Basicity and solvatochromism of concave pyridines with extended π-systems in protic and nonprotic solvents

Article abstract of DOI:10.1002/ejoc.200300053

Arylalkyne substituents have been connected to the 4-positions of concave pyridines to give substituted concave pyridines 3, which possess absorption maxima above 300 nm in their UV spectra. Their protonation and their interaction with polar solvents have

Full text of DOI:10.1002/ejoc.200300053

FULL PAPER
Basicity and Solvatochromism of Concave Pyridines with Extended π-Systems
in Protic and Nonprotic Solvents[‡]
Ole Storm[a] and Ulrich Lüning*[a]
Keywords: Hydrogen bonds / Macrocycles / Nitrogen heterocycles / Sonogashira coupling / Solvatochromism
Arylalkyne substituents have been connected to the 4-posi-
tions of concave pyridines to give substituted concave pyrid-
ines 3, which possess absorption maxima above 300 nm in
their UV spectra. Their protonation and their interaction with
polar solvents have been studied. Firstly, with strong acids,
protonation occurs, and relative basicities (logKass) have
been determined. Substitution at the remote aryl ring influ-
a linear relation between logKass and the electron density of
the remote aryl ring. Secondly, concave pyridines 3 are cap-
able of ‘‘sensing’’ hydrogen bonds between their pyridine ni-
trogen atom and an alcohol. Shifts of the absorption maxima
to longer wavelengths are observed when certain quantities
of alcohol are added.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ences the basicity of the pyridine, and Hammett plots show Germany, 2003)
Introduction
The intensive study of supramolecular processes[1Ϫ3] in
recent decades has produced deep insights into molecular
recognition processes. One potential application of this
knowledge is in the construction of chemical sensors.[4Ϫ6]
The two key features of a sensor molecule are: (i) the recog-
nition process, and (ii) the production of a signal. In par-
ticular, sensors that produce optical signals are very useful,
because they can be applied for the detection of very tiny
amounts of analytes and, through the use of a (fluor-
escence) microscope, structural details of surfaces can be
investigated visually. If, for instance, different OH groups Ϫ
on cellulose or silica gel, to name some materials Ϫ are to
Scheme 1
1 (Scheme 1) are a class of concave reagents that mimic the
be analysed, the formation of a hydrogen bond between the
OH groups of the analyte and a hydrogen bond acceptor
could be used for recognition.
In order to construct a selective sensor for different OH
groups on these surfaces, the hydrogen bond recognition
site has to bind the OH groups differently, and it also has
to be connected with a reporter group that produces the
optical signal.
nature of enzymes[7] in the incorporation of a functional
group in a concave environment.[8] By use of concave pyri-
dines 1 as catalysts, alcohols can be acylated by ketenes[9]
with remarkable selectivities. The selective recognition of a
specific OH group of an alcohol,[10,11] including carbo-
hydrates,[12,13] by the concave pyridine is governed by the
shielding of the pyridine nitrogen atom.
The synthesis of concave pyridines 1 is well estab-
lished:[14,15,16] the bis(macrocyclic) concave pyridines are ac-
cessible from pyridine-2,6-dialdehydes through two sub-
sequent macrocyclizations. The chains Y and Z and the
substituent X in the 4-position can be widely varied, and
by use of halo-substituted concave pyridines 1, even an aryl-
alkyne-substituted concave pyridine Ϫ 3a Ϫ has been syn-
thesized by Sonogashira coupling with the terminal arylal-
kyne 2a.[17]
Concave pyridines 1 are known to interact differently
with varying OH groups. These bis(macrocyclic) pyridines
[‡]
Concave Reagents, 39. Part 38: Ref.[17]
[a]
Institut für Organische Chemie, Christian-Albrechts-
Universität zu Kiel,
Olshausenstr. 40, 24098 Kiel, Germany
Fax: (internat.) ϩ49-(0)431-8801558
E-mail: luening@oc.uni-kiel.de
Eur. J. Org. Chem. 2003, 3109Ϫ3116
DOI: 10.1002/ejoc.200300053
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3109

O. Storm, U. Lüning
FULL PAPER
The introduction of the additional conjugated π-system gen bonds between the pyridine nitrogen atom and the OH
in 3a results in a long-wave absorption band in the UV/Vis groups of alcohols. There is, however, a competing reaction
spectrum, which may be used to gain deeper insight into between pyridines and acidic hydrogen atoms: protonation,
the mechanism of the catalysis discussed above.[17,18] In this which also results in changes in the UV spectra. The step-
work we describe the synthesis of a family of arylalkyne- wise transfer of a hydrogen atom from an alcohol to a pyri-
substituted concave pyridines 3aϪf and study the pro- dine is shown in Scheme 3.
tonation of and hydrogen bond formation by the pyridine
nitrogen atoms in 3.
Results and Discussion
The successful[17] coupling of the iodo-substituted bi-
macrocyclic concave pyridine 1a with phenylacetylene
opens a general route to arylalkynyl-substituted concave
pyridines 3 (Scheme 2). The iodo-bis(macrocycle) 1a was
Scheme 3
therefore coupled with several arylalkynes 2[19Ϫ22] to give
new 4-substituted concave pyridines 3. For comparison, the
4-iodopyridine-2,6-dicarboxylate 4[17,23] was also coupled
In order to be able to distinguish between the UV
with different arylalkynes 2, resulting in the formation of 4- changes caused by protonation and those produced by the
substituted pyridinediesters 5. Most of the terminal acety- formation of hydrogen bonds, the protonation of all pyri-
lenes 2 had to be synthesized; a Sonogashira reaction was dines 3 and 5 had been investigated first. Trifluoroacetic
also used for this purpose.[24,25] Palladium-catalysed coup- acid was chosen for this purpose, as a relatively strong acid,
ling of trimethylsilylacetylene and the respective iodoarene soluble in dichloromethane and causing no significant ab-
gave the terminal arylethynes 2 in good yields after depro- sorption in the UV, and the UV changes observed during
tection with a base.
titrations of the pyridines with this acid were recorded. Fig-
The new concave pyridines 3 and all diesters 5 were ure 1 shows the protonation of 3a by trifluoroacetic acid as
characterized spectroscopically, although some of the esters an example, and Tables 1 and 2 list the absorption maxima
5 had already been described in the literature, some of and absorption coefficients for all pyridines 3 and 5 in pro-
them, though, with only marginal characterization.[24,25] tonated and unprotonated forms. The observation of clear
Because of the amide bridgeheads, the new 4-substituted isosbestic points argues for the existence of only two species
concave pyridines 3 exist as mixtures of conformers, as does in these titrations of the pyridines 3 and 5 with a strong
the starting material 1a.[14,17]
acid. For reaction partners with less acidic hydrogen atoms,
As explained in the Introduction, the arylalkyne residue a third kind of UV spectrum, different from the neutral
was attached to the concave pyridine with the goal of al- base and different from the protonated species, is to be ex-
lowing photometric investigation of the formation of hydro- pected (see below).
Scheme 2
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Basicity and Solvatochromism of Concave Pyridines with Extended π-Systems
FULL PAPER
Table 2. Maxima of absorption of dimethyl phenylethynylpyridine-
2,6-dicarboxylates 5aϪf in dichloromethane. The extinction coef-
ficients are given in 1000 cm2·molϪ1
λmax [nm]
εmax
logKass
5a[a]
298
313
387.5
396
332.5
313.5
357
38500
40000
47000
59600
46100
48700
46300
0.81
5b
5c
5d
5e
5f
2.41
3.57
1.24
0.69
2.06
[a]
Two maxima have been found.
Figure 1. UV spectra from the titration of the concave phenylethy-
nyl pyridine 3a with trifluoroacetic acid in dry dichloromethane
(concentration of 3a: 4.95·10Ϫ6 mol·LϪ1); trifluoroacetic acid was
added stepwise but not constantly with the same amount; the final
concentration was 3.2·10Ϫ4 mol·LϪ1
The basicities of all new arylalkynyl-substituted pyridines
3 and 5 were quantified by photometric titrations. Both
classes 3 and 5 were investigated in dichloromethane, while
the basicities of the concave pyridines 3 were also deter-
mined in methanol. The analogous experiments in meth-
anol could not be interpreted for the diesters 5, due to their
reduced basicities. Even for the concave pyridines 3, the ti-
trations in methanol should not be overinterpreted. When
trifluoroacetic acid was added to the methanol solutions of
3, the first droplets of acid were buffered, resulting in no
change in absorption at the beginning of the titration. With
larger amounts of acid added, a normal titration curve
could be observed. Although all solvents were purified tho-
roughly, we cannot rule out that impurities may be respon-
sible for this ‘‘buffer effect’’. These titration data have there-
fore been analysed in two ways: with and without correction
for the buffer capacity {see Equation (1) (from ref.[18] ignor-
ing buffer capacity) and Equation (2) (considering buffer
capacity B). A ϭ absorption, HA ϭ trifluoroacetic acid,
S ϭ pyridine substrate, Kass ϭ [S·HA]/[S][HA], index 0 ϭ
total initial concentration, B ϭ buffer capacity, determined
empirically from the titration curve}. Two sets of data
therefore exist for the titrations in methanol, but both sug-
gest the same conclusions (see Figure 2).
Figure 2. Hammett plot of the relative basicities (logKass) of the
concave pyridines 3a, 3b, 3d, and 3e in dichloromethane (black
square) and in methanol (black diamond and black triangel), ver-
sus the substituents’ σϩ constants; because methanol is protonable
itself and buffers the added trifluoroacetic acid, the titrations in
methanol result in two sets of log Kass values depending on the
formula used for their calculation [Equation (1), ignoring buffer
capacity: black diamond, and Equation (2), considering buffer
capacity: black triangel)
A ϭ (AS ϩ ASHA·Kass·[HA]0)/(1 ϩ Kass·[HA]0)
(1)
(2)
A ϭ {AS ϩ ASHA·Kass·([HA]0 Ϫ B)}/{1 ϩ Kass·([HA]0 Ϫ B)}
Relative basicities (logKass) were calculated by use of
these equations; all logKass results are listed in Tables 1 and
Table 1. Maxima of absorption of unsubstituted 4-(phenylethynyl)pyridine[26] (9) (in cyclohexane) and concave phenylethynylpyridines
3aϪf (unprotonated and protonated) in dichloromethane and methanol; the wavelengths are given in nm; the extinction coefficients are
given in 1000 cm2·molϪ1 (n. d.: not determinable)
CH2Cl2
unprotonated
MeOH
unprotonated
protonated
protonated
λmax1
εmax1 λmax2 εmax2 λmax εmax
logKass λmax1 εmax1 λmax2 εmax2 λmax εmax
logKass logKass
buffer
with B without B capacity B
9
281
3a 286
27500 298.8 25000
37100 303.5 33600 338.5 28500 4.36
284.5 43400 301
39400 305/ 27400/ 3.21
2.99
5.18·10Ϫ4
331.5 31100
3b 360
3d 303
3e 315
48300 Ϫ 457.5 53800 4.59
Ϫ
359
47200 Ϫ
Ϫ
441.5 46500 4.11
3.69
3.13
2.37
1.56·10Ϫ4
4.66·10Ϫ4
0
34700 318.5 33900 371.5 39700 4.46
304.5 44800 313.5 44500 362
38400 3.43
50100 2.37
44100 Ϫ
Ϫ
320/ 49300/ 4.06
308.5 44200 Ϫ
331 30200 Ϫ
Ϫ
Ϫ
317
337
24000 406
46700
3f 325
24600 339
36200 4.39
396.5 35300 3.53
n. d.
14.4·10Ϫ4
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O. Storm, U. Lüning
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2. In all cases, the amino-substituted compounds 3b, 5b,
and 5c are the most basic pyridines, while the nitro-substi-
tuted pyridines 3e and 5e possess the smallest basicities. Al-
though only the remote phenyl ring is substituted, the sub-
stituents at this aryl ring do have an influence on the ba-
sicity of the pyridine nitrogen atom.
The influence of substitution at the 4-position of a pyri-
dine ring on its basicity is well documented in the
literature,[26Ϫ28] and Hammett ρ values have been calculated
for several classes of substituted pyridines. Table 3 com-
pares these literature or derived ρ values for the protonation
of the pyridines 6Ϫ9 (Scheme 4) with the ρ values calcu-
lated from the logKass values of the concave pyridines 1 and
3. Although only a few data points could be determined for
3, the Hammett plots fit nicely, arguing for protonation
only of the pyridine nitrogen atom (see Figure 2).
Figure 3. Absorption maxima of the concave pyridine 3a (12.3 µ)
in dichloromethane (X ϭ 0) with gradual addition of different sol-
vents (X ϭ 0 Ǟ X ϭ 1): acetonitrile: open triangle, methanol: black
square, 2-propanol: open diamond, trifluoroethanol: ؋
Table 3. Comparison of the ρ-values for the protonation of concave
phenylethynyl pyridines 3 with the ρ-values for the protonation of
4-substituted pyridines 6, 4-aryl pyridines 7, 4-styryl pyridines 8,
4-phenylethynyl pyridines 9, and concave pyridines 1bϪd. The ρ
values for 6,[26] 7,[27] 8,[28] and 9[28] were taken from the literature,
the ρ value for 1[29] was determined by use of σϩ [30,31] values
Figure 3 shows the shifts of the absorption maximum at
327 nm for 3a in mixtures of different solvents.
The addition of a more polar solvent to a dichlorometh-
ane solution of 3a always has an influence on the position
of the absorption maximum. Thus, the change in solvent
polarity from 0 to 100% of acetonitrile in a dichlorometh-
ane/acetonitrile mixture results in a linear shift from
326.8 nm to 324.0 nm. When alcohols are mixed with di-
chloromethane, the absorption maxima also change with in-
creasing content of the alcohol, but not in a linear way.
Also, with alcohols that are more polar than dichlorometh-
ane, the final absorption wavelength at X ϭ 1 is smaller in
neat alcohol than in neat dichloromethane (X ϭ 0). When
only a small amount of alcohol is added (e.g., X ϭ 0.2),
however, the wavelengths of the absorption maxima are
even larger than in neat dichloromethane.
Pyridine
Solvent
ρ
Pyridines 6
4-Arylpyridines 7
4-Styrylpyridines 8
4-(Phenylethynyl)pyridines 9
Concave pyridines 1bϪd
Concave sensors 3
Concave sensors 3
H2O
Ϫ5.71Ϯ0.30
Ϫ0.97Ϯ0.03
Ϫ0.85Ϯ0.07
Ϫ0.44Ϯ0.04
Ϫ2.10Ϯ0.18
Ϫ0.66Ϯ0.10
Ϫ0.20Ϯ0.04
H2O/EtOH (98:2)
H2O/EtOH (98:2)
H2O/EtOH (98:2)
EtOH
MeOH
CHCl2
This behaviour may be explained by two effects: (i) a
change in solvent polarity influencing the whole molecule
and resulting in a shift to shorter wavelengths, as can be
observed with acetonitrile, and (ii) the formation of hydro-
gen bonds between alcohols and the pyridine. However, the
higher polarity of alcohols than of dichloromethane also
results in a general shift as observed with acetonitrile. The
results in Figure 3 may be discussed and interpreted in the
following way: there is potential for the formation of hydro-
gen bonds between the pyridine nitrogen atom and the al-
Scheme 4
With the UV spectra for protonated and unprotonated cohol, which results in a shift of the absorption maxima to
concave pyridines 3 now known, additional experiments in longer wavelengths. This shift can already be observed at
the presence of acidic molecules could then be carried out small mixture ratios X, because the formation of hydrogen
to determine whether compounds 3 could be used to study bonds is strong in relation to solvation only.[1Ϫ3] When the
the formation of hydrogen bonds. When the UV spectra of percentage of alcohol is raised considerably, however, the
the unprotonated concave pyridines 3 and 5 were compared overall solvation of the concave pyridine 3a by the polar
in different solvents (e.g., dichloromethane and methanol), solvent also becomes recognizable and gradually gives rise
solvatochromism was observed for the concave pyridines 3. to absorption maxima at shorter wavelengths, just as ob-
Relatively broad maxima were observed for most of the served with the polar solvent acetonitrile, which, in contrast
concave pyridines 3, with the sharpest signal being shown to the alcohols, can only solvate the whole molecule, and
by the parent phenylethynyl-substituted bimacrocycle 3a. cannot form a hydrogen bond.
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Basicity and Solvatochromism of Concave Pyridines with Extended π-Systems
FULL PAPER
MS spectra were recorded on a Finnegan MAT 8230 instrument.
Elemental analyses were carried out with a VarioEl machine (Ele-
mentaranalysensysteme GmbH). UV spectra were recorded with
PerkinϪElmer Lambda 14. The relative basicities were determined
as described.[15,16,33]
This assumption is supported by the fact that the shifts
of the absorption maxima to longer wavelengths are larger
for trifluoroethanol than for methanol or 2-propanol. Be-
cause of the fluoro substitution, trifluoroethanol is more
acidic than methanol or 2-propanol[32] and should therefore
form stronger hydrogen bonds.
General Procedure for the Sonogashira Couplings
The iodoarene (1 or 3, ca. 3.2 mmol), Pd(PPh3)2Cl2 (0.06 mmol)
and copper() iodide (0.33 mmol), dissolved in a mixture of dry
THF (15 mL) and dry triethylamine (15 mL), were subjected to
ultrasound treatment under argon atmosphere for 5 min. The ter-
minal alkyne 2aϪf (3.9 mmol), dissolved in dry THF (5 mL), was
added by syringe. The reaction mixture was stirred for 3.5 to 4 h
at 40 to 60 °C. The solvents were removed in vacuo, and the residue
was dissolved in chloroform (30 mL) and extracted four times with
water (10 mL each). The organic layer was separated and dried,
and the solvent was removed in vacuo. The residue was purified
by chromatography.
Conclusion
Concave pyridines have been connected to arylalkyne
substituents through their 4-positions to give substituted
concave pyridines 3, which possess absorption maxima
above 300 nm in their UV spectra. Their protonation and
their interactions with polar solvents were studied. Three
different processes could be observed:
(i) Proton transfer from an acid to the pyridine nitrogen
atom results in UV spectra with large shifts in their absorp-
tion maxima. The existence of isosbestic points suggests a
simple protonation/deprotonation equilibrium, for which
relative basicities (logKass) were determined. Substitution at
the remote aryl ring influences the basicity of the pyridine,
and Hammett plots show a linear relationship between log-
Kass and the electron density on the remote aryl ring.
(ii) Polar solvents may also shift the absorption maxima
to longer wavelength, but the shift is considerably smaller
than that observed by protonation.
(iii) When the polar solvent is able to form hydrogen
bonds to the pyridine nitrogen atom, shifts to longer wave-
lengths were observed when a certain quantity of alcohol
(10Ϫ30%) was added. The more acidic the alcohol, the
larger the observed shift. Unfortunately, alcohols may also
cause a shift to shorter wavelengths by polar solvation,
which dominates when the percentage of alcohol is large.
Overall, concave pyridines 3 are capable of sensing hydro-
gen bonds between their pyridine nitrogen atom and an al-
cohol, but the sensitivity of the system is still low. The new
concave pyridines 3 therefore require further improvement.
Unless stated otherwise, the amounts of solvent were chosen as
listed above.
29-[4-(Dimethylamino)phenylethynyl]-1,14,33-triaza-17,20,23-
trioxatricyclo[12.11.7.127,31]tritriaconta-27(33),28,30-triene-2,13-
dione (3b): Compound 1a (883 mg, 1.43 mmol), Pd(PPh3)2Cl2
(24 mg, 34 µmol), and CuI (35 mg, 0.18 mmol) in THF (7.5 mL)
and triethylamine (7.5 mL) were allowed to react with 4-(dimeth-
ylamino)ethynylbenzene (2b, 274 mg, 1.89 mmol) for 4 h at 60 °C
according to the General Procedure, Rf (dichloromethane/ethanol,
10:1) ϭ 0.35 (yellow fluorescence). Yield: 683 mg (75%). IR (KBr):
ν˜ ϭ 2924 (m, aliph. CH), 2853 (m), 2198 (m, CϵC), 1642 (s, CϭO),
1
1591 (s, arom. CϭC), 1121 (m, CϪO) cmϪ1. H NMR (300 MHz,
CDCl3): δ ϭ 0.90Ϫ2.55 (m, ca. 20 H, CH2), 3.03 [s, 6 H, N(CH3)2],
3.20Ϫ4.00 (m, ca. 16 H, OCH2), 4.60Ϫ5.30 (m, 4 H, PyCH2), 6.68
(d, 3J ϭ 9.1 Hz, 2 H, Ar-2,6-H), 6.99 (d, 4J ϭ 1.25 Hz, 0.34 H, ZE,
4
Py-H), 7.08 (s, 1.40 H, ZZ, Py-H), 7.24 (d, J ϭ 1.25 Hz, 0.26 H,
ZE, Py-H), 7.45 (d, 3J ϭ 9.1 Hz, 2 H, Ar-3,5-H) ppm; ratio of
conformers ZZ/ZE/EE Ͻ70:Ͻ30:not assignable. 13C NMR
(75 MHz, CDCl3):[34] δ ϭ 24.38 (t, CH2CH2CϭO), 26.93Ϫ29.50
(many t, CH2CH2CH2), 32.09 (t, CH2CϭO), 40.12 [q, N(CH3)2],
47.95 (t, NCH2CH2), 55.40 (t, NCH2Py), 70.53Ϫ71.13 (many t,
OCH2), 85.46 (s, Ar-CϵC), 95.50 (s, Py-CϵC), 108.15 (s, Ar-C1),
111.68 (d, Ar-C3, Ar-C5), 119.46 (d, Py-C3, Py-C5), 128.58 (s, Py-
C4), 132.13 (d, Ar-C2, Ar-C6), 150.70 (s, Ar-C4), 158.19 (s, Py-C2,
Py-C6), 174.68 (s, CϭO) ppm. EI-MS (70 eV): m/z (%) ϭ 632 (71)
[Mϩ], 602 (48), 290 (39), 250 (100). CI-MS (isobutane): m/z (%) ϭ
633 (100) [Mϩ ϩ1], 69 (73). C37H52N4O5 (632.83): calcd. C 70.22,
H 8.28, N 8.85. C37H52N4O5·0.2CH3CH2OH·0.3CH2Cl2: calcd. C
67.83, H 8.12, N 8.38; found. C 67.98, H 8.21, N 7.99.
Experimental Section
General Remarks: The following chemicals were obtained commer-
cially and were used without further purification: bis(triphenyl-
phosphanyl)palladium() dichloride (Fluka), copper() iodide
(Fluka), phenylacetylene (2a, Janssen). 29-Iodo-1,14,33-triaza- 29-(4-Methoxyphenylethynyl)-1,14,33-triaza-17,20,23-trioxatri-
17,20,23-trioxatricyclo[12.11.7.127,31]tritriaconta-27(33),28,30- cyclo[12.11.7.127,31]tritriaconta-27(33),28,30-triene-2,13-dione (3d):
triene-2,13-dione (1a)[17] and dimethyl 4-iodopyridine-2,6-dicarb-
oxylate (4)[17] were prepared by literature procedures. The terminal
Compound 1a (889 mg, 1.44 mmol), Pd(PPh3)2Cl2 (24 mg, 34
µmol), and CuI (35 mg, 0.18 mmol) in THF (7.5 mL) and triethyl-
alkynes 2b,[19] 2c,[20] 2d,[20] 2e,[21] and 2f[22] were prepared from the amine (7.5 mL) were allowed to react with 4-methoxyethynylben-
iodoarenes by Sonogashira coupling according to the cited litera-
ture. The synthesis of 3a has already been described.[17] THF was General Procedure, Rf (dichloromethane/ethanol, 10:1) ϭ 0.43 (yel-
dried by distillation from lithium aluminium hydride, and dry tri- low fluorescence). Yield: 692 mg (78%). IR (dissolved in dichloro-
ethylamine was prepared by azeotropic distillation (only the dry methane): ν˜ ϭ 2926 (s, CH2), 2209 (w, CϵC), 1646 (s, CϭO), 1594
zene (2d, 258 mg, 1.95 mmol) for 4 h at 40 °C according to the
middle fraction was used). The solvents for spectroscopic measure-
(s, arom. CϭC), 1511 (s), 1251 (s, CϪO), 834 (w, Ar-C-H) cmϪ1
1H NMR (300 MHz, CDCl3): δ ϭ 0.90Ϫ2.55 (m, ca. 20 H, CH2),
.
ments were dried before use. Column chromatography was carried
out on silica gel. 1H NMR and 13C spectra were recorded with 3.20Ϫ4.40 (m, ca. 19 H, OCH3, OCH2), 4.00Ϫ5.30 (m, 4 H,
Bruker AC 200, Bruker AM 300 or Bruker DRX 500
(200Ϫ500 MHz and 50Ϫ125 MHz, respectively) instruments. IR
spectra were recorded with a PerkinϪElmer 1600 Series machine.
PyCH2), 6.93 (d, 3J ϭ 9.0 Hz, 2 H, Ar-2,6-H), 7.01 (d, 4J ϭ 1.1 Hz,
0.32 H, ZE, Py-H), 7.11 (s, 1.42 H, ZZ, Py-H), 7.26 (d, 4J ϭ
3
1.1 Hz, 0.26 H, ZE, Py-H), 7.52 (d, J ϭ 9.0 Hz, 2 H, Ar-3,5-H)
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O. Storm, U. Lüning
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ppm; ratio of conformers ZZ/ZE/EE Ͻ71:Ͻ39:not assignable. 13C
CH2CH2CH2), 32.16 (t, CH2CϭO), 47.76 (t, NCH2CH2), 55.22 (q,
NMR (75 MHz, CDCl3):[34]
δ ϭ 24.89 (t, CH2CH2CϭO), Ar-4-OCH3), 55.87 (q, Ar-2,6-OCH3), 58.01 (t, NCH2Py),
26.93Ϫ29.43 (many t, CH2CH2CH2), 32.16 (t, CH2CϭO), 48.01 70.60Ϫ72.62 (many t, OCH3), 87.94 (s, Ar-CϵC), 90.21 (d, Ar-C3,
(t, NCH2CH2), 55.38 (q, OCH3), 55.43 (t, NCH2Py), 70.71Ϫ71.14 Ar-C5), 93.80 (s, Py-CϵC), 106.65 (s, Ar-C1), 119.66 (d, Py-C3,
(many t, OCH2), 85.80 (s, Ar-CϵC), 94.48 (s, Py-CϵC), 113.89 (s, Py-C5), 133.71 (s, Py-C4), 157.85 (s, Py-C2, Py-C6), 159.04 (s, Ar-
Ar-C1), 114.20 (d, Ar-C3, Ar-C5), 119.25 (d, Py-C3, Py-C5), C4), 162.49 (s, Ar-C2, Ar-C6), 174.647 (s, CϭO) ppm. EI-MS
128.43 (s, Py-C4), 133.06 (d, Ar-C2, Ar-C6), 158.42 (s, Py-C2, Py-
(70 eV): m/z (%) ϭ 680 (100) [Mϩ], 650 (32), 297 (66). CI-MS
C6), 160.45 (s, Ar-C4), 174.68 (s, CϭO) ppm. EI-MS (70 eV): m/z (isobutane): m/z (%) ϭ 681 (100) [Mϩ ϩ1], 490 (92).
(%) ϭ 619 (100) [Mϩ], 523 (65), 489 (62), 237 (59), 69 (39). CI-
Dimethyl 4-(Phenylethynyl)pyridine-2,6-dicarboxylate (5a): Di-
MS (isobutane): m/z (%) ϭ 620 (100) [Mϩ ϩ1], 279 (53), 99 (25).
methyl 4-iodopyridine-2,6-dicarboxylate (4, 1000 mg, 3.12 mmol),
C36H49N3O6 (619.79): calcd.
C
69.76,
H
7.97,
N 6.78.
Pd(PPh3)2Cl2 (40 mg, 0.06 mmol), and CuI (67 mg, 0.35 mmol)
were allowed to react with phenylacetylene (2a, 380 mg, 3.73 mmol)
for 3.5 h at 50 °C according to the General Procedure, Rf (pen-
tane) ϭ 0.05. Yield: 436 mg (48%, 84%[24]). m.p. 147 °C (153Ϫ154
°C[24]). IR (film): ν˜ ϭ 2214 (w, CϵC), 1752 (s, CϭO), 1720 (s, Cϭ
O), 1602 (m, arom. CϭC), 1442 (s), 1259 (s, CϪO) cmϪ1. 1H NMR
(200 MHz, CDCl3): δ ϭ 4.04 (s, 6 H, OCH3), 7.4Ϫ7.6 (m, 5 H, Ar-
H), 8.37 (s, 2 H, Py-H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ
53.18 (q, OCH3), 85.29 (s, Ar-CϵC), 96.80 (s, Py-CϵC), 121.28 (s,
Ar-C1), 128.53 (d, Ar-C4), 129.53 (d, Ar-C3, Ar-C5), 129.74 (d,
Ar-C2, Ar-C6), 132.00 (d, Py-C3, Py-C5), 134.37 (s, Py-C4), 148.38
(s, Py-C2, Py-C6), 164.63 (s, CϭO) ppm. EI-MS (70 eV), m/z (%) ϭ
295 (12) [Mϩ], 237 (100), 205 (44), 177 (34). CI-MS (isobutane),
m/z (%) ϭ 296 (100) [Mϩ ϩ1]. HRMS (C17H13NO4): calcd.
295.08447; found 295.08420; (C1613CH13NO4): calcd. 296.08780;
found 296.08770. C17H13NO4: (295.30): calcd. C 69.15, H 4.44, N
4.74. C17H13NO4·0.25 CH3OH (303.30): calcd. C 68.31, H 4.65, N
4.62; found C 68.35, H 4.42, N 4.66.
C36H49N3O6·CH3CH2OH·0.2CH2Cl2: calcd. C 67.19, H 8.18, N
6.15; found. C 67.06, H 8.51, N 6.09.
29-(4-Nitrophenylethynyl)-1,14,33-triaza-17,20,23-trioxatri-
cyclo[12.11.7.127,31]tritriaconta-27(33),28,30-triene-2,13-dione (3e):
Compound 1a (440 mg, 0.72 mmol), Pd(PPh3)2Cl2 (12 mg, 17
µmol), and CuI (17 mg, 0.089 mmol) in THF (7.5 mL) and triethyl-
amine (7.5 mL) were allowed to react with 4-nitroethynylbenzene
(2e, 149 mg, 1.03 mmol) for 6 h at 60 °C according to the General
Procedure, Rf (TLC, dichloromethane) ϭ 0.06, in the purification
step, the column was finally washed with dichloromethane/ethanol
(1:1). Yield: 370 mg (81%). IR (dissolved in dichloromethane): ν˜ ϭ
2926 (s, CH2), 1647 (s, CϭO), 1599 (m, arom. CϭC), 1519 (m),
1343 (s, CϪO), 856 (m, ArϪCϪH) cmϪ1 1H NMR (300 MHz,
.
CDCl3): δ ϭ 0.90Ϫ2.55 (m, ca. 20 H, CH2), 3.20Ϫ4.40 (m, ca. 16
4
H, OCH2), 4.00Ϫ5.30 (m, 4 H, PyCH2), 7.06 (d, J ϭ 1.2 Hz, 0.38
H, ZE, Py-H), 7.16 (s, 1.18 H, ZZ, Py-H), 7.32 (d, 4J ϭ 1.2 Hz,
0.36 H, ZE, Py-H), 7.56 (s, 0.08 H, EE, Py-H), 7.73 (d, 3J ϭ 9.0 Hz,
2 H, Ar-3,5-H), 8.28 (d, 3J ϭ 9.0 Hz, 2 H, Ar-2,6-H) ppm; ratio of
conformers ZZ/ZE/EE 59:37:4. 13C NMR (75 MHz, CDCl3):[34]
δ ϭ 24.87 (t, CH2CH2CϭO), 26.90Ϫ29.46 (many t, CH2CH2CH2),
32.12 (t, CH2CϭO), 48.11 (t, NCH2CH2), 55.48 (t, NCH2Py),
70.60Ϫ72.62 (many t, OCH2), 91.33 (s, Ar-CϵC), 108.54 (s, Py-
CϵC), 112.83 (s, Ar-C1), 119.96 (d, Ar-C3, Ar-C5), 123.75 (d, Py-
C3, Py-C5), 131.25 (s, Py-C4), 132.70 (d, Ar-C2, Ar-C6), 147.66 (s,
Ar-C4), 158.89 (s, Py-C2, Py-C6), 174.65 (s, CϭO) ppm. EI-MS
(70 eV): m/z (%) ϭ 634 (30) [Mϩ], 523 (100), 489 (70), 277 (53),
149 (70). CI-MS (isobutane): m/z (%) ϭ 635 (61) [Mϩ ϩ1], 524
(63), 279 (70), 71 (100). HRMS (C35H46N4O7): calcd. 634.33667;
found 634.33620; (C3413CH46N4O7): calcd. 635.34003; found
635.34000. C35H46N4O7 (634.76): calcd. C 66.23, H 7.30, N 8.83.
C35H46N4O7·0.2CH2Cl2 (668.74): calcd. C 63.58, H 7.05, N 8.38;
found C 63.57, H 7.16, N 8.02.
Dimethyl 4-[4-(Dimethylamino)phenylethynyl]pyridine-2,6-dicarb-
oxylate (5b): Dimethyl 4-iodopyridine-2,6-dicarboxylate (4,
1000 mg, 3.12 mmol), Pd(PPh3)2Cl2 (40 mg, 0.06 mmol) and CuI
(65 mg, 0.34 mmol) were allowed to react with 4-(dimethylamino)-
ethynylbenzene (2b, 538 mg, 3.71 mmol) for 3.5 h at 50 °C accord-
ing to the General Procedure, Rf (diethyl ether) ϭ 0.32. Yield:
1086 mg (quant., 48%[25]). m.p. 192 °C (215Ϫ216 °C[25]). IR (Film):
ν˜ ϭ 2956 (w, CH2), 2203 (m, CϵC), 1757 (s, CϭO), 1715 (s, Cϭ
O), 1593 (s, arom. CϭC), 1443 (s), 1244 (s, CϪO), 975 (m,
ArϪCϪH), 814 (m, ArϪCϪH) cmϪ1 1H NMR (200 MHz,
.
CDCl3): δ ϭ 3.03 (s, 6 H, NCH3), 4.03 (s, 6 H, OCH3), 6.66 (d,
3J ϭ 9.0 Hz, 2 H, Ar-2,6-H), 7.45 (d, 3J ϭ 9.0 Hz, 2 H, Ar-3,5-H),
8.30 (s, 2 H, Py-H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 39.96
(q, NCH3), 53.11 (q, OCH3), 84.49 (s, Ar-CϵC), 99.64 (s, Py-
CϵC), 107.44 (s, Py-C4), 111.58 (d, Ar-C3, Ar-C5), 129.03 (d, Ar-
C2, Ar-C6), 133.49 (d, Py-C3, Py-C5), 135.39 (s, Ar-C1), 148.16
(s, Py-C2, Py-C6), 150.96 (s, Ar-C4), 164.87(s, CϭO) ppm. EI-MS
(70 eV): m/z (%) ϭ 338 (100) [Mϩ], 220 (21). CI-MS (isobutane):
m/z (%) ϭ 339 (100) [Mϩ ϩ1]. HRMS (C19H18N2O4): calcd.
338.12665; found 338.12660; (C1813CH18N2O4): calcd. 339.13000;
found 339.12980. C19H18N2O4 (338.36): calcd. C 67.45, H 5.36, N
8.28. C19H18N2O4·CH3OH (370.40): calcd. C 64.85, H 5.99, N 7.57;
found C 64.91, H 5.41, N 7.91.
29-(2,4,6-Trimethoxyphenylethynyl)-1,14,33-triaza-17,20,23-tri-
oxatricyclo[12.11.7.127,31]tritriaconta-27(33),28,30-triene-2,13-dione
(3f): Compound 1a (980 mg, 1.59 mmol), Pd(PPh3)2Cl2 (44.5 mg,
60.8 µmol), and CuI (36.7 mg, 0.193 mmol) in THF (7.5 mL) and
triethylamine (7.5 mL) were allowed to react with 2,4,6-trimethoxy-
ethynylbenzene (2f, 370 mg, 1.03 mmol) for 4 h at 60 °C according
to the General Procedure, Rf (dichloromethane/ethanol, 10:1) ϭ
0.45. The product contains notable amounts of starting material
1a; the starting material signals are not listed below. Therefore, no
correct elementary analysis could be obtained. Yield: 620 mg (max.
Dimethyl
4-[4-(Diethylamino)phenylethynyl]pyridine-2,6-dicarb-
oxylate (5c): Dimethyl 4-iodopyridine-2,6-dicarboxylate (4,
88%). IR (KBr): ν˜ ϭ 2926 (s, CH2), 2854 (s, CH), 2203 (m, CϵC), 1000 mg, 3.12 mmol), Pd(PPh3)2Cl2 (42 mg, 0.06 mmol), and CuI
1645 (s, CϭO), 1592 (s, arom. CϭC), 1463 (s), 1340 (s), 1128 (s), (61 mg, 0.31 mmol) were allowed to react with 4-(diethylamino)-
813 (m), 733 (m) cmϪ1 1H NMR (300 MHz, CDCl3): δ ϭ ethynylbenzene (2c, 640 mg, 3.70 mmol) for 3.5 h at 60 °C according
.
0.90Ϫ2.55 (m, ca. 20 H, CH2), 3.20Ϫ4.40 (m, ca. 25 H, OCH3, to the General Procedure, Rf (diethyl ether) ϭ 0.49. Yield: 705 mg
OCH2), 4.00Ϫ5.30 (m, 4 H, PyCH2), 6.13 (s, 2 H, Py-3-H), 7.05 (62%). m.p. 119 °C. IR (KBr): ν˜ ϭ 2970 (m, CH2), 2202 (m, CϵC),
(d, 4J ϭ 1.2 Hz, 0.38 H, ZE, Py-H), 7.13 (s, 1.2 H, ZZ, Py-H), 7.30 1719 (s, CϭO), 1591 (s, arom CϭC), 1520 (s), 1372 (s), 1263 (s,
(d, 4J ϭ 1.2 Hz, 0.32 H, ZE, Py-H), 7.47 (s, 0.11 H, EE, Py-H)
CϪO), 1204 (s, CϪO), 781 (m, ArϪCϪH) cmϪ1 1H NMR
.
ppm; ratio of conformers ZZ/ZE/EE 60:35:5. 13C NMR (75 MHz, (200 MHz, CDCl3): δ ϭ 1.19 (t, 3J ϭ 7 Hz, 6 H, CH2CH3), 3.40
CDCl3):[34] δ ϭ 24.23 (t, CH2CH2CϭO), 26.71Ϫ28.34 (many t, (q, J ϭ 7 Hz, 4 H, CH2CH3), 4.03 (s, 6 H, OCH3), 6.64 (d, J ϭ
3
3
3114  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 3109Ϫ3116

Basicity and Solvatochromism of Concave Pyridines with Extended π-Systems
FULL PAPER
3
9 Hz, 2 H, Ar-2,6-H), 7.42 (d, J ϭ 9 Hz, 2 H, Ar-3,5-H), 8.67 (s,
6 H, COOCH3), 6.13 (s, 2 H, Ar-H), 8.38 (s, 2 H, Py-H) ppm. 13C
2 H, Py-H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 12.46 (q, NMR (75 MHz, CDCl3): δ ϭ 53.26 (q, COOCH3), 55.53 (q, Ar-
CH2CH3), 44.34 (t, NCH2), 53.11 (q, OCH3), 84.40 (s, Ar-CϵC), C4-OCH3), 56.10 (q, Ar-C2,C6-OCH3), 90.40 (d, Ar-C3, Ar-C5),
100.01 (s, Py-CϵC), 106.43 (s, Py-C4), 111.07 (d, Ar-C3, Ar-C5),
91.38 (s, Py-CϵC), 92.78 (s, Ar-CϵC), 129.48 (d, s, Py-C3, Py-C5,
128.98 (d, Ar-C2, Ar-C6), 133.79 (d, Py-C3, Py-C5), 135.53 (s, Ar- Py-C4), 135.67 (s, Ar-C1), 148.10 (s, Py-C2, Py-C6), 163.01 (s, Cϭ
C1), 148.15 (s, Py-C2, Py-C6), 148.59 (s, Ar-C4), 164.92 (s, CϭO) O), 163.21 (s, Ar-C4), 165.01 (s, Ar-C2, Ar-C6) ppm. EI-MS
ppm. EI-MS (70 eV): m/z (%) ϭ 366 (59) [Mϩ], 351 (100). CI-MS (70 eV): m/z (%) ϭ 385 (100) [Mϩ], 327 (60). CI-MS (isobutane): m/
(isobutane): m/z (%) ϭ 367 (100) [Mϩ ϩ1]. HRMS (C21H22N2O4):
z (%) ϭ 386 (100) [Mϩ ϩ1], 117 (86). HRMS (C20H19NO7): calcd.
calcd. 366.15796; found 366.15780; (C2013CH22N2O4) calcd. 385.11615; found 385.11600; (C1913CH19NO7): calcd. 386.11951;
367.16132; found 367.16102. C21H22N2O4 (366.41): calcd. C 68.84,
H 6.05, N 7.64; found C 68.52, H 6.28, N 7.57.
found 386.11950. C20H19NO7 (385.37): calcd. C 62.36, H 4.97, N
3.63. C20H19NO7·0.5 CH3OH[34] (401.39): calcd. C 61.34, H 5.27,
N 3.49; found C 61.53, H 5.01, N 3.53.
Dimethyl
4-(4-Methoxyphenylethynyl)pyridine-2,6-dicarboxylate
(5d): Dimethyl 4-iodopyridine-2,6-dicarboxylate (4, 1003 mg,
3.12 mmol), Pd(PPh3)2Cl2 (41 mg, 0.058 mmol), and CuI (68 mg,
0.36 mmol) were allowed to react with 4-methoxyethynylbenzene
(2d, 538 mg, 4.08 mmol) for 4 h at 60 °C according to the General
Procedure, (diethyl ether) ϭ 0.38. Yield: 669 mg (66%). m.p.
140Ϫ141 °C. IR (film): ν˜ ϭ 2956 (w, aliph. C-H), 2211 (m, CϵC),
1750 (s, CϭO), 1719 (s, CϭO), 1592 (s, arom. CϭC), 1442 (s), 1253
[1]
J.-M. Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995.
[2]
Comprehensive supramolecular chemistry, executive Ed.: J. L.
Atwood, chairman of the editorial board: J.-M. Lehn, Oxford,
Pergamon, 1996.
J. W. Steed, J. L. Atwood, Supramolecular chemistry, John
Wiley & Sons, New York, 2000.
Sensors update, Vol. 1Ϫ11 (Eds.: H. Baltes, W. Göpel, J. Hesse),
[3]
(s, CϪO) cmϪ1
.
1H NMR (200 MHz, CDCl3): δ ϭ 3.86 (s, 3 H,
[4]
Ar-4-OCH3), 4.04 (s, 6 H, COOCH3), 6.93 (d, 3J ϭ 9.0 Hz, 2 H,
3
WileyInterScience/Wiley-VCH, 1996؊2002.
Ar-3,5-H), 7.53 (d, J ϭ 9.0 Hz, 2 H, Ar-2,6-H), 8.34 (s, 2 H, Py-
[5]
J. J. Lavigne, E. V. Anslyn, Angew. Chem. 2001, 113,
H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 53.26 (q, COOCH3),
55.34 (q, Ar-OCH3), 84.54 (s, Ar-CϵC), 97.48 (s, Py-CϵC), 113.25
(s, Py-C4), 114.24 (d, Ar-C3, Ar-C5), 129.40 (d, Ar-C2, Ar-C6),
133.75 (d, Py-C3, Py-C5), 134.84 (s, Ar-C1), 148.26 (s, Py-C2, Py-
C6), 160.78 (s, Ar-C4), 164.76 (s, CϭO) ppm. EI-MS (70 eV): m/z
(%) ϭ 325 (81) [Mϩ], 267 (100), 235 (37), 207 (46). CI-MS
(isobutane): m/z (%) ϭ 326 (100) [Mϩ ϩ1]. HRMS (C18H15NO5):
calcd. 325.09503; found 325.09490; (C1713CH15NO5): calcd.
326.09839; found 326.09840. C18H15NO5 (325.31): calcd. C 66.46,
H 4.65, N 4.31; found C 66.17, H 4.75, N 4.25.
3212Ϫ3225.
[6]
J. J. Lavigne, E. V. Anslyn, Angew. Chem. Int. Ed. 2001, 40,
3118Ϫ3130.
See biochemistry textbooks, e.g. L. Stryer, Biochemistry, 4th
[7]
ed., W. H. Freeman and Company, New York, 1995.
[8]
U. Lüning, J. Mater. Chem. 1997, 7, 175Ϫ182.
[9]
U. Lüning, R. Baumstark, W. Schyja, Liebigs Ann. Chem.
1991, 999Ϫ1002.
[10]
W. Schyja, S. Petersen, U. Lüning, Liebigs Ann. 1996,
2099Ϫ2105.
[11]
U. Lüning, S. Petersen, W. Schyja, W. Hacker, T. Marquardt,
K. Wagner, M. Bolte, Eur. J. Org. Chem. 1998, 1077Ϫ1084.
Dimethyl 4-(4-Nitrophenylethynyl)pyridine-2,6-dicarboxylate (5e):
[12]
U. Lüning, W. Schyja, in: NATO ASI Series, Series C: Math-
Dimethyl
4-iodopyridine-2,6-dicarboxylate
(4,
1000 mg,
ematical and Physical Sciences (Ed.: J. S. Siegel) Supramolecular
Stereochemistry, 1995, 473, 223Ϫ226.
3.12 mmol), Pd(PPh3)2Cl2 (43 mg, 0.061 mmol), and CuI (66 mg,
0.35 mmol) were allowed to react with 4-nitroethynylbenzene (2e,
576 mg, 3.97 mmol) for 3.5 h at 40Ϫ60 °C according to the General
Procedure, Rf (dichloromethane) ϭ 0.5. Yield: 670 mg (63%). m.p.
162 °C. IR (Film): ν˜ ϭ 2222 (w, CϵC), 1720 (s, CϭO), 1601 (s,
[13]
S. Petersen, U. Lüning, Eur. J. Org. Chem. 1999, 847Ϫ854.
[14]
U. Lüning, Liebigs Ann. Chem. 1987, 949Ϫ955.
[15]
U. Lüning, R. Baumstark, K. Peters, H. G. von Schnering,
Liebigs Ann. Chem. 1990, 129Ϫ143.
U. Lüning, R. Baumstark, M. Müller, Liebigs Ann. Chem.
arom. CϭC), 1523 (s), 1343 (s, CϪO), 856 (m, ArϪCϪH) cmϪ1
.
[16]
1H NMR (200 MHz, CDCl3): δ ϭ 4.06 (s, 6 H, OCH3), 7.76 (d,
1991, 987Ϫ998.
[17]
3
3J ϭ 8.7 Hz, Ar-2,6-H), 8.29 (d, J ϭ 8.7 Hz, Ar-3,5-H), 8.41 (s, 2
O. Storm, U. Lüning, Eur. J. Org. Chem. 2002, 3680Ϫ3685.
[18]
H, Py-H) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 53.27 (q, OCH3),
89.35 (s, Ar-CϵC), 93.75 (s, Py-CϵC), 123.73 (d, Ar-C3, Ar-C5),
127.86 (s, Py-C4), 129.55 (d, Ar-C2, Ar-C6), 132.81 (d, Py-C3, Py-
C5), 133.08 (s, Ar-C1), 147.92 (s, Ar-C4), 148.61 (s, Py-C2, Py-C6),
164.39 (s, CϭO) ppm. EI-MS (70 eV): m/z (%) ϭ 340 (2.8) [Mϩ],
282 (100). CI-MS (isobutane): m/z (%) ϭ 341 (100) [Mϩ ϩ1].
H.-J. Schneider, A. Yatsimirsky, Principles and Methods in
Supramolecular Chemistry, J. Wiley & Sons Ltd., Chichester,
2000.
S. Akiyama, S. Nakatsuji, K. Yoshida, K. Nakashima, T. Hagi-
wara, H. Tsuruta, T. Yoshida, Bull. Chem. Soc., Jpn. 1983,
56, 361Ϫ362.
[19]
[20]
With slightly different conditions: M. I. Al Hassan, J. Or-
C17H12N2O6 (340.29): calcd.
C 60.00, H 3.55, N 8.23.
ganomet. Chem. 1990, 395, 227Ϫ229.
[21]
C17H12N2O6·0.2 CH2Cl2 (357.29): calcd. C 57.82, H 3.50, N 7.84;
found C 58.05, H 3.64, N 7.68.
M. S. Wong, J. F. Nicoud, Tetrahedron Lett. 1994, 6113Ϫ6116.
[22]
L. Dulog, B. Körner, J. Heinze, J. Yang, Liebigs Ann. Org. Bi-
oorg. Chem. 1995, 1663Ϫ1672.
The iodopyridinedicarboxylate 4 is an intermediate in the syn-
[23]
Dimethyl
4-(2,4,6-Trimethoxyphenylethynyl)pyridine-2,6-dicarb-
oxylate (5f): Dimethyl 4-iodopyridine-2,6-dicarboxylate (4, 521 mg,
1.62 mmol), Pd(PPh3)2Cl2 (26 mg, 0.037 mmol), and CuI (31 mg,
0.16 mmol) in THF (7.5 mL) and triethylamine (7.5 mL) were al-
lowed to react with 2,4,6-trimethoxyethynylbenzene (2f, 400 mg,
2.08 mmol) for 4 h at 60 °C according to the General Procedure,
Rf (diethyl ether) ϭ 0.26. Yield: 460 mg (74%). m.p. 236 °C. IR
(Film): ν˜ ϭ 2950 (w, CH3), 2206 (s, CϵC), 1750 (s, CϭO), 1716
(s), 1592 (s, arom. CϭC), 1442 (m), 1336 (s, OCH3), 1130 (s), 810
(w, Ar-C-H), 780 (w, Ar-C-H) cmϪ1. 1H NMR (300 MHz, CDCl3):
δ ϭ 3.87 (s, 3 H, Ar-4-OCH3), 3.92 (s, 6 H, Ar-2,6-OCH3), 4.03 (s,
thesis of the concave pyridines 3. The conditions for the Sono-
gashira coupling were therefore first checked with this ‘‘cheap-
er’’ compound, which is why the resulting esters 5 were investi-
gated for comparison.
H. Takalo, J. Kankare, Acta Chem. Scand., Ser. B 1987,
219Ϫ222.
[24]
[25]
H. Takalo, J. Kankare, E. Häminen, Acta Chem. Scand., Ser.
B 1988, 42, 448Ϫ454.
[26]
H. H. Jaffe, G. O. Doak, J. Am. Chem. Soc. 1955, 77,
4441Ϫ4444.
[27]
A. R. Katritzky, P. Simmons, J. Chem. Soc. 1960, 1511Ϫ1516.
Eur. J. Org. Chem. 2003, 3109Ϫ3116
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3115

O. Storm, U. Lüning
FULL PAPER
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CF3CH2OH 23.5.
U. Lüning, M. Müller, Liebigs Ann. Chem. 1989, 367Ϫ374.
Three sets of signals can be distinguished, but only the signals
of the most intensive set (Z,Z) are given. Between 20 and
70 ppm the assignment of the signals may be incorrect, due to
intense signal density.
1960, 1516Ϫ1518.
[29]
The ρ value for 1 has been calculated from only three data
points (R ϭ H, OMe, and NEt2)[16]
.
[33]
[34]
[30]
[31]
T. H. Lowry, K. S. Richardson, Mechanismen und Theorie in
der Organischen Chemie, VCH, Weinheim, 1980, Kap. 1.
C. Hansch, A. Leo, Substituent Constants for Correlation
Analysis in Chemistry and Biology, John Wiley & Sons, New
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K. Izutsu, Acid-Base Dissociation Constants in Dipolar Aprotic
Solvents (IUPAC Chemical Data Series No. 35), Blackwell
[35]
The samples for elementary analysis were additionally recrys-
tallized from methanol.
[32]
Received January 31, 2003
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