Anion binding of N-(o-Methoxybenzamido)thioureas: Contribution of the intramolecular hydrogen bond in the N-benzamide moiety

Article abstract of DOI:10.1002/asia.200900519

N-(o-Methoxybenzamido)- thioureas (2X/2Y) are found to show an enhanced anion binding affinity with binding constants over 10⁷ mol ^-1L orders of magnitude for AcO^- and a redshifted absorption of the anion binding complexes in acetonitrile (MeCN) relative to those of N-benzamidothioureas (1) that bear no o- OMe in the N-benzamide moiety, despite the electron-donating character of o-OMe. Absorption of the anion-2X/ 2Y complex was shown to be of the same charge-transfer nature as that of the anion-1 complex, but its dependence on substituent X is interestingly influenced by the o-MeO···HNC=O six-membered-ring intramolecular hydrogen bond identified in 2X/2Y. Such an intramolecular hydrogen bond is suggested to be responsible for the enhanced anion binding affinity. In the presence of this intramolecular hydrogen bond, the anion binding constant of 2X was found to be independent of substituent X at the N-phenyl ring, as in the case of 1, whereas that of 2Y showed an amplified dependence on substituent Y at the N′-phenyl ring, but to a lower extent than that of 1. A similar ring intramolecular hydrogen bond was purported to exist in 2Za, 2Zd, and 2Ze, which bear NHMe, F, and Cl as the ortho substituent in the N-benzamide moiety. In terms of the current roles of thiourea in not only anion recognition and sensing but also organocatalysis and crystal engineering, the present finding would be of significance for a wider structural diversity of smart thiourea derivatives with predesigned functions.

Full text of DOI:10.1002/asia.200900519

DOI: 10.1002/asia.200900519
Anion Binding of N-(o-Methoxybenzamido)thioureas: Contribution of the
Intramolecular Hydrogen Bond in the N-Benzamide Moiety
Qian-Qian Jiang, Burenkhangai Darhkijav, Hao Liu, Fang Wang, Zhao Li, and
Yun-Bao Jiang*[a]
Dedicated to the 150th anniversary of Japan–UK diplomatic relations
Abstract: N-(o-Methoxybenzamido)-
thioureas (2X/2Y) are found to show
an enhanced anion binding affinity
influenced by the o-MeO···HNC=O
six-membered-ring intramolecular hy-
drogen bond identified in 2X/2Y. Such
an intramolecular hydrogen bond is
suggested to be responsible for the en-
hanced anion binding affinity. In the
presence of this intramolecular hydro-
gen bond, the anion binding constant
of 2X was found to be independent of
substituent X at the N-phenyl ring, as
in the case of 1, whereas that of 2Y
showed an amplified dependence on
substituent Y at the N’-phenyl ring, but
to a lower extent than that of 1. A sim-
ilar ring intramolecular hydrogen bond
was purported to exist in 2Za, 2Zd,
and 2Ze, which bear NHMe, F, and Cl
as the ortho substituent in the N-benz-
amide moiety. In terms of the current
roles of thiourea in not only anion rec-
ognition and sensing but also organoca-
talysis and crystal engineering, the
present finding would be of signifi-
cance for a wider structural diversity of
smart thiourea derivatives with prede-
signed functions.
with binding constants over 107 molÀ1
L
orders of magnitude for AcOÀ and a
redshifted absorption of the anion
binding complexes in acetonitrile
(MeCN) relative to those of N-benz-
amidothioureas (1) that bear no o-
OMe in the N-benzamide moiety, de-
spite the electron-donating character of
o-OMe. Absorption of the anion–2X/
2Y complex was shown to be of the
same charge-transfer nature as that of
the anion–1 complex, but its depend-
ence on substituent X is interestingly
Keywords: amidothioureas
anions arylamides
transfer · hydrogen bonds
·
·
·
charge
Introduction
binding to the anion, which provides positive feedback to re-
À
inforce the anion binding. The original twisted N N single
In searching for new thiourea-based receptors for anions, we
found that N-benzamidothioureas (1, Scheme 1) that bear a
para or meta substituent X in the N-benzamide moiety
showed higher anion binding affinity than that of the corre-
bond in 1 was concluded to become planar upon anion bind-
sponding classic N-phenylthiourea counterparts, despite the
[1]
À
lower acidity of the thioureido NH protons in 1. This was
assumed to result from a charge transfer (CT) in 1 upon
[a] Q.-Q. Jiang, B. Darhkijav, H. Liu, F. Wang, Prof. Dr. Z. Li,
Prof. Dr. Y.-B. Jiang
Department of Chemistry
College of Chemistry and Chemical Engineering
and the MOE Key Laboratory of Analytical Sciences
Xiamen University, Xiamen 361005 (China)
Fax : (+86)592-218-5662
E-mail: ybjiang@xmu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.200900519. It includes absorption
Scheme 1. Hydrogen-bonding interaction of N-benzamidothioureas with
the AcOÀ anion and hydrogen-bonding networks in the anion binding
complexes. Substituent X or Y is at the para or meta position.
1
spectra of 2Xa–g and 2Ya–d in MeCN and H and 13C NMR spectra
of 2Xa–g, 2Ya–d, and 2Za–f.
Chem. Asian J. 2010, 5, 543 – 549
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543

FULL PAPERS
ing and a hydrogen-bonding network was suggested to form
in the anion binding complex that involves both C=
O···HNC=S and O=CNH···S=C, in addition to the double
hydrogen bonds of thiourea with the anion (Scheme 1).
Recent efforts in arylamide-based foldamers have demon-
strated an interesting contribution of the ortho substituent
such as o-OMe and o-F in rigidifying the arylamide moiety
by forming a six-membered-ring intramolecular hydrogen
bond like o-MeO···HNC=O- or o-F···HNC=O.[2] It was
therefore expected that with N-benzamidothioureas that
bore an ortho substituent capable of forming an intramolec-
ular hydrogen bond (2, Scheme 1) such intramolecular hy-
drogen bonds would facilitate the final hydrogen-bonding
network in their anion binding complexes (Scheme 1). This
would accordingly lead to an enhanced anion binding rela-
tive to that of 1. Previously, intramolecular hydrogen bond-
ing has been employed to preorganize the conformation of
anion receptors for better performance.[3] We therefore de-
cided to examine N-benzamide ortho-substituted counter-
parts of 1 (2Z, Scheme 2, and 2Zc with Z=H is included
for comparison). The investigation was started with the o-
OMe derivative (2Zb), in which an intramolecular hydrogen
bond was expected following the behavior of o-methoxybenz-
amide.[2] Indeed, we found that the anion binding constant
of 2Zb in MeCN was substantially enhanced compared with
that of 2Zc without such intramolecular hydrogen bonding
in the N-benzamide moiety. A similar enhancement in anion
binding was observed with 2Za, 2Zd, 2Ze, and 2Zf. In the
cases of ortho-substituent NHMe (2Za), OMe (2Zb), F
(2Zd), and Cl (2Ze), the absorption of AcOÀ–2Z binding
complex in MeCN was found to shift to the blue with de-
creasing electron-donating or increasing electron-withdraw-
ing ability of the ortho substituent, which is opposite to that
observed with 1 that bears a para/meta substituent X (Y=
H, Scheme 1).[1b,d,i] We concluded that the intramolecular hy-
drogen bond in the N-benzamide moiety promoted anion
binding in 2Zb and in 2Za, 2Zd, and 2Ze as well. Extended
investigations into series 2X and 2Y were carried out to fur-
ther demonstrate the contribution of such intramolecular
hydrogen bonds on anion binding. The results reported here
provide expanded diversity of thiourea-based functional spe-
cies for not only anion receptors[4] but organocatalysts,[5]
among others.
Results and Discussion
Although in the cases of o-OMe- and o-F-substituted benz-
amides an intramolecular hydrogen bond has been identi-
fied,[2,6] we found evidence for such intramolecular hydrogen
bonds in the corresponding N-
benzamidothioureas from X-ray
crystal structural analysis and
2D NMR spectroscopic data.
We succeeded in growing crys-
tals of 2Zb[7] and 2Xb,[8] which
allowed for the identification of
the intramolecular hydrogen
bond between o-OMe and
À
Scheme 2. Structure of N-(ortho-substituted)benzamidothioureas 2Z, 2X, and 2Y. The NH proton number-
ing is given in 2Z.
HNC=O. Figure 1 shows the
crystal structure of 2Zb grown
in CH2Cl2, which clearly indi-
cates the six-membered-ring in-
tramolecular hydrogen bond. In the 2D NMR spectra of
Abstract in Chinese:
2Zb in CDCl3, the coupling between o-OCH3 and N-benz-
À
amido NH protons was identified (Figure 2), thus support-
ing this ring intramolecular hydrogen bonding. From the
crystal structure (Figure 1), it is noted that the o-methoxy-
benzamide moiety in 2Zb is now planar with an expected
À
higher rigidity. The N N single bond in 2Zb is found to be
Figure 1. Crystal structure of 2Zb grown in CH2Cl2. The dashed line indi-
cates the six-membered-ring intramolecular hydrogen bond between
MeO1···H1NC=O with an O···H distance of 1.90 ꢁ.
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Anion Binding of N-(o-Methoxybenzamido)thioureas
Figure 4. Job plot for the binding of AcOÀ to 2Zb in MeCN by monitor-
ing the difference of absorbance of the mixture of AcOÀ and 2Zb and
that of 2Zb at 341 nm. The total concentration of AcOÀ and 2Zb was
Figure 2. NOESY spectrum of 2Zb in CDCl3. Circles highlight coupling
between H1 and Ha. H1, H2, and H3 are NH protons; for their number-
À
5.0ꢂ10À5 molLÀ1
.
ing, see Scheme 2. Ha is an o-OCH3 proton.
À
À
À
NO3 , HSO4 , and ClO4 led to no appreciable change in
the absorption spectrum. By employing a reported nonlinear
fitting procedure,[9] we determined the AcOÀ binding con-
stant of 2Zb in MeCN to be over 107 molÀ1 L; that is much
higher than that of 1 (X=Y=H) at 105 molÀ1 L orders of
magnitude.[1i] It is thus made clear that the intramolecular
hydrogen bond in the N-benzamide moiety can further en-
hance the anion binding ability. Another important feature
is that the new absorption band of the AcOÀ–2Zb complex
in MeCN that peaked at 341 nm is redshifted from that of
AcOÀ–1 (X=Y=H) at 337 nm, despite the electron-donat-
ing character of the o-OMe substituent in 2Zb. Previously it
was shown that the absorption of the AcOÀ–1 (Y=H) com-
plex in MeCN is of a charge-transfer (CT) nature[1i] in that it
shifts to the blue when X is an electron-donating para/meta
substituent. If the absorption of AcOÀ–2Zb can be proven
to be of a CT nature, the intramolecular hydrogen bond in
the N-benzamide moiety of 2Zb appears not only to exert
steric influence but an electronic effect as well, as it makes
the N-benzamide moiety more electron-withdrawing despite
the electron-donating nature of the o-OMe substituent.
We next examined the AcOÀ binding properties of other
members in the 2Z series. Figure 5 shows the absorption
spectral traces of 2Z upon addition of the AcOÀ anion in
MeCN. The new absorption band was found to shift in gen-
eral to the blue from 2Za to 2Zf. It has recently been
shown that the effect of the ortho substituent consists
mainly of the inductive and resonance polar effect; the pKa
value of the o-substituted benzoic acid thereby reflects the
polar effect of the ortho substituent.[10] It therefore follows
that the absorption of AcOÀ–2Z binding complex shifts to
the blue with the decreasing electron-donating or increasing
electron-withdrawing ability of the ortho substituent. This is
opposite to that previously observed with the absorption of
AcOÀ–1 (Y=H),[1i] in the latter case it shifts to the red
when X becomes less electron donating or more electron
withdrawing. Taking the pKa value of the corresponding
less twisted than that in 1, as the H-N1-N2-H dihedral angle
(<208) is much smaller than that in 1 (around 708).[1b,d]
Proton NMR spectra of 2X and 2Y showing substituent de-
À
pendence of NH agrees well with this observation and will
be described later (in Figures 8 and 9). This means that the
influence of the intramolecular hydrogen bonding has ex-
tended to the N-benzoylhydrazine moiety.
Anion binding of 2Zb was monitored in MeCN by ab-
sorption spectral titrations. Traces presented in Figure 3 in-
dicate that upon addition of AcOÀ anions, the original ab-
sorption band of 2Zb that peaked at 269 nm is redshifted to
278 nm and enhanced, and two new bands appear at 235
and 341 nm, respectively. An isosbestic point is identified at
245 nm, which is indicative of a well-defined interaction be-
tween 2Zb and AcOÀ. A Job plot confirmed that the bind-
À
ing stoichiometry was 1:1 (Figure 4). With FÀ and H2PO4 ,
similar variations in the absorption spectrum of 2Zb were
found (Figure 3b), whereas other anions such as ClÀ, BrÀ,
Figure 3. a) Absorption spectra of 2Zb in MeCN in the presence of
AcOÀ, and b) plots of absorbance at 341 nm of 2Zb versus anion concen-
tration. [2Zb]=1.0ꢂ10À5 molLÀ1
.
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545

Y.-B. Jiang et al.
FULL PAPERS
might be in the form of o-MeNH···O=CNH;[13] further ex-
periments are however needed to clarify the bonding mode.
In the case of 2Zf, the bulky o-Br decreases the planarity of
the N-benzamide moiety so that the arylamide becomes a
somewhat aliphatic amide. As a consequence, the anion
binding constant is higher and the absorption of the anion–
2Zf complex is blueshifted (Figure 6), as expected from a
comparison of N-acetamidothioureas with N-benzamido-
thioureas.[1a]
To better understand the contribution of the intramolecu-
lar hydrogen bond in 2Z, the nature of the absorption of
the AcOÀ–2Z complex was addressed. The anion binding
character of 2X (Scheme 2), which differs from 1 (Y=H)
by an o-OMe in the N-benzamide moiety, was therefore ex-
amined. The crystal structure of 2Xb[8] also shows the six-
membered-ring intramolecular hydrogen bond with an o-
MeO···HNC(O) distance of 1.86 ꢁ. This implies that the 5-
OMe substituent in the N-benzamide moiety of 2Xb does
not destroy this intramolecular hydrogen bond. The H-N-N-
H dihedral angle is approximately 148, which suggests that
the N-benzoylhydrazine moiety is almost planar. The ab-
sorption spectral traces of 2X in the presence of AcOÀ in
MeCN are similar to those shown in Figures 3 and 5; they
are characterized by the appearance of a new and redshifted
absorption band (see the Supporting Information). The
energy of this new band was found to be linearly related to
the substituent constant of X in 2X by hn=3.60À0.28sX
(Figure 7), with the absorption shifting to the red with in-
creasing electron-withdrawing or decreasing electron-donat-
ing ability of X. This informs the CT character of the new
absorption, as in the case of 1 (Y=H).[1i] It therefore ap-
pears that the intramolecular hydrogen bond in the N-ben-
zamide moiety reverses the electronic character of the elec-
tron-donating o-substituent, which behaves like an electron-
withdrawing substituent. Both the intercept and slope in the
case of 2X (Figure 7) are lower in value than the corre-
Figure 5. Absorption spectra of 2Za–2Zf (1.0ꢂ10À5 molLÀ1) in MeCN in
the presence of AcOÀ of increasing concentration.
ortho-substituted benzoic acid of 2Z as a measure of the
ortho-substituent constant, we found that the absorption
energy of the AcOÀ–2Z complex held a good linear rela-
tionship with the pKa value (Figure 6) except for the cases
without an ortho substituent (2Zc) or with a bulky o-Br
(2Zf), since in these two cases no intramolecular hydrogen
bond is expected. The observed linear correlation in
Figure 6 might suggest that an intramolecular hydrogen
À
bond also exists between the o-Cl and N-benzamido NH
proton in 2Ze.[12] AcOÀ binding constants of 2Za, 2Zd,
2Ze, and 2Zf were all found to be over 107 molÀ1 L; these
are much higher than that of 2Zc. The intramolecular hy-
drogen bond therefore appears to promote anion binding at
least in the cases of 2Za, 2Zb, 2Zd, and 2Ze. It should be
pointed out that the intramolecular hydrogen bond in 2Za
sponding correlation found with
1 (Y=H) of hn=
3.67À0.34sX.[1i] It thus follows that the intramolecular hydro-
gen bond in the N-benzamide moiety generally lowers the
Figure 6. Absorption energy of AcOÀ–2Z in MeCN versus pKa of the
corresponding ortho-substituted benzoic acid. Note the linear correlation
between pKa of para-/meta-substituted benzoic acid and the Hammett
substituent constant s of pKa =À1.03s+4.21 can be obtained by using
data given in ref. [11]. Assuming this holds for the ortho-substituted ben-
zoic acid, a linear relationship for the absorption energy of AcOÀ–2Z of
hn=3.61+0.12s was derived, which is indeed opposite in s dependence
to what was reported for that of AcOÀ–1 (hn=3.67À0.34s).[1i]
Figure 7. Absorption energy of the AcOÀ–2X complex in MeCN versus
the Hammett constant of substituent X in 2X. Note a correlation of hn=
3.67À0.34sX has previously been reported for the absorption of AcOÀ–1
(Y=H).[1i]
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Anion Binding of N-(o-Methoxybenzamido)thioureas
absorption energy of the AcOÀ–2X binding complex and
slightly weakens the influence of the para/meta substituent
X on this absorption. AcOÀ binding constants of 2X in
MeCN were found to be over 107 molÀ1 L orders of magni-
tude, which is much higher than that of 1 (Y=H). They
were, however, almost independent of the substituent X,
similar to that observed with 1 (Y=H).[1i]
In the case of 2Y (Scheme 2), the absorption of AcOÀ
binding complexes in MeCN at approximately 340 nm was
not found to be very dependent on substituent Y (see the
Supporting Information). The AcOÀ binding constants in
pure MeCN were found to be over 107 molÀ1 L, thus not al-
lowing for an analysis of their dependence on Y. In MeCN
containing 2% H2O by volume, the binding constants de-
creased to 105 molÀ1 L orders of magnitude, which thereby
enables a credible correlation. The obtained correlation of
À
Figure 8. Chemical shifts of NH protons of 2X in CDCl3 versus the
Hammett constant of substituent X.
lnKACHTUNGTRENNUNG
(AcOÀ)=12.84+2.68sY (n=4, R=0.8875) suggests that
an amplification of the effect of substituent Y on the binding
constant of 2Y exists, as in the case of 1.[1a,g] This amplifica-
tion in 2Y, however, is to a lesser extent than that of N-acet-
amido-N’-(substituted-phenyl)thioureas, the corresponding
slopes of which are 7.64, 5.44, and 4.31 in MeCN containing
0, 1, and 3% H2O by volume, respectively.[1a] The presence
of the amplification of substituent Y on anion binding of 2Y
is understandable, since anion-binding-induced CT is also in-
dicated by the appearance of redshifted absorption. Crystal
structures of 2Zb[7] and 2Xb[8] show that the N N bond in 2
À
is less twisted than that in 1, which means that the confor-
mational changes in 2 upon its binding to an anion, if any,
are smaller. This explains the observed lower amplification
of the effect of substituent Y on anion binding of 2Y. NMR
À
spectroscopic signals of the NH protons in 2X and 2Y
versus the Hammett constants of substituent X or Y (Fig-
À
Figure 9. Chemical shifts of NH protons of 2Y in CDCl3 versus the
Hammett constant of substituent Y.
À
ures 8 and 9) do suggest a twisted N N single bond. The dis-
1
À
continuity in the slopes of the N-benzamido NH and of
2
3
À
À
the thioureido NH and NH protons indicates that the
substituent electronic effect is to some extent blocked by
The absorption of the anion–2X complex was found to be
of a CT nature, the wavelength being in general longer than
that of anion–1 (Y=H) and its dependence on substituent
X being weaker. It appears that the intramolecular hydro-
gen bond buffers the substituent effect by increasing the
conjugation in the N-benzamide moiety, presumably owing
to its enhanced planarity and rigidity. Despite this intramo-
lecular hydrogen bond in the N-benzamide moiety, the
anion binding constant of 2X was found to be independent
of substituent X, similar to that with 1 (Y=H), whereas the
effect of substituent Y on the anion binding constant of 2Y
is amplified to a lesser extent than that in the case of having
À
the N N bond.
Conclusion
A six-membered-ring intramolecular hydrogen bond was in-
dicated by X-ray crystal structural analysis and NMR spec-
troscopy to exist in N-(o-methoxybenzamido)thioureas (2X
and 2Y), which makes the N-benzamide moiety rigid and
planar. Actually, such intramolecular hydrogen bonding
À
À
even makes the N N single bond much less twisted in 2X
no such bond. Less conformational change in the N N bond
and 2Y relative to that in 1, which bears no o-OMe substitu-
ent in the N-benzamide moiety. Although anion binding
constants of 1 (Y=H) were previously shown to be inde-
pendent of substituent X, the electron-donating o-OMe sub-
stituent was found to increase the anion binding affinity of
2Zb with this intramolecular hydrogen bond relative to that
of 2Zc, which lacks such a bond. This clearly demonstrates
the promotion of the intramolecular hydrogen bond in
anion binding.
of 2X
N
ble for the latter observation.
The present finding that the intramolecular hydrogen
bond in the N-benzamide moiety promotes anion binding of
N-(o-methoxybenzamido)thioureas provides further support
for the formation of a hydrogen-bonding network in the
anion/N-amidothiourea binding complex. This allows
wider structural diversity of functional thiourea derivatives
to be created. For example, the fact that substituent X in
a
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d=181.1, 166.0, 139.3, 132.5, 131.9, 128.2, 127.9, 126.1, 125.1 ppm; HRMS
(ESI): m/z calcd for C14H14N3OS+: 272.0858; found: 272.0854. Compound
2Zd: 1H NMR (400 MHz, [D6]DMSO): d=10.34 (s, 1H), 9.83 (s, 1H),
9.73 (s, 1H), 7.85 (s, 1H), 7.60 (q, J=6.0 Hz, 1H), 7.45 (s, 2H), 7.33 (q,
J=7.2 Hz, 3H), 7.17 (t, J=7.0 Hz, 1H), 7.15 ppm (t, J=7.5 Hz, 1H);
13C NMR (100 MHz, [D6]DMSO): d=181.1, 163.3, 160.9, 158.4, 139.1,
133.3, 130.7, 128.1, 125.8, 125.0, 124.3, 121.7, 116.3, 116.1 ppm; HRMS
(ESI): m/z calcd for C14H13FN3OS+: 290.0763; found: 290.0760. Com-
pound 2Ze: 1H NMR (400 MHz, [D6]DMSO): d=10.46 (s, 1H), 9.84 (s,
1H), 9.67 (s, 1H), 7.80 (d, J=6.8 Hz, 1H), 7.55–7.43 (m, 5H), 7.36 (t, J=
7.6 Hz, 2H), 7.17 ppm (t, J=7.8 Hz, 1H); 13C NMR (100 MHz,
[D6]DMSO): d=181.8, 165.6, 139.0, 133.9, 131.6, 130.7, 129.9, 129.8,
128.2, 126.9, 126.5, 124.9 ppm; HRMS (ESI): m/z calcd for
C14H13ClN3OS+: 306.0468; found: 306.0474. Compound 2Zf: 1H NMR
(400 MHz, [D6]DMSO): d=10.47 (s, 1H), 9.85 (s, 1H), 9.59 (s, 1H), 7.77
(d, J=7.2 Hz, 1H), 7.70 (d, J=6.8 Hz, 1H), 7.49 (t, J=6.8 Hz, 3H), 7.44
(d, J=6.0 Hz, 1H), 7.36 (t, J=7.6 Hz, 2H), 7.18 ppm (t, J=7.4 Hz, 1H);
13C NMR (100 MHz, [D6]DMSO): d=181.4, 166.4, 139.0, 135.9, 133.0,
131.7, 129.9, 128.2, 127.4, 125.9, 124.9, 119.6 ppm; HRMS (ESI): m/z
calcd for C14H13BrN3OS+: 349.9963; found: 349.9969.
2X does not affect the anion affinity of 2X suggests that N-
(aliphatic amido)thioureas that bear an intramolecular hy-
drogen bond in the N-amide moiety may function similarly
to that of 2X. This would be of significance for developing
new thiourea-based organocatalysts.[1a,14] Our finding also
suggests that a six-membered o-Cl···HNC=O ring intramo-
lecular hydrogen bond may exist in o-chlorobenzamide, a
subject that is still controversial.[12]
Experimental Section
General Methods
Chemicals for syntheses were commercially available and used as re-
ceived. Solvents for spectral investigations were further purified by distil-
lation to ensure no fluorescence impurities at the chosen excitation wave-
length. The anions employed for binding titrations in organic solvents
were their commercially available nBu4N+ salts.
Absorption spectral titrations for anion binding were recorded using a
Thermo Evolution 300 spectrophotometer with a 1 cm cell by adding an
aliquot of anion solution to a bulk receptor solution of given volume and
concentration. 1H and 13C NMR spectra in CDCl3, [D6]DMSO, and
CD3CN were acquired using a Bruker AV400 NMR spectrometer with
TMS as an internal standard. HRMS spectra were obtained using a Mi-
cromass LCT spectrometer with methanol as the solvent. IR spectra
were taken from the KBr pellet samples using a Nicolet IR200 instru-
ment. Single-crystal X-ray diffraction data were collected using a Bruker
Smart APEX 2000 CCD diffractometer.
Synthesis and Characterization of 2X
Potassium carbonate (2.07 g, 15 mmol) was added to a solution of substi-
tuted 2-hydroxybenzoic acid (5 mmol) in acetone (10.0 mL). CH3I
(1.3 mL, 20 mmol) was added dropwise to the stirred mixture at room
temperature. The mixture was heated at reflux in the dark for 12 h. All
precipitates were filtered off and the filtrates were evaporated under re-
duced pressure to get methyl-substituted 2-methoxybenzoate. The ester
was dissolved in ethanol (5 mL), and excess aqueous hydrazine (80%)
was added. The mixture was heated to 808C for 8 h. After removing the
solvent, the residue was washed with iced ethanol and then dried, thus
producing substituted 2-methoxybenzoylhydrazine. It was then reacted
with phenyl isothiocyanate in ethanol (10.0 mL) for 12 h at room temper-
ature. After removing the solvent, the residue was purified by recrystalli-
zation from MeCN to lead to 2X. Compound 2Xa: 1H NMR (400 MHz,
CDCl3): d=12.22 (s, 1H), 11.04 (s, 1H), 9.30 (s, 1H), 7.80 (s, 1H), 7.55
(d, J=7.2 Hz, 2H), 7.38 (t, J=7.4 Hz, 2H), 7.29 (d, J=8.4 Hz, 1H), 7.22
(t, J=7.0 Hz, 1H), 6.94 (d, J=8.4 Hz, 1H), 4.09 (s, 3H), 2.16 ppm (s,
3H); 13C NMR (100 MHz, [D6]DMSO): d=180.4, 165.2, 155.4, 139.1,
133.5, 130.8, 129.5, 128.2, 124.8, 122.6, 120.7, 112.1, 56.2, 19.8 ppm;
HRMS (ESI): m/z calcd for C16H18N3O2S+: 316.1120, found: 316.1122.
Compounds 2Z, 2X, and 2Y were synthesized from the reaction of phe-
nylisothiocyanate with the corresponding benzoylhydrazine that was ob-
tained from benzoate ester and hydrazine. All the prepared compounds
were fully characterized by 1H and 13C NMR spectroscopy and HRMS.
Copies of the 1H and 13C NMR spectra can be found in the Supporting
Information.
CCDC-696246 (2Zb)[7] and -696247 (2Xb)[8] contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre at
www.ccdc.cam.ac.uk/data_request/cif.
1
Compound 2Xb: H NMR (400 MHz, CDCl3): d=12.07 (s, 1H), 10.58 (s,
Synthesis and Characterization of 2Z
1H), 8.86 (s, 1H), 7.56 (s, 1H), 7.48 (d, J=8.0 Hz, 2H), 7.38 (t, J=
7.6 Hz, 2H), 7.23 (d, J=7.2 Hz, 1H), 7.05 (d, J=8.8 Hz, 1H), 6.98 (d, J=
9.2 Hz, 1H), 4.07 (s, 3H), 3.57 ppm (s, 3H); 13C NMR (100 MHz,
[D6]DMSO): d=180.6, 164.8, 153.0, 151.3, 139.0, 128.2, 125.2, 124.7,
122.5, 118.4, 115.1, 113.6, 56.5, 55.5 ppm; HRMS (ESI): m/z calcd for
C16H18N3O3S+: 332.1069; found: 332.1075. Compound 2Xc: 1H NMR
(400 MHz, CDCl3): d=12.04 (s, 1H), 10.75 (s, 1H), 8.97 (s, 1H), 8.07 (d,
J=7.6 Hz, 1H), 7.51 (m, 3H), 7.38 (t, J=8.0 Hz, 2H), 7.22 (t, J=7.2 Hz,
1H), 7.04 (t, J=8.6 Hz, 2H), 4.12 ppm (s, 3H); 13C NMR (100 MHz,
[D6]DMSO): d=180.6, 165.2, 157.2, 139.1, 133.1, 130.8, 128.2, 124.9,
124.8, 122.5, 120.6, 112.1, 56.1 ppm; HRMS (ESI): m/z calcd for
C15H16N3O2S+: 302.0963; found: 302.0966. Compound 2Xd: 1H NMR
(400 MHz, CDCl3): d=11.68 (s, 1H), 10.00 (s, 1H), 8.33 (s, 1H), 8.02 (d,
J=8.0 Hz, 1H), 7.42–7.43 (m, 4H), 7.29 (m, 1H), 7.07 (d, 1H), 7.04 (m,
1H), 4.11 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=180.4,
164.4, 157.9, 139.0, 137.3, 132.2, 128.1, 125.4, 124.8, 122.7, 120.6, 112.6,
56.6 ppm; HRMS (ESI): m/z calcd for C15H15ClN3O2S+: 336.0574; found:
336.0579. Compound 2Xe: 1H NMR (400 MHz, CDCl3): d=11.75 (s,
1H), 9.85 (s, 1H), 8.20 (s, 1H), 8.08 (d, 1H), 7.43–7.47 (m, 5H), 7.31 (d,
J=6.8 Hz, 1H), 6.98 (d, J=8.8 Hz, 1H), 4.10 ppm (s, 3H); 13C NMR
(100 MHz, [D6]DMSO): d=180.5, 164.0, 156.0, 139.1, 132.3, 129.9, 128.2,
125.8, 125.0, 124.4, 122.9, 114.2, 56.5 ppm; HRMS (ESI): m/z calcd for
C15H15ClN3O2S+: 336.0574; found: 336.0564. Compound 2Xf: 1H NMR
(400 MHz, CDCl3): d=11.73 (s, 1H), 9.84 (s, 1H), 8.22 (s, 2H), 7.60 (d,
J=8.4 Hz, 1H), 7.44–7.47 (m, 4H), 7.31 (d, J=6.4 Hz, 1H), 6.93 (d, J=
7.6 Hz, 1H), 4.10 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=
180.3, 163.9, 156.4, 139.0, 138.9, 135.2, 132.7, 128.1, 125.7, 124.9, 123.2,
Compound 2Z was synthesized in three steps starting from ortho-substi-
tuted benzoic acid. Methyl benzoate was first prepared by esterification
of the substituted benzoic acid in methanol heated at reflux in the pres-
ence of concentrated H2SO4. This benzoate then reacted with aqueous
hydrazine (80%) in ethanol heated at reflux for 8 h. The formed precipi-
tates were filtered, washed with iced ethanol (3ꢂ5.0 mL) and iced water
(3ꢂ10.0 mL), then dried, thereby leading to substituted benzoylhydra-
zine, which was finally reacted in ethanol at room temperature with
phenyl isothiocyanate until TLC showed the completion of the reaction.
The as-obtained products were purified by recrystallization from ethanol.
Compound 2Za: 1H NMR (400 MHz, [D6]DMSO): d=10.30 (s, 1H),
9.78ACHTUNGTRENNUNG(s, 1H), 9.58 (s, 1H), 7.74 (s, 1H), 7.44 (s, 2H), 7.33 (q, J=7.6 Hz,
3H), 7.15 (t, J=7.2 Hz, 1H), 6.67 (t, J=7.2 Hz, 1H), 6.57 (t, J=7.2 Hz,
1H), 2.8 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=181.2, 168.7,
150.5, 139.2, 133.2, 129.2, 127.9, 125.9, 124.9, 113.7, 112.1, 110.6,
29.3 ppm; HRMS (ESI): m/z calcd for C15H17N4OS+: 301.1123; found:
301.1129. Compound 2Zb: 1H NMR (400 MHz, CDCl3): d=12.04 (s,
1H), 10.75 (s, 1H), 8.97 (s, 1H), 8.07 (d, J=7.6 Hz, 1H), 7.51 (m, 3H),
7.38 (t, J=8.0 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.04 (t, J=8.6 Hz, 2H),
4.12 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=180.6, 165.2,
157.2, 139.1, 133.1, 130.8, 128.2, 124.9, 124.8, 122.5, 120.6, 112.1,
56.1 ppm; HRMS (ESI): m/z calcd for C15H16N3O2S+: 302.0963; found:
302.0966. Compound 2Zc:[1i] 1H NMR (400 MHz, [D6]DMSO): d=10.54
(s, 1H), 9.82 (s, 1H), 9.72 (s, 1H), 7.96 (d, J=7.50 Hz, 2H), 7.58 (t, J=
7.32 Hz, 1H), 7.50 (t, J=7.32 Hz, 2H), 7.43
ACHTUNGERTN(NUNG s, 2H), 7.33 (t, J=7.54 Hz,
2H), 7.16 ppm (t, J=7.32 Hz, 1H); 13C NMR (100 MHz, [D6]DMSO):
548
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 543 – 549

Anion Binding of N-(o-Methoxybenzamido)thioureas
114.6, 111.9, 56.4 ppm; HRMS (ESI): m/z calcd for C15H15BrN3O2S+:
380.0068; found: 380.0076. Compound 2Xg: H NMR (400 MHz, CDCl3):
f) W. X. Liu, Y. B. Jiang, Org. Biomol. Chem. 2007, 5, 1771–1775;
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1
d=11.65 (s, 1H), 9.61 (s, 1H), 9.03 (s, 1H), 8.40 (d, J=8.8 Hz, 1H), 7.96
(s, 1H), 7.48 (t, J=7.4 Hz, 2H), 7.33–7.39 (m, 3H), 7.15 (d, J=9.2 Hz,
1H), 4.24 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=180.6,
162.0, 140.4, 139.0, 128.2, 128.1, 126.3, 125.9, 125.0, 123.4, 122.2, 113.1,
57.2 ppm; HRMS (ESI): m/z calcd for C15H15N4O4S+: 347.0814; found:
347.0823.
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[7] Crystal structure data for 2Zb: C12H12N2.4O1.6S0.8; a=10.439(3), b=
11.681(3), c=12.527(3) ꢁ; a=96.413(5), b=108.390(5), g=
95.946(5)8; V=1424.8(6) ꢁ3; Z=5; final R1=0.0603, wR2=0.1567
(I>2s(I)).
[8] Crystal structure data for 2Xb: C21.33H22.67N4O4S1.33; a=6.0739(2),
b=10.6574(4), c=24.3162(7) ꢁ; a=90, b=95.899(3), g=908; V=
1565.70(9) ꢁ3; Z=3; final R1 =0.0438, wR2=0.1032 (I>2s(I)).
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Synthesis and Characterization of 2Y
o-Methoxybenzoic acid (5 mmol) was dissolved in methanol (15 mL).
The resulting solution was heated at reflux in the presence of concentrat-
ed H2SO4 for 6 h. The solvent was removed under reduced pressure and
water was added to the residue. The solution pH was adjusted to 8.0
using sodium bicarbonate, thus leading to methyl o-methoxybenzoate. It
was reacted with excess aqueous hydrazine (80%) in ethanol while heat-
ing at reflux for 8 h. A precipitate was formed, which after filtration was
washed with iced water and dried to produce o-methoxybenzoylhydra-
zine. Phenyl isothiocyanate was added to a solution of o-methoxyben-
zoylhydrazine in ethanol and the solution was stirred at room tempera-
ture for 12 h. Compound 2Y was prepared after removing the solvent
and purified by recrystallization from MeCN. Compound 2Ya: 1H NMR
(400 MHz, CDCl3): d=11.70 (s, 1H), 9.75 (s, 1H), 8.12 (s, 1H), 8.08 (d,
J=8.0 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 7.32 (d, J=8.8 Hz, 2H), 7.05 (q,
J=8.0 Hz, 2H), 6.94 (t, J=8.8 Hz, 2H), 4.10 (s, 3H), 3.82 ppm (s, 3H);
13C NMR (100 MHz, [D6]DMSO): d=180.2, 164.9, 157.1, 156.6, 133.0,
131.8, 130.7, 126.8, 125.8, 120.5, 113.3, 112.0, 56.0, 55.1 ppm; HRMS
(ESI): m/z calcd for C16H18N3O3S+: 332.1069; found: 332.1075. Com-
pound 2Yb: 1H NMR (400 MHz, CDCl3): d=11.88 (s, 1H), 10.29 (s,
1H), 8.54 (s, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.33
(d, J=8.4 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 7.05 (t, J=8.2 Hz, 2H), 4.11
(s, 3H), 2.35 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=180.5,
165.4, 157.7, 136.9, 134.5, 133.6, 131.1, 129.2, 125.7, 123.3, 120.8, 112.6,
56.0, 21.0 ppm; HRMS (ESI): m/z calcd for C16H18N3O2S+: 316.1120;
found: 316.1125. Compound 2Yc: 1H NMR (400 MHz, CDCl3): d=12.04
(s, 1H), 10.75 (s, 1H), 8.97 (s, 1H), 8.07 (d, J=7.6 Hz, 1H), 7.51 (m,
3H), 7.38 (t, J=8.0 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.04 (t, J=8.6 Hz,
2H), 4.12 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=180.6,
165.2, 157.2, 139.1, 133.1, 130.8, 128.2, 124.9, 124.8, 122.5, 120.6, 112.1,
56.1 ppm; HRMS (ESI): m/z calcd for C15H16N3O2S+: 302.0963; found:
302.0966. Compound 2Yd: 1H NMR (400 MHz, CDCl3): d=12.04 (s,
1H), 10.90 (s, 1H), 9.12 (s, 1H), 8.03 (d, J=6.0 Hz, 1H), 7.54 (t, J=
7.8 Hz, 1H), 7.48 (d, J=8. 8 Hz, 2H), 7.32 (d, J=8.8 Hz, 2H), 7.06 (t, J=
6.8 Hz, 2H), 4.13 ppm (s, 3H); 13C NMR (100 MHz, [D6]DMSO): d=
180.5, 165.0, 157.2, 138.6, 133.7, 131.4, 128.8, 127.9, 126.8, 124.7, 120.6,
112.6, 56.6 ppm; HRMS (ESI): m/z calcd for C15H15ClN3O2S+: 336.0574;
found: 336.0576.
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Acknowledgements
We thank the organizers of the symposium “Catalysis and Sensing for
our Environment” (CASE) that brings scientists of catalysis and chemical
sensing together and promotes our ongoing projects on thiourea-based
functional molecules. The National Science Foundation of China is
thanked for financial support (grants 20675069 and 20835005 to Y.B.J.
and J0630429 to H.L.). B.D., on leave from the Mongolian Academy of
Sciences, thanks the Chinese Scholar Council for partial support.
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Ruan, Y.-B. Jiang, Org. Biomol. Chem. 2009, 7, 4021–4028; b) Z. Li,
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Received: October 2, 2009
Published online: February 1, 2010
Chem. Asian J. 2010, 5, 543 – 549
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
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