132.5 (2 C, C3), 128.9 (1 C, C1), 62.1 (1 C, C6), 14.4 (1 C,
C7).
According to the general procedure using 4-iodo-1,1′-biphenyl (280
mg, 1.0 mmol, 1.0 equiv), acetonitrile (4 mL), water (4 mL), NaOCl (2
mL) and conc. HCl (2 mL). The reaction mixture was stirred at ambi-
MS (EI): m/z (%) = 311.1 (1) [M – Cl]•+, 276.0 (52) [M – Cl2]•+, 149.1 (8)
[M – ICl2]•+.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I

I
J. C. Sarie et al.
Special Topic
Synthesis
Dichloro[4-(trifluoromethyl)phenyl]-3-iodane (2h)
(5) Cotter, J. L.; Andrew, L. J.; Keefer, R. M. J. Am. Chem. Soc. 1962,
84, 793.
According to the general procedure using 1-iodo-4-(trifluorometh-
yl)benzene (1.09 g, 4.0 mmol, 1.0 equiv), acetonitrile (16 mL), water
(16 mL), NaOCl (8 mL) and conc. HCl (8 mL). The reaction mixture was
stirred at ambient temperature for 2 h to afford, after work-up, di-
chloro[4-(trifluoromethyl)phenyl]-3-iodane (2h) as a yellow solid
(1.27 g, 3.7 mmol, 93%).
(6) (a) Molnár, I. G.; Gilmour, R. J. Am. Chem. Soc. 2016, 138, 5004.
(b) Molnár, I. G.; Thiehoff, C.; Holland, M. C.; Gilmour, R. ACS
Catal. 2016, 6, 7167. (c) Scheidt, F.; Thiehoff, C.; Yilmaz, G.;
Meyer, S.; Daniliuc, C. G.; Kehr, G.; Gilmour, R. Beilstein J. Org.
Chem. 2018, 14, 1021. (d) Scheidt, F.; Schäfer, M.; Sarie, J. C.;
Daniliuc, C. G.; Molloy, J. J.; Gilmour, R. Angew. Chem. Int. Ed.
2018, 57, 16431. (e) Scheidt, F.; Neufeld, J.; Schäfer, M.;
Thiehoff, C.; Gilmour, R. Org. Lett. 2018, 94, 8073.
Mp 125–127 °C.
1H NMR (400 MHz, CDCl3):  = 8.35 (m, 2 H, H2), 7.74 (m, 2 H, H3).
13C{1H} NMR (151 MHz, CDCl3):  = 134.4 (2 C, C2), 134.3 (q, 2JFC = 33.6
Hz, 1 C, C4), 128.5 (q, 3JFC = 3.7 Hz, 2 C, C3), 127.5 (5JFC = 1.3 Hz, 1 C, C1),
123.0 (1JFC = 273.1 Hz, 1 C, C5).
(7) Bloomfield, G. F. J. Chem. Soc. 1944, 114.
(8) (a) Breslow, R.; Dale, J. A.; Kalicky, P.; Liu, S. Y.; Washburn, W. N.
J. Am. Chem. Soc. 1972, 94, 3276. (b) Snider, B. B.; Corcoran, R. J.;
Breslow, R. J. Am. Chem. Soc. 1975, 97, 6791.
19F NMR (564 MHz, CDCl3):  = –63.2 (s, 3 F, F5).
(9) For selected examples, see: (a) Shellhamer, D. F.; Ragains, M. L.;
Gipe, B. T.; Heasley, V. L.; Heasley, G. E. J. Fluorine Chem. 1982,
20, 13. (b) Michinori, O.; Jiro, T.; Yoriko, S.; Kazuhiro, M.; Nobuo,
N. Bull. Chem. Soc. Jpn. 1988, 61, 4303. (c) Garve, L. K. B.;
Barkawitz, P.; Jones, P. G.; Werz, D. B. Org. Lett. 2014, 16, 5804.
(d) Kaiho, T.; Zhdankin, V. V. Industrial Applications, In Patai’s
Chemistry of Functional Groups; Rappoport, Z., Ed.; John Wiley &
Sons: New York, 2018, 1–13.
MS (EI): m/z (%) = 307 (1) [M – Cl]•+, 272.1 (100) [M – Cl2]•+, 145.0 (92)
[M – ICl2]•+.
Dichloro(4-nitrophenyl)-3-iodane (2i)
Acording to the general procedure using 1-iodo-4-nitrobenzene (996
mg, 4.0 mmol, 1.0 equiv), acetonitrile (16 mL), water (16 mL), NaOCl
(8 ml) and conc. HCl (8 mL). The reaction mixture was stirred at ambi-
ent temperature for 2 h to afford, after work-up, dichloro(4-nitrophe-
nyl)-3-iodane (2i) as a yellow solid (1.18 g, 3.7 mmol, 92%).
(10) Nicolaou, K. C.; Simmons, N. L.; Ying, Y.; Heretsch, P. M.; Chen, J.
S. J. Am. Chem. Soc. 2011, 133, 8134.
(11) (a) Podgorsek, A.; Jurisch, M.; Stavber, S.; Zupan, M.; Iskra, J.;
Gladysz, J. A. J. Org. Chem. 2009, 74, 3133. (b) Thorat, P. B.;
Bhong, B. Y.; Karade, N. N. Synlett 2013, 24, 2061.
(12) (a) Kitamura, T.; Tazawa, Y.; Morshed, M. H.; Kobayashi, S.
Synthesis 2012, 44, 1159. (b) Granados, A.; Jia, Z.; del Olmo, M.;
Vallribera, A. Eur. J. Org. Chem. 2019, 2812.
Mp 174–175 °C.*
1H NMR (400 MHz, CDCl3):  = 8.43 (m, 2 H, H2), 8.31 (m, 2 H, H3).
13C{1H} NMR (151 MHz, CDCl3):  = 149.8 (1 C, C4), 135.0 (2 C, C2),
129.1 (1 C, C1), 126.3 (2 C, C3).
MS (EI): m/z (%) = 284 (1) [M – Cl]•+, 249.1 (100) [M – Cl2]•+.
(13) For examples, see: (a) Archer, E. M.; van Schalkwyk, T. G. D. Acta
Crystallogr. 1953, 6, 88. (b) Carey, J. V.; Chaloner, P. A.;
Hitchcock, P. B.; Neugebauer, T.; Seddon, K. R. J. Chem. Res. 1996,
2031. (c) Montanari, V.; DesMarteau, D. D.; Pennington, W. T.
J. Mol. Struct. 2000, 550-551, 337.
* In agreement with the literature.15
Funding Information
(14) (a) Mishra, A. K.; Olmstead, M. M.; Ellison, J. J.; Power, P. P. Inorg.
Chem. 1995, 34, 3210. (b) Protasiewicz, J. D. J. Chem. Soc., Chem.
Commun. 1995, 1115. (c) Minkwitz, R.; Berkei, M. Inorg. Chem.
1999, 38, 5041. (d) Nikiforov, V. A.; Karavan, V. S.; Miltsov, S. A.;
Selivanov, S. I.; Kolehmainen, E.; Wegelius, E.; Nissinen, M.
ARKIVOC 2003, (vi), 191. (e) Bekoe, D. A.; Hulme, R. Nature
1956, ; this article reports the structure of p-ClC6H4ICl2 but
without including bond distances or angles 177, 1230.
(15) Zhao, X.-F.; Zhang, C. Synthesis 2007, 551.
We acknowledge generous financial support from Westfälische
Wilhelms-Universität Münster.()
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611886.
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orti
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orit
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(16) Wu, Y.; Shafir, A. NMR of Hypervalent Iodine Compounds, In
Patai’s Chemistry of Functional Groups; Rappoport, Z., Ed.; John
Wiley & Sons: New York, 2018.
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–I