A colorimetric proton sponge

Article abstract of DOI:10.1021/jo101381r

1,8-Bis(dimethylamino)naphthalene ( Proton Sponge ) and bromomaleic anhydride react quickly at room temperature, generating 3-(4,5-bis(dimethylamino)napthalen-1-yl)furan-2,5-dione (4-maleicanhydridoproton sponge or MAPS ). MAPS is a deep purple solid that exhibits positive solvatochromism in solution. It is a weaker base than Proton Sponge. When protonated in solution, MAPS loses its color, but the color change can be reversed by deprotonation with a stronger base. MAPS thus acts as a colorimetric version of a proton sponge.

Full text of DOI:10.1021/jo101381r

pubs.acs.org/joc
Vilsmeier-Haack reaction,7 etc.). Reactions with carbon elec-
trophiles are typically slow, except with very exotic and strong
A Colorimetric Proton Sponge
electrophiles.3,8-12
Charles D. Swor, Lev N. Zakharov, and David R. Tyler*
Maleic anhydrides readily undergo hydrophosphination
with secondary phosphines.13,14 More specifically, bromo-
maleic anhydride (BMA) reacts with 2 equiv of secondary
phosphine, forming unique bisphosphines that can be used
as bidentate ligands.15 After addition of 1 equiv of phos-
phine, HBr is eliminated, re-forming the double bond and
allowing the second equivalent of phosphine to react. While
investigating the utility of this reaction with coordinated
secondary phosphines, we combined coordinated phos-
phine, bromomaleic anhydride, and Proton Sponge to neu-
tralize the HBr byproduct. Upon addition of Proton Sponge
to the reaction mixture, a deep purple product formed within
seconds. Control reactions showed that Proton Sponge and
bromomaleic anhydride reacted in the absence of the metal
complex or the phosphine to generate this new product. Slow
evaporation of the reaction solution resulted in deep purple
crystals suitable for X-ray diffraction, which were found to
be 4-maleicanhydridoproton sponge (MAPS).
Department of Chemistry, University of Oregon, Eugene,
Oregon 97403
dtyler@uoregon.edu
Received July 13, 2010
Proton Sponge and bromomaleic anhydride react within
seconds at room temperature in a variety solvents (chloro-
form, dichloromethane, acetonitrile, THF). This reaction
can be viewed as both an electrophilic aromatic substitution,
with bromomaleic anhydride acting as the electrophile, and
as a Michael reaction, with Proton Sponge acting as the
nucleophile. Because HBr is a byproduct of this coupling,
2 equiv of Proton Sponge are needed for the reaction to reach
completion. One equivalent couples with BMA, while the
other neutralizes HBr (Scheme 1). Attempts at using a different
base (such as sodium methoxide) to avoid using 2 equiv of
Proton Sponge in the reaction resulted in decomposition of the
product.
1,8-Bis(dimethylamino)naphthalene (“Proton Sponge”) and
bromomaleic anhydride react quickly at room temperature,
generating 3-(4,5-bis(dimethylamino)napthalen-1-yl)furan-
2,5-dione (4-maleicanhydridoproton sponge or “MAPS”).
MAPS is a deep purple solid that exhibits positive solvato-
chromism in solution. It is a weaker base than Proton
Sponge. When protonated in solution, MAPS loses its color,
but the color change can be reversed by deprotonation with a
stronger base. MAPS thus acts as a colorimetric version of a
proton sponge.
SCHEME 1. Coupling of Proton Sponge and Bromomaleic
Anhydride
1,8-Dimethylaminonaphthalene, trademarked by Aldrich as
Proton Sponge, is a widely used base in organic and inorganic
chemistry. It is often chosen due to its high basicity (BHþ pKa =
12.34 in H2O1 and 18.62 in MeCN2) and slow uptake of protons.
It is also generally regarded as an innocent, non-nucleophilic,
and noncoordinating base relative to other amines. However, it
has been shown that Proton Sponge (PS) can act as a carbon
nucleophile in electrophilic aromatic substitution reactions.3
Due to the electron-donating nature of the amino groups,
Proton Sponge (like other anilines) is more reactive than
unsubstituted aromatics to typical electrophilic aromatic sub-
stitution reactions (nitration,4,5 Friedel-Crafts acylation,6
(7) Ryabtsova, O. V.; Pozharskii, A. F.; Ozeryanskii, V. A.; Vistorobskii,
N. V. Russ. Chem. Bull. 2001, 50, 854–859.
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Commun. 1993, 856–857.
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O. B. Russ. J. Org. Chem. 1997, 33, 565–566.
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(13) Fenske, D.; Becher, H. J. Chem. Ber. 1974, 107, 117–122.
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130–134.
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Chem. Commun. 1968, 723–724.
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Koppel, I. A. J. Org. Chem. 2005, 70, 1019–1028.
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1986, 51, 409–411.
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Chernyshev, A. I.; Goryaev, S. S.; Chikina, N. L. Zh. Org. Khim. 1983, 19,
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1552.
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Trans. 2 1990, 479–485.
DOI: 10.1021/jo101381r
r
Published on Web 09/21/2010
J. Org. Chem. 2010, 75, 6977–6979 6977
2010 American Chemical Society

Swor et al.
JOCNote
TABLE 1. Selected Structural Parameters of MAPS and PS
naphthalene-maleic
anhydride torsion
angle (deg)
N-N
molecule distance (A) torsion angle (deg)
C1-C9-C10-C4 sum of C-N-C
N1-C1-C9
(R) (deg)
N2-C8-C9
(β) (deg)
C1-C9-C8
(γ) (deg)
angles (deg)
Λ-MAPS
Δ-MAPS
PS
2.825
2.832
2.79
16.7
17.7
15.9
16.8
8.9
353.5
348.6
350.8
347.2
347.1
121.1
121.1
120.1
119.9
120.2
120.8
123.1
124.1
125.8
26.8
25.0
n/a
10.5
FIGURE 2. UV-vis spectra of MAPS in various solvents.
naphthalene ring of MAPS is more distorted than PS, with
internal (C1-C9-C10-C4) torsion angles of 15.9-17.7° vs
8.9-10.5° for PS. Thus, the N-N interatomic distances of
MAPS are slightly longer than PS at 2.825 and 2.832 A (vs
2.79 A for PS).17 On the basis of the torsion angle θ between
the nitrogen lone pairs and the naphthalene ring plane, the
four nitrogen lone pairs (in the two independent molecules)
are between 68% and 77% conjugated to the aromatic ring.
(These percentages were calculated using the equation
M = M0 cos2 θ, where M is the percent conjugation.16) This
is more conjugated than PS (59%) and is consistent with the
decreased basicity of MAPS compared to PS.18 (The de-
creased basicity is due to the electron-withdrawing maleic
anhydride group, which removes electron density from the
amine moieties, causing MAPS to be less basic than Proton
Sponge.) Finally, note that the geometry of each nitrogen is
slightly more planar than PS, with C-N-C angles totaling
347.2° to 353.5° (vs 347.1 for PS).
FIGURE 1. ORTEP plot of MAPS. The ellipsoids are drawn at 50%
probability, and the hydrogen atoms have been omitted for clarity.
Researchers following the procedure in the Experimental
Section for the synthesis of MAPS may wonder why the THF
solvent needs to be removed and then reintroduced following
the reaction. The PSHþBr- byproduct of the reaction is
insoluble in THF, which may lead some to conclude that
it can be removed by filtration at this point. However,
PSHþBr- does not quickly precipitate from the THF reac-
tion solution. When the solvent is evaporated under reduced
pressure, both products precipitate from solution, but only
MAPS redissolves in THF. Thus, from a practical standpoint,
it is easier to conduct the reaction in THF, evaporate off the
solvent, redissolve the products in THF, and filter than to wait
for the PSHþBr- byproduct to precipitate from solution.
The HBr byproduct of the reaction is almost entirely neu-
tralized by PS, suggesting that MAPS is a weaker base than PS.
To quantify this, the pKa of MAPS was determined by titration
with PSHþCl- in acetonitrile. The pKa was found to be 18.00,
slightly less basic than the parent proton sponge.
X-ray crystallography confirms the structure of MAPS
(Figure 1). The unit cell is monoclinic, with two inequivalent
molecules per unit cell. The naphthalene rings, and therefore
the dimethylamino groups, are twisted, with the first mole-
cule having a Λ (left-handed) twist and the second having a
Δ (right-handed) twist. Table 1 lists important structural para-
meters. The maleic anhydride ring is twisted 25° out of plane
from the naphthalene ring in one of the independent molecules
and 27° in the other.
In solution, MAPS exhibits solvatochromism, ranging from
orange in hexanes to purple in chloroform (Figure 2). Table 2
lists λmax values and the extinction coefficients in various sol-
vents. MAPS exhibits positive solvatochromism in halogen-free
30
solvents, with λmax correlating with Reichardt’s ET polarity
parameter.19 Positive solvatochromism has been observed for
other substituted proton sponges in their free base and/or
protonated forms.20-23 However, MAPS remains purple in
(17) Einspahr, H.; Robert, J. B.; Marsh, R. E.; Roberts, J. D. Acta
Crystallogr. B Struct. Crystallogr. Cryst. Chem. 1973, 29, 1611–1617.
(18) Korzhenevskaya, N. G.; Schroeder, G.; Brzezinski, B.; Rybachenko,
V. I. Russ. J. Org. Chem. 2001, 37, 1603–1610.
(19) Reichardt, C. Chem. Rev. 1994, 94, 2319–2358.
(20) Pozharskii, A. F.; Kuz’menko, V. V.; Aleksandrov, G. G.; Dmitrienko,
D. V. Russ. J. Org. Chem. 1995, 31, 525.
(21) Szemik-Hojniak, A.; Deperasinska, I.; Buma, W.; Balkowski, G.;
Pozharskii, A.; Vistorobskii, N.; Allonas, X. Chem. Phys. Lett. 2005, 401, 189–195.
(22) Pozharskii, A.; Vistorobskii, N.; Bardin, A.; Filatova, E. Russ. J.
Org. Chem. 2006, 42, 131–135.
The most important structural parameters of derivatized
proton sponges are the orientation of the dialkylamino
groups and the planarity of the aromatic system.16 The
(16) Pozharskii, A. F.; Ozeryanskii, V. A. Proton Sponges. In The
Chemistry of Anilines; John Wiley & Sons Ltd., 2007; Vol. 2, pp 931-1139.
(23) Mekh, M. A.; Pozharskii, A. F.; Ozeryanskii, V. A. Pol. J. Chem.
2009, 83, 1609–1621.
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Swor et al.
JOCNote
TABLE 2. UV-vis Spectral Data in Various Solvents
with various maleic anhydrides to form dyes.29 In addition,
maleic anhydrides can undergo condensation reactions with
primary amines to form maleimides. Work is ongoing in our
laboratory to synthesize solid-supported proton sponges,31,32
which could be used for easy column-purification of products
or as heterogeneous catalysts.
solvent
ET(30)
color
λmax (nm)
ε (M-1 cm-1
)
n-hexane
THF
t-butyl alcohol
acetonitrile
chloroform
31
37
43
46
35
orange
red
red
red
purple
480
504
516
521
536
83200
65200
53700
68500
70300
Experimental Section
SCHEME 2. Acid-Base Switchable Colorimetric Behavior in
Acetonitrile
X-ray Crystallography. X-ray diffraction intensities for MAPS
were collected at 173(2) K on a Bruker Apex CCD diffractometer
using Mo KR radiation λ = 0.71073 A.33 The space group was
determined on the basis of systematic absences. The absorption
correction was applied by SADABS.34 The structure was
solved by direct methods and Fourier techniques and refined
on F2 using full-matrix least-squares procedures. All non-H
atoms were refined with anisotropic thermal parameters. H
atoms were found from the residual map and refined with
isotropic thermal parameters. An absolute configuration could
not be determined because the compound is a weak anomalous
scatterer. All calculations were performed by the Bruker
SHELXTL (v. 6.10) package.35
chloroform (λmax=536 nm) and dichloromethane, even though
these solvents are less polar than acetonitrile (λmax=521 nm).
The apparently anomalous λmax values in these two solvents
may be due to their hydrogen-bonding ability, as indicated by
their large R values.24
The deep color of the neutral compound is presumably due to
the presence of conjugated electron-donor (amine) and electron-
acceptor (anhydride) groups on the molecule. The standard
interpretation25,26 is that excitation by visible light causes the
nitrogen lone pair to donate via conjugation to the maleic
anhydride moiety. Protonation of the nitrogen atoms should
prevent this mode of excitation. In fact, MAPS can be proto-
nated in wet acetonitrile by glacial acetic acid, resulting in a loss
of color. When PS is added to the acetonitrile solution of proto-
nated MAPS, MAPS is deprotonated and color is restored
(Scheme 2).
Synthesis of 4-Maleicanhydridoproton Sponge (MAPS). 1,8-
Bis(dimethylamino)naphthalene (954 mg, 0.45 mmol) in 10 mL of
THF was added to bromomaleic anhydride (393 mg, 0.22 mmol) in
5 mL of THF with stirring. Upon mixing, the reaction mixture
immediately turned deep red. After the mixture was stirred for 15
min, the solvent was removed under reduced pressure, and the
residue was redissolved in 50 mL of THF and filtered to remove
PSHBr. The solvent was removed under reduced pressure, yielding
1
a purple hygroscopic solid (645 mg, 94%): mp 116-127 °C; H
NMR (500 MHz, CDCl3, COSY, NOESY) δ 2.81 (s, 2CH3), 2.95
(s, 2CH3), 6.87(d, J= 8.65 Hz, H2), 6.88 (s, H14), 6.96 (d, J= 7.56
Hz, H7), 7.41 (t, J = 8.01 Hz, H6), 7.58 (d, J = 8.52 Hz, H5), 7.91
(d, J = 8.51 Hz, H3); 13C δ 43.2 (CH3), 43.3 (CH3), 109.4 (CH),
112.4 (CH), 115.3, 116.1 (CH), 121.6 (CH), 128.0 (CH), 131.8
(CH), 135.0, 136.2, 146.2, 151.7, 154.8, 165.3, 166.6; IR 2962.5 (m),
1824.4 (m), 1754.9 (s), 1660.0 (s), 801.8 (m). Anal. Calcd for
C18H18N2O3 1/3H2O: C, 68.34; H, 5.95; N, 8.86. Found: C,
3
68.42; H, 6.07; N, 8.95.
Although the reaction of PS and bromomaleic anhydride
was unanticipated, similar reactivity has previously been
seen with other tertiary anilines and activated alkenes. For
example, tertiary anilines are known to act as carbon nucleo-
philes toward tetracyanoethylene27 as well as halogenated
maleic anhydrides and maleimides.28,29 Note, however, that
this type of reactivity has not previously been observed for
Proton Sponge, even though it has been reacted before in the
presence of tetracyanoethylene.30
Acknowledgment. We thank Professors John Keana and
Michael Haley for fruitful discussions. This material is based
upon work supported by the National Science Foundation
under Grant Nos. DGE-0742540 and CHE-0809393.
Supporting Information Available: NMR spectra of
MAPS (1H, 13C, 1H-1H COSY, and 1H-1H NOESY), pKa
titration data, and crystallographic data tables. This material is
available free of charge via the Internet at http://pubs.acs.org.
The coupling of PS with BMA is not only a synthetic
curiosity but may allow for efficient functionalization of
proton sponges. Dimethylaniline has been functionalized
Note Added after ASAP Publication. The correct chemical
name, 1,8-bis(dimethylamino)naphthalene, was added to the
beginning of the last paragraph in the Experimental Section in
the version reposted ASAP September 24, 2010.
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