DFT-based quantitative prediction of regioselectivity: Cycloaddition of nitrilimines to methyl propiolate

Full text of DOI:10.1021/jo0156159

5252
J . Org. Chem. 2001, 66, 5252-5255
To predict quantitative regioselectivity ratios, one
DF T-Ba sed Qu a n tita tive P r ed iction of
should locate the transition states and compute their
energy. This being a difficult task, there is current effort7
aimed at obtaining activation energies from isolated
reactants’ properties without locating transition states.
In this framework, a generalization of the HSAB prin-
ciple has been very recently introduced,8 which enables
one to compute, from µ and s of the reactants only, the
grand potential9 variation ∆Ω due to the bond-forming
interaction between specific atoms of the reactants. Since
in 1,3-DCs the relative energy of transition states is
paralleled by the relative energy of the weakly interacting
complexes forming in the early stage of the reaction,10
∆Ω is closely related to the transition state energy and
can provide a quantitative prediction of regioselectivity.
Regioselectivity: Cycloa d d ition of
Nitr ilim in es to Meth yl P r op iola te
Alessandro Ponti*,† and Giorgio Molteni‡
Centro per lo Studio delle Relazioni tra Struttura e
Reattivita` Chimica, Consiglio Nazionale delle Ricerche,
via Golgi 19, 20133 Milano, Italy, and Dipartimento di
Chimica Organica e Industriale, Universita` degli Studi di
Milano, via Golgi 19, 20133 Milano, Italy
ponti@csrsrc.mi.cnr.it
Received March 6, 2001
In the last two decades, many important concepts and
indices useful to understand chemical reactivity have
been rationalized within the framework of the density
functional theory (DFT).1 Relevant reactivity indices2 are
the electron chemical potential µ, a molecular quantity
that measures the escaping tendency of electrons, and
the local softness s(r ), which represents the sensitivity
of the molecular electron density at point r to a change
in µ. Local softness is therefore well suited to compare
reactivity at different sites within one molecule. Integra-
tion of s(r ) over the molecular volume gives the global
softness S, which contains information on the reactivity
of the molecule as a whole. The link between the DFT
indices and chemical reactivity is provided by the hard-
soft acid-base principle (HSAB),3 which also found a
convenient theoretical framework within the DFT. This
principle is well suited to study chemical reactions since
it only requires that temperature is constant and allows
for variation in both chemical and external (nuclear)
potential. This is at variance with the principle of
maximum hardness,4 which requires that also the chemi-
cal and external potentials are constant. The HSAB
principle states that when molecule A of softness SA may
react with several partner X of equal chemical potential,
it reacts with that partner for which |SA - SX| is
minimum, i.e., hard likes hard and soft likes soft. The
local version5 of the HSAB principle predicts between
which atoms on A and X the new chemical bond forms
by using local softness as a reactivity index. Indeed,
reliable qualitative prediction of regioselectivity has been
obtained6 for several 1,3-dipolar cycloadditions (1,3-DC)
by this method.
As a first demonstration of this novel method, we
turned our attention to nitrilimine 1,3-DCs. These rep-
resent a very general route for the construction of a large
array of compounds containing the pyrazole ring.11
Despite the synthetic usefulness of this approach, there
is a paucity of data concerning the theoretical aspects of
nitrilimine chemistry.12 For the cycloaddition of nitril-
imines to both electron-poor and -rich dipolarophiles,
FMO theory predicts full regioselectivity toward the
5-substituted ∆2-pyrazolines.10 This prediction is obeyed
in the vast majority of 1,3-DCs of nitrilimines to mono-
substituted ethenes.11b,c Conversely, addition of diphen-
ylnitrilimine to methyl propiolate yields a mixture of
regioisomeric 5- and 4-pyrazolines in 78:22 ratio.13 We
were thus prompted to investigate the regiochemistry of
the 1,3-DC between a series of C-carbomethoxy-N-(4-
substituted)phenyl nitrilimines 2 to methyl propiolate 3
(see Scheme 1). In particular, we show how the DFT/
HSAB approach corrects this FMO theory prediction, and
we demonstrate the validity of the novel quantitative
(7) (a) Ga´zquez, J . L. J . Phys. Chem. 1997, 101, 8967-8969. (b) Toro-
Labbe`, A. J . Phys. Chem. 1999, 103, 4398-4403. (c) Clark, L. A.; Ellis,
D. E.; Snurr, R. Q. J . Chem. Phys. 2001, 114, 2580-2591.
(8) Ponti, A. J . Phys. Chem. A 2000, 104, 8843-8846.
(9) The grand potential Ω ) E - Nµ, where E is energy, N is the
number of electrons, and µ is the electron chemical potential, is the
natural thermodynamic quantity to describe the behavior of the
reactants’ atoms, which are open subsystems freely exchanging energy
and electrons.
(10) Houk, K. N.; Sims, J .; Watts, C. R.; Luskus, L. J . J . Am. Chem.
Soc. 1973, 95, 7301-7315.
(11) (a) Caramella, P.; Gru¨nanger, P. In 1,3-Dipolar Cycloaddition
Chemistry; Padwa, A., Ed.; J ohn Wiley & Sons: New York, 1984; Vol.
1, Chapter 3, pp 291-392. (b) Claus, P. K. In Methoden der Organis-
chen Chemie (Houben-Weil); Klaman, D., Hageman, H., Eds.; Georg
Thieme Verlag: Stuttgart, 1990; Band E14b, Teil 1, pp 33-73. (c)
Shawali, A. S.; Pa`rka`ni, C. J . Heterocycl. Chem. 1980, 17, 833-854.
(d) Bianchi, G.; De Micheli, C.; Gandolfi, R. In The Chemistry of Double
Bonded Functional Groups; Patai, S., Ed.; Wiley: London, 1977; Part
I, Chapter 6, pp 369-532. (e) Padwa, A. In Comprehensive Organic
Synthesis; Trost, B., Ed.; Pergamon Press: New York, 1992; Vol. 4,
Chapter 4/9, pp 1069-1109. (f) Wade, P. A. In Comprehensive Organic
Synthesis, Trost B. Ed.; Pergamon Press: New York, 1992; Vol. 4,
Chapter 4/10, pp 1110-1168. (g) Bertrand, G.; Wentrup, C. Angew.
Chem., Int. Ed. 1994, 33, 527-545. (h) Molteni, G.; Zecchi, G. Trends
Heterocyclic Chem. 1997, 5, 127-133. (i) Broggini, G.; Molteni, G.;
Zecchi, G. Heterocycles 1998, 47, 541-557. (j) Broggini, G.; Garanti,
L.; Molteni, G.; Pilati, T.; Ponti, A.; Zecchi, G. Tetrahedron: Asymmetry
1999, 10, 2203-2212. (k) Broggini, G.; Molteni, G. J . Chem. Soc.,
Perkin Trans. 1 2000, 1685-1689.
* To whom correspondence should be addressed. Fax (+39)-
0270638129.
† Consiglio Nazionale delle Ricerche.
‡ Universita` degli Studi di Milano.
(1) Parr, R. G.; Yang, W. Density Functional Theory of Atoms and
Molecules; Oxford University Press: Oxford, 1989.
(2) Chermette, H. J . Comput. Chem. 1999, 20, 129-154.
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Chattaraj, P. K.; Lee, H.; Parr, R. G. J . Am. Chem. Soc. 1991, 113,
1855-1856. (c) Cedillo, A.; Chattaraj, P. K.; Parr, R. G. Int. J . Quantum
Chem. 2000, 77, 403-407.
(4) Parr, R. G.; Chattaraj, P. K. J . Am. Chem. Soc. 1991, 113, 1854-
1855.
(5) Ga´zquez, J . L.; Me´ndez, F. J . Phys. Chem. 1994, 98, 4591-4593.
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10.1021/jo0156159 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/28/2001

Notes
J . Org. Chem., Vol. 66, No. 15, 2001 5253
Ta ble 2. Resu lts of B3LYP /6-311+G(d ,p) Ca lcu la tion s.
Ch em ica l P oten tia l Differ en ce betw een Nitr ilim in es 2
a n d Meth yl P r op iola te 3 a n d ∆∆Ω Differ en cea a n d
P r ed icted 4:5 Yield Ra tio for Th eir Mu tu a l Cycloa d d ition
Sch em e 1. Cycloa d d ition of Nitr ilim in es 2 w ith
P r op iola te 3.
µ(2) - µ(3)
δ∆Ω
predicted ratiob
entry
(eV)
(kJ mol-1
)
4:5n
a
b
c
d
e
f
1.85
2.17
1.57
1.43
1.35
-0.64
56:44
66:34
54:46
54:46
54:46
51:49
-1.70
-0.34
-0.34
-0.39
-0.08
-0.49 × 10-4
a
Difference in grand potential variation for the pathways
b
leading to products 4 and 5. From computed δ∆Ω and eq 3;
uncertainty (1%.
provide a clear-cut prediction since the two HOMO-
LUMO interactions are comparable in size.
From the electron chemical potential µ and the local
softness s (condensed to individual atoms), one can
compute the charge transfers between interacting atom
pairs.5 For instance, the charge transfer from N1 of 2 to
C1 of 3 amounts to (see Scheme 1 for numbering)
Ta ble 1. Exp er im en ta l Rea ction Tim es a n d Yield s a n d
4:5 Yield Ra tio of th e Cycloa d d ition betw een Nitr ilim in es
2 a n d Meth yl P r op iola te 3
yieldsa (%)
time
yield ratiob
entry
(min)
1
4 + 5
4:5
a
b
c
d
e
f
20
30
45
60
60
6
0
8
11
10
0
63
95
69
48
50
6
56:44
66:34
56:44
53:47
52:48
51:49
∆q(N1 f C1) )
-[µ(2) - µ(3)] s(N1) s(C1) [s(N1) + s(C1)]-1 (1)
It is noteworthy that, except for 2f, the atom-atom
charge transfers mimic the usual arrow notation. C1 (C2)
accepts (donates) electrons irrespective of the resulting
cycloadduct. Conversely, N1 (C3) accepts (donates) elec-
trons when isomer 5 is formed but the reverse occurs
when the product is 4. However, local softness is most
important in the context of regioselectivity prediction. As
selectivity criterion,8 we used the grand potential change
due to two bond-forming interactions between 2 and 3,
because of the general agreement about the concerted-
ness of 1,3-DC reactions.10 The grand potential change
for the pathway leading to isomer 4 is
240
Isolation yields. Deduced from 1H NMR of reaction crudes.
a
b
method by comparing the regioisomeric ratio obtained
from experiment to that computed from DFT reactivity
indices via the generalized HSAB principle and finding
very good agreement.
Labile intermediates 2 were generated in situ by base
treatment of the corresponding hydrazonoyl chlorides 114
according to a well-established procedure.13 Subsequent
reaction with 3 gave the isomeric adducts 4 and 5, and
their structure was firmly established by 1H NMR, since
protons in the 4- and 5- positions of the pyrazolic ring
show resonances in perfect agreement with literature
values.15 Reaction times and yields are reported in Table
1. Despite the modest regioselectivity, the favored prod-
uct clearly is the 4-substituted regioisomer.
∆Ω(4) )
-(1/2) [µ(2) - µ(3)]2 {s(N1) s(C1) [s(N1) + s(C1)]-1
+
s(C3) s(C2) [s(C3) + s(C2)]-1} (2)
The main results of DFT calculations at the B3LYP/
6-311+G(d,p) level are reported in Table 2. The electron
chemical potential difference between 2 and 3 determines
the direction of the overall charge flow upon interaction
of the reactants, as electrons flow toward regions at low
µ. It turns out that 2a -e act as nucleophiles whereas 2f
acts as electrophile (note, however, that the chemical
potentials of 2f and of 3 are very close to each other).
Notwithstanding that our calculations show that reac-
tions of 3 with 2a -e are HOMO-dipole controlled in
agreement with FMO theory, the latter predicts that
nitrilimines 5a -e are the favored regioisomers, in con-
trast with experiment. As for the reaction of 3 with the
electron-poor nitrilimine 2f, FMO theory is not able to
∆Ω(5) can be obtained by exchanging s(C1) and s(C2). The
difference δ∆Ω ) ∆Ω(4) - ∆Ω(5) is reported in Table 2.
As stated previously, one expects that δ∆Ω accounts
for most of the energy difference between the transition
states leading to 4 and 5. The negative sign of δ∆Ω shows
that, in the considered 1,3-DCs, isomer 4 is the major
one, in line with the experimental results but in contrast
to FMO theory. We now proceed one step further by
demonstrating that δ∆Ω is a quantitative regioselectivity
index for 1,3-DC reactions. The difference in activation
energy δ∆E of the two reaction paths can be obtained as
δ∆E ) -RT log(Y), where T ) 373 K is the reaction
temperature and Y is the experimental 4:5 ratio. Esti-
mating the error in Y at (1%, weighted least-squares
linear regression results in
(14) (a) 1a ,b,e: Cusumano, G.; Macaluso, G.; Hinz, W.; Buscemi,
S. Heterocycles 1987, 26, 1283-1289. (b) 1c: El-Abadelah, M. M.;
Hussein, A. Q.; Kamal, M. R.; Al-Ashami, K H. Heterocycles 1988, 27,
917-924. (c) 1d ,f: El-Abadelah, M. M.; Hussein, A. Q.; Saadeh, H. A
Heterocycles 1991, 32, 1063-1079.
(15) (a) Batterham, T. J . NMR Spectra of Simple Heterocycles;
Wiley: New York, 1973. (b) Katritzky, A. R.; Lagowski, J . M. In
Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W.,
Eds.; Pergamon Press: Oxford, 1985; Vol. 5, Chapter 4.01, pp 2-38.
δ∆Ω ) (1.15 ( 0.07) δ∆E - (0.06 ( 0.05) (3)
with correlation coefficient F ) 0.956 (see Figure 1). The
statistically insignificant intercept shows that δ∆Ω is
truly proportional to the difference in transition-state
energy. The predicted 4:5 ratios (Table 2), obtained from

5254 J . Org. Chem., Vol. 66, No. 15, 2001
Notes
regiochemistry of 1,3-DCs,6 so that our results can be directly
compared with existing literature. It has also been recently
considered as an appropriate local descriptor of charge.19 Reac-
tivity indices were computed within the finite difference ap-
proximation:1 µ ) -(IP + EA)/2 and S ) (IP - EA)-1, where IP
and EA are the (vertical) ionization potential and electron
affinity, respectively. The local softness s (condensed to each
individual atom20) was computed as s ) S [p(N0 + 1) - p(N0)]
for electrophiles, and as s ) S [p(N0) - p(N0 - 1)] for nucleo-
philes, where p(N), N ) N0 - 1, N0, N0 + 1, is the atomic electron
population of the cationic, neutral, and anionic system, respec-
tively.
Gen er a l Meth od s. Melting points were determined in open
tubes and are uncorrected. IR spectra were recorded with a FT-
IR spectrophotometer. Mass spectra were determined with a 70
1
eV EI apparatus. H NMR (300 MHz), 13C NMR (75 MHz), and
F igu r e 1. Linear relationship between the computed differ-
ence δ∆Ω in grand potential variation for the pathways leading
to products 4 and 5 and the correspondent difference in
activation energy δ∆E, computed from the experimental ratio.
The error bars show the uncertainty in δ∆E due to the error
in the 4:5 ratio, estimated at 1%.
19F NMR (282 MHz) spectra were taken in CDCl3 solutions at
297 K. Chemical shifts are given as ppm from tetramethylsilane
(hexafluorobenzene for 19F NMR); J values are given in Hz.
Cycloaddition between Nitrilimines 2 and Methyl Propiolate
3: General Procedure. A solution of 1 (2.0 mmol) and 3 (0.34 g,
4.0 mmol) in dry toluene (20 mL) was added with triethylamine
(1.01 g, 10 mmol) and then heated to 100 °C for the time
indicated in Table 1. Evaporation of the solvent in vacuo gave a
residue which was chromatographed on a silica gel column with
ethyl acetate-hexane 1:1. Unreacted 1 was eluted first, followed
by the pyrazolic cycloadduct 4; further elution gave 5. Crystal-
lization from diisopropyl ether gave analytically pure 4 and 5.
4a : 0.16 g, 28%; pale yellow solid; mp 103-105 °C; 1H NMR
(300 MHz, CDCl3): δ 3.83 (3H, s), 3.90 (3H, s), 3.95 (3H, s), 7.48
(1H, s), 7.10-7.30 (4H, m); 13C NMR (75 MHz, CDCl3) δ 44.12
(q), 52.13 (q), 53.50 (q), 120.0-127.0, 128.20 (d), 135.21 (s),
137.26 (s), 144.13 (s), 158.66 (s), 161.21 (s), 162 0.10 (s); IR
(Nujol) 1730 cm-1; MS m/z 290 (M+). Anal. Calcd for C14H14N2-
O5: C, 57.93; H, 4.86; N, 9.65. Found: C, 57.87; H, 4.80; N, 9.62.
4b: 0.18 g, 32%; white solid; mp 96-97 °C; 1H NMR (300
MHz, CDCl3) δ 2.42 (3H, s), 3.81 (3H, s), 3.96 (3H, s), 7.20-7.30
(4H, m), 7.50 (1H, s); 13C NMR (75 MHz, CDCl3) δ 20.82 (q),
52.60 (q), 52.88 (q), 120.0-125.4, 128.16 (d), 135.02 (s), 136.60
(s), 142.10 (s), 158.95 (s), 161.55 (s), 162 0.90 (s); IR (Nujol) 1725
cm-1; MS m/z 274 (M+). Anal. Calcd for C14H14N2O3: C, 61.31;
H, 5.14; N, 10.21. Found: C, 61.23; H, 5.17; N, 10.24.
computed δ∆Ω via eq 3, are in good agreement with the
experimental values (Table 1).
The very low selectivity of the reaction of 2f with 3 is
due to two concurrent causes. First, µ(2f) and µ(3) are so
close that ∆Ω (and hence δ∆Ω) is nearly 3 orders of
magnitude smaller than in the remaining cases. Besides,
the grand potential change due to the formation of the
N1-C1 bond is close to that for the N1-C2 bond; the same
occurs for the C3-C1 and the C3-C2 bonds. At the other
extreme, 2b shows higher selectivity toward 4b, a fact
somewhat unexpected on the basis of the usual substitu-
ent effect. Indeed, 2b has the highest chemical potential
(see Table 2) but this fact alone is not sufficient to account
for the large difference in ∆Ω. Dissecting the latter into
bond contributions, it turns out that the high selectivity
is caused by the particularly unfavorable interaction
between N1 and C2.
We have thus shown that the combined use of DFT
reactivity indices (of the reactants) with the HSAB
principle is superior to FMO theory in predicting the
favored regioisomer, and most important, it provides
quantitative prediction of regioselectivity and insight into
the details of atom-atom interactions in 1,3-DC reactions
without the need of locating transition states or even
characterizing products.
1
4c: 0.16 g, 30%; white solid; mp 100-102 °C; H NMR (300
MHz, CDCl3) δ 3.81 (3H, s), 3.94 (3H, s), 7.40-7.46 (5H, m),
7.51 (1H, s); 13C NMR (75 MHz, CDCl3) δ 52.21 (q), 52.0 (q),
114.0-128.0, 128.99 (d), 134.31 (s), 139.65 (s), 143.27 (s), 158.76
(s), 161.90 (s); IR (Nujol) 1720 cm-1; MS m/z 260 (M+). Anal.
Calcd for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C,
59.98; H, 4.60; N, 10.71.
4d : 0.13 g, 23%; pale yellow solid; mp 73-74 °C; 1H NMR
(300 MHz, CDCl3) δ 3.81 (3H, s), 3.95 (3H, s), 7.25-7.40 (4H,
m), 7.53 (1H, s); 13C NMR (75 MHz, CDCl3) δ 52.67 (q), 52.75
(q), 118.0-125.0, 127.98 (d), 133.72 (s), 135.80 (s), 159.95 (s),
160.80 (s), 162.06 (s); 19F NMR (282 MHz, CDCl3) δ -96.42; IR
Exp er im en ta l Section
(Nujol) 1735 cm-1; MS m/z 278 (M+). Anal. Calcd for C13H11
-
Com p u ta tion a l Meth od s. DFT calculations were performed
by means of the GAUSSIAN 94 program suite.16 The hybrid
B3LYP functional was employed with the standard 6-311+G-
(d,p) basis set. Geometry of 2a -f and 3 was fully optimized and
characterized with vibrational analysis at the same level of
theory. The anion and cation of 2a -f and 3 were treated at the
UB3LYP/6-311+G(d,p) level using the geometry of the neutral
systems. Atomic electron populations were evaluated following
the Merz-Kollman scheme.17 This scheme, which already proved
to be reliable,18 has been used in most DFT calculations of
FN2O4: C, 56.12; H, 3.98; N, 10.07. Found: C, 56.15; H, 4.04;
N, 10.11.
4e: 0.15 g, 26%; pale yellow solid; mp 102-103 °C; 1H NMR
(300 MHz, CDCl3) δ 3.80 (3H, s), 3.96 (3H, s), 7.25-7.32 (4H,
m), 7.46 (1H, s); 13C NMR (75 MHz, CDCl3) δ 51.90 (q), 53.22
(q), 116.0-124.8, 128.90 (d), 135.23 (s), 138.39 (s), 153.12 (s),
161.22 (s), 164.13 (s); IR (Nujol) 1730 cm-1; MS m/z 295 (M+).
Anal. Calcd for C13H11ClN2O4: C, 52.98; H, 3.76; N, 9.51.
Found: C, 52.92; H, 3.73; N, 9.57.
4f: 18 mg, 3%; yellow solid; mp 114-116 °C; 1H NMR (300
MHz, CDCl3) δ 3.76 (3H, s), 3.96 (3H, s), 7.59 (1H, s), 7.75-8.20
(4H, m); 13C NMR (75 MHz, CDCl3) δ 52.28 (q), 54.11 (q), 122.1-
126.7, 129.90 (d), 139.10 (s), 154.43 (s), 160.02 (s), 161.97 (s),
165.53 (s); IR (Nujol) 1740 cm-1; MS m/z 305 (M+). Anal. Calcd
for C13H11N3O6: C, 51.15; H, 3.63; N, 13.77. Found: C, 51.18;
H, 3.69; N, 13.70.
(16) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . P.; Head-Gordon, M.; Gonzalez, C.; Pople, J . A. Gaussian
94; Revision E.1; Gaussian, Inc.: Pittsburgh, PA, 1995.
(18) De Proft, F.; Martin, J . M. L.; Geerlings, P. Chem. Phys. Lett.
1996, 250, 393-401.
(19) Chattaraj, P. K. J . Phys. Chem. 2001, 105, 511-513.
(20) Yang, W.; Mortier, W. J . J . Am. Chem. Soc. 1986, 108, 5708-
5711.
(17) (a) Singh, U. C.; Kollman, P. A. J . Comput. Chem. 1984, 5, 129-
145. (b) Besler, B. H.; Merz, K. M., J r.; Kollman, P. A. J . Comput.
Chem. 1990, 11, 431-439.

Notes
5a : 0.20 g, 35%; pale yellow solid; mp 94-95 °C; 1H NMR
J . Org. Chem., Vol. 66, No. 15, 2001 5255
1730, 1720 cm-1; MS m/z 278 (M+). Anal. Calcd for C13H11
FN2O4: C, 56.12; H, 3.98; N, 10.07. Found: C, 56.05; H, 4.02;
N, 10.15.
-
(300 MHz, CDCl3) δ 3.84 (3H, s), 3.89 (3H, s), 3.93 (3H, s), 7.08
(1H, s), 7.10-7.30 (4H, m). 13C NMR (75 MHz, CDCl3) δ 46.36
(q), 53.16 (q), 53.25 (q), 116.14 (d), 118.5-129.0, 137.18 (s),
5e: 0.14 g, 24%; pale yellow solid; mp 95-96 °C; 1H NMR
(300 MHz, CDCl3) δ 3.80 (3H, s), 3.95 (3H, s), 7.20 (1H, s), 7.25-
7.32 (4H, m); 13C NMR (75 MHz, CDCl3) δ 52.30 (q), 52.39 (q),
118.05 (d), 120.0-133.0, 134.11 (s), 137.33 (s), 157.76 (s), 160.79
(s), 162.24 (s); IR (Nujol) 1735, 1730 cm-1; MS m/z 295 (M+).
Anal. Calcd for C13H11ClN2O4: C, 52.98; H, 3.76; N, 9.51.
Found: C, 53.05; H, 3.80; N, 9.49.
139.46 (s), 159.54 (s), 162.18 (s); IR (Nujol) 1730, 1720 cm-1
;
MS m/z 290 (M+). Anal. Calcd for C14H14N2O5: C, 57.93; H, 4.86;
N, 9.65. Found: C, 57.89; H, 4.81; N, 9.71.
5b: 0.34 g, 63%; white solid; mp 92 °C; H NMR (300 MHz,
1
CDCl3) δ 2.41 (3H, s), 3.81 (3H, s), 3.95 (3H, s), 7.15 (1H, s),
7.20-7.30 (4H, m); 13C NMR (75 MHz, CDCl3) δ 20.97 (q), 52.62
(q), 53.25 (q), 114.54 (d), 120.0-129.0, 138.16 (s), 143.27 (s),
158.84 (s), 161.93 (s); IR (Nujol) 1730, 1720 cm-1; MS m/z 274
(M+). Anal. Calcd for C14H14N2O3: C, 61.31; H, 5.14; N, 10.21.
Found: C, 61.25; H, 5.11; N, 10.15.
1
5f: 19 mg, 3%; yellow solid; mp 105 °C; H NMR (300 MHz,
CDCl3) δ 3.82 (3H, s), 3.96 (3H, s), 7.24 (1H, s), 7.75-8.20 (4H,
m); 13C NMR (75 MHz, CDCl3) δ 51.56 (q), 52.96 (q), 118.12 (d),
123.0-135.0, 139.30 (s), 160.19 (s), 162.87 (s), 166.80 (s); IR
(Nujol) 1740, 1730 cm-1; MS m/z 305 (M+). Anal. Calcd for
5c: 0.20 g, 39%; white solid; mp 90-92 °C; 1H NMR (300
MHz, CDCl3) δ 3.81 (3H, s), 3.94 (3H, s), 7.25 (1H, s), 7.40-7.48
(5H, m); 13C NMR (75 MHz, CDCl3): δ 52.19 (q), 52.91 (q), 118.27
(d), 114.0-128.0, 134.42 (s), 139.51 (s), 143.34 (s), 155.75 (s),
161.77 (s); IR (Nujol) 1730, 1720 cm-1; MS m/z 260 (M+). Anal.
Calcd for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C,
59.93; H, 4.62; N, 10.69.
C
13H11N3O6: C, 51.15; H, 3.63; N, 13.77. Found: C, 51.11; H,
3.59; N, 13.82.
Su p p or tin g In for m a tion Ava ila ble: Geometry, energy,
ionization potential, electron affinity, electron chemical po-
tential, and global softness of 2 and 3. Merz-Kolmann atomic
charge, local softness, and charge transfer of selected atoms
of 2 and 3. This material is available free of charge via the
Internet at http://pubs.acs.org.
5d : 0.14 g, 25%; pale yellow solid; mp 70-71 °C; 1H NMR
(300 MHz, CDCl3) δ 3.80 (3H, s), 3.96 (3H, s), 7.08 (1H, s), 7.25-
7.40 (4H, m); 13C NMR (75 MHz, CDCl3) δ 52.11 (q), 52.40 (q),
115.17 (d), 119.0-130.0, 135.16 (s), 136.44 (s), 155.75 (s), 159.90
(s), 161.77 (s); 19F NMR (282 MHz, CDCl3) δ -101.80; IR (Nujol)
J O0156159