Synthesis of O-alkylbenzohydroximoyl iodides and a comparison of their structures to other oxime derivatives

Article abstract of DOI:10.1007/s10870-007-9257-y

The first general synthesis of (Z)-O-alkylbenzohydroximidoyl iodides [ArC(I)=NOR] is reported. X-ray crystallographic structures of two of these compounds confirm that they are in the Z-configuration: p-NO₂ArC(I)= NOCH₃ crystallizes in space group Pnma with lattice constants a = 12.682(2) A, b = 6.5217(15) A, and c = 11.755(2) A, and p-ClArC(I)=NOCH₃ crystallizes in space group P2₁/n with lattice constants a = 15.670(4) A, b = 5.742(4) A, and c = 27.156(7) A and beta angle 102.71(2). Their structures are compared to other O-alkylbenzohydroximoyl halides including p-NO₂ArC(F)=NOCH ₃ which crystallizes in space group P2₁/c with lattice constants a = 3.8475(10) A, b = 22.501(5) A, and c = 10.088(2) A and beta angle 91.130(11). The synthesis of two additional compounds containing the N-alkoxyimine moiety {methyl (Z)-O-methyl-4- nitrobenzothiohydroximate [p-NO₂ArC(SCH₃)=NOCH ₃] which crystallizes in space group P2₁/n with lattice constants a = 11.8046(15) A, b = 7.0774(10) A, and c = 12.2741(15) A and beta angle 100.401(9) and (Z)-O-methyl-4-nitrobenzohydroximoyl azide [p-NO₂ArC(N₃)=NOCH₃] which crystallizes in space group P2₁/c with lattice constants a = 11.753(2) A, b = 11.310(3) A, and c = 7.351(2) A and beta angle 103.805(15) are also reported. Their structures are compared to (Z)-ethyl benzohydroximate [PhC(OEt)=NOH] and (Z)-O-methyl-4-nitrobenzohydroximoyl cyanide [p-NO ₂ArC(CN)=NOCH₃] respectively. Characterizations include spectrometric identifications employing IR, ¹H-NMR, ¹³C-NMR and mass spectrometry.

Full text of DOI:10.1007/s10870-007-9257-y

J Chem Crystallogr (2007) 37:837–846
DOI 10.1007/s10870-007-9257-y
ORIGINAL PAPER
Synthesis of O-Alkylbenzohydroximoyl Iodides and a Comparison
of their Structures to other Oxime Derivatives
Debra D. Dolliver Æ Smitty Smith Æ David B. Delatte Æ Kavi D. Patel Æ
Tiffany E. Thomas Æ Julie Chagnard Æ James E. Johnson Æ Diana C. Canseco Æ
Frank R. Fronczek Æ Clinton D. Bryan Æ JoAnn R. Muller Æ Jeffrey E. Rowe Æ
Artie S. McKim
Received: 25 June 2007 / Accepted: 27 September 2007 / Published online: 16 October 2007
ꢀ Springer Science+Business Media, LLC 2007
Abstract The first general synthesis of (Z)-O-alkyl-
benzohydroximidoyl iodides [ArC(I)=NOR] is reported.
X-ray crystallographic structures of two of these com-
pounds confirm that they are in the Z-configuration:
p-NO2ArC(I)=NOCH3 crystallizes in space group Pnma
91.130(11). The synthesis of two additional compounds
containing the N-alkoxyimine moiety {methyl (Z)-O-
methyl-4-nitrobenzothiohydroximate [p-NO2ArC(SCH3)=
NOCH3] which crystallizes in space group P21/n with lat-
˚
tice constants a = 11.8046(15) A, b = 7.0774(10) A, and
˚
˚
with lattice constants a = 12.682(2) A, b = 6.5217(15) A,
˚
˚
c = 12.2741(15) A and beta angle 100.401(9) and (Z)-O-
˚
and c = 11.755(2) A, and p-ClArC(I)=NOCH3 crystallizes
in space group P21/n with lattice constants a =
methyl-4-nitrobenzohydroximoyl azide [p-NO2ArC(N3)=
NOCH3] which crystallizes in space group P21/c with
˚
15.670(4) A, b = 5.742(4) A, and c = 27.156(7) A and
˚
˚
˚
lattice constants a = 11.753(2) A, b = 11.310(3) A, and
˚
˚
c = 7.351(2) A and beta angle 103.805(15) are also
beta angle 102.71(2). Their structures are compared to
other
O-alkylbenzohydroximoyl
p-NO2ArC(F)=NOCH3 which crystallizes in space group
halides
including
reported. Their structures are compared to (Z)-ethyl
benzohydroximate [PhC(OEt)=NOH] and (Z)-O-methyl-4-
nitrobenzohydroximoyl cyanide [p-NO2ArC(CN)=NOCH3]
respectively. Characterizations include spectrometric iden-
˚
P21/c with lattice constants a = 3.8475(10) A, b =
˚
22.501(5) A, and c = 10.088(2) A and beta angle
˚
1
tifications employing IR, H-NMR, 13C-NMR and mass
spectrometry.
D. D. Dolliver (&) Á S. Smith Á D. B. Delatte Á
K. D. Patel Á T. E. Thomas Á J. Chagnard
Keywords Imidoyl iodide Á Imidoyl azide Á
N-alkoxyimine Á N-alkoxyimidoyl halide Á
Oxime thioether Á Thiohydroximate
Department of Chemistry and Physics, SLU 10878, Southeastern
Louisiana University, Hammond, LA 70402, USA
e-mail: ddolliver@selu.edu
J. E. Johnson Á D. C. Canseco
Department of Chemistry and Physics, Texas Woman’s
University, Denton, TX 76201-5859, USA
Introduction
F. R. Fronczek
Department of Chemistry, Louisiana State University,
Baton Rouge, LA 70803, USA
The use of the oxime ether or N-alkoxyimine moiety
(C=N–OR) in pharmaceutical and agricultural compounds
is becoming more widespread [1]. Current methods to
incorporate this functional group often result in both geo-
metric isomers of the oxime ether which then need to be
identified and separated [1a,b,f, 2]. The differences in the
1H- and 13C-NMR chemical shifts between the Z and E
isomers of N-methoxyimines are small and assignment of
configuration cannot be unambiguously made on the basis
of spectroscopic measurements. Attempts to assign geo-
metric configurations in N-methoxyimines using dipole
C. D. Bryan Á J. R. Muller
Department of Physical Sciences, Cameron University,
Lawton, OK 73505, USA
J. E. Rowe
School of Chemistry, La Trobe University, Bundoora,
VIC 3086, Australia
A. S. McKim
Gaylord Chemical Company, L.L.C., Bogalusa, LA 70427, USA
123

838
J Chem Crystallogr (2007) 37:837–846
OCH3
moment measurements have lead to incorrect assignments
[3].
Br
OCH3
F
KF/DMSO
150 C
C
N
C
N
There is particular interest in developing new methods
of incorporating the N-alkoxyimine moiety into molecules
in a single, predictable E or Z configuration. We are cur-
rently working on techniques that begin with imidoyl
halides (1Za-1Zn). Additionally, N-methoxyimines (C=N–
OCH3) that contain a leaving group attached to the carbon
of the carbon-nitrogen double bond have high barriers to
thermal Z/E isomerization and are therefore ideally suited
for studies on the stereochemistry and mechanisms of
nucleophilic substitution (Scheme 1) at the carbon-nitrogen
double bond. Because both the synthetic method develop-
ment and the mechanistic investigations require accurate
knowledge of the configurations (Z or E) of compounds
containing the N-alkoxyimine group, this paper examines
the structure and geometry of the N-alkoxyimidoyl
halides and the azide and thioether products produced
from the imidoyl halides as determined by X-ray
crystallography.
NO2
NO2
1Zh
1Za
+
OCH3
CH3S
C
N
1Zo
NO2
Scheme 2 Synthesis of 1Za and 1Zo
compounds has been previously reported [5]. In the present
work the structure 1Zo has been unambiguously deter-
mined by X-ray crystallography. Additionally, we have
found that reaction of 1Zh with sodium azide ion results
in O-methyl-4-nitrobenzohydroximoyl azide (1Zp). The
X-ray structure of this compound too is discussed.
The syntheses of O-alkylbenzohydroximoyl chlorides
and bromides have been known for some time. We have
recently published the synthesis of the O-alkylbenzo-
hydroximoyl fluorides (N-alkoxybenzenecarboximidoyl
fluorides) like 1Za (Scheme 2) [4]. The assignment of
geometric configuration of the fluorides at that time was
based on 1H-NMR chemical shifts of the N-methoxy
groups and by analogy with the previously prepared imi-
doyl chlorides. We now confirm that geometric assignment
with an X-ray crystal structure of 1Za.
The imidoyl fluorides were initially made in the interest
of further understanding the mechanism of nucleophilic
substitution at the carbon atom of the C=N bond of an
N-alkoxyimine. It was found that the fluorides react much
faster than the bromide (1Zc-h and 1Ec-h) or chloride
(1Zb or 1Eb) analogue in these reactions and result
exclusively in retained stereochemistry about the C=N
bond [6]. These findings have opened up synthetic oppor-
tunities involving nucleophilic substitution by carbon
nucleophiles at the C=N bond of N-alkoxyimidoyl halides
which are currently being explored [7].
A second product produced in the synthesis of the flu-
orides is a thioether 1Zo. 1Zo presumably arises from
reaction of 1Za with the solvent (DMSO). The isolation,
characterization, and an alternate synthetic method of these
To complete the series of N-alkoxyimidoyl halides, we
now report the first general synthesis of O-alkylbenzohydr-
oximoyl iodides (N-methoxybenzocarboxyimidoyl iodides).
The synthesis of N-hydroxyimidoyl iodides has been
reported by the reaction of an organometallic reagent with a
b-nitrostyrene to generate the nitronate for subsequent
reaction with hydroiodic acid [8]. Only one iodide com-
pound (2,2-diphenylpropanohydroximoyl iodide) was
synthesized by this method as other attempts yielded com-
pounds too unstable to characterize. N-alkylimidoyl iodides
have also been reported to be generated in situ by reaction of
an acylated oxime with trimethylsilyl iodide or diethylalu-
minum iodide [9]. Generation of these iodide compounds
was inferred from NMR studies and subsequent reaction
with nucleophiles, but the compounds were not isolated.
The synthesis of N-(benzyloxy)-2,2,2-trifluoroacetimidoyl
iodide has been reported [10], but to our knowledge this is
the only incident of an N-alkoxyimidoyl iodide having been
synthesized. The synthesis of N-aryltrifluoroacetimidoyl
∆
LG
Ar
LG
Ar
OCH3
C
N
C
N
OCH3
E imine reactant
Z imine reactant
-
-
Nu
Nu
Nu
Nu
OCH3
C
N
C
N
and/or
Ar
Ar
OCH3
Scheme 1 Thermal stability of N-alkoxyimidoyl compounds and the
potential stereochemistry of the products of nucleophilic substitution
123

J Chem Crystallogr (2007) 37:837–846
839
iodides have also been reported [11]. These compounds
were made by the reaction of the corresponding chloride
compound with sodium iodide in acetone. We have found
this procedure to be ineffective in the synthesis of
N-alkoxyimidoyl iodides. This paper reports a modification
to this procedure whereby N-alkoxyimidoyl iodides (1Zi-
1Zn) are synthesized from the corresponding N-alkoxyimi-
doyl bromide (1Zc-1Zh). These compounds prove to be
stable enough for purification and isolation. X-ray crystal
structure determination has been performed on two of the
Z-imidoyl iodides (1Zm and 1Zn), and these structures are
compared to those of the other imidoyl halides. The struc-
tures of all the N-alkoxyimidoyl halides, thioether, and azide
will be compared to one another and to other compounds
containing the N-alkoxyimine or N-hydroxyimine group,
paying special attention to the planarity of these molecules
(Table 1).
Experimental Data
General Methods
1H-NMR spectra were acquired at 300.13 MHz, and the
13C-NMR spectra at 75.47 MHz using a Bruker AC 300
spectrometer in (2H) chloroform. Low resolution GC-MS
data was collected on a Hewlett-Packard 5890 Series II GC
with a HP-1 crosslinked methyl silicone gum column
(12 m · 0.2 mm · 0.33 lm film thickness) and a Hewlett-
Packard 5971 series mass selective detector. Ultraviolet
spectral data were recorded with 95% ethanol as a solvent
on a Shimadzu UV-2101PC Spectrometer. Infrared spectral
data were recorded on a Perkin-Elmer 16 PC FTIR or a
Nicolet Magna 560 FTIR over the frequency range of
4000–600 cm–1. New compounds gave a single peak in the
GC-MS and showed the required number of carbons in the
Table 1 N-alkoxyimines
X
X
OR
C
N
C
N
OR
1Z
1E
Y
Y
Compounds 1Z and 1E
X
Y
R
1Za & 1Ea
F
NO2
NO2
H
CH3
CH3
CH3
CH3
CH3
CH3
i-Pr
b
c
d
e
f
Cl
Br
Br
Br
Br
Br
Br
I
CH3
OCH3
Cl
g
h
i
Cl
NO2
H
CH3
CH3
CH3
CH3
CH3
i-Pr
j
I
CH3
OCH3
Cl
k
l
I
I
m
n
o
p
q
I
Cl
I
NO2
NO2
NO2
NO2
CH3
CH3
CH3
CH3
SCH3
N3
CN
123

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J Chem Crystallogr (2007) 37:837–846
13C-NMR spectrum. The iodo compounds were further
characterized from their high-resolution mass spectra.
Exact masses were obtained by the Central Science Lab-
oratory at the University of Tasmania. Elemental analyses
were performed by Midwest Microlabs, LLC, in India-
napolis, IN.
crystals (16.177 g, 73%). A second recrystallization in
methanol yielded white crystals (12.210 g, 55%), mp 37.0–
37.5 ꢁC, Rf (hexane, alumina) = 0.88. FT-IR (nujol mull)
829, 996, 1092, 1465, 1583, 1592 cm–1. 1H-NMR
(300 MHz, CDCl3) d 1.39 (d, JHH = 6.4 Hz, 6H, CH3),
4.61 (m, JHH = 6.2, 1H, OCH), 7.36 (d, JHH = 8.6 Hz, 2H,
ArH), 7.79 (d, JHH = 8.6 Hz, 2H, ArH); 13C-NMR
(75 MHz, CDCl3) d 21.6, 77.8, 127.9, 128.5, 129.3, 132.8,
136.3. GC-MS: m/z 277 (18%), 275 (M, 13), 235 (11), 233
(9), 198 (4), 196 (14), 156 (32), 154 (100), 139 (11), 137
(35), 125 (11), 123 (20), 113 (9), 111 (29), 102 (23), 75
(18). Anal. Calcd. For C10H11ClBrNO (%): C, 43.43; H,
4.01; Br, 28.89; Cl, 12.82; N, 5.06; Found: C, 43.22; H,
4.02; Br, 28.51; Cl, 12.66; N, 4.96.
X-ray Data Collection and Structure Determination1
Intensity data were collected using graphite monochro-
˚
mated MoKa radiation (k = 0.71073 A) on a Nonius
KappaCCD diffractometer fitted with an Oxford Cryo-
stream cooler. Data reduction included absorption
corrections by the multi-scan method for 1Zn and 1Zo.
Crystal data and experimental details are given in Table 2.
Structures were solved by direct methods and refined by
full-matrix least squares, using SHELXL97 [12]. Hydrogen
atoms were treated as riding in idealized positions, with a
torsional parameter refined for each methyl group.
General Procedure for the Preparation
of N-Alkoxyimidoyl Iodides (1Zi-1Zn)
The corresponding N-alkoxyimidoyl bromide (1Zc-1Zh)
(*2 mmol) and sodium iodide (*20 mmol) in sulfolane
(12 mL) were heated between approximately 95 and
105 ꢁC for 2–4 days under nitrogen purge. On cooling, this
mixture was poured into 100 mL of saturated sodium
thiosulfate solution. This was extracted with hexane
(5 · 100 mL). The hexane extract was dried with anhy-
drous magnesium sulfate, filtered, and the solvent was
removed by rotary evaporation. Samples were purified by
preparative GLC for spectral analysis and characterization.
For 1Zm, X-ray data were collected on an ENRAF-
Nonius CAD-4 diffractometer with monochromated MoKa
˚
radiation (k = 0.71073 A). Crystals were mounted by
epoxy on glass fibers. Data were collected using a h–2h
technique. Data reduction included absorption corrections
by the w-scan method. Crystal data and experimental
details are also given in Table 2. Structures were solved by
direct methods and refined by full-matrix least squares,
using NRC386 (PC version of NRCVAX) [13]. Hydrogen
atoms were treated as riding in idealized positions, with
map positions for each methyl group that were subse-
quently idealized.
(Z)-O-Methylbenzohydroximoyl Iodide (1Zi)
This compound was obtained as a viscous liquid by the
above procedure with the temperature being maintained at
105 ꢁC for approximately two days (yield *51%). No
other compound was seen by GC-MS after work-up. FT-IR
(neat): 942, 1046, 1249, 1444, 1556, 1584, 2817, 2896,
2936, 2975, 3057 cm–1. 1H-NMR (300 MHz, CDCl3) d
4.21 (s, 3H, OCH3), 7.38 (m, 3H, ArH), 7.78 (d, J 6.1 Hz,
2H, ArH). 13C-NMR (75 MHz, CDCl3) d 62.58, 116.78,
128.26, 129.36, 130.29, 136.13. GC-MS: m/z 261 (M,
7.9%), 134 (100), 127 (23.4), 119 (80.8), 103 (72.1), 91
(13.0), 76 (37.3). (Found: M+Á, 260.96506. C8H8INO
requires 260.96506).
General Procedure for the Preparation
of N-Alkoxyimidoyl Bromides (1Zc-1Zh)
The procedure for the synthesis of these compounds is as
that described by Johnson et al. [14] in their synthesis of
(Z)-O-methyl-4-nitrobenzohydroximoyl bromide (1Zh).
O-Isopropyl-4-chlorobenzohydroximoyl Bromide (1Zg)
Following the above general procedure, using O-isopropyl-
4-chlorobenzohydroxamate (17.218 g, 0806 mol) a yellow
semi-solid material was obtained which was recrystallized
in methanol. The first recrystallization yielded light tan
(Z)-O-Methyl-4-methylbenzohydroximoyl Iodide (1Zj)
1
Supplementary crystallographic data for this paper in CIF format
This compound was obtained as a viscous liquid by the
above procedure with temperature being maintained at
97 ꢁC for approximately three days. GC-MS revealed this
to be 98.6% 1Zj and 1.4% starting material 1Zb. (Yield of
can be obtained, free of charge, via http://www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, U.K. (Fax: 44–1223–336033
or e-mail: deposit@ccdc.cam.ac.uk)
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J Chem Crystallogr (2007) 37:837–846
841
Table 2 Crystal data, data collection and refinement parameters
Compound
1Zm
1Zn
1Za
1Zo
1Zp
CCDC deposition #
Formula
CCDC 646439
CCDC 645654
C8H7N2O3I
Colorless needle
306.1
CCDC 645655
C8H7N2O3F
Colorless needle
198.2
CCDC 645656
C9H10N2O3S
Colorless fragment
226.3
CCDC 645657
C8H7N5O3
Colorless fragment
221.2
C
10H11NOClI
Color/shape
Colorless slice
323.6
Formula weight
Crystal system
Space group
Temp., K
Monoclinic
P21/n
Orthorhombic
Pnma
Monoclinic
P21/c
Monoclinic
P21/n
Monoclinic
P21/c
293
110
110
110
115
Cell constants
˚
a, A
15.670(4)
5.742(4)
27.156(7)
102.71(2)
2383.5(19)
8
12.682(2)
6.5217(15)
11.755(2)
–
3.8475(10)
11.8046(15)
7.0774(10)
12.2741(15)
100.401(9)
1008.6(2)
4
11.753(2)
11.310(3)
7.351(2)
103.805(15)
948.9(4)
4
˚
b, A
22.501(5)
˚
c, A
10.088(2)
b, deg.
˚
Cell volume, A
91.130(11)
3
972.2(3)
4
873.2(3)
Formula units/cell
calc, g/cm–3
calc, mm–1
4
D
1.803
2.091
1.507
1.490
1.548
l
2.85
3.276
0.130
0.309
0.123
Transm. coeff.
Diffractometer/scan
Radiation
0.701–0.997
0.639–0.695
–
0.913–0.941
Nonius KappaCCD/x
–
Enraf-Nonius CAD4/h–2h Nonius KappaCCD/x
Nonius KappaCCD/x
Nonius KappaCCD/x
˚
˚
˚
˚
˚
MoKa (k = 0.71073 A)
MoKa (k = 0.71073 A) MoKa (k = 0.71073 A) MoKa (k = 0.71073 A) MoKa (k = 0.71073 A)
Crystal size, mm
Reflections measured
Rint
0.2 · 0.4 · 0.5
4449
0.12 · 0.13 · 0.15
12,477
0.08 · 0.12 · 0.27
10,870
0.20 · 0.25 · 0.30
20,423
0.17 · 0.30 · 0.42
11,399
0.085
0.022
0.022
0.019
0.022
Independent reflections
h range, deg
2226
2383
1777
3431
2165
2 \ h \ 20
15, 0–5, 0–26
1638
3.2 \ h \ 35.6
20, 10, 18
1905
2.5 \ h \ 26.4
4, 27, 12
1392
2.5 \ h \ 32.6
17, 10, 18
2790
2.5 \ h \ 27.5
Range of h, k, l
Reflections observed
Criterion for observed
Data/parameters
R (obs)
15, 14,
1695
9
I [ 2.5r (I)
2226/253
0.053
I [ 2r (I)
2383/91
0.028
I [ 2r (I)
1777/128
0.040
I [ 2r (I)
3431/138
0.038
I [ 2r (I)
2165/147
0.035
Rw, F2 (all data)
0.084
0.068
0.107
0.099
0.096
GOF
1.53
1.068
1.054
1.059
1.031
–3
˚
Max resid. Peaks (eA
)
0.89, –1.22
1.04, –1.30
0.24, –0.27
0.41, –0.39
0.25, –0.23
1Zj *81%) FT-IR (neat): 817, 875, 943, 1019, 1046,
1180, 1247, 1578, 2936 cm–1. 1H-NMR d 2.39 (s, 3H,
CH3), 4.19, (s, 3H, OCH3), 7.17 (d, J 8.5 Hz, 2H, ArH),
7.66 (d, J 8.5 Hz, 2H, ArH). 13C-NMR d 21.30, 62.52,
116.98, 128.98, 129.31, 133.50, 140.65. GC-MS: 275 (M,
8.2%), 148 (100), 133 (60.2), 117 (89.4), 104 (8.0), 89
(14.2). (Found: M+Á, 274.98160. C9H10INO requires
274.98072).
OCH3), 7.34 (d, J 8.5 Hz, 2H, ArH), 7.72 (d, J 8.5 Hz, 2H,
ArH). 13C-NMR d 62.73, 115.30, 128.45, 130.55, 134.59,
136.50. GC-MS: 297 (3.7%), 295 (M, 11.1), 170 (31.1),
168 (94.3), 155 (24.8), 153 (75.1), 139 (33.1), 137 (100),
127 (23.6), 102 (31.4), 75 (16.0). (Found: M+Á, 294.92659.
C8H7ClINO requires 294.92609).
(Z)-O-Methyl-4-nitrobenzohydroximoyl Iodide (1Zn)
(Z)-O-Methyl-4-chlorobenzohydroximoyl Iodide (1Zl)
This compound was obtained as a crystalline solid by the
above procedure with the temperature being maintained
between 95 and 97 ꢁC for approximately four days. GC-
MS revealed this to be 94.8% 1Zn, 3.6% 1Zh and 1.6%
4-nitrobenzonitrile. (Yield of 1Zn *95%, m.p. 94.2–
95.2 ꢁC) FT-IR (Nujol mull): 955, 1039, 1343, 1456, 1514,
1543 cm–1. 1H-NMR d 4.25 (s, 3H, OCH3), 7.97 (d, J
8.5 Hz, 2H, ArH), 8.23 (d, J 8.5 Hz, 2H, ArH). 13C-NMR d
This compound was obtained as a viscous liquid by the
above procedure with the temperature being maintained at
93 ꢁC for approximately three days. GC-MS revealed this
to be 93.5% 1Zl and 6.5% starting material 1Zd. (Yield of
1Zl *77%.) FT-IR (neat): 828, 873, 949, 1013, 1047,
1
1094, 1242, 1483, 1574, 2937. H-NMR d 4.20 (s, 3H,
123

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J Chem Crystallogr (2007) 37:837–846
63.19, 113.82, 123.41, 130.21, 141.65, 148.63. GC-MS:
306 (M, 4.9%), 179 (100), 164 (7.9), 134 (17.5), 102
(13.7), 90 (5.7), 75 (4.2). (Found: M+Á, 305.95018.
C8H7IN2O3 requires 305.95014).
using dichloromethane/hexane (2:1) as the eluting solvent.
Recrystallization from hexane gave the desired product
(1Zo, 0.20 g, 23%) as a slightly creamy crystalline solid,
m.p. 113–114 ꢁC. Anal. Calcd. for C9H10N2O3S: C, 47.78;
H, 4.46; N, 12.38; S, 14.17. Found C, 47.66; H, 4.50; N,
12.06; S, 14.05. FT-IR (Nujol, cm–1): 1598 m (C=N),
1558 m, 1519 vs, 1346 vs, 1309 s, 1272 s, 1049 s, 1015 s,
997 s, 967 s, 856 s, 847 s. UV: one kmax at 248 nm (log
e = 4.02) and two inflections at 260 nm (log e = 4.00) and
314 nm (log e = 3.72) were determined. GC-MS: 226 (M,
35%), 225 (91), 209 (81), 195 (21), 179 (84), 164 (54), 149
(63), 134 (100), 120 (20), 118 (21), 103 (33), 102 (56), 90
(50), 76 (46), 75 (55), 63 (23), 51(35), 50 (40). 1H-NMR (d,
ppm): 2.07 (s, 3H, SCH3), 4.01 (s, 3H, OCH3), 7.61 (d, 2H,
J = 8.6 Hz, aromatic H), 8.21 (d, 2H, J = 8.6 Hz, aromatic
H). 13C-NMR (d, ppm): 15.27 (SCH3), 62.99 (OCH3),
123.72, 129.62 (aromatic CH), 139.12 and 148.17 (aro-
matic C), 152.62 (C=N).
(Z)-O-Methyl-4-methoxybenzohydroximoyl Iodide (1Zk)
This compound was obtained as a viscous liquid by the
above procedure with the temperature being maintained at
95 ꢁC for approximately two days. GC-MS revealed this to
be 100% 1Zk. (Yield of 1Zk *87%) FT-IR (neat): 1034,
1050, 1173, 1246, 1257, 2854, 2924 cm–1. 1H-NMR d 3.85
(s, 3H, OCH3), 4.17 (s, 3H, OCH3), 6.88 (d, J 8.5 Hz, 2H,
ArH), 7.72 (d, J 8.5 Hz, 2H, ArH). 13C-NMR d 55.42,
62.45, 113.60, 116.60, 128.73, 130.85, 161.28. GC-MS:
291 (M, 6.9%), 164 (52.7), 133 (100), 103 (15.4), 90
(20.4). (Found: M+Á, 290.97561. C9H10INO2 requires
290.97563).
Preparation of (Z)-N-Methoxy-4-
nitrobenzenecarboximidoyl Azide (1Zp)
(Z)-N-Isopropoxy-4-chlorobenzenecarboximidoyl Iodide
(1Zm)
In a 40 mL screw top vial were combined anhydrous
DMSO (35 mL), hydroximoyl bromide 1Zh (0.689 g,
2.71 mmol), and sodium azide (0.8827 g, 13.6 mmol). The
mixture was stirred magnetically for 4 days at room tem-
perature, until the starting material was consumed (as
monitored using HPLC). The reaction mixture was slowly
poured onto ice water (120 g), which caused the crude
product to precipitate as a solid. The solid was isolated by
suction filtration and was recrystallized to provide 1Zp as
an off-white crystalline solid (521 mg, 87%), m.p. 70.0–
70.9 ꢁC. IR (Nujol): 2156, 2097, 1599, 1565, 1520, 1321,
1261, 1045, 861 cm–1. 1H-NMR (300 MHz, CDCl3): d
4.06 (s, 3 H, OCH3); 7.94 (d, J 8.9 Hz, 2H, ArH); 8.20 (d, J
8.9 Hz, 2H, ArH). 13C-NMR (CDCl3): d 63.24, 123.35,
126.73, 136.41, 140.81, 148.49. Anal. Calcd. for
C8H7N5O3: C, 43.44; H, 3.19; N, 31.66; Found: C, 43.32;
H, 3.30; N, 31.40.
This compound was obtained as light tan, feathery crystals
by the above procedure with the temperature being main-
tained at 105 ꢁC for approximately two days. GC-MS
revealed this to be 93.5% 1Zm and 6.5% 1Zg. (Yield of
1ZM *64%, m.p. 46.9–47.5 ꢁC.) FT-IR (nujol mull): 987,
1
1461, 828, 1377 cm–1. H-NMR d 1.41 (d, J 6.3 Hz, 6H,
CH3), 4.69 (m, J 6.3, 1H, OCH), 7.33 (d, J 8.6 Hz, 2H,
ArH), 7.72 (d, J 8.6 Hz, 2H, ArH). 13C-NMR d 21.81,
77.57, 114.48, 128.39, 130.58, 135.06, 136.21. GC-MS 323
(M, 4.7%), 198 (16.5), 196 (48.9), 156 (32.4), 154 (100),
139 (14.5), 137 (44.2), 127 (8.1), 113 (6.5), 111 (19.5), 102
(21.4), 90 (6.7), 75 (9.9). (Found: M+Á, 322.95738.
C9H10INO2 requires 322.95739).
Preparation of Methyl (Z)-O-Methyl-4-
nitrobenzothiohydroximate (1Zo)
(Z)-N-methoxy-4-nitrobenzenecarboximidoyl
bromide
Results and Discussion
(1Zh, 1.0 g, 3.9 mmol) and spray dried potassium fluoride
(0.75 g, 13 mmol) in dry DMSO (12 mL) were heated and
stirred at 115 ꢁC for 4 h and then at 140 ꢁC for 68 h. On
cooling, saturated sodium chloride solution (30 mL) was
added and the organic products were extracted into ether
(3 · 20 mL). The ether solution was washed with 5%
sodium hydroxide solution (2 · 15 mL), dried (MgSO4)
and the solvent removed by evaporation to give 0.32 g of
crude product containing both 1Za and 1Zo. The products
were separated by dry column chromatography on silica
O-Alkylbenzohydroximoyl iodides (1Zi-1Zn) were pre-
pared in acceptable to excellent yields (51–95%) by
reacting the corresponding O-alkylbenzohydroximoyl bro-
mide (1Zc-1Zh) compound with sodium iodide in
sulfolane (Scheme 3). These reactions prove to be highly
sensitive to temperature. At low temperatures the reaction
takes an exorbitant length of time; at higher temperatures
an elimination reaction to form a nitrile prevails. It was
found that temperature ranges between 95 and 105 ꢁC
123

J Chem Crystallogr (2007) 37:837–846
843
angles, and torsional angles of the two molecules agree to
within 2r except for those angles involving the C–O bond
in the isoproxy moiety. The molecules are not planar; the
central carbon and one terminal carbon of each isopropoxy
OR
Br
Ar
OR
I
NaI/sulfolane
95-105 °C
C
N
C
N
Ar
1Zi-n
˚
group are at least 1 A out of the phenyl plane. The mean
1Zc-h
˚
C=N distance is 1.280(19) A, and the mean C–I distance is
˚
2.090(13) A. The C–I bonds form a mean dihedral angle of
Scheme 3 Synthesis of N-alkoxyimidoyl iodides
29.5ꢁ with the phenyl plane. Intermolecular interactions
shorter than the sum of van der Waals radii were not
observed.
provided the best conversion to the iodide while mini-
mizing the formation of the nitrile.
While conversion of the N-alkoxyimidoyl bromide to
the N-alkoxyimidoyl iodide appeared to proceed almost
quantitatively by these conditions in most instances, small
amounts of the bromide starting material (between 1.4%
and 6.5% in most cases) remained unreacted. The isolation
of pure N-alkoxyimidoyl iodide, therefore, proved to be
almost an intractable problem due to the very similar
polarity of the N-alkoxyimidoyl bromide starting material
and the lability of the C–I bond in the product. Attempts at
fractional vacuum distillation failed because of the partial
decomposition of the iodide compound with the heating
necessary to accomplish distillation. Analytical samples
were therefore produced by low temperature preparative
GLC (at temperatures lower than 105 ꢁC to prevent for-
mation of the nitrile).
The structure of 1Zn is shown in Fig. 2. The molecule
lies on a mirror plane in the crystal, thus it is perfectly
planar, except for methyl H atoms. The C=N distance is
˚
1.286(3) A, and the C–I distance is 2.096(2) A.
˚
Attempts at producing the E-isomer under the irradiation
conditions used to produce the E isomer of the N-alkoxy-
imidoyl bromide [15], chloride [16], and fluoride [4]
compounds have failed with the N-alkoxyimidoyl iodides.
Irradiation of a benzene solution of 1Zm under conditions
for the preparation of either an (E)-O-alkylbenzohydroxi-
moyl chloride, fluoride or bromide led to rapid
decomposition of 1Zm to 4-chlorobenzonitrile.
Comparison of the crystal structures of the (Z)-O-
methyl-4-nitrobenzohydroximoyl halides (1Za, 1Zb, and
1Zn) reveals that the planarity of the molecule is impacted
by the halogen atom. The assignment of the Z configura-
tion to 1Za had previously been made based upon
comparison of NMR and reactivity data of 1Za to that of
1Zb. The X-ray structure substantiates that the stereo-
chemistry of 1Za had been previously appropriately
assigned [4].
These reactions were also found to form a single geo-
metric isomer. X-ray crystallographic studies have
demonstrated that this is the Z-isomer in the case of 1Zm
and 1Zn. It is presumed therefore that all these reactions
proceed with retention of the stereochemistry about the
C=N bond.
The structure of 1Zm is shown in Fig. 1. There are two
molecules arranged in the asymmetric unit in a manner that
mimics mirror plane symmetry. The bond distances, bond
The structure of 1Za is shown in Fig. 3. The molecule
deviates slightly from planarity, with all atoms but methyl
˚
C8 exhibiting mean deviation 0.045 A, and C8 lying
Fig. 1 X-ray crystal structure
of 1Zm
I1
I2
C9
C19
O2
O1
N1
C20
C17
C7
C4
C18
C8
C10
C5
C13
N2
C14
C15
C3
C12
C11
C6
C1
C16
C2
CL2
CL1
123

844
J Chem Crystallogr (2007) 37:837–846
As seen in Table 3, the halogen atom affects the mag-
nitude of the dihedral angle h. As the van der Waals radius
of the halogen increases from fluorine to chlorine to iodine,
I1
O1
C8
˚
the C–X bond lengthens from 1.3462 A (1Za) to 1.731 A
˚
in compound (1Zb) [17] and to 2.090 A in compound
˚
C1
(1Zm). Additionally, the angle h increases from 7ꢁ (1Za)
to 17ꢁ (1Zb) to 27ꢁ (1Zm).
N1
C7
Surprisingly, the angle h in the iodide-containing mol-
ecule (1Zn) is 0ꢁ. This is unusual when compared to both
1Zm and to 1-phenyl-1-iodoethylene (PhC(I)=CHR)
compounds. Both the cis and trans geometric isomers of
1-phenyl-1-iodoethylenes display a twist to the aromatic
ring relative to the plane defined by the I–C=C bonds [21].
The planarity of 1Zn could be caused by intermolecular
interactions (‘‘packing forces’’). This planarity allows
the molecules to stack with perpendicular distance of
C2
C6
C3
C4
C5
O3
˚
N2
b/2 = 3.26 A. Also, there is a C–HÁÁÁI intermolecular
interaction which might be relevant. Such contacts are
expected to be quite weak, but this one is nearly linear
(C–HÁÁÁI angle 174ꢁ) with C3–H3ÁÁÁI1 (at x–1/2, 1/2–y,
O2
Fig. 2 X-ray crystal structure for 1Zn (ellipsoid probabilities are
50%)
˚
˚
1/2–z), CÁÁÁI 3.976 A, and HÁÁÁI 3.03 A.
Substitution reactions using N-methoxyimidoyl halides
as starting materials are of interest because of the potential
to produce a single geometric isomer of the product [4].
Again, whether the stereochemistry about the C=N bond in
the product is E or Z has been difficult to unambiguously
ascertain by NMR and dipole measurements. X-ray crys-
tallography has been performed on two of the substitution
products (1Zo and 1Zp) derived from N-methoxyimidoyl
halides which happen to be crystalline substances, and both
have been found to be in the Z-configuration.
˚
0.267(2) A from that plane. The nitro group is twisted
slightly out of the phenyl plane, with torsion angle –5.1(2)ꢁ
about C5-N2. The oxime plane is also twisted slightly out
of the phenyl plane, with torsion angle 7.9(2)ꢁ about C1-
˚
C2. The C=N distance is 1.266(2) A, and the C–F distance
˚
is 1.346(2) A. While (Z)-N-methoxy-4-nitrobenzenecar-
boximidoyl bromide (1Zh) is also crystalline, crystal
quality was sufficient only to confirm the identity of the
compound, and the structure is not included here.
The structure of 1Zo is shown in Fig. 4. The C=N dis-
˚
˚
tance is 1.286(2) A, and the C–S distance is 1.7552(12) A.
The S–Me bond is essentially anti to C=N (torsion angle
about C1–S1 18.29(11)ꢁ), and the phenyl group is twisted
out of the oxime plane, with torsion angle 62.13(15)ꢁ about
C1–C2. The nitro group is nearly coplanar with the phenyl
group, having torsion angle 5.1(2)ꢁ about C5–N2.
A Comparison of the Methyl (Z)-O-methyl-4-nitro-
benzothiohydroximate (1Zo) to the (Z)-ethyl benzohydro-
ximate (1Zr) shows that both of these compounds twist the
aromatic ring out of the plane to avoid a steric interaction
with the ‘‘X’’ substituent (Table 3). Here the thiomethyl
group causes a large dihedral angle between these two
planes of 61ꢁ, presumably because of the atomic radius of
the sulfur atom.
O1
F1
C8
C1
N1
C7
C2
C6
C3
C4
C5
The structure of 1Zp is shown in Fig. 5. Azide 1Zp has
˚
˚
C=N distance 1.285(2) A and C1–N3 distance 1.402(2) A.
The azide substituent is slightly nonlinear, with angle
167.49(13)ꢁ about N4. The molecule is roughly planar,
with all atoms other than methyl C8 having mean deviation
N2
O3
O2
˚
˚
0.039 A from a common plane, and C8 0.279(1) A out of
that plane. The molecule is slightly bowed, with all phenyl
Fig. 3 X-ray crystal structure of 1Za (ellipsoid probabilities are
50%)
123

J Chem Crystallogr (2007) 37:837–846
845
Table 3 Dihedral angle between the aryl plane and the N=C–X plane
X
X
N
θ
θ
Y
Y
C
C
O
N
R
O
R
E
Z
Compound
X
Y
R
Isomer
Dihedral angle (h), deg
Reference
1Zm
1Zn
1Zb
1Eb
1Za
1Zo
1Zr
1Er
1Zp
1Zq
1Eq
I
Cl
i-Pr
CH3
CH3
CH3
CH3
CH3
H
Z
Z
Z
E
Z
Z
Z
E
Z
Z
E
27
0
This work
This work
[17]
I
NO2
NO2
NO2
NO2
NO2
H
Cl
17
50
7
Cl
[3]
F
This work
This work
[18]
SCH3
61
29
39
1.5
9.1
4.7
OCH2CH3
OCH2CH3
N3
H
H
[18]
NO2
NO2
NO2
CH3
CH3
CH3
This work
[19]
CN
CN
[20]
N5
N4
S1
O1
N1
C9
C8
O1
N1
C8
N3
C1
C1
C3
C2
C2
C7
C7
C3
C6
C6
C4
C4
C5
C5
O3
N2
N2
O3
O2
O2
Fig. 4 X-ray crystal structure of 1Zo (ellipsoid probabilities are
50%)
Fig. 5 X-ray crystal structure of 1Zp (ellipsoid probabilities are
50%)
123

846
J Chem Crystallogr (2007) 37:837–846
University Research Enhancement Program for support of this work.
The purchase of the KappaCCD diffractometer was made possible by
Grant No. LEQSF (1999–2000)-ENH-TR-13, administered by the
Louisiana Board of Regents.
C atoms lying on one side of the best plane, and the nitro
group and oxime substituent lying on the opposite side.
The final comparison is between substituents in which
the atoms of the group can also have p-bond overlap with
the C=N bond (1Zp) and (1Zq). As seen, this additional
conjugation, along with a lack of steric crowding, appears
to favor the molecule adopting an almost planar geometry.
Information about the geometry of N-methoxyimines
could prove valuable in further studies of the reactivities of
these molecules. The dihedral angle (Table 3) of the aro-
matic ring relative to the C=N bond has been considered as
a possible contributor to the large differences in methoxide
substitution reaction rates with the O-methyl derivative of
1Er where h is 39ꢁ reacting slower (kZ/kE = 300) [22] than
the O-methyl derivative of 1Zr where h is 29ꢁ. This factor,
however, was thought to have little effect in the rate of
nucleophilic substitution of compounds similar to 1Zb (h of
17ꢁ) and 1Eb (h of 50ꢁ). In compounds that differ from 1Zb
and 1Eb only in the fact that there is no substituent on the
aromatic ring, both the Z and E isomers undergo substitu-
tion by methoxide at similar rates [3]. It is reasonable to
expect that N-methoxyimine molecules in which the C=N
bond and the aromatic ring are co-planar would exhibit a
greater-than-expected stability due to resonance effects.
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Conclusion
A general synthesis of O-alkylbenzohydroximoyl iodides
has been developed. The geometric stereochemistry of two
of these compounds has been determined by X-ray crys-
tallography to be in the Z configuration. Comparison of the
structure of these compounds to other O-alkylbenzohydr-
oximoyl halides reveals that the planarity of the molecule
is impacted both by the halogen atom and by the sub-
stituent present on the aromatic ring. The structures of two
compounds produced by substitution of the halogen of an
O-methyl-4-nitrobenzohydroximoyl halide (O-methyl-4-
nitrobenzohydroximoyl azide and methyl O-methyl-4-
nitrobenzothiohydroximate) have also been determined by
X-ray crystallography. They too have been found to be in
the Z configuration. It is found that the azide compound is
almost planar due to extended conjugation and lack of
steric crowding. The thiohydroximate is found to have the
largest deviation from planarity of all these molecules due
to the bulkiness of the thiomethyl group.
Acknowledgments Acknowledgment is made to the State of Lou-
isiana Board of Regents Grant (LEQSF(2006-09)-RD-A-25),
Southeastern Louisiana University’s Faculty Development Grant,
Southeastern Louisiana University’s OSCAR/STAR Grant, the
Minority Biomedical Research Support Program of the National
Institutes of Health (NIH-MBRS Grant R25-GM55380), The Robert
A. Welch Foundation (Grant No. M-0200) and the Texas Woman’s
22. Johnson JE, Nalley EA, Weidig C, Arfan M (1981) J Org Chem
46:3623
123