Thieno[3,4-b]pyrazines: Synthesis, structure, and reactivity

Article abstract of DOI:10.1021/jo0262255

A general synthetic route has been developed for the efficient preparation of 2,3-disubstituted thieno[3,4-b]-pyrazines. These methods eliminate problems in the preparation of the precursor 3,4-diaminothiophene and utilize α-diones prepared through the reaction of the appropriate organocuprates with oxalyl chloride. This combination allows the convenient preparation of thieno[3,4-b]pyrazine and its 2,3-disubstituted analogues (where substituent = methyl, hexyl, octyl, decyl, dodecyl, and phenyl) in high yield. Characterization of the structure and reactivity of this class of compounds is also described, including the results of structural, electrochemical, and pK_a studies.

Full text of DOI:10.1021/jo0262255

SCHEME 1
Th ien o[3,4-b]p yr a zin es: Syn th esis,
Str u ctu r e, a n d Rea ctivity
Don D. Kenning, Kari A. Mitchell, Tessa R. Calhoun,
Melanie R. Funfar, Daniel J . Sattler, and
Seth C. Rasmussen*
Department of Chemistry, North Dakota State University,
Fargo, North Dakota 58105
seth.rasmussen@ndsu.nodak.edu
Received J uly 22, 2002
Abstr a ct: A general synthetic route has been developed for
the efficient preparation of 2,3-disubstituted thieno[3,4-b]-
pyrazines. These methods eliminate problems in the prepa-
ration of the precursor 3,4-diaminothiophene and utilize
R-diones prepared through the reaction of the appropriate
organocuprates with oxalyl chloride. This combination allows
the convenient preparation of thieno[3,4-b]pyrazine and its
2,3-disubstituted analogues (where substituent ) methyl,
hexyl, octyl, decyl, dodecyl, and phenyl) in high yield.
Characterization of the structure and reactivity of this class
of compounds is also described, including the results of
structural, electrochemical, and pKa studies.
In 1992, Pomerantz and co-workers applied the meth-
ods of Outurquin and Paulmier to the synthesis of 2,3-
dihexylthieno[3,4-b]pyrazine utilizing tetradecane-7,8-
dione prepared by the oxidation of the corresponding
alkyne.1 Shortly thereafter, Kuzmany and co-workers
also used these methods to prepare a series of 2,3-
disubstituted analogues (where substituent ) methyl,
ethyl, hexyl, undecyl, tridecyl, and 2-thienyl).2 However,
while properties of the resulting polythieno[3,4-b]pyra-
zines were reported, neither author reported the syn-
thetic details or any characterization of the monomeric
precursors. In addition, the needed alkynes for this
approach are typically not readily available.
Here we report a general synthetic route to 2,3-
disubstituted thieno[3,4-b]pyrazines resulting from vari-
ous improvements on the work of Outurquin and Paul-
mier combined with an optimization of the methods of
Marchese and co-workers for the production of R-diones.8
This synthetic route allows convenient access to the
desired long-chain alkyl-functionalized precursors needed
for the production of soluble polythieno[3,4-b]pyrazines
and can be applied to the production of a variety of
symmetrically substituted thieno[3,4-b]pyrazines. In ad-
dition, we include here the first full characterization of
thieno[3,4-b]pyrazines, including the results of structural,
electrochemical, and pKa studies.
Syn th esis. Thieno[3,4-b]pyrazine and its 2,3-disubsti-
tuted analogues can be readily synthesized from thiophene
as shown in Scheme 1. While compounds 1 and 2 are
commercially available, we have found it much more cost-
effective and reliable to prepare these materials directly.
Compound 2 was readily produced by the nitration of
1 via fuming HNO3 and H2SO4. Without the use of the
fuming acids, only the mononitro product was produced.
Likewise, an extended 3 h reaction time was required,
as lesser times resulted in mixtures of mono- and dinitro-
products. X-ray data show that the double bonds of 2 are
slightly shorter than those of the parent thiophene,9 while
the C-C single bond is slightly elongated. This bond
localization in 2 can be attributed to the donor-acceptor
nature of the substituents as well as steric repulsion
between the two NO2 groups.
Thieno[3,4-b]pyrazines have been shown to be excellent
precursors for the production of low band gap conjugated
polymers.1-4 However, for these compounds to be fully
utilized in such applications, a general synthetic route
must be developed that allows access to a large number
of different functionalities in the 2- and 3-positions. Such
functionalities are necessary to tune and modulate the
physical, electronic, and optical properties of the polymers.
The first report of a thieno[3,4-b]pyrazine was the
synthesis of 2,3-diphenylthieno[3,4-b]pyrazine reported
by Imoto and co-workers in 1957.5 Binder and co-workers
later reported a modified synthesis for the dimethyl
analogue in 1981.6 The first attempt at a general route
to these compounds was published a year later by
Outurquin and Paulmier.7 Their approach applied modi-
fications of the earlier methods to the preparation of
thieno[3,4-b]pyrazine and its 2-substituted and 2,3-
disubstituted analogues (where substituent ) methyl or
phenyl). This work, however, was still limited to com-
mercially available R-diones and glyoxal for the formation
of the pyrazine ring.
(1) Pomerantz, M.; Chaloner-Gill, B.; Harding, L. O.; Tseng, J . J .;
Pomerantz, W. J . J . Chem. Soc., Chem. Commun. 1992, 1672.
(2) (a) Kastner, J .; Kuzmany, H.; Vegh, D.; Landl, M.; Cuff, L.;
Kertesz, M. Synth. Met. 1995, 69, 593. (b) Kastner, J .; Kuzmany, H.;
Vegh, D.; Landl, M.; Cuff, L.; Kertesz, M. Macromolecules 1995, 28,
2922.
(3) (a) Kitamura, C.; Tanaka, S.; Yamashita, Y. J . Chem. Soc., Chem.
Commun. 1994, 1585. (b) Ferraris, J . P.; Bravo, A.; Kim, W.; Hrncir,
D. C. J . Chem. Soc. Chem. Commun. 1994, 991. (c) Roncali, J . Chem.
Rev. 1997, 97, 173. (d) Akoudad, S.; Roncali, J . Chem. Commun. 1998,
2081.
(4) (a) Kenning, D. D.; Funfar, M. R.; Rasmussen, S. C. Polym. Prepr.
2001, 42, 506. (b) Kenning, D. D.; Mitchell, K. A.; Funfar, M. R.;
Rasmussen, S. C. Polym. Prepr. 2001, 42, 665. (c) Kenning, D. D.;
Ogawa, K.; Rothstein, S. D.; Rasmussen, S. C. Polym. Mater. Sci. Eng.
2002, 86, 59.
(5) Motoyama, R.; Sato, D.; Imoto, E. Nippon Kagaku Zasshi 1957,
78, 793; Chem. Abstr. 1960, 54, 22560e.
(6) Binder, D.; Noe, C. R.; Geisler, F.; Hillebrand, F. Arch. Pharm.
(Weinheim, Ger.) 1981, 314, 564.
(7) (a) Outurquin, F.; Paulmier, C. Bull. Soc. Chim. Fr., II 1983,
153. (b) Outurquin, F.; Paulmier, C. Bull. Soc. Chim. Fr., II 1983, 159.
(8) Babudri, F.; Fiandanese, V.; Marchese, G.; Punzi, A. Tetrahedron
Lett. 1995, 36, 7305.
(9) Katritzky, A. R.; Pozharskii, A. F. Handbook of Heterocyclic
Chemistry, 2nd ed.; Pergamon: New York, 2000; pp 24, 61.
10.1021/jo0262255 CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/19/2002
J . Org. Chem. 2002, 67, 9073-9076
9073

Treatment of 2 with Sn and HCl both reduced the NO2
functionalities and removed the Br protecting groups. As
the reduction was carried out under acidic conditions, the
isolated precipitate is the diammonium salt of 3 (3‚2H+
salt). In the procedure reported by Outurquin and Paul-
mier, the isolated 3‚2H+ salt was purified by diethyl ether
and acetone washes.7 While this is necessary to remove
impurities and residual HCl solution, it was found that
if the salt was not adequately washed with ether first,
the acetone wash resulted in complete product decom-
position. This decomposition seemed to be initiated by
the reaction of acetone with an ether-soluble impurity.
Thus, it was difficult to determine when this reactive
impurity was completely removed and it was safe to start
the acetone wash. Working with various solvents, how-
ever, it was found that purification could be accomplished
much easier using acetonitrile rather than acetone.
Acetonitrile effectively removes the unwanted impurities
but does not react with any remaining impurities as
previously described for acetone.
F IGURE 1. Ellipsoid Plot of 2,3-Dimethylthieno[3,4-b]pyra-
zine.
conditions, isolated yields were still only ∼10-20%. In
this process, it was found that in order to adequately
inhibit the homocoupling side reaction, the temperature
must be very carefully controlled. For example, both the
conversion of the Grignard reagent to the organocuprate
and its subsequent reaction with the oxalyl chloride are
exothermic. Thus, even with an initial temperature of
-78 °C, it is quite easy to achieve temperatures from -40
to -30 °C during the various reaction steps and favor
homocoupling during these periods. By cooling the mix-
ture to even lower initial temperatures (-100 °C),
however, and by adding the remaining reagents slowly
over time, it was possible to keep the reaction mixture
below -70 °C at all times. Such temperature control
minimized unwanted homocoupling and resulted in R-di-
one yields of 70-90%.
Condensation of 3 with the R-diones readily occurred at
room temperature in an ethanol solution. While previous
methods utilized short periods of heating (i.e., 50-70 °C
for 10-15 min),7b it was found that by allowing the
reaction to run at room temperature for longer periods
of time, unwanted polymerization reactions were reduced
and the thieno[3,4-b]pyrazines were recovered in higher
yields. The initially isolated products were all relatively
free of impurities, and analytical samples could be
prepared by either recrystallization or chromatography.
Str u ctu r e. X-ray quality crystals of 5b could be grown
by the slow evaporation of acetonitrile solutions, and the
resulting crystal structure is shown in Figure 1. Selected
bond angles and distances for 5b, thiophene, and pyra-
zine are given in Table 1. Comparing the bond lengths
of 5b with the gas-phase distances of thiophene and
pyrazine,9 it can be seen that the thiophene ring of 5b is
nearly identical to the parent thiophene. The pyrazine
portion of 5b, however, shows some bond fixation in
comparison to the parent pyrazine. For example, while
the delocalized structure of pyrazine results in four
equivalent C-N bonds, the pyrazine ring of 5b exhibits
elongation of the thiophene-N bonds and shortening of
the exterior C-N bonds. In fact, the bond lengths of these
exterior C-N bonds (i.e., C(5)-N(1) ) 1.308 Å) are very
close to the 1.28 Å length of localized CdN bonds.11 In
addition, the C(5)-C(6) unit separating these CdN units
is also greatly elongated in comparison to pyrazine. Thus,
5b can be viewed to be more similar to a diimine-capped
thiophene than a truly delocalized structure.
In the original reports by either Imoto5 or Binder,6 the
3‚2H+ salt is given the formula 3‚2HCl‚SnCl4, while
Outurquin and Paulmier refer to it as a hexachlorostan-
nate (SnCl62-) diammonium salt.7a As SnCl4 is a liquid
at room temperature and usually adopts a six-coordinate
geometry in the presence of additional ligands,10 all of
these formulations seem to refer to SnCl62- counterions.
Elemental analysis of the isolated 3‚2H+ salt, however,
does not agree with a simple SnCl62- salt. In addition, the
corresponding yield of the free base 3 is also not consis-
tent with such a composition. These observations indicate
that the 3‚2H+ dication is present in higher quantities
than would be consistent with the mass ratio of a pure
SnCl62- salt. As the solution from which the salt precipi-
tates contains roughly 4 times the amount of Cl- com-
pared to SnCl62-, we believe that the isolated salt consists
of a mixture of Cl- and SnCl6 counterions with the
2-
general composition [3‚2H+]x[SnCl6
]
1/2y)[Cl-]y and
2-
(x
-
therefore has a lower molecular weight than a pure
SnCl62- salt. Attempts to determine the exact ratio of Cl-
2-
to SnCl6 have been unsuccessful, as the ratio seems
very dependent on the exact conditions during the salt
precipitation and can change from one isolation to the
next. For this reason, the free base 3 was always isolated
prior to further reaction in order to determine an accurate
molar quantity.
With the exception of glyoxal, 2,3-butanedione, and
benzil, the R-diones necessary for the condensation with
3 to produce the desired thieno[3,4-b]pyrazines 5a -g are
not commercially available. While Pomerantz1 and Kuz-
many2 had previously utilized symmetric alkynes as
precursors to the required R-diones, a more direct syn-
thetic approach was desired. Such an approach was
reported by Marchese and co-workers for the preparation
of symmetrical R-diones from oxalyl chloride.8 However,
while the procedure was fairly direct, the yields reported
by Marchese could not be achieved due to the production
of a large amount of homocoupled alkane byproduct.
Marchese points out that lower temperatures (i.e., -78 °C)
are required for the production of dialkyl R-diones in
order to reduce such homocoupling, but even under such
The only previous crystal data for a thieno[3,4-b]-
pyrazine were for the mixed trimer 2,3-dimethyl-5,7-di-
(2-thienyl)thieno[3,4-b]pyrazine3a (6). Selected bond angles
and distances for trimer 6 are given in Table 1. As seen
(10) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements;
Pergamon Press: New York, 1984; pp 443-444.
(11) CRC Handbook of Chemistry and Physics; Lide, D. R., Fred-
erikse, H. P. R., Eds.; CRC Press: Boca Raton, FL, 1995; pp 9-6.
9074 J . Org. Chem., Vol. 67, No. 25, 2002

TABLE 1. Exp er im en ta l Geom etr ica l P a r a m eter s of 2,3-Dim eth ylth ien o[3,4-b]p yr a zin e (5b), Th iop h en e, P yr a zin e, a n d
2,3-Dim eth yl-5,7-d i(2-th ien yl)Th ien o[3,4-b]p yr a zin e (6) a n d Ca lcu la ted P a r a m eter s of Th ien o[3,4-b]p yr a zin e (5a )
5a
5a
5a
parameter
5b
6a
(calcd)b
(calcd)c
(calcd)d
thiophenee
pyrazinee
S(1)-C(1)
1.691
1.372
1.427
1.377
1.308
1.460
1.495
94.27
110.52
112.44
121.35
116.05
121.51
117.60
1.719
1.407
1.418
1.371
1.301
1.469
1.503
95.03
108.89
113.86
121.35
116.21
122.22
118.46
1.706
1.384
1.442
1.378
1.310
1.433
1.70
1.36
1.45
1.41
1.30
1.45
1.67
1.38
1.47
1.40
1.31
1.47
1.714
1.370
1.423
C(1)-C(2)
C(2)-C(3)
1.403
1.339
1.339
1.403
C(2)-N(1)
N(1)-C(5)
C(5)-C(6)
C(5)-C(7)
C(1)-S(1)-C(4)
S(1)-C(1)-C(2)
C(1)-C(2)-C(3)
N(1)-C(2)-C(3)
C(5)-N(1)-C(2)
C(6)-C(5)-N(1)
N(1)-C(5)-C(7)
92.8
111.7
111.9
120.4
116.3
123.3
95.3
110.9
111.4
121.1
115.5
123.4
92.17
111.47
112.45
122.2
115.6
122.2
a
b
d
From ref 3a. From ref 12a. c From ref 12b. From ref 12c. e From ref 9.
TABLE 2. Electr och em ica l Da ta for a Ser ies of
2,3-Disu bstitu ted Th ien o[3,4-b]p yr a zin esa
oxidation
reduction
∆E, mV
R
Epa, V
E1/2, V
H
CH3
C6H13
C8H17
1.55
1.33
1.35
1.35
1.33
1.35
1.27
-2.04
-2.01
-1.99
-1.99
-1.96
-1.27
85
150
130
140
130
300
F IGURE 2. Cyclic Voltammogram of 2,3-Dimethylthieno[3,4-
b]pyrazine (5b).
C
C
10H21
12H25
Ph
gram is shown in Figure 2. As expected for thiophene
derivatives, 5a -g exhibit a well-defined irreversible
oxidation presumably corresponding to the formation
and rapid coupling of thiophene-based radical cations
(τ < 10-5 s), thus leading to oligomeric and polymeric
species.13,14a For the series 5b-f, the peak oxidation
potentials (Epa) are fairly consistent and occur at ∼1.35
V vs Ag/Ag+. In the case of 5a , the compound does not
benefit from the electron donation of the alkyl groups and
thus undergoes oxidation at a slightly higher potential.
In contrast, 5g exhibits the lowest oxidation (1.27 V) due
to the partial overlap of the thieno[3,4-b]pyrazine π-sys-
tem with that of the phenyl substituents. Overall, the
oxidations of 5a -g occur at much lower potentials than
the J2 V of typical thiophenes.14 These lower potentials
can be attributed to the increased conjugation of the
fused-ring compound and agree well with the oxidation
potentials of other analogous fused-ring thiophene sys-
tems (1.1-1.5 V).14b
In addition to the thiophene-based oxidation, a quasi-
reversible reduction is also exhibited at approximately
-2.0 V. This observation agrees well with the previously
reported electrochemical study of the reduction of 5b by
Armand and co-workers, which showed that this redox
wave corresponds to the one-electron reduction of the
pyrazine ring.12c In comparison to the previous oxidations,
there is slightly more variation in the half-potentials
(E1/2) of the reductions with the potentials decreasing
slightly with increasing substituent chain length. The
main exception to this trend is 5a , which does not exhibit
a reduction. In this case, it is possible that the reduction
All potentials are vs Ag/Ag+. Voltammetric data were mea-
sured in millimolar argon-sparged CH3CN solutions with 0.1 M
TBAPF6 as a supporting electrolyte.
a
in the structure of 5b, trimer 6 also exhibits the same
bond fixation in the pyrazine ring with bond lengths
closely approximating that of 5b and a CdN bond length
of 1.301 Å. As might be expected, however, the central
thiophene ring of trimer 6 differs significantly from 5b
due to conjugation effects with the two thienyl endgroups.
In addition to the experimental data, various calcu-
lated structures of the parent 5a have been reported
(Table 1). The first calculated structure was reported by
Schneller and co-workers in 1976 and was limited to the
bond length determinations using the CNDO/2 method.12a
More complete calculations were then later reported by
Marynick and co-workers12b using the PRDDO method
and by Armand and co-workers using the MNDO
method.12c All three calculated structures actually pre-
dicted the bond localization of the pyrazine ring quite well
with an agreement of (0.008 Å for the CdN bond
lengths. The studies also modeled the thiophene ring
fairly closely, with the major deviation being that all
studies predicted an elongation of the C-C bond fused
between the two heterocyclic rings, which was not seen
in the structure of 5b. In this case, the calculations
predicted that both of the C-C bonds within the pyrazine
ring were of equal length, rather than the asymmetric
structure shown by the X-ray data.
Electr och em istr y. The electrochemical data of 5a -g
are given in Table 2, and a representative cyclic voltammo-
(12) (a) Schneller, S. W.; Clough, F. W.; Skancke, P. N. J . Heterocycl.
Chem. 1976, 13, 581. (b) Nayak, K.; Marynick, D. S. Macromolecules
1990, 23, 2237. (c) Armond, J .; Bellec, C.; Boulares, L.; Chaquin, P.;
Masure, D.; Pinson, J . J . Org. Chem. 1991, 56, 4840.
(13) Audebert, P.; Hapiot, P. Synth. Met. 1995, 75, 95.
(14) (a) Rasmussen, S. C.; Pickens, J . C.; Hutchison, J . E. Chem.
Mater. 1998, 10, 1990. (b) Roncali, J . Chem. Rev. 1992, 92, 711.
J . Org. Chem, Vol. 67, No. 25, 2002 9075

TABLE 3. p Ka Da ta for P yr a zin es, Qu in oxa lin es, a n d
Th ien o[3,4-b]p yr a zin es
similar methyl group-induced increase in basicity is seen
but to a lesser extent (∼0.39 pH units).15a Assuming that
the methyl group effect is also additive for the thieno-
[3,4-b]pyrazines, this would correspond to an increase of
∼0.55 pH units/methyl moiety. Thus the methyl group
effect for the thieno[3,4-b]pyrazines falls approximately
halfway between that of pyrazines and quinoxalines. It
is possible that the larger π-systems of the thieno[3,4-b]-
pyrazines and quinoxalines result in the diminished effect
of the methyl groups in comparison to that of pyrazine.
As with 5a , a third protic species of 5b can be seen at
low pH. In this case, however, the formation of this
species occurs under less acidic conditions and is the pre-
dominate species in 12 M HCl. The pKa value determined
for this second protonation is -1.29, much more basic
than the corresponding value of -5.51 for pyrazine (Table
3). Unfortunately, the pKa2 values for quinoxaline or its
methyl analogue have not been determined. However,
one could make the argument that the larger π-system
of the fused-ring systems facilitates a greater delocal-
ization of the cation’s positive charge in comparison to
pyrazine, thereby diminishing the electrostatic barrier
to the second protonation. While R-protonation of the
thiophene ring is also possible, this typically promotes
substitution and/or polymerization. In addition, Cook and
co-workers17 have shown that R-protonation of 2,5-di-tert-
butylthiophene occurs with a pKa of -10.16. Thus R-pro-
tonation is expected to be much less favorable than the
protonation of the second pyrazine nitrogen. It has also
been shown by others that protonation of the sulfur
heteroatom is even less favored than R-protonation.17a
In conclusion, 2,3-difunctionalized thieno[3,4-b]pyra-
zines can be prepared simply and efficiently via the room-
temperature condensation of 3 and an appropriate R-di-
one. In turn, the R-diones can be conveniently prepared
from the reaction of alkylcuprates with oxalyl chloride.
The resulting thieno[3,4-b]pyrazines exhibit the charac-
teristics and reactivity of the parent heterocycles, al-
though somewhat modified by the increased π-conjuga-
tion, as might be expected.
compound
pKa1
pKa2
pyrazinea
0.57
1.41
2.24
0.56
0.95
0.55
1.66
-5.51
-4.89
-4.17
2-methylpyrazinea
2,3-dimethylpyrazinea
quinoxalineb
2-methylquinoxalineb
thieno[3,4-b]pyrazine (5a )
2,3-dimethylthieno[3,4-b]pyrazine (5b)
-1.29
a
b
From ref 16. From ref 15a.
occurs just outside the solvent potential window of the
acetonitrile. In addition to this first reduction, Armand
and co-workers showed that by scanning to more negative
potentials (ca. -2.4 V), the pyrazine ring of 5b could be
irreversibly reduced to produce the corresponding 1,4-
dihydro derivative.12c
p Ka Stu d ies. Spectrometric pH titrations of com-
pounds 5a and 5b were carried out in order to quantify
the basicity of the pyrazine nitrogens. The pKa values
determined from these studies are given in Table 3, along
with the corresponding values for pyrazine, quinoxaline,
and their methyl derivatives.
Typically, pyrazines and their derivatives are relatively
weak bases. For example, the first protonation of pyra-
zine occurs with a pKa of 0.57 in comparison to the much
more basic pKa of pyridine at 5.23. The lower basicity of
pyrazine relative to that of pyridine is due to the strong
inductive and mesomeric effects of the sp2 nitrogen para
to N(1).15 In addition, the annulation of benzene rings to
these aromatic bases generally only causes a small
change in basicity.15a Thus, as seen in Table 3, the pKa
of quinoxaline is essentially the same as that of pyrazine.
The basicity of 5a agrees well with that of both
pyrazine and quinoxaline, giving a pKa value of 0.55 for
the first protonation (pKa1, Table 3). Thus, while the
structural data above indicate bond fixation within the
pyrazine ring, the effect of the para nitrogen can still be
effectively communicated, resulting in a pKa typical of
pyrazine. As expected, the effect of the fused thiophene
ring is similar to a fused benzene ring and thus has little
effect on the basicity. Following the initial protonation
of 5a , the UV-vis spectra show a third species forming
at ∼pH 0. However, even in 12 M HCl, very little of this
third species was present at equilibrium and the pKa for
the second protonation could not be reliably determined.
This is hardly surprising, as the analogous pKa values
of pyrazines have been determined to be ca. -5 (Table 3).
In comparison to 5a , the methyl analogue 5b exhibits
increased basicity and a pKa1 value of 1.66. This increased
basicity with added methyl groups is typical for pyrazines
(Table 3). The increased basicity is due to the electron-
donating effect of the methyl moiety and is additive
(∼0.84 pH units/methyl group).15b,16 For quinoxaline, a
Ack n ow led gm en t. The authors thank the donors
of the Petroleum Research Fund, administered by the
American Chemical Society, for partial support of this
research. Additional support was provided by North
Dakota EPSCoR, the National Science Foundation
(CHE-0132886), and North Dakota State University. We
also thank Dean Grier and Dr. Charles Campana
(Bruker Nonius) for assistance with the X-ray crystal
analysis and Dr. Kenton Rodgers for help with the
global analysis of the spectrophotometric data.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for the synthesis and characterization of 1-5 and 2,3-
dimethylthieno[3,4-b]pyrazine‚2HCl, spectroscopic data and
global analysis results used in the pKa determinations, and
full crystallography data for compounds 2 and 5b. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O0262255
(16) Gumbley, S. J .; Lee, T. W. S.; Stewart, R. J . Heterocycl. Chem.
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