Substituted phenylarsonic acids; structures and spectroscopy

Article abstract of DOI:10.1016/j.jorganchem.2008.04.033

Full NMR and ESI-MS spectra, and differential scanning calorimeter data are presented for 15 substituted phenylarsonic acids, including two new fluoro-substituted examples. X-ray crystal structure determinations of five examples (phenylarsonic acid and the 4-fluoro-, 4-fluoro-3-nitro-, 3-amino-4-hydroxy- and 3-amino-4-methoxy-substituted derivatives) were determined and the H-bonding crystal-packing patterns analysed.

Full text of DOI:10.1016/j.jorganchem.2008.04.033

Journal of Organometallic Chemistry 693 (2008) 2443–2450
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Substituted phenylarsonic acids; structures and spectroscopy
*
Nicholas C. Lloyd, Hugh W. Morgan, Brian K. Nicholson , Ron S. Ronimus
School of Science and Engineering, University of Waikato, Private Bag 3105, Hamilton 3240, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
Full NMR and ESI-MS spectra, and differential scanning calorimeter data are presented for 15 substituted
phenylarsonic acids, including two new fluoro-substituted examples. X-ray crystal structure determina-
tions of five examples (phenylarsonic acid and the 4-fluoro-, 4-fluoro-3-nitro-, 3-amino-4-hydroxy- and
3-amino-4-methoxy-substituted derivatives) were determined and the H-bonding crystal-packing pat-
terns analysed.
Received 25 February 2008
Received in revised form 15 April 2008
Accepted 23 April 2008
Available online 30 April 2008
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Phenyl arsonic acid
Crystal structure
Hydrogen-bonding
NMR spectra
R2
1. Introduction
OH
As part of a project to re-investigate the composition and
biological activity of the historically-important arsenical remedy
for syphilis, Salvarsan, we required a series of substituted arylar-
sonic acids, RAsO3H2 [1]. There is revived interest in organo-
arsenic compounds with the recognition that they are still
of pharmaceutical use [2] despite their obvious toxicity, and
with a developing understanding of the biological pathways
for activity [3].
R1
As
OH
O
1
2
3
4
5
6
7
8
R1 = H
R2 = H
9
R1 = EtO R2 = NO2
R1 = OH
R1 = OH
R2 = H
10 R1 = F
11 R1 = H
R2 = H
R2 = NO2
R2 = NO2
R1 = NH2 R2 = H
R1 = NO2 R2 = H
R1 = MeO R2 = H
12 R1 = MeO R2 = NO2
Since only
a few examples such as phenylarsonic acid,
3-nitro-4-hydroxyphenylarsonic acid (‘‘Roxarsone”) and o- or
p-aminophenylarsonic acid (‘‘arsanilic acid”) are readily
available commercially, others needed to be synthesized.
Much of the literature on these species is quite old [4],
so we have taken the opportunity to re-examine the series
1–15 with modern spectroscopic techniques and to structur-
ally define key examples, 1, 10, 13–15, by single crystal X-
ray diffraction.
13 R1 = F
R2 = NO2
R2 = NH2
14 R1 = OH
R1 = Me
R1 = EtO
R2 = H
R2 = H
15 R1 = MeO R2 = NH2
2. Experimental
2.1. General
PhAsO3H2 (1) (BDH), 4-HOC6H4AsO3H2 (2) (TCI), 3-NO2-4-HO-
C6H3AsO3H2 (3) (Aldrich) and 4-H2NC6H4AsO3H2 (4) (TCI) were
commercially available.
NMR spectra were recorded on Bruker AC300 or AC400 spec-
trometers in d6-DMSO as solvent and internal standard. Assign-
ments were by standard proton-carbon HSQC and HMBC
* Corresponding author. Fax: +64 7 838 4219.
E-mail address: b.nicholson@waikato.ac.nz (B.K. Nicholson).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.04.033

2444
N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
experiments. ESI-MS were measured on a Bruker MicrOTOF spec-
trometer, using MeOH or H2O as solvent. DSC data were obtained
on a Perkin–Elmer DSC6 machine.
2.2.4. Preparation of 4-methylphenylarsonic acid (7) [11]
Similarly from 4-methylaniline (10.7 g, 0.10 mmol), 4-meth-
ylphenylarsonic acid was obtained as white crystals. ESI-MS: m/z
[MÀH]À 214.9697 (Calc. 214.9689).
2.2. Syntheses
2.2.5. Preparation of 4-ethoxyphenylarsonic acid (8)
Under the same conditions in EtOH, from 4-fluoroaniline
(11.1 g, 0.10 mmol) fine yellow crystals of 4-ethoxyphenylarsonic
acid were obtained. Anal. Calc. for C8H11O4As: C, 39.04; H, 4.51.
Found: C, 38.94; H, 4.36%. ESI-MS: m/z [MÀH]À 244.9777 (Calc.
244.9795).
Detailed examples of synthesis of arylarsonic acids using the
Bart [5] and Scheller [6] methods are taken from the older litera-
ture, and are reproduced here for convenience.
2.2.1. Preparation of phenylarsonic acid (1) using the Bart procedure
(cf. Ref. [7])
Anhydrous Na2CO3 (400 g, 3.77 mol), As2O3 (200 g, 1.01 mol)
and CuSO4 Á 5H2O (10 g, 0.06 mol) were suspended in water
(800 mL) in a 5 L beaker and warmed with stirring. When most
of the solid had dissolved the solution was allowed to cool.
In a separate 5 L beaker, aniline (150 g, 1.6 mol) was carefully
2.2.6. Preparation of 4-ethoxy-3-nitrophenylarsonic acid (9)
Similarly, 4-fluoro-3-nitroaniline (15.6 g, 0.10 mmol) gave 4-
ethoxy-3-nitrophenylarsonic acid as fine yellow crystals of the
monohydrate. Anal. Calc. for C8H10NO6As Á H2O: C, 31.09; H, 3.91;
N, 4.53. Found: C, 30.42; H, 3.06; N, 4.73%. ESI-MS: m/z [MÀH]À
289.9669 (Calc. 289.9646).
added to
a solution of concentrated HCl (320 mL), water
(800 mL) and enough ice to make approximately 2.4 L. To this a
saturated aqueous solution of NaNO2 (112 g) was slowly added.
The resulting diazonium salt solution was slowly added over 1 h
to the arsenite mixture, with cooling to keep the temperature be-
low 15 °C. Small amounts of acetone were added to minimize
foaming, caused by the effervescing N2 gas.
The resulting slurry was stirred overnight to allow complete
evolution of nitrogen. The mixture was filtered and the volume re-
duced to 1 L on a hot plate. Activated carbon was added and the
mixture filtered to give a brown solution. This was acidified by
adding conc. HCl until a brown oil precipitated. The mixture was
filtered through Celite which absorbed the oil. The filtrate
was treated again with carbon and re-filtered. More conc. HCl
was slowly added, precipitating off-white crystals which were col-
lected by filtration and dried under vacuum. On standing over-
night, the mother liquor precipitated a further crop of crystals.
Total crude yield was 89.3 g (44%). Recrystallisation from hot water
with further activated carbon treatment gave pure phenylarsonic
acid (66.3 g, 32%) as white crystals. ESI-MS: m/z [MÀH]À
200.9537 (Calc. 200.9533).
2.2.7. Preparation of 4-fluorophenylarsonic acid (10)
Using the same general method but with THF (220 mL) as sol-
vent instead of EtOH, 4-fluoroaniline (11.1 g, 0.10 mmol) gave 4-
fluorophenylarsonic acid as fine white crystals (11.3 g, 51%). Anal.
Calc. for C6H6O3FAs: C, 32.75; H, 2.75. Found: C, 33.01; H, 2.77%.
ESI-MS: m/z [MÀH]À 218.9475 (Calc. 218.9439).
2.2.8. Preparation of 3-nitrophenylarsonic acid (11) (cf. Refs. [8,9])
Phenylarsonic acid (8.08 g, 0.04 mol) was dissolved in concen-
trated H2SO4 (30 mL) and cooled to À8 °C in an ice/salt bath. A mix-
ture of concentrated HNO3 and H2SO4 acids (1:1, 5.6 mL) was
added slowly ensuring that the temperature was <0 °C. The mix-
ture was left to return to room temperature overnight with stir-
ring, then poured over 200 g ice and left in the fridge for a
further 24 h. Yellow crystals were collected and recrystallised from
boiling water to give 3-nitrophenylarsonic acid as pale yellow crys-
tals. Anal. Calc. for C6H8AsNO4: C, 29.17; H, 2.45; N, 5.67. Found: C,
29.54; H, 2.44; N, 5.40%. ESI-MS: m/z [MÀH]À 245.9399 (Calc.
245.9384).
2.2.2. Preparation of 4-nitrophenylarsonic acid (5) using the Scheller
method (cf. Refs. [6,8,9])
2.2.9. Preparation of 4-methoxy-3-nitrophenylarsonic acid (12)
Similarly from 4-methoxyphenylarsonic acid (9.2 g, 0.04 mol),
nitration with conc. H2SO4/HNO3 gave pale yellow crystals from
water of 4-methoxy-3-nitrophenylarsonic acid (7.21 g, 73%). Anal.
Calc. for C7H8AsNO6: C, 30.35; H, 2.91; N, 5.06%. Found: C, 30.60; H,
2.90; N, 4.83%. ESI-MS: m/z [MÀH]À 275.9505 (Calc. 275.9489).
Concentrated H2SO4 (10 g) was added to 4-nitroaniline (13.8 g,
0.1 mol) in absolute ethanol (250 mL). AsCl3 (28 g, 0.16 mol) was
added and the mixture cooled to <5 °C in an ice bath. A solution
of sodium nitrite (8.28 g, 0.12 mol) in water (12 mL) was added
slowly to the cooled mixture with thorough stirring.
CuBr (1 g) was added to the mixture and it was warmed to 60 °C
for 6 h before cooling overnight. The solution was transferred to a
round-bottomed flask and steam distilled to remove solvent and
unreacted aniline. The liquid residue in the still-pot was trans-
ferred to a beaker while still hot. Activated carbon (10 g) was
added and the mixture boiled for 10 min and filtered. The green
solution was placed in the fridge to crystallize overnight. Yellow
crystals were collected and recrystallised from the minimum boil-
ing water to give 4-nitrophenylarsonic acid as fine yellow crystals,
8.13 g, (33%). Anal. Calc. for C6H6NO5As: C, 29.17; H, 2.45; N, 5.67.
Found: C, 29.40; H, 2.44; N, 5.38%. ESI-MS: m/z [MÀH]À 245.9414
(Calc. 245.9384).
2.2.10. Preparation of 4-fluoro-3-nitrophenylarsonic acid (13)
4-Fluorophenylarsonic acid (13.2 g, 0.06 mol) was dissolved in
conc. H2SO4 (45 mL). To this solution fuming nitric acid (6 mL)
was added. The mixture was heated with stirring in a water bath
for approximately 6 h. The heat was then turned off and the mix-
ture left overnight to cool. The mixture was poured over ice
(300 g) and stored in the fridge. The precipitate was filtered and
dried.
Anal. Calc. for C6H5FAsNO5: C, 27.19; H, 1.90; N, 5.28. Found: C,
27.42; H, 1.85; N, 5.06%. ESI-MS: m/z [MÀH]À 263.9284 (Calc.
263.9289).
2.2.11. Preparation of 3-amino-4-hydroxyphenylarsonic acid (14) (cf.
Refs. [1,12])
2.2.3. Preparation of 4-methoxyphenylarsonic acid (6) (cf. [10])
This was prepared by the Scheller procedure, as described
above, from p-anisidine (12.3 g, 0.10 mmol). Recrystallisation
from boiling water gave 4-methoxyphenylarsonic acid as white
crystals (14.3 g, 61%). Anal. Calc. for C7H9O4As: C, 36.23; H,
3.91. Found: C, 36.91; H, 3.92%. ESI-MS: m/z [MÀH]À 230.9651
(Calc. 230.9639).
3-Nitro-4-hydroxyphenylarsonic acid (13.1 g, 0.05 mol) was
dissolved in a solution of aqueous NaOH (100 mL, 1 mol LÀ1) and
cooled to 0 °C in an ice/salt slush bath with stirring. Na2S2O4
(30.25 g) was added in one portion with vigorous stirring. The
solution effervesced vigorously. As soon as the colour changed
from orange to pale yellow, concentrated HCl (12 mL) was added.

N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
2445
This mixture was held at <0 °C until the frothing ceased and the
product had precipitated from the solution. This was filtered and
washed twice with ice-cold water to give crude 3-amino-4-
hydroxyphenylarsonic acid (6.50 g, 56%) as a cream coloured solid
which was dried under vacuum. The crude product (6 g) was dis-
solved in a mixture of H2O (25 mL) and conc. HCl (2 mL) and stirred
with decolourising carbon for 15 min before filtering. To the fil-
trate, sodium acetate solution (25%) was added until the solution
was no longer acidic to Congo Red. The solution was cooled in a
fridge for 20 min. and the precipitated crystals were collected by
filtration and dried under vacuum. Yield was 4.7 g, 78%, of pure
14 as off-white microcrystals. Anal. Calc. for C6H8AsNO4: C,
30.90; H, 3.43; N, 6.01. Found: C, 30.76; H, 3.41; N, 6.32%. ESI-
MS: m/z [MÀH]À 231.9604 (Calc. 231.9591).
The Bart or Scheller reactions were found to be the most conve-
nient method of synthesis in this present study. Reasonable yields
of most of the acids were achieved. However, when 4-fluoroaniline
was used as a substrate for the Scheller reaction using the usual
EtOH as solvent, the product of the reaction was 4-EtOC6H4AsO3H2
(8) and not the expected 4-FC6H4AsO3H2 (10), arising from efficient
nucleophilic displacement of the fluorine by ethoxide from the sol-
vent under the conditions of the reaction. Similarly, 3-NO2-4-F-
C6H3NH2 gave the ethoxy compound 9, not 13. Aromatic C–F bonds
are known to be particularly susceptible to nucleophilic substitu-
tion reactions, despite the high C–F bond energy [17]. This problem
could be circumvented by carrying out the reaction in THF, when
the previously uncharacterised 4-fluorophenyl arsonic acid was
produced in 51% yield.
Nitro-aryl arsonic acids could be prepared either from the
appropriate nitro-aniline or by direct nitration of other arylarsonic
acids, and these in turn could be reduced to give amino-arylarsonic
acids using established methods with dithionite or ferrous sulfate
as reducing agents [13].
Using these methods, arsonic acids 1–15 were prepared and
were investigated in this report. Most of the acids have been re-
ported previously, but the EtO-substituted examples 8 and 9, and
the fluorinated compounds 10 and 13, have had only brief mention
in the literature. The synthesis of 3-NO2-4-FC6H3AsO3H2, 13, was
claimed [18] but without characterisation, and our studies would
suggest that it was the 4-EtO rather than the 4-F compound that
would result from the procedure used.
2.2.12. Preparation of 3-amino-4-methoxyphenylarsonic acid (15)
4-Methoxy-3-nitrophenylarsonic acid (5 g) was reduced with
ferrous sulfate following the method of Jacobs et al. [13]. Anal. Calc.
for C7H11AsNO4: C, 34.03; H, 4.08; N, 5.67. Found: C, 34.14; H, 4.05;
N, 5.40%. ESI-MS: m/z [MÀH]À 245.9747 (Calc. 245.9748).
2.3. X-ray crystallography
X-ray intensity data for compounds 1, 10, 13–15 were obtained
from a Bruker SMART CCD diffractometer, and were processed
using standard software. Crystal data and refinement details are
summarised in Table 1. Corrections for absorption were carried
out using SADABS [14]. The structures were solved and refined using
the SHELX programs [15], operating under WINGX [16]. All H atoms
were located from penultimate difference maps and refined, except
for 14 and 15 where only the NH2 and OH hydrogen atoms were
refined, and the others were placed in calculated positions. Analy-
ses were straightforward, except for PhAsO3H2 which was refined
as a racemic twin, with the twinning parameter converging to a va-
lue of 0.44.
3.2. Spectroscopic properties
1H and 13C NMR data are listed in Table 2, together with their
assignments, which were reasonably straightforward using stan-
dard proton-carbon HSQC and HMBC techniques.
ESI-MS was a useful technique for characterising the acids, with
clean [MÀH]À ions for each showing in negative ion mode when
run in H2O as solvent. If MeOH was used then ions of the type
[MÀOH+OMeÀH]À were seen through formation of methyl esters
of the acid, as has been reported earlier [19].
Arylarsonic acids often decompose before melting, so were sur-
veyed using DSC. As summarised in Table 3, these generally
showed one or two endothermic feature in the range 140-180 °C,
presumably lattice water loss (if present) and/or water-elimination
giving condensed acids, followed by an exothermic process just
above 300 °C which will be an oxidative degradation. A typical
example is shown in Fig. 1.
3. Results and discussion
3.1. Syntheses of RAsO3H2
There are three general methods for the preparation of arylar-
sonic acids [4]. The Bart reaction [5] involves the addition of an
aqueous alkaline solution of sodium arsenate to the diazonium salt
of the pre-requisite amine. The reaction requires a catalyst [usually
Cu(I)] and gives the maximum yield when buffered with sodium
carbonate.
OH
-
3.3. Crystal structures
AsO2
NaNO2
-
NH2
N
N HSO 4
As
O
OH
Cu(I)/Na2CO3
H2SO4/H2O
Selected arsonic acids were subjected to single crystal structural
analysis, to add to the existing bond parameter data by including
new substituent patterns, and to explore the hydrogen-bonding
networks formed in the crystal. A number of crystal structures of
arylarsonic acids are known, dating from about 1960, but many
of the earlier ones involved photographic data and consequently
gave relatively imprecise refinements.
Crystal and refinement data for the compounds determined in
the present study are summarised in Table 1. All were low-temper-
ature data sets with very good refinement factors, so are more pre-
cise than most of the earlier examples. None of the acids
structurally investigated in the present work crystallise with water
in the lattice, presumably because of strong intermolecular hydro-
gen-bonding networks involving the –AsO3H2 group.
There are several variations of this reaction, the most useful
being the Scheller [6] variation, which can be adapted into a one
pot synthesis, where the diazo compound is prepared and decom-
posed with a cuprous bromide catalyst in the presence of arsenic
trichloride in an alcoholic solution. This variation also eliminates
the excessive foaming sometimes encountered in the Bart reaction.
O
EtOH, H2SO4, AsCl3,
NaNO2, CuBr, heat.
H2O
heat
NH2
As
OH
OH
The Bechamp reaction [4] involves heating aromatic amines,
phenols or phenyl ethers with syrupy arsonic acid under reflux
for several hours. The yield for this reaction is rarely over 25%,
but is historically of interest as the first method to be reported.
The individual molecular structures will be discussed initially,
followed by a discussion of the crystal-packing and hydrogen-
bonding patterns.

2446
N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
Table 1
Crystal data and refinement details for arylarsonic acids
PhAsO3H2 (1)
4-FC6H4AsO3H2 (10)
3-NO2-4-F-C6H3AsO3H2 (13)
3-NH2-4-MeOC6H3AsO3H2 (15)
3-NH2-4-HO-C6H3AsO3H2 (14)
Formula
Mr
T (K)
C6H7AsO3
202.04
93(2)
C6H6AsFO3
220.03
84(2)
C6H5AsFNO5
265.03
84(2)
C7H10AsNO4
247.08
84(2)
C6H8AsNO4
233.05
84(2)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
Orthorhombic
P212121
4.6854(1)
10.3540(3)
14.8614(4)
90
Orthorhombic
Pbca
8.4575(3)
10.7817(3)
16.5150(5)
90
Orthorhombic
Pca21
10.4661(2)
7.5937(1)
21.3387(3)
90
Monoclinic
P21/n
4.6581(1)
28.2798(4)
20.4669(3)
90
Monoclinic
P21/c
7.1511(2)
15.8277(4)
7.3779(2)
90
a (°)
b (°)
90
90
720.97(3)
4
1.861
90
90
90
90
90.33(1)
90
2696.06(8)
12
1.826
3.76
116.25(1)
90
748.93(3)
4
2.067
4.51
c (°)
V (Å3)
Z
1505.94(8)
8
1.941
1695.92(5)
8
2.076
q (g cmÀ3
)
)
l (mmÀ1
4.66
4.48
4.02
Size (mm3)
0.80 Â 0.58 Â 0.40
0.34 Â 0.26 Â 0.22
0.32 Â 0.28 Â 0.18
0.46 Â 0.12 Â 0.12
0.26 Â 0.11 Â 0.05
F(000)
400
864
1040
1488
464
hmax (°)
29.6
26.4
26.5
26.3
26.3
Reflections collected
9541
10803
9640
15644
4408
T max, min
Unique reflections (Rint
Parameters
0.257, 0.118
2028 (0.025)
121
0.440, 0.333
1544 (0.020)
331
0.451, 0.295
3257 (0.0269)
293
0.719, 0.537
5435 (0.0245)
392
0.696, 0.416
1526 (0.0302)
129
)
R1 [I > 2r(I)]
0.0117
0.0332
1.004
0.0173
0.0465
1.151
0.0173
0.0420
1.046
0.010(6)
0.0243
0.0523
1.107
0.0286
0.0745
1.034
wR2 (all data)
Goodness-of-fit on F2
Flack x parameter
0.441(8)
Table 2
NMR data for arylarsonic acids 1–15
1H NMR data (d)
Compound
H-2
H-3
H-4
H-5
H-6
CH2
CH3
OH
1
2
3
4
5
6
7
8
7.78(d)
7.59(d)
8.19
7.59(m)
6.97(d)
–
6.71
8.40(d)
7.13(d)
7.41(d)
7.11(d)
–
7.65(m)
–
–
–
–
–
–
–
7.59(m)
6.97(d)
7.31(d)
6.71
7.78(d)
7.59(d)
7.84(d)
7.40
5.45
4.79
4.35
7.40
8.04(d)
7.70(d)
7.64(d)
7.67(d)
8.17(d)
7.83(dd)
8.48(s)
8.18(s)
8.41(d)
6.98(s)
7.01(s)
8.40(d)
7.13(d)
7.41(d)
7.11(d)
7.54(d)
7.42(t)
7.90(t)
7.57(d)
7.78(m)
6.84(d)
6.96(d)
8.04(d)
7.70(d)
7.64(d)
7.67(d)
7.96(d)
7.83(dd)
8.46(d)
7.99(d)
8.14(m)
6.84(d)
6.94(d)
4.37
5.06
3.93
3.95
4.84
4.52
4.56
4.43
4.51
3.79
2.37
1.32(t)
1.33(t)
4.08(q)
4.27(q)
9
–
–
10
11
12
13
14
15
7.42(t)
–
–
8.17(d)
–
–
3.99
–
3.80
CH2
13C NMR data (d)
Compound
C-1
C-2
C-3
C-4
C-5
C-6
CH3
1
2
3
4
5
6
7
8
133.2
122.3
123.2
116.8
140.3
124.2
130.4
124.4
124.9
129.5
135.5
124.9
130.7
122.7
124.3
130.4
132.7
128.3
131.5
132.1
132.2
130.2
132.2
127.2
133.5
125.0
127.2
128.7
115.4
114.1
129.9
117.0
137.7
113.8
124.5
115.3
130.2
115.5
139.7
117.3
148.2
139.5
137.7
137.9
138.9
133.5
162.2
156.2
153.2
150.5
163.1
143.5
162.2
154.8
165.4
136.6
155.5
157.7
148.8
149.9
129.9
117.0
121.0
113.8
124.5
115.3
130.2
115.5
116.5
117.3
131.7
115.9
120.8
114.9
110.9
130.4
132.7
136.6
131.5
132.1
132.3
130.2
132.2
136.4
133.5
127.9
136.5
138.5
119.6
118.8
55.8
21.4
14.6
14.4
63.8
66.2
9
10a
11
12
13b
14
15
57.5
55.8
a
JF–C (Hz): C-1 3.1; C-2,6 9.2; C-3,5 22.0; C-4251.6.
JF–C (Hz): C-1 4.2; C-2 1.8; C-3 7.1; C-4268.6; C-5 21.6; C-6 10.3.
b
3.3.1. Individual molecules
substituted species. PhAsO3H2 crystallises as a racemic twin (not
apparent in the earlier determinations [20]), but despite this it re-
fined cleanly, with all hydrogen atoms located (Fig. 2). The As@O
bond length is 1.6617(10) Å, the two As–O lengths are equal at
3.3.1.1. PhAsO3H2 (1). This compound has been analysed twice be-
fore, in 1960 [20], but neither determination was precise so the
structure was repeated to provide an accurate benchmark for the

N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
2447
Table 3
DSC data for arsonic acids 1–15
C(2)
C(3)
O(3)
Compound
First endo (°C)
Second endo (°C)
Final exo (°C)
H(31)
1
2
3
4
5
6
7
8
160
175
184
165
162
165
160
170
148
175
160
170
145
200
180
392
332
320
250
332
352
380
355
303
None <400
330
315
310
–
188
C(4)
F(1)
O(1)
C(1)
245
180
As(1)
9
225
182
175
245
H(21)
10
11
12
13
14
15
C(5)
C(6)
O(2)
Fig. 3. The structure of 4-FC6H4AsO3H2 (10) (50% ellipsoids) showing numbering
scheme. Selected bond lengths (Å): As(1)–C(1) 1.8974(16); As(1)–O(1) 1.6567(11);
As(1)–O(2) 1.7076(12) and As(1)–O(3) 1.7167(12).
240
–
pected effect of shortening the aryl C–C bonds adjacent to the 4-
position, but having no significant effect on the bond lengths
around the As atom, where the As@O [1.6567(11) Å], As–OH
[1.7121(12) Å], and As–C [1.8974(16) Å] bonds are essentially the
same as in PhAsO3H2. There is a wider variation in the angles
around the As atom (105–115°) but this is presumably to accom-
modate the different H-bonding network in the crystal.
3.3.3. 3-NO2-4-F-C6H3AsO3H2 (13)
This crystallises with two independent molecules in the asym-
metric unit, but they differ only in small details (Fig. 4). The most
apparent are the degree of twisting of the plane of the –NO2 group
from the plane of the phenyl ring (35° and 30°) and the displace-
ment of the As atom from the phenyl plane (0.18 and 0.83 Å),
respectively. Otherwise the individual bond parameters are indis-
tinguishable from the corresponding ones in the 4-F example 10.
3.3.4. 3-NH2-4-MeO-C6H3AsO3H2 (15)
Fig. 1. The DSC trace for 4-O2NC6H4AsO3H2.
This has a complicated structure with three independent mole-
cules in the asymmetric unit. Interestingly, they are all molecular
species (Fig. 5), in contrast to the closely related 3-NH2-4-HO-
C6H3AsO3H2 which packs in the zwitterionic form (see below).
The three independent molecules show only small variations in
bond parameters, so the discussion here is based on average val-
ues. The As@O [1.664(2) Å] and As–OH [1.719(2) Å] bonds are
essentially the same as in the simpler examples, as is the As–C
O(2)
C(3)
C(2)
H(02)
O(1)
As(1)
C(4)
C(1)
C(15)
C(16)
C(11)
C(6)
H(03)
H(12)
As(1)
C(5)
O(12)
O(3)
F(1)
Fig. 2. The structure of PhAsO3H2 (1) (50% ellipsoids) showing numbering scheme.
Selected bond lengths (Å): As(1)–C(1) 1.8882(12); As(1)–O(1) 1.6617(10); As(1)–
O(2) 1.7074(10) and As(1)–O(3) 1.7065(10).
O(11)
H(13)
C(14)
O(14)
O(13)
C(13)
1.7070(10) Å and the As–C(1) bond is 1.8882(12) Å. The geometry
around the As atom shows small deviations from tetrahedral, with
angles in the range 106–112°. These more reliable parameters give
shorter As–C and As–O, and longer As@O, bonds than those previ-
ously reported for this compound.
C(12)
N(1)
O(15)
3.3.2. 4-FC6H4AsO3H2 (10)
Fig. 4. The structure of one of the two independent molecules of 3-O2N-4-FC6H3-
AsO3H2 (13). Selected bond lengths (Å): As(1)–C(1) 1.893(2), 1.893(2); As(1)–O(1)
1.6539(14), 1.6598(13); As(1)–O(2) 1.7165(19), 1.7110(18) and As(1)–O(3)
1.7096(15), 1.7110(18).
This crystallises with one molecule comprising the asymmetric
unit. The structure (Fig. 3) is similar to that of the unsubstituted
example with the electronegative 4-F substituent having the ex-

2448
N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
whereas the –OMe in the previous example has no intermolecular
C(15)
C(16)
interactions. One consequence of the zwitterion packing is a rela-
tively high density for this compound (2.07 g cmÀ3) compared with
the methoxy analogue (1.83 g cmÀ3) which indicates a tighter
packing for the ionic arrangement. 4-H2NC6H4AsO3H2 is the only
other arsonic acid reported to be a zwitterion in the solid state
[21], while the corresponding 2- and 3-H2NC6H4AsO3H2 pack in
their molecular forms [22,23], so there is no obvious predictability.
Overall, these arsonic acid structures show very little variation
with substitution patterns. The As–C (1.888–1.895 Å), As@O
(1.657–1.664 Å) and As–O (1.707–1.719 Å) bonds cover a narrow
range for the compounds with molecular packing, and these con-
form to the other examples in the literature. For the zwitterionic
compound 14, the As–C (1.904 Å), As@O (1.677 Å) and As–O
(1.728 Å) are all longer than the equivalent bonds in the molecular
examples, possibly because of the stronger participation of hydro-
gen bonding in the charged species. The tetrahedral geometry
around the As atoms in all of the examples shows some flexibility
with angles ranging between 103° and 115°, presumably to accom-
modate the hydrogen bonding, as discussed below.
O(11)
C(17)
C(14)
C(11)
O(12)
O(13)
H(114)
O(14)
H(113)
C(12)
C(13)
N(11)
H(111)
H(112)
Fig. 5. The structure of one of the three independent molecules of 3-NH2-4-MeO-
C6H3AsO3H2 (15). Selected bond lengths (Å): As–C(1) 1.915(2), 1.888(2), 1.895(2);
As–O(1) 1.654(2), 1.675(2), 1.663(2); As–O(2) 1.712(2), 1.705(2), 1.719(2) and As–
O(3) 1.733(1), 1.716(2), 1.730(2).
[1.899(2) Å]. The most noticeable effect of the substituents is bond
alternation within the aryl ring – the C(3)–C(4) bond between the
two adjacent groups is the longest (1.419 Å), presumably because
of steric crowding, and this has induced significantly longer
C(1)–C(2) (1.405 Å) and C(5)–C(6) (1.399 Å) bonds than the C(1)–
C(6) (1.392 Å), CC(2)–C(3) (1.390 Å) and C(4)–C(5) (1.394 Å) ones.
This effect is much more noticeable here than for the 3-NO2-4-F
example 13 discussed above.
3.3.6. Hydrogen-bonding networks
The arsonic acids described here have many possibilities for H-
bonding interactions in the crystals. In addition to those involving
the AsO3H2 moieties, the –NH2, –OH or –NO2 groups on the phenyl
rings are also likely to act as donors or acceptors.
For PhAsO3H2, molecules pack in the crystal so they form single
chains parallel to the a axis. Each of the two As–O–H groups acts as
a donor to the As@O of two adjacent molecules, with each As@O
acting as an acceptor to two separate O–H donors, forming 10-
membered rings as shown in 1A. The OÁ Á ÁO distances between do-
nor and acceptor are all about 2.57 Å, making them on the strong/
moderate borderline using Jeffrey’s classification [24,25]. This
arrangement is also further stabilised by allowing the phenyl rings
to p-stack parallel to each other at 3.4 Å apart. There are only Van
der Waals interactions cross-linking these chains. This particular
H-bonding arrangement was also found for 2-H2NC6H4AsO3H2 [22].
The angles around the As atoms are again within the 103–113°
range.
3.3.5. 3-NH2-4-HO-C6H3AsO3H2 (14)
This structure is quite different from the others discussed, in
that it packs in the crystal as zwitterions, 3-+H3N-4-HO-
C6H3AsO3HÀ (Fig. 6). This is readily seen from the pattern of two
shorter As@O bonds [1.677(2) Å] and one long As–OH
[1.728(2) Å], and from the location in the penultimate difference
map of the three H atoms on the nitrogen. There is no immediately
apparent reason why this compound should pack in this form,
while the analogous methoxy compound does not, since the substi-
tution of an –OH group for a –OMe is not expected to change the
pKa values of the acid nor the pKb value for the –NH2 group. Pre-
sumably it is simply a consequence of accommodating the opti-
mum H-bonding interactions in the crystal. It may be significant
that the –OH group in the zwitterion is involved in H-bonding,
O
O
As
O
As
O
H
H
As
Ph
H
H
O
O
O
O
O
Ph
H
As
As
R
O
H
O
R
As
O
O
O
H
O
As
Ph
H
O
H
H
O
H
H(21)
H(22)
O
O
As
As
N(1)
H(31)
O(3)
H(23)
(10A)
(1A)
C(2)
C(3)
For 4-FC6H4AsO3H2 (10), there are no significant interactions
involving the fluoride atom, which is not unexpected since C–F
groups are known to be weak H-bond acceptors [17]. The basic mo-
tif is a dimer, about a crystallographic inversion centre, reminis-
cent of those commonly formed by carboxylic acids [24,25] with
As–O–HÁ Á ÁO@As interactions characterised by an OÁ Á ÁO distance
of 2.58 Å. These generate nearly planar eight-membered rings, as
shown in 10A. These dimers are further linked into two-dimen-
sional sheets perpendicular to the c axis, by the remaining As–O–
H bonding to an As@O of an adjacent molecule, so that each As@O
acts as an acceptor to As–O–H from two separate molecules.
This same basic arrangement is also seen for 3-NO2-4-FC6H3As-
O3H2, where the two independent molecules in the lattice form a
dimer with each other. This gives an eight-membered ring with
As(1)
C(1)
O(4)
O(2)
C(4)
H(11)
O(1)
C(5)
C(6)
Fig. 6. The zwitterionic structure of 3-NH2-4-HOC6H3AsO3H2 (14). Selected bond
lengths (Å): As(1)–C(1) 1.904(3), As(1)–O(1) 1.670(2), As(1)–O(2) 1.684(2) and
As(1)–O(3) 1.728(2).

N.C. Lloyd et al. / Journal of Organometallic Chemistry 693 (2008) 2443–2450
2449
2.60 Å OÁ Á ÁO separations, but this is distinctly chair-shaped. The
As3
remaining As–O–HÁ Á ÁO@As linkages again generate a two-dimen-
sional sheet in the ab plane, as in (10A). There is no H-bonding
involvement of either the F or NO2 substituents, although there
is a relatively close OÁ Á ÁO (2.98 Å) contact between one of the oxy-
gen atoms of the NO2 group and an As@O group. This contrasts
with the reported structure of 3-NO2-4-MeOC6H3AsO3H2 where
strong H-bonding between an As–O–H and an adjacent NO2 group
links molecules nose-to-tail, with additional As–O–HÁ Á ÁO@As
interactions completing the network [26]. The basic eight-mem-
bered ring dimer motif is common for arylarsonic acids, with at
least seven other examples known [27,28], however the way these
dimers stack varies in each case. For example, 4-HOC6H3AsO3H2
also has the chair-shaped dimer unit, further linked into tetrameric
units held by alternating H-bonds between the C–O–H group act-
ing as both a donor and acceptor, and As@O and As–O–H groups
acting as acceptors and donors respectively, giving 12-membered
rings [26].
For 3-NH2-4-MeOC6H3AsO3H2 (15) the packing is very compli-
cated. There are three independent molecules in the asymmetric
unit, and each of these is involved in different H-bonding arrange-
ments to generate three cross-linked strands, each parallel to the
short a axis.
The As(1) molecules form a simple strand based on strong As–
O–HÁ Á ÁO@As links, with the remaining As–O–H donating to the
NH2 group of As(2) molecules as in 15A.
O
H
H
N1
N
H
O
H
O
O
H
O
N2
H
N
H
H
H
H
H
O
O
H
N+
R
As3
O
O
H
-
As
O
O
O
O
H
As3
O
As
H
H
O
N1
H
H
H
As
N
(15C)
(14A)
For the zwitterionic 3-+H3N-4-HOC6H3AsO3HÀ compound 14,
there is a strong H-bonding network, as shown in 14A. Each of
the three N–H hydrogens is linked to the As–O groups of three dif-
ferent molecules (NÁ Á ÁO 2.77–2.82 Å), with the phenolic –OH also
bonded to an As–O of another one (OÁ Á ÁO 2.60 Å). At the other
end of the molecule, the As–O–H is donating to an As–O with
OÁ Á ÁO 2.64 Å, one of the As–O groups accepts an H-bond from both
an N–H and an As–O–H, while the other As–O is involved as an
acceptor in three hydrogen bonds; one from the phenolic –O–H
(OÁ Á ÁO 2.60 Å), and two from two different N–Hs (NÁ Á ÁO 2.78 and
2.82 Å). This arrangement accommodates an offset p-stacking
arrangement of the phenyl rings, 3.57 Å apart. All these strong
interactions undoubtedly give rise to the higher density of this
compound compared with the others.
H
As3
O
O
H
O
As2
O
O
H
O
R
As2
O
R
H
O
H
H
O
H
N
As3
O
H
H
Acknowledgements
H
As1
O
MeO
O
H
O
We thank Dr Tania Groutso, University of Auckland for collec-
tion of X-ray intensity data, and Professor A. L. Wilkins for assis-
tance with NMR. We also thank the Marsden Fund, administered
by the Royal Society of New Zealand, for financial support.
O
H
As2
R
R
As2
O
O
H
O
H
O
O
H
H
N2
As1
H
Appendix A. Supplementary material
(15B)
(15A)
CCDC 678806, 678807, 678808, 678809 and 678810 contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplemen-
tary data associated with this article can be found, in the online
version, at doi:10.1016/j.jorganchem.2008.04.033.
The As(2) molecules form a double chain based on slightly
chair-shaped eight-membered dimers, formed about an inversion
centre, similar to the arrangement 10A found for compounds 10
and 13, with OÁ Á ÁO distances of 2.57 Å. These stack up the a axis,
with further 2.52 Å OÁ Á ÁO links between the remaining As–O–H
and the As@O of adjacent molecules to give 12-membered rings,
with each As@O acting as acceptor to two As–O–H groups, as
shown in (15B). The –NH2 group acts as an acceptor to an As–OH
from As(1) molecules, and as an N–H donor to the O of an As–O–
H of As(3) molecules. The 8/12-membered alternating ring motif
was also found for 4-NO2-C6H4AsO3H2, though with a small varia-
tion in the 12-membered ring [28].
The As(3) strand links the others together through a variety of
interactions. The single chain is based on As–O–H groups H-bond-
ing as a donor to the As@O group of the adjacent molecules (OÁ Á ÁO
2.52 Å), as also found for the As(1) molecules. This –OH further acts
as an acceptor from an –NH2 group of an As(1) molecule (NÁ Á ÁO
2.94 Å). The As@O also accepts a H-bond from the –NH2 group of
an As(2) molecule (NÁ Á ÁO 2.97 Å), while the remaining As(3)–O–H
acts as an H-bond donor to the –NH2 group of an As(1) molecule.
This is summarised in 15C. For this As(3) molecule the –NH2 group
does not participate in any H-bonding interactions.
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