Solid-state structure and tautomerism of 2-aminotroponimines studied by X-ray crystallography and multinuclear NMR spectroscopy

Article abstract of DOI:10.1002/ejoc.200400389

Structural studies in the solid state by X-ray crystallography and by ¹³C and ¹⁵N CPMAS NMR spectroscopy carried out on a series of 2-aminotroponimine derivatives 2-5 has allowed to establish the existence of hydrogen bonding and to determine the most stable tautomer. Almost all the structures reflect the classical double-well potential function for the N-H...N hydrogen bonds. Only in the case of the compound N-(pyrrol-1-yl)-2-(pyrrol-1-ylamino)troponimine (5) the crystal structure shows two independent molecules, one with a classical hydrogen bond and another with either a single-well or a low-barrier hydrogen bond. The structure of this compound is discussed with the use of the solid-state NMR spectroscopic data. 2-Aminotropones, as intermediates to the 2-aminotroponimines, show the oxo-tautomer as the stable form. B3LYP/6-31G* calculations are used to rationalise the experimental results. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400389

FULL PAPER
Solid-State Structure and Tautomerism of 2-Aminotroponimines Studied by
X-ray Crystallography and Multinuclear NMR Spectroscopy
[a]
[a]
[a]
[b]
´
Rosa M. Claramunt,* Dionisia Sanz, Marta Perez-Torralba, Elena Pinilla,
[b]
[c]
´
M. Rosario Torres, and Jose Elguero
Keywords: Hydrogen bond / Tautomerism / Aminotroponimines / Aminotropones / X-ray diffraction / NMR spectroscopy /
Density functional calculations
Structural studies in the solid state by X-ray crystallography
and by 13C and 15N CPMAS NMR spectroscopy carried out
on a series of 2-aminotroponimine derivatives 2−5 has al-
lowed to establish the existence of hydrogen bonding and to
determine the most stable tautomer. Almost all the structures
reflect the classical double-well potential function for the
classical hydrogen bond and another with either a single-
well or a low-barrier hydrogen bond. The structure of this
compound is discussed with the use of the solid-state NMR
spectroscopic data. 2-Aminotropones, as intermediates to the
2-aminotroponimines, show the oxo-tautomer as the stable
form. B3LYP/6-31G* calculations are used to rationalise the
N−H···N hydrogen bonds. Only in the case of the compound experimental results.
N-(pyrrol-1-yl)-2-(pyrrol-1-ylamino)troponimine (5) the crys-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
tal structure shows two independent molecules, one with a
Germany, 2004)
Introduction
8: R1 ϭ p-bromophenyl, 9: R1 ϭ p-chlorophenyl, 10: R1 ϭ
pyrrol-1-yl, 11: R1 ϭ 1,2,4-triazol-4-yl). Compounds 1 and
6 are model compounds for theoretical studies, as 2-amino-
troponimines and 2-aminotropones could exist in two tau-
tomeric forms a and b (Scheme 1). Tropolone itself (12) has
been used as a reference compound for structural and pro-
ton-transfer studies,[3] in particular for those concerning the
barriers of proton-transfers.
In search of new intramolecular hydrogen-bonded
(IMHB) systems, we turned our attention to 2-aminotro-
ponimines 1Ϫ5 and 2-aminotropones 6Ϫ11 as their inter-
mediates. These compounds, which are diaza and monoaza
derivatives of tropolone (12), are formally analogues of β-
diketones (13),[1] in which the central hydrogen-bonded six-
membered ring has been replaced by a five-membered one.
In previous papers we already explored the case of 6-amino-
fulvene-1-aldimines 14Ϫ17, with a central hydrogen-bonded
seven-membered ring.[2] Our purpose is therefore to provide
a complete overview on how these three structural motifs
(five-, six- and seven-pseudorings) affect tautomerism, hy-
drogen bonding and proton transfer, and these changes
should be reflected in the NMR parameters.
This paper deals with five 2-aminotroponimines (1: R1 ϭ
R2 ϭ H, 2: R1 ϭ R2 ϭ phenyl, 3: R1 ϭ R2 ϭ p-bromophe-
nyl, 4: R1 ϭ pyrrol-1-yl R2 ϭ phenyl, 5: R1 ϭ R2 ϭ pyrrol-
1-yl) and six 2-aminotropones (6: R1 ϭ H, 7: R1 ϭ phenyl,
[a]
´
´
´
Departamento de Quımica Organica y Bio-Organica, Facultad
de Ciencias, UNED,
Senda del Rey 9, 28040 Madrid, Spain
Fax: (internat.) ϩ 34-91-398-8372
E-mail: rclaramunt@ccia.uned.es
[b]
[c]
´
Laboratorio de Difraccion de Rayos X, Departamento de
´
´
´
Quımica Inorganica, Facultad de Ciencias Quımicas,
Universidad Complutense,
28040 Madrid, Spain
´
´
Centro de Quımica Organica ‘‘Manuel Lora-Tamayo’’, Instituto
´
´
de Quımica Medica, CSIC,
Scheme 1. Tautomeric forms for 2-aminotroponimines and 2-
aminotropones
Juan de la Cierva 3, 28006 Madrid, Spain
4452
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400389
Eur. J. Org. Chem. 2004, 4452Ϫ4466

Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
synthesis of 2-(tosyloxy)tropone (18, 82% yield)[7] with a
good leaving group to be replaced by anilines and 1-amino-
azoles.[8] For the second step, we modified the method of
Rasika et al.[9] by reducing the excess amine (from 13:1 to
1:1). This second step occurs with moderate yields (8Ϫ11,
22Ϫ40%), but a greater yield is obtained in the case of ani-
line itself (7, 77%).
Results and Discussion
Synthesis of 2-Aminotroponimines via 2-Aminotropones
Although N-phenyl-2-(phenylamino)troponimine (2) had
already been prepared from 5,5,6,6- and 6,6,7,7-tetrafluoro-
1,3-cycloheptadiene,[4Ϫ6] we have used the more outstand-
ing approach depicted in Scheme 2. The first step was the
To transform the 2-aminotropones 7Ϫ11 into 2-amino-
troponimines 2Ϫ5 it was necessary to quaternise them
either with triethyloxonium tetrafluoroborate,[9] methyl tri-
fluoromethanesulfonate,[10] or dimethyl sulfate.[11] We selec-
ted the triethyloxonium tetrafluoroborate and finally iso-
lated the intermediates 19 and 20. The reaction with p-
bromoaniline and 1-aminopyrrole affords the desired com-
pounds 3Ϫ5 (44Ϫ73% yield). The diphenyl derivative 2 was
prepared directly from 7 with 26% yield.
Some labelled derivatives of the four 2-aminotroponim-
ines were analogously prepared: 2-15N2 (N-1, N-9), 2-2H1
(10-D), 2-15N2-2H1 (N-1, N-9, 10-D); 3-2H1 (10-D); 4-15N
(N-1), 4-2H1 (10-D), 4-15N-2H1 (N-1, 10-D); 5-2H1 (10-D)
(Figure 1).
Crystal and Molecular Structures
A search through the Cambridge Crystallographic Data
Base (version 5.25, November 2003) resulted in only three
X-ray structures of related compounds: N-methyl-2-
methylamino)troponimine (21),[12] N-isopropyl-2-(isopro-
pylamino)troponimine (22)[9] and (R)-α-N-methylbenzyl-2-
[(R)-α-(methylbenzylamino)]troponimine (23).[13] In com-
pounds 22 (ZIPKEO, trigonal, P3, Z ϭ 6) and 23
(VAWTES, orthorhombic, P212121, Z ϭ 4), the hydrogen
atom is always localised on N1 and the system presents a
clear alternation of single and double bonds. From com-
pound 21 (MAMICH, orthorhombic, Iba2, Z ϭ 8), the au-
thors concluded from the X-ray data that the two nitrogen
atoms are chemically equivalent, but they were unable to
locate the proton of the hydrogen bond bridge.
Scheme 2. Outline of the synthetic route used to prepare the com-
pounds
Eur. J. Org. Chem. 2004, 4452Ϫ4466
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R. M. Claramunt, D. Sanz, M. Perez-Torralba, E. Pinilla, M. R. Torres, J. Elguero
FULL PAPER
bifurcated hydrogen bond which connects both molecules
through a weak hydrogen bond N11ϪH11···Br(12). This
fact leads to dimer pair units as depicted in Figure 3. In the
case of the N-(pyrrol-1-yl)-2-(phenylamino)troponimine (4),
both molecules have an intramolecular hydrogen bond but
their relative disposition can be considered as back-to-back
(Figure 4). In compound 5, one molecule has an intramol-
ecular hydrogen bond, N11ϪH11···N91, whereas in the se-
cond molecule the hydrogen bond involving H12 appears
to be centred to both N atoms (Figure 5) and could there-
fore be considered a symmetric hydrogen bond. This as-
sumption is corroborated by the distances found for
˚
˚
N(12)···H(12) (1.48 A) and N(92)···H(12) (1.56 A), as seen
in Table 2.
˚
Table 1. Selected bond lengths (A) and angles (°) for 2-aminotro-
ponimines 2, 3, 4 and 5
2
M1
3
M1
4
M1
5
M1
Molecule
N11ϪC21
1.36(1)
1.43(1)
1.48(2)
1.31(1)
1.43(1)
1.358(6)
1.426(6)
1.494(6)
1.310(6)
1.429(6)
1.885(5)
1.895(5)
1.367(3)
1.407(3)
1.470(3)
1.312(2)
1.407(2)
1.370(4)
1.380(3)
1.465(4)
1.314(4)
1.414(4)
N11ϪEl[a] 101
C21ϪC81
C81ϪN91
N91ϪEl[b]161
C131ϪBr11
C191ϪBr21
C21ϪN11ϪEl[a] 101 128(1)
129.1(4)
130.4(2)
120.7(3)
Figure 1. 2-Aminotroponimines 2Ϫ5
C21ϪN11ϪH11
117(5)
115.9
114.9
106.6
122.4
120.5
118.8
El[a]101ϪN11ϪH11 115(5)
N11ϪC21ϪC81
C21ϪC81ϪN91
114(1)
112(1)
112.9(5)
112.4(5)
121.7(4)
111.7(2)
112.6(2)
116.9(2)
111.3(4)
112.2(3)
114.8(3)
C81ϪN91ϪEl[b] 161 123(1)
Molecule
M2
M2
M2
M2
N12ϪC22
1.35(1)
1.37(1)
1.49(2)
1.32(1)
1.38(1)
1.345(6)
1.360(3)
1.341(4)
N12ϪEl[a]102
C22ϪC82
1.397(6)
1.471(7)
1.316(6)
1.407(6)
1.917(5)
1.892(6)
1.410(3)
1.484(3)
1.316(3)
1.410(2)
1.394(4)
1.472(5)
1.336(4)
1.384(4)
C82ϪN92
N92ϪEl[b]162
C132ϪBr12
C192ϪBr22
C22ϪN12ϪEl[a]102 126(1)
128.0(5)
129.5(2)
118.0(3)
C22ϪN12ϪH12
115(5)
116.0
116.0
111.9
118.5
104.4
136.8
El[a]102ϪN12ϪH12 117(5)
N12ϪC22ϪC82
C22ϪC82ϪN92
111(1)
114(1)
111.0(5)
114.1(5)
125.7(5)
111.8(2)
111.6(2)
116.2(2)
111.4(4)
111.7(4)
117.2(3)
C82ϪN92ϪEl[b]162 120(1)
In the case of the new 2-aminotroponimines 2Ϫ5 ana-
lysed by X-ray diffraction, we have found two monoclinic
crystal systems with space group P21/c for compounds 2
[a]
[b]
El ϵ C for 2, 3 and 4 and N for 5. El ϵ C for 2 and 3, and
N for 4 and 5.
¯
and 5 and two triclinic crystal systems with space group P1
for derivatives 3 and 4 (see Exp. Sect.).
Multinuclear NMR Studies
In all cases there are two independent molecules in the
asymmetric unit that show slight differences with respect to
the hydrogen bond. Selected bond lengths and angles are
collected in Table 1. In N-phenyl-2-(phenylamino)tropon-
Solid State
The 13C and 15ⁿ CPMAS NMR chemical shifts of 2-ami-
imine (2), both molecules are disposed face-to-face (Fig- notroponimines 2Ϫ5 are presented in Table 3 and are con-
ure 2) with the localisation of protons that present intra- sistent with the results obtained from the X-ray diffraction
molecular hydrogen bonds, N11ϪH11···N91 and analysis. The assignments have been made on the basis of
N12ϪH12···N92 (Table 2). Additionally, in the p-bromo- the solution NMR spectroscopic data (see below and Exp.
phenyl derivative 3, one molecule contains an asymmetrical Sect.).
4454
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Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
Figure 2. X-ray asymmetric unit of N-phenyl-2-(phenylamino)troponimine (2)
˚
Table 2. Hydrogen bonds for 2, 3, 4 and 5 (d, A)
Compound
molecule
DϪH···A
d(DϪH)
d(H···A)
d(D···A)
Ͻ(DHA)
2 M1
2 M2
3 M1
3 M1
3 M2
4 M1
4 M2
5 M1
5 M2
N(12)ϪH(12)···N(92)
N(11)ϪH(11)···N(91)
N(11)ϪH(11)···Br(12)
N(12)ϪH(12)···N(92)
N(11)ϪH(11)···N(91)
N(11)ϪH(11)···N(91)
N(12)ϪH(12)···N(92)
N(11)ϪH(11)···N(91)
N(12)···H(12)···N(92)
1.05(9)
0.98(10)
0.97
0.87
0.97
1.05
1.05
1.17
1.48
1.98(8)
2.05(10)
3.10
2.04
2.06
1.81
1.90
2.00
1.56
2.51(1)
2.52(2)
109(6)
107(7)
161.7
112.8
108.2
118.4
110.7
98.5
4.031(4)
2.505(6)
2.532(6)
2.482(3)
2.480(3)
2.464(4)
2.455(4)
108.1
Figure 3. X-ray asymmetric unit of N-(p-bromophenyl)-2-(p-bromophenylamino)troponimine (3)
In all cases, we observed signals due to the presence of localised proton, N-1/10-H, intramolecularly bonded to N-
two independent molecules in the asymmetric unit cell. In 9, the 15N NMR chemical shift for N-1 appears at about
compounds 2Ϫ4, in which the two molecules contain a Ϫ252 ppm (between Ϫ223.2 and Ϫ268.2 ppm), whereas for
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´
R. M. Claramunt, D. Sanz, M. Perez-Torralba, E. Pinilla, M. R. Torres, J. Elguero
FULL PAPER
Figure 4. X-ray asymmetric unit of N-(pyrrol-1-yl)-2-(phenylamino)troponimine (4)
are close to the above-mentioned values for N-1 (δ ϭ
Ϫ253.9 ppm) and for N-9 (δ ϭ Ϫ111.5 ppm). In contrast,
only very broad signals in the range of Ϫ190/Ϫ170 ppm
corresponding to the two types of nitrogen atoms (note that
the average of Ϫ252 and Ϫ122 is Ϫ187 ppm) are detected in
the second molecule. Sharp signals assigned to the pyrrole
nitrogen atoms are observed at δ ϭ Ϫ194.0 ppm and
Ϫ200.6 ppm (Table 3, ∆δ ϭ 6.6 ppm). For the other inde-
pendent molecule 5, these signals appear with a greater sep-
aration (∆δ ϭ 28.3 ppm).[14]
In order to better understand this observation, we had a
closer look at selected solid-state chemical shifts (Table 3)
and tried to align them to geometrical parameters (Table 2).
The selected chemical shifts were those corresponding to
N-1/N-9 and to C-2/C-8, which are expected to be more
sensitive to a/b tautomerism in 2-aminotroponimines. Note
that the crystallographic data shows two independent mol-
ecules (M1 and M2), but it is practically impossible to dif-
ferentiate between them by use of CPMAS NMR for com-
pounds 2Ϫ5. Thus, we decided to simply assume a ‘‘nor-
mal’’ molecule in the case of 5 M1 and a ‘‘proton-shared
molecule’’ in the case of 5 M2. The most significant NMR
spectroscopic results show the differences in chemical shifts
(∆δ ppm), whereas the most useful crystallographic data
show the differences between distances, i.e. d(H···A) and
d(DϪH), which is a frequent and useful way (usually also
described as r1 Ϫ r2) to discuss hydrogen bonds in crystal-
lography[15] and NMR spectroscopy.[16] As summarised in
Table 4, all parameters could be correlated with sometimes
moderate correlation coefficients. Note that all slopes are
positive, as expected.
Figure 5. X-ray asymmetric unit of N-(pyrrol-1-yl)-2-(pyrrol-1-yl-
amino)troponimine (5)
N-9 the average value is Ϫ122 ppm (between δ ϭ Ϫ103.8
and Ϫ161.1 ppm). The difference between the N-1/N-9 val-
ues of both independent molecules is due to the effect of the
substituent on the chemical shift. The observed 15N NMR
chemical shift values for the NH2 group in aniline (δ ϭ
Ϫ322.0 ppm), p-bromophenylaniline (δ ϭ Ϫ319.7 ppm) and
1-aminopyrrole (δ ϭ Ϫ309.5 ppm) support this statement.
It is well known that the 15N NMR spectroscopy is more
The most interesting case, N-(pyrrol-1-yl)-2-(pyrrol-1-yl- sensitive to tautomerism and steric effects and pertur-
amino)troponimine (5), also presents two molecules in the bations than 13C NMR spectroscopy due to the closeness
unit cell. 15N NMR chemical shifts for one of the molecules of the relevant atoms to the tautomeric site and the larger
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Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
Table 3. 13C and 15N CPMAS NMR chemical shifts (δ, ppm) of 2, 3, 4 and 5
Compound
2
3
4
5
M1
140.2
108.9
133.5
125.4
132.3
118.9
151.0
M2
M1
139.3
112.2
133.8
125.6
132.8
120.6
153.9
M2
M1
M2
M1
149.6
113.1
135.7
125.5
134.5
115.6
160.6
Ϫ
121.9/120.9
108.8/108.1
Ϫ253.9 (br.)
Ϫ111.5 (br.)
M2
C-2
C-3
C-4
C-5
C-6
C-7
C-8
141.8
110.5
133.9
125.4
132.9
120.5
154.5
141.1
110.1
133.8
125.6
132.8
118.9
151.5
139.2
110.8
135.3
122.5
135.3
120.2
160.8
144.4
118.0
105.7
Ϫ268.2
Ϫ107.1
137.2
110.0
135.3
122.5
135.3
119.5
161.4
144.4
118.3
105.7
Ϫ268.2
Ϫ103.8
153.8 (br.)
117.5 (br.)
134.5 (br.)
124.9
134.5
117.5 (br.)
156.3 (br.)
[a]
i-Carom.
150.7 (2 C)/150.3/149.3
148.6/147.1 (2 C)/144.8
C-2Ј/C-5Ј
C-3Ј/C-4Ј
N-1
Ϫ
Ϫ
Ϫ239.9
Ϫ134.5
Ϫ
Ϫ
120.1 (br.)
107.0 (br.)
ca. Ϫ190 (v br.)
ca. Ϫ170 (v br.)
Ϫ261.5
Ϫ114.2
Ϫ251.8 Ϫ
Ϫ129.4
223.2
Ϫ161.1
N-9
Ϫ102.4
N-1Ј
Ϫ
Ϫ
Ϫ185.5
Ϫ183.9
Ϫ183.6/Ϫ211.9
Ϫ194.0/Ϫ200.6
[a]
For compound 1: o-Carom. 124.1/123.5/121.9 (4 C)/121.5/120.5, m-Carom. 132.9/130.1(br., 7 C), p-Carom. 127.8 (br)/126.5 (br); for com-
pound 2: o-Carom. 125.6 (2 C)/124.2 (2 C)/121.9(2 C)/120.6(2 C), m-Carom. 133.8 (br)/132.8 (br)/128.6, p-Carom. 115.9 (br); for compound
3: o-Carom. 123.9, m-Carom. 131.0 (br), p-Carom. 125.4.
˚
Table 4. Most relevant CPMAS NMR spectroscopic data (Table 3, ppm) and crystallographic data [Table 2 (A)]
Comp.
2 (M1)
2 (M2)
3 (M1)
3 (M2)
4 (M1)
4 (M2)
5 (M1)
5 (M2)
∆δ (N-9/N-1)
∆δ (C-8/C-2)
r1 Ϫ r2
105.4
10.8
0.93
1.038
0.0382
147.3
12.7
1.07
1.023
0.0227
122.4
14.6
1.17
1.037
0.0366
62.1
10.4
1.09
1.022
0.0220
161.1
21.6
0.76
1.042
0.0419
165.1
24.4
0.85
1.033
0.0334
142.4
11.0
0.83
1.043
0.0426
ഠ 20
2.5
0.08
1.004
0.0037
ratio[a]
ratio Ϫ1
Correlations (no intercept)[b]
∆δ (N-9/N-1) ϭ (8.2Ϯ0.7) ∆δ (C-8/C-2), r2 ϭ 0.95
∆δ (N-9/N-1) ϭ (129Ϯ18) (r1 Ϫ r2), r2 ϭ 0.88
ratio Ϫ1 ϭ (0.25Ϯ0.02) 103 ∆δ (N-9/N-1), r2 ϭ 0.94
[a]
[b]
The ratio is defined as d(N1ϪC2)/d(C8ϪN9) (Table 1). All these properties became 0 when the proton is in the middle or when the
exchange between tautomers is fast in the NMR time scale.
chemical shift anisotropy. By Considering compound 4a as maining three cases (2 M2 with δ ϭ 105 ppm, 3 M1 with
the model compound without tautomerism or proton dis- δ ϭ 122 ppm and 2 M2 with 62 ppm) are indicative of some
order and with 15N NMR chemical shift values of δ ϭ dynamic asymmetric disorder with different a/b populations
Ϫ268 ppm [ϪN1(H)ϪPh] and Ϫ105 ppm (ϭN9ϪPyrr), we of both tautomers.
have estimated the effect of the replacement of substituents
(phenyl ring by a p-bromophenyl ring or a 1-pyrrolyl
Solution NMR Studies Related to Tautomerism
ring[17Ϫ20]) on the 15N chemical shifts. The results are
1
2
The H NMR, H NMR, 13C NMR, 15N NMR and 17O
NMR chemical shifts and coupling constants for 2-amino-
troponimines 2Ϫ5 and 2-aminotropones 7Ϫ11 are reported
in the Exp. Sect. (see Scheme 2 for numbering of the
NMR positions).
shown in Figure 6 as chemical shifts differences ∆δ
(N-9/N-1).
A comparison of the estimated values with those of
Table 3 shows on one hand that the average values for 2, 3
and 5 are similar to the values presented in Table 3, which
are also very similar to the chemical shifts measured in
solution. On the other hand, the differences always lie in
the 145Ϫ150 ppm range; only 2 M1 and 5 M1 show differ-
ences (147 and 142 ppm, respectively). This is in agreement
with the presence of only one tautomer with a localised
proton in the solid state. In the case of 5 M2, the chemical
shift difference of about 20 ppm corresponds to a situation
in which two tautomers are present with a very fast proton
Assignments have been made with the help of H-1H gs-
1
1
1
1
COSY, H-1H gs-NOESY, H-13C gs-HMQC and H-13C
gs-HMBC experiments. 15N NMR chemical shifts and
coupling constants J(N-1,10-H) were obtained by 2D in-
1
verse proton detection heteronuclear shift correlation
spectra gs-HMBC, as depicted for compounds 7 and 10 in
Figure 7.
With regard to tautomerism, from the data gathered in
exchange rate. By X-ray crystallography the foregoing situ- Table 5, we can conclude that in the 2-aminotropones only
ation cannot be distinguished from another with a localised tautomer a is present with δ15N-1 ranges from Ϫ266.8 ppm
proton in the centre of both nitrogens (N-1/N-9). The re- to Ϫ288.7 ppm and δ17O-9 from 381.5 ppm to 395.4 ppm.
Eur. J. Org. Chem. 2004, 4452Ϫ4466
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R. M. Claramunt, D. Sanz, M. Perez-Torralba, E. Pinilla, M. R. Torres, J. Elguero
FULL PAPER
Figure 6. 15N CPMAS NMR spectroscopic data for 2-aminotroponimines 2Ϫ5
Table 5. Summary of the most relevant NMR spectroscopic data in CDCl3 at room temperature for aminotroponimines and aminotro-
pones (for the remaining data see the Exp. Sect.)
Compound
δ 10-1H
δ 10-2H[a]
δ15N-1
δ15N-9
δ17O-9
1J(N-1,10-H)
2hJ(N-1,N-9)
2
9.20
9.04
8.75
8.96
8.76
8.67
8.68
8.88
8.98
9.09
8.99
8.72
8.93
8.74[e]
8.65
8.66
8.87
8.94
Ϫ193.7
Ϫ196.3
Ϫ271.6
Ϫ188.4
Ϫ271.7
Ϫ274.4
Ϫ274.0
Ϫ266.8
Ϫ288.7
Ϫ193.7
Ϫ196.3
Ϫ114.4
Ϫ188.4
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
384.8
381.5
386.6
395.4
n.o.[g]
44.6[b]
Ϫ
5.3[c]
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
Ϫ
3
4
89.9[d]
Ϫ
5
7
92.4[f]
92.2[f]
92.6[f]
103.5[f]
n.o.[g]
8
9
10
11
[a]
[b]
[c]
[d]
[e]
CDCl3 ϩ D2O.
[D6]DMSO, 2-15N2.
Obtained by iterative analysis using Win-Daisy 3.0.[23]
[D8]THF, 4-15N(N-1).
7-15N.
[f] Determined by gs-HMBC. n.o.: not observed.
[g]
The 13C and 15N NMR spectra of N-phenyl-2-(phenyl- due to the difference between solid and aqueous am-
amino)troponimine (2) had previously been recorded by monium chloride.[22]
Jackman et al.[21] in deuteriobromoform at 26 °C, and val-
For the symmetric derivatives 3 (R1 ϭ R2 ϭ p-bromophe-
ues close to those described in this paper were observed. nyl) and 5 (R1 ϭ R2 ϭ pyrrol-1-yl), only one signal in the
These authors report a chemical shift for δ15N-1/N-9 of 15N NMR spectra is also observed. In the case of N-(pyrrol-
164.8 ppm referenced to external 1.0  aqueous 15NH4Cl, 1-yl)-2-(phenylamino)troponimine (4), tautomer a is ob-
compared with our experimental value of 144.4 ppm using served, as demonstrated by δ15N-1 at Ϫ271.6 ppm and
solid 15NH4Cl [in Table 5 our value was referenced to exter- δ15N-9 at Ϫ114.4 ppm.
1
nal NO2CH3 using the relationship δ(external NO2CH3) ϭ
The H NMR spectra of 2-15N2 were recorded in differ-
δ(solid 15NH4Cl) Ϫ 338.1 ppm]. The 20 ppm difference is ent solvents in order to measure the 1J(N-1,10-H) coupling.
4458
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Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
In an attempt to block the proton transfer, we cooled
down the solution of 2-15N2 in [D8]THF and [D18]HMPA,
but without success (Figure 8). The signals sharpened in
[D18]HMPA, and it was also possible to observe the doublet
corresponding to the 10-H proton in the equilibrium
15NϪH10···14N w 15N···H10Ϫ14N (marked with * in Fig-
ure 8) due to the small amount of 14N aniline present in
15N aniline.
1
Figure 8. Variable temperature H NMR of 2-15N2 (10-H region)
in [D18]HMPA and [D8]THF
It was expected that 1H and 2H chemical shift values
should be the same, and this was indeed the case for amino-
tropones 7Ϫ11. In the case of aminotroponimines 2Ϫ5
these values are only proportional [δ2H ϭ (1.5Ϯ0.7) ϩ
(0.83Ϯ0.08)δ1H]. We assign this effect to a modification of
the geometry of the hydrogen bond produced by the re-
placement of H by D. In the case of aminotropones, if com-
pound 11 is not considered, there is a proportionality be-
tween the 15N and 1H chemical shift values [δ15N ϭ
Ϫ(585Ϯ18) ϩ (36Ϯ2)δ1H; the value predicted for 11 is
Ϫ253.4 ppm]. A last observation involves the 2hJ(N-1,N-9)
value for compound 2 (5.3 Hz); this coupling constant was
determined at 325 K and increases to 10.5 Hz when the
temperature is lowered to 237 K (which is similar to the
value of 10.6 Hz measured for 14). As reported earlier in
the literature, this is due to a contraction of the N···N dis-
tance on cooling [i.e. the value of 2hJ(N-1,N-9) increases
when r1 Ϫ r2 decreases].[2c]
Figure 7. gs-HMBC correlation spectra: a) compound 7 in CDCl3;
b) compound 10 in CDCl3
In CDCl3 (δ 10-1H, 9.20), CD3CN (δ 10-1H, 9.20) and
[D8]THF (δ 10-1H, 9.32 ppm), only a single signal is ob-
served. However in [D6]DMSO and [D18]HMPA a triplet
centred at δ ϭ 9.25 ppm and 9.31 ppm, respectively, with
a coupling constant value of 44.6 Hz is observed. The
2hJ(N-1,N-9) value was indirectly estimated as 5.3 Hz from
DFT Calculations
The calculations were carried out at the hybrid B3LYP/
the 13C NMR spectra of 2-15N2 in CDCl3, by iterative 6-31G* level (see Exp. Sect.). Tautomer a (R ϭ H) of the
analysis using the Win-Daisy 3.0 program.[23] All these re- 2-aminotropone 6 is much more stable than tautomer b by
sults prove that, apparently, at 300 K, the proton is 47.3 kJ·molϪ1 (48.1 kJ·molϪ1 with ZPE). This is consistent
symmetrically located but actually corresponds to a pair of with our findings and it is a general finding for all tauto-
rapidly equilibrating degenerate tautomers 2a/2b.
mers involving conjugated CϭO and CϭNH bonds (for in-
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R. M. Claramunt, D. Sanz, M. Perez-Torralba, E. Pinilla, M. R. Torres, J. Elguero
FULL PAPER
stance, enamino ketones, the monoaza derivatives of 12),
except when they are part of an aromatic ring (e.g. pyri- hydrogen-bonded dimers 12 have been observed in the solid
done/hydroxypyridine). state. Nevertheless, for model compound 1, we have calcu-
For the experimentally studied 2-aminotroponimines no
Before discussing the kinetic aspects of the proton trans- lated the intramolecular barrier for the monomer
fer in 2-aminotroponimines 1Ϫ5, let us briefly summarise (51.2 kJ·molϪ1) and the dimer 12 (TS C2, 62.8 kJ·molϪ1).
the results for tropolone (12). Experimentally, two barriers The ZPE correction results in barriers of 39.9 and
have been measured for this compound, one corresponding 39.2 kJ·molϪ1, respectively.
to the monomer either in the gas phase, 57.3 kJ·molϪ1 [3b,3c]
or included in cyclodextrin, between 39 and
,
a
51 kJ·mol .
Ϫ1 [3f] In the solid state, the barrier is much higher,
Conclusions
109Ϯ21 kJ·molϪ1
or 99Ϯ8.[3h] This interpretation has
[3a]
In the solid state, the most relevant conclusions on the
tautomerism of 2-aminotroponimines 2Ϫ5 comparatively
with that of 6-aminofulvene-1-aldimines (14: R1 ϭ R2 ϭ
phenyl, 15: R1ϭ pyrrol-1-yl, R2 ϭ phenyl, 16: R1 ϭ R2 ϭ
pyrrol-1-yl, 17: R1 ϭ 1,2,4-triazol-4-yl, R2 ϭ phenyl) [see
Figure 10] are that the unsymmetrical compounds (R1 ϶
R2) behave similarly in both series; the NϪH amino proton
is located on N-1. In the symmetrical derivatives, the N-
phenyl-2-(phenylamino)troponimine (2) presents the proton
located on the N-1 but in the N,NЈ-diphenyl-6-aminoful-
vene-1-aldimine (14) there is a rapid proton transfer at
300 K that could only be frozen at low temperature (δ15N-
1 Ϫ196.7 ppm and δ15N-9 Ϫ131.0 ppm at 126 K, 7.1T).[14]
1) X-ray crystal structure determination of the N-phenyl-
2-(phenylamino)troponimine (2) affords a NϪH bond
been contested by Detken, Zimmermann, Haeberle and Luz
who proposed a different mechanism with barriers of 29
and 23 kJ·molϪ1 [3j]
These dramatic differences in the bar-
.
rier (KSSE, kinetic solid-state effect)[24] are due to the struc-
ture of tropolone in the solid state, in which it forms two
near planar dimers (122, Figure 9[25] The equilibrium be-
tween tropolone tautomers in the solid state involves not
only a proton transfer (usually lower in the solid state due
to tunneling effects) but a complete reorganisation of the
molecule 122 in the crystal.
˚
length of 1.02Ϯ0.10 A and a CiϪNϪH bond angle of
108Ϯ7° (average of two independent molecules, Table 2).
Taking into account crystal packing effects, the agreement
between the geometry of the hydrogen bond, determined
Figure 9. 2-Aminotroponimine and tropolone dimers
Several authors have calculated the barrier for tropolone
monomer 12,[3e,3g,3k] the most exhaustive work being that of
Redington and Bock.[3d] These authors obtain a reasonable,
although low, value at the MP4(DQ) level (41.6 kJ·molϪ1
)
that decreases to 15.2 kJ·molϪ1 at the MP2/6-311G** level.
These difficulties could be related to the transfer of the pro-
ton through the out-of-plane pathway instead of through
the in-plane pathway.[3s,3t]
At the B3LYP/6-31G* level, a value of 22.3 kJ·molϪ1 for
the monomer (intramolecular) and 39.3 kJ·molϪ1 for the di-
mer (intermolecular) was obtained, allowing for a twisted
TS (C2) in the second case. If planarity of 122 in the TS is
imposed, the barrier increases to 73.8 kJ·molϪ1. ZPE cor-
rections lowers these figures to 12.2, 16.9 and
48.6 kJ·molϪ1, respectively.
Figure 10. 15N CPMAS NMR spectroscopic data[2d,2e,14] for 6-
aminofulvene-1-aldimines 14Ϫ17
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Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
for 2 in CDBr3 solution, the NϪH bond length of pounds afford the following averaged data: aminotropon-
˚
1.072Ϯ0.004 A and the CiϪNϪH bond angle of 116Ϯ3°, imines 2Ϫ5 (Table 2, excluding 5 M2 for distances and
˚
using spin-lattice relaxation times, is excellent. The position angles): 2.50
A
and 109°; aminofulvenealdimines
of the mobile proton clearly establishes the symmetric 14Ϫ17:[2b,2c,2f] 2.82 A and 154°. Information on β-enamino-
˚
double-well nature of the hydrogen bond.[21a]
imines is scarce, only the X-ray structure of 24 (EAI, R ϭ
˚
2) The molecule M2 of compound 5 presents a very inter- Ph, RЈ ϭ Me) has been described before (N···N ϭ 2.67 A,
esting structure. The position of the H-12 hydrogen bond NϪH···N ϭ 138.9°).[26] In the gas phase (theoretical calcu-
centred to both N atoms (Figure 5) can be explained as lations), the barrier to NHN proton transfer is lower in AFI
arising as a result of a single-well situation or, a double- than in ATI, therefore only the first are low barrier hydro-
well symmetric situation where a short N···N distance is gen bonds. In solution the 2hJ(N-1,N-9) coupling constant
present and where the proton is disordered between two is larger for AFI than for ATI and in the solid state there
close positions. Because it is always difficult to localise the are cases of proton disorder in both series. In summary, the
proton in crystallography, we focussed our discussion on linearity of the NϪH···N angle is more important than the
the ratio of the N1ϪC2 to C8ϪN9 distances (Table 4). In shortness of the N···N distance for strong hydrogen bonds
a symmetric situation the ratio is 1; for a more asymmetric (Figure 12).
structure, the value will deviate from 1. A closer look at
Table 4 shows that the average ratio is 1.034; however, for 5
M2, the ratio is 1.004 (Figure 11).
Figure 11. View of the situation present in 2-aminotroponimines
regarding the exocyclic CϪN bonds
Figure 12. Experimental distances and angles involved in hydrogen
bonding for 2-aminotroponimines (ATI), β-enaminoimines (EAI)
and 6-aminofulvene-1-aldimines (AFI)
Note finally, that the two independent molecules of 5
correspond to the extreme situations, proof that the packing
Comparison of the experimental geometries with those
effects alter the geometry of the molecule to the extent of of the corresponding regular polygons (the distance for the
˚
transforming a classical hydrogen bond into a low barrier pentagon has been fixed at 2.50 A) shows that the exper-
hydrogen bond.
imental distances are very similar to the regular polygon
3) Assuming that δ ϭ 145 ppm is the maximum value for distances. This is not the case for the the angles, the angles
∆δ (N-9/N-1) and that the exchange rate is fast in the NMR are the same for the five-membered rings, but much higher
time scale, the differences observed in Table 4 correspond for the six- and seven-membered rings, which suggests that
to the following percentages of the presence of the proton the proton moves inside the pseudoring.
on N1: 2 M1 100%, 2 M2 86%, 3 M1 92%, 3 M2 71%, 5
Finally, are our results concerning NN compounds simi-
M1 100% and 5 M2 57%. Since no proton disorder was lar to the corresponding OO compounds? Gilli and Bertola-
found by crystallography, these values should be taken with si[1b] consider that tropolones are α-diketones in which the
caution. It is possible that close contacts with bromine in 3 OϪH···O closes a five-membered ring or ζ-diketones con-
M2 modify the 15N chemical shifts (Table 3 and Table 4).
sidering the seven-membered ring periphery. In tropolones
4) The relative properties of 6-aminofulvene-1-aldimines the hydrogen bond is weak due to the unfavourable geo-
(AFI), β-enaminoimines (EAI) and 2-aminotroponimines metry of the five-membered ring with an OϪH···O angle of
˚
(ATI) should be related to the geometry of the hydrogen- about 110° (the O···O distances are about 2.59 A), which is
bonded pseudocycle, a five, six or seven-membered ring. A quite far from the usual, almost linear OϪH···O angle of
hydrogen bond is stronger the more linear the NϪH···N β-diketones (in the case of acetylacetone, OϪH···O ϭ 151°,
[27]
˚
bond and the shorter the N···N distance; this, in turn, deter- O···O ϭ 2.54 A).
On the other hand, although 6-
mines the proton transfer abilities and the 2hJ(N-1,N-9) hydroxy-1-fulvenecarboxaldehydes could be classified as γ-
coupling constants. Experimentally, for the two systems we diketones, they are better described as ζ-diketones with
have studied (AFI and ATI), X-ray geometries of these com- much stronger hydrogen bonds than the tropolones
Eur. J. Org. Chem. 2004, 4452Ϫ4466
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FULL PAPER
˚
2-(Phenylamino)tropone (7): A solution of 18 (1.00 g, 3.6 mmol) in
(OϪH···O ϭ 173°, O···O ϭ 2.47 A). There is a perfect
correlation between NϪH···N and OϪH···O angles (NHN
angle ϭ 30 ϩ0.72OHO angle, r2 ϭ 1.000) for the three com-
pounds; this is not the case for the N···N/O···O lengths. This
may be because tropolone is a dimer with intermolecular
hydrogen bonds.[1b]
EtOH (30 mL) was refluxed with aniline (0.37 mL, 4.04 mmol) for
26 h 30 min. The solvent was evaporated, and the crude was puri-
fied by column chromatography (EtOAc/hexane, 1:20) to afford 7
1
as a brown oil (550 mg, 77%). H NMR (CDCl3): δ ϭ 8.76 (br. s,
1 H, 10-H), 7.43 (m, 2 H, m-Harom.), 7.33 [ddd, 3J(6-H,7-H) ϭ 11.7,
3J(6-H,5-H) ϭ 8.2, 4J(6-H,4-H) ϭ 1.1 Hz, 1 H, 6-H], 7.30 (m, 3 H,
o-Harom. and 7-H), 7.25 (m, 1 H, p-Harom.), 7.18 [dd, 3J(3-H,4-H) ϭ
4
3
10.4, J(3-H,5-H) ϭ 1.3 Hz, 1 H, 3-H], 7.12 [ddd, J(4-H,5-H) ϭ
9.7 Hz, 1 H, 4-H], 6.77 [tdd, 4J(5-H,7-H) ϭ 1.3 Hz, 1 H, 5-H] ppm.
13C NMR (CDCl3): δ ϭ 177.0 (C-8), 153.7 (C-2), 138.3 (i-Carom.),
Experimental Section
137.5 (1J ϭ 154.0 Hz, C-6), 135.9 (1J ϭ 155.6, J ϭ 9.2 Hz, C-4),
3
General: Melting points were determined by DSC with a SEIKO
DSC 220C connected to a Model SSC5200H Disk Station. Ther-
mograms (sample size 0.003Ϫ0.010 g) were recorded with a scan
rate of 2.0 °C·minϪ1. Unless otherwise stated, column chromatog-
raphy was performed on silica gel (Merck 60, 70Ϫ230 mesh). The
Rf values were measured on aluminium-backed TLC plates of silica
gel 60 F254 (Merck, 0.2 mm) with the indicated eluent. Com-
pounds 2Ϫ5 and 7Ϫ11 have been fully characterised by electros-
pray mass spectrometry.[28] In addition, mass spectra (HRMS) at
70 eV using electron impact mode was performed with a VG
130.6 (1J ϭ 158.2, 3J ϭ 10.0 Hz, C-7), 129.7 (1J ϭ 163.0 Hz, m-
Carom.), 125.9 (1J ϭ 162.9 Hz, p-Carom.), 124.5 (1J ϭ 159.9, 3J ϭ
3J ϭ 9.7 Hz, C-5), 124.1 (1J ϭ 161.1 Hz, o-Carom.), 110.4 (1J ϭ
153.7, J ϭ 10.7, J ϭ 6.0 Hz, C-3) ppm. 15N NMR (CDCl3): δ ϭ
Ϫ271.7 [1J(N-1,10-H) ϭ 92.4 Hz, N-1] ppm. 17O NMR (CDCl3):
δ ϭ 384.8 (O-9) ppm. C13H11NO (197.08): calcd. C 79.16, H 5.62,
N 7.10; found C 78.93, H 5.797, N 7.029.
3
3
[15N]-2-(Phenylamino)tropone: A solution of 18 (1.00 g, 3.6 mmol)
in EtOH (30 mL) was refluxed with labelled aniline (400 mg,
3.98 mmol) for 26 h 30 min. The solvent was evaporated, and the
crude product was purified by column chromatography (EtOAc/
hexane, 1:20) to afford 7-15N as a brown oil (380 mg, 52%). 1H
´
AUTOSPEC spectrometer by Laboratorio de Espectrometrıa de
Masas-UAM, Madrid. Elemental analyses were performed using
PerkinϪElmer 240 by Centro de Microanalisis Elemental-UCM,
´
Madrid.
1
NMR (CDCl3): δ ϭ 8.75 [d, J(10-H,N-1) ϭ 92.3 Hz, 1 H, 10-H],
DFT Calculations: The optimisation of the structures of all com-
pounds discussed in this paper was carried out at the hybrid
B3LYP/6-31G* level.[29,30]
3
3
7.43 (m, 2 H, m-Harom.), 7.33 [ddd, J(6-H,7-H) ϭ 11.7, J(6-H,5-
H) ϭ 8.2, 4J(6-H,4-H) ϭ 1.1 Hz, 1 H, 6-H], 7.30 (m, 3 H, o-Harom.
and 7-H), 7.25 (m, 1 H, p-Harom.), 7.18 [dd, 3J(3-H,4-H) ϭ 10.4,
4J(3-H,5-H) ϭ 1.3 Hz, 1 H, 3-H], 7.12 [ddd, 3J(4-H,5-H) ϭ 9.7 Hz,
1 H, H-4], 6.77 [tdd, 4J(5-H,7-H) ϭ 1.3 Hz, 1 H, 5-H] ppm. 13C
NMR (CDCl3): δ ϭ 177.0 (C-8), 153.7 [1J(C,N) ϭ 17.5 Hz, C-2],
138.3 [1J(C,N) ϭ 16.1 Hz, i-Carom.], 137.5 (C-6), 135.9 (C-4), 130.6
(C-7), 129.7 [3J(CϪN) ϭ 1.9 Hz, m-Carom.], 126.0 (p-Carom.), 124.6
(C-5), 124.1 [2J(C,N) ϭ 2.0 Hz, o-Carom.], 110.5 (C-3) ppm. Com-
pound 7-15N-2H1 was prepared directly in the NMR sample tube
by agitating the CDCl3 solution with D2O: Only 10-H exchange.
The NMR spectroscopic data for the corresponding 10-D deuter-
ated derivative; 2H NMR (CDCl3 ϩ D2O): δ ϭ 8.74 [1J(N,D) ϭ
14.1 Hz, 10-D] ppm. 13C NMR (CDCl3 ϩ D2O): δ ϭ 176.9
[2J(CϪN) ϭ 0.9 Hz, C-8], 153.5 [1J(C,N) ϭ 18.2 Hz, C-2], 138.2
[1J(C,N) ϭ 16.5 Hz, i-Carom.], 137.5 (C-6), 136.0 [3J(C,N) ϭ 1.9 Hz,
C-4], 130.7 (C-7), 129.7 [3J(C,N) ϭ 1.9 Hz, m-Carom.], 126.0 (p-
Carom.), 124.6 (C-5), 124.1 [2J(C,N) ϭ 1.8 Hz, o-Carom.], 110.5
[2J(C,N) ϭ 1.8 Hz, C-3] ppm. 15N NMR (CDCl3 ϩ D2O): δ ϭ
Ϫ272.4 (1J(N-1,10ϪD) ϭ 14.1 Hz, N-1) ppm.
NMR Parameters: 1H (400.13 MHz), 13C (100.61 MHz), 2H
(61.42 MHz), 15N (40.56 MHz) and 17O NMR (54.26 MHz) spec-
tra in solution were obtained with a Bruker DRX-400 instrument
at 300 K. Chemical shifts (δ) are given from internal CHCl3 (7.26)
for H NMR, CDCl3 (7.25) for H NMR, 13CDCl3 (77.0) for 13C
NMR, external nitromethane (0.00) for 15N NMR and external
D2O (0.00) for 17O NMR spectroscopy. Coupling constants (J in
Hz) are accurate to Ϯ 0.2 Hz for 1H, and Ϯ 0.6 Hz for 13C and
15N. 2D-Inverse proton detected homonuclear shift correlation
spectra gs-COSY, and heteronuclear shift correlation spectra gs-
HMQC and gs-HMBC were obtained with the standard pulse se-
quences.[31] Solid-state 13C (100.73 MHz) and 15N (40.59 MHz)
CPMAS NMR spectra have been obtained with a Bruker WB-400
spectrometer at 300 K with a wide-bore 4-mm DVT probehead at
rotational frequencies of approximately 5Ϫ10 kHz. Samples were
carefully packed in ZrO2 rotors, and the standard CPMAS pulse
sequence and NQS technique (Non Quaternary Suppression to ob-
serve only the quaternary C atoms) were employed.[31]
1
2
2-(p-Bromophenylamino)tropone (8): A solution of 18 (1.75 g,
6.3 mmol) in EtOH (60 mL) was refluxed with p-bromoaniline
(1.25 mL, 7.3 mmol) for 54 h. The solvent was evaporated, and the
2-(Tosyloxy)tropone (18): Compound 18 was synthesised according
to a published procedure.[9] M.p. 156.9 °C (EtOH), (ref. m.p.
159.0Ϫ159.5 °C)[7]. 1H NMR (CDCl3): δ ϭ 7.92 (m, 2 H, o-Harom.), crude product was purified by column chromatography (EtOAc/
7.45 [dd, 3J(7-H,6-H) ϭ 9.3, 4J(7-H,5-H) ϭ 0.9 Hz, 1 H, 7-H], 7.34
hexane, 1:20) to afford 8 (690 mg, 39%). M.p. 158.2 °C (CHCl3/
3
4
1
(m, 2 H, m-Harom.), 7.20 [ddd, J(4-H,5-H) ϭ 7.8, J(4-H,6-H) ϭ hexane). H NMR (CDCl3): δ ϭ 8.67 (br. s, 1 H, 10-H), 7.55 (m,
1.2 Hz, 1 H, 4-], 7.13 [d, J(3-H,4-H) ϭ 12.2 Hz, 1 H, 3-H], 7.08 2 H, m-Harom.), 7.34 [dd, 3J(6-H,7-H) ϭ 11.8, 3J(6-H,5-H) ϭ
3
3
[ddd, J(5-H,6-H) ϭ 10.9 Hz, 1 H, 5-H], 6.97 [ddd, 1 H, 6-H], 2.45
8.5 Hz, 1 H, 6-H], 7.27 (br. d, 1 H, 7-H), 7.18 (m, 2 H, o-Harom.),
(s, 3 H, CH3) ppm. 13C NMR (CDCl3): δ ϭ 179.4 (C-8), 155.1 (C- 7.14Ϫ7.10 (m, 2 H, 3-H and 4-H), 6.80 (m, 1 H, 5-H) ppm. 13C
2), 145.5 (p-Carom.), 141.2 (1J ϭ 162.6, 3J ϭ 8.8 Hz, C-4), 136.3 NMR (CDCl3): δ ϭ 177.1 (C-8), 153.1 (C-2), 137.6 [1J ϭ 155.3 Hz,
3
(1J ϭ 158.5, 3J ϭ 11.0 Hz, C-3), 134.6 (1J ϭ 161.9, 3J ϭ 3J ϭ
9.7 Hz, C-5), 133.4 (i-Carom.), 130.8 (1J ϭ 163.7, 3J ϭ 9.2 Hz, C-
C-6], 137.5 (i-Carom.), 135.8 (1J ϭ 154.2, J ϭ 9.1 Hz, C-4), 131.8
(1J ϭ 167.1 Hz, m-Carom.), 131.1 (1J ϭ 158.6, 3J ϭ 9.9 Hz, C-7),
6), 129.9 (1J ϭ 158.1, J ϭ 11.2 Hz, C-7), 129.6 (1J ϭ 161.7, J ϭ 125.5 (1J ϭ 163.4 Hz, o-Carom.), 125.1 (1J ϭ 160.0, 3J ϭ 3J ϭ
3
3
9.6 Hz, C-5), 118.8 (p-Carom.), 110.5 (1J ϭ 153.4, J ϭ 11.1, J ϭ
3
3
3
3J ϭ 5.2 Hz, m-Carom.), 128.6 (1J ϭ 166.7, J ϭ 5.4 Hz, o-Carom.),
21.7 (1J ϭ 127.3, 3J ϭ 4.4 Hz, CH3) ppm. 17O NMR (CDCl3): δ ϭ 5.4 Hz, C-3) ppm. 15N NMR (CDCl3): δ ϭ Ϫ274.4 [1J(N-1,10-
477.9 (O-9), 168.4 (SO2) ppm. C14H12O4S (276.31): calcd. C 60.86,
H 4.38, S 11.61; found C 60.79, H 4.487, S 11.64.
H) ϭ 92.2 Hz, N-1] ppm. 17O NMR (CDCl3): δ ϭ 381.5 (O-9)
ppm. Compound 8-2H1 was prepared directly in the NMR sample
4462
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 4452Ϫ4466

Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
3
tube by agitating the CDCl3 solution with D2O, only 10-H ex-
change. The NMR spectroscopic data for the corresponding 10-D
177.1 (C-8), 152.7 (C-2), 143.3 (1J ϭ 215.1, J ϭ 4.1 Hz, C-2Ј and
C-5Ј), 135.1 (1J ϭ 160.7, J ϭ 9.4 Hz, C-4 and C-7), 138.4 (1J ϭ
3
2
3
3
3
deuterated derivative; H NMR (CDCl3 ϩ D2O): δ ϭ 8.65 (10-D)
156.1, J ϭ 11.5 Hz, C-6), 128.4 (1J ϭ 163.6, J ϭ J ϭ 10.3 Hz,
ppm. C13H10BrNO (274.99): calcd. C 56.55, H 3.65, N 5.07; found C-5), 111.3 (1J ϭ 152.3, 3J ϭ 11.2 Hz, C-3) ppm. 15N NMR
C 55.85, H 3.70, N 5.16.
(CDCl3): δ ϭ Ϫ288.7 (N-1), Ϫ203.7 (N-1Ј), Ϫ60.7 (N-3Ј and N-
4Ј) ppm. Compound 11-2H1 was prepared directly in the NMR
sample tube by agitating the CDCl3 solution with D2O, only 10-H
exchange. The NMR spectroscopic data for the corresponding 10-
D deuterated derivative; H NMR (CDCl3 ϩ D2O): δ ϭ 8.94 (10-
D) ppm. C9H8N4O (188.07): calcd. C 57.44, H 4.28, N 29.77; found
C 57.36, H 4.244, N 29.63.
2-(p-Chlorophenylamino)tropone (9): A solution of 18 (1.75 g,
6.3 mmol) in EtOH (60 mL) was refluxed with p-chloroaniline
(0.91 mL, 7.12 mmol) for 54 h. The solvent was evaporated, and the
crude product was purified by column chromatography (EtOAc/
hexane, 1:20) to afford 9 (320 mg, 22%). M.p. 141.0 °C (CHCl3/
2
1
hexane). H NMR (CDCl3): δ ϭ 8.68 (br. s, 1 H, 10-H), 7.39 (m,
2 H, m-Harom.), 7.34 [dd, 3J(6-H,7-H) ϭ 11.7, 3J(6-H,5-H) ϭ 2-(p-Bromophenylimine)-O-ethyltropone (19): Prepared using the
8.4 Hz, 1 H, 6-H], 7.28 (br. d, 1 H, 7-H), 7.24 (m, 2 H, o-Harom.), procedure described in ref.[11]. Triethyloxonium tetrafluoroborate
7.16Ϫ7.09 (m, 2 H, 3-H and 4-H), 6.79 (m, 1 H, 5-H) ppm. 13C (2.22 g, 11.7 mmol) in dry dichloromethane (12 mL) was slowly ad-
NMR (CDCl3): δ ϭ 177.0 (C-8), 153.3 (C-2), 137.6 (1J ϭ 154.7 Hz, ded to a solution of 8 (3.00 g, 10.9 mmol) in dry dichloromethane
C-6), 137.0 (i-Carom.), 135.8 (1J ϭ 154.5, J ϭ 9.0 Hz, C-4), 131.1
(40 mL) at room temperature under argon. After the addition was
3
(p-Carom.), 131.0 (1J ϭ 158.4, 3J ϭ 10.0 Hz, C-7), 129.8 (1J ϭ completed, the reaction was stirred for one week. The solvent was
167.2 Hz, m-Carom.), 125.3 (1J ϭ 162.5 Hz, o-Carom.), 125.0 (1J ϭ
evaporated, and the crude product was purified by column chroma-
159.9, J ϭ J ϭ 9.7 Hz, C-5), 110.5 (1J ϭ 153.4, J ϭ 11.1, J ϭ tography with the following eluents: EtOAc/hexane (1:5), 8, CHCl3/
5.3 Hz, C-3) ppm. 15N NMR (CDCl3): δ ϭ Ϫ274.0 [1J(N-1,10- EtOH (5:1), 19. Yield for 19 (1.99 g, 47%). M.p. 100.0 °C. 1H NMR
H) ϭ 92.6 Hz, N-1] ppm. 17O NMR (CDCl3): δ ϭ 386.6 (O-9) (CDCl3): δ ϭ 7.46 (m, 2 H, m-Harom.), 6.89Ϫ6.75 (m, 5 H, o-Harom.
ppm. Compound 9-2H1 was prepared directly in the NMR sample
4-H, 6-H and 7-H), 6.58 (m, 2 H, 3-H and 5-H), 4.26 [q,
tube by agitating the CDCl3 solution with D2O, only 10-H ex- 3J(CH2,CH3) ϭ 6.9 Hz, 2 H, CH2], 1.54 (t, 3 H, CH3) ppm. 13C
change. The NMR spectroscopic data for the corresponding 10-D NMR (CDCl3): δ ϭ 160.1 (C-8), 158.4 (C-2), 148.3 (i-Carom.), 134.0
deuterated derivative; H NMR (CDCl3 ϩ D2O): δ ϭ 8.66 (10-D) (1J ϭ 157.2 Hz, C-6), 132.5 (1J ϭ 165.8, 3J ϭ 5.5 Hz, m-Carom.),
3
3
3
3
,
2
3
3
ppm. C13H10ClNO (231.05): calcd. C 67.40, H 4.35, N 6.05; found
C 66.72, H 4.41, N 6.13.
132.0 (1J ϭ 154.1 Hz, C-4), 126.5 (1J ϭ 161.4, J ϭ J ϭ 9.1 Hz,
C-5), 126.3 (1J ϭ 159.3, 3J ϭ 9.2 Hz, C-7), 122.7 (1J ϭ 162.3, 3J ϭ
5.0 Hz, o-Carom.), 116.6 (C-4Ј), 111.0 (1J ϭ 151.6, 3J ϭ 11.9 Hz, C-
3), 65.4 (1J ϭ 145.2, 2J ϭ 4.0 Hz, CH2), 14.2 (1J ϭ 127.3 Hz, CH3)
ppm. 15N NMR (CDCl3): δ ϭ Ϫ274.3 (N-1) ppm. C15H14BrNO
(303.03): calcd. C 59.23, H 4.64, N 4.60; found C 58.99, H 4.55,
N 4.90.
2-(Pyrrol-1-ylamino)tropone (10):
A solution of 18 (1.00 g,
3.6 mmol) in EtOH (30 mL) was refluxed with N-aminopyrrole
(0.33 mL, 3.99 mmol) for 6 h. The solvent was evaporated, and the
crude product was purified by column chromatography (EtOAc/
hexane, 1:20) to afford 10 (270 mg, 40%). M.p. 108.4 °C (CHCl3/
hexane). 1H NMR (CDCl3): δ ϭ 8.88 (br. s, 1 H, 10-H), 7.36 [ddd,
O-Ethyl-2-(pyrrol-1-ylimine)tropone (20): Prepared using the pro-
3J(6-H,7-H) ϭ 11.7, 3J(6-H,5-H) ϭ 8.6, 4J(6-H,4-H) ϭ 1.2 Hz, 1 cedure described in ref.[11]
.
Triethyloxonium tetrafluoroborate
H, 6-H], 7.27 (ddd, 1 H, 7-H), 7.10 [dddd, 3J(3-H,4-H) ϭ 10.1, (1.32 g, 7.0 mmol) in dry dichloromethane (9 mL) was slowly added
3J(4-H,5-H) ϭ 8.6, 5J(4-H,7-H) ϭ 0.7 Hz, 1 H, 4-H], 6.83 [ddt,
to a solution of 10 (1.15 g, 6.2 mmol) in dry dichloromethane
4J(5-H,7-H) ϭ 1.1, 4J(5-H,3-H) ϭ 0.7 Hz, 1 H, 5-H], 6.71 (m, 2 H, (13 mL) at room temperature under argon. After the addition was
2Ј-H and 5Ј-H), 6.27 (m, 2 H, 3Ј-H and 4Ј-H), 6.12 (dd, 1 H, 3-H)
completed, the reaction was stirred for one week. The solvent was
ppm. 13C NMR (CDCl3): δ ϭ 176.7 (C-8), 155.1 (C-2), 137.7 (1J ϭ evaporated, and the crude product was purified by column chroma-
155.0, 3J ϭ 10.8 Hz, C-6), 135.9 (1J ϭ 156.5, 3J ϭ 9.9 Hz, C-4), tography with the following eluents: EtOAc/hexane (1:5), 10,
133.5 (1J ϭ 159.1, 3J ϭ 9.5 Hz, C-7), 126.2 (1J ϭ 159.7, 3J ϭ 3J ϭ
CHCl3/EtOH (5:1), 20. Yield for 20 (580 mg, 31%). M.p. 83.5 °C.
10.2 Hz, C-5), 120.9 (1J ϭ 188.8 Hz, C-2Ј and C-5Ј), 110.5 (1J ϭ 1H NMR (CDCl3): δ ϭ 6.73 (m, 2 H, 2Ј-H and 5Ј-H), 6.69Ϫ6.57
154.0, 3J ϭ 11.5 Hz, C-3), 108.6 (1J ϭ 172.6 Hz, C-3Ј and C-4Ј) (m, 4 H, 3-H, 4-H, 6-H and 7-H), 6.39 (m, 1 H, 5-H), 6.29 [br. d,
ppm. 15N NMR (CDCl3): δ ϭ Ϫ266.8 [1J(N-1,10-H) ϭ 103.5 Hz, 3J(3-H,4-H) ϭ 9.2 Hz, 1 H, 3-H], 6.18 (m, 2 H, 3Ј-H and 4Ј-H),
N-1], Ϫ217.0 (N-1Ј) ppm. 17O NMR (CDCl3): δ ϭ 395.4 (O-9)
ppm. Compound 10-2H1 was prepared directly in the NMR sample
tube by agitating the CDCl3 solution with D2O, only 10-H ex-
4.18 [q, 3J(CH2,CH3) ϭ 7.0 Hz, 2 H, CH2], 1.53 (t, 3 H, CH3) ppm.
3
13C NMR (CDCl3): δ ϭ 161.5 (3J ϭ J ϭ 9.8 Hz, C-8), 157.3 (C-
3
3
2), 133.2 (1J ϭ 158.6, J ϭ 13.0 Hz, C-6), 130.8 (1J ϭ 156.2, J ϭ
change. The NMR spectroscopic data for the corresponding 10-D
8.7 Hz, C-4), 125.8 (1J ϭ 159.2, 3J ϭ 3J ϭ 9.9 Hz, C-5), 123.9 (1J ϭ
2
deuterated derivative; H NMR (CDCl3 ϩ D2O): δ ϭ 8.87 (10-D) 161.0, 3J ϭ 9.1 Hz, C-7), 117.0 (1J ϭ 187.4 Hz, C-2Ј and C-5Ј),
ppm. C11H10N2O (186.08): calcd. C 70.95, H 5.41, N 15.04; found
C 71.05, H 5.435, N 15.04.
110.0 (1J ϭ 151.7, 3J ϭ 11.6 Hz, C-3), 106.8 (1J ϭ 171.5, 3J ϭ 3J ϭ
7.6, 2J ϭ 3.0 Hz, C-3Ј and C-4Ј), 65.1 (1J ϭ 144.5, 2J ϭ 4.5 Hz,
CH2), 14.3 (1J ϭ 127.3, 2J ϭ 2.4 Hz, CH3) ppm. C13H14N2O
(214.11): calcd. C 72.87, H 6.59, N 13.07; found C 72.82, H 6.72,
N 12.95.
2-(1,2,4-Triazol-1-ylamino)tropone (11): A homogeneous mixture of
18 (1.00 g, 3.6 mmol) and 4-amine-1,2,4-triazole (610 mg,
7.25 mmol) was melted at 120Ϫ130 °C for 5 h. The crude product
was purified by column chromatography (CHCl3/EtOH, 10:1) to
N-Phenyl-2-(phenylamino)troponimine (2): Triethyloxonium tetra-
afford a mixture of 11 and 4-amine-1,2,4-triazole. The unchanged fluoroborate (720 mg, 3.78 mmol) in dry dichloromethane (4 mL)
amine was then removed using acetone, and 11 remained (230 mg,
was slowly added to a solution of 7 (700 g, 3.55 mmol) in dry di-
chloromethane (4 mL) at room temperature under argon. After
stirring for 3 h, aniline (4.15 mL, 45.54 mmol) was slowly added to
1
33%). M.p. 253.0 °C (dec.). H NMR (CDCl3): δ ϭ 8.98 (br. s, 1
3
H, 10-H), 8.33 (s, 2 H, 2Ј-H and 5Ј-H), 7.44 [ddd, J(6-H,7-H) ϭ
11.9, 3J(6-H,5-H) ϭ 8.5, 4J(6-H,4-H) ϭ 1.1 Hz, 1 H, 6-H], 7.33 (d, the solution. The mixture was then stirred for 32 h. The solvent
1 H, 7-H), 7.12 (br. t, 1 H, 4-H), 6.97 (br. t, 1 H, 5-H), 6.14 [d,
was evaporated, and the crude product was purified by column
3J(3-H,4-H) ϭ 9.7 Hz, 1 H, 3-H] ppm. 13C NMR (CDCl3): δ ϭ chromatography (EtOAc/hexane, 1:30) to afford 2 (250 g, 26%).
Eur. J. Org. Chem. 2004, 4452Ϫ4466
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4463

´
R. M. Claramunt, D. Sanz, M. Perez-Torralba, E. Pinilla, M. R. Torres, J. Elguero
FULL PAPER
M.p. 78.4 °C (ref.[5] m.p. 86.5Ϫ87.0 °C). 1H NMR (CDCl3): δ ϭ N-(Pyrrol-1-yl)-2-(phenylamino)troponimine (4): A solution of 20
9.20 (br. s, 1 H, 10-H), 7.41 (m, 4 H, m-Harom.), 7.15 (m, 2 H, p-
(450 g, 1.49 mmol) and aniline (1.6 mL, 17.9 mmol) in dichloro-
Harom.), 7.14 (m, 4 H, o-Harom.), 6.84 [dd, 4J(3-H,7-H/5-H) ϭ methane (37 mL) was stirred for 6 days at 40 °C. The solvent was
3
0.8 Hz, 2 H, 3-H and 7-H], 6.73 [dd, J(4-H/6-H,3-H/7-H) ϭ 12.1, evaporated, and the crude product was purified by column chroma-
3J(4-H/6-H,5-H) ϭ 9.2 Hz, 2 H, 4-H and 6-H], 6.34 (tt, 1 H, 5-H) tography (EtOAc/hexane, 1:30) to afford the desired product 4, ac-
3
ppm. 13C NMR (CDCl3): δ ϭ 151.9 (3J ϭ J ϭ 10.0 Hz, C-2 and
companied by 2. The mixture was separated by preparative TLC,
and the plate was eluted three times (EtOAc/hexane, 1:30) to give
C-8), 145.2 (3J ϭ 3J ϭ 8.7 Hz, i-Carom.), 133.4 (1J ϭ 155.0, 3J ϭ
3
10.7 Hz, C-4 and C-6), 129.5 (1J ϭ 158.3, J ϭ 8.0 Hz, m-Carom.), pure 4 (255 mg, 66%). M.p. 125.9 °C. 1H NMR (CDCl3): δ ϭ 8.75
123.9 (1J ϭ 159.6, J ϭ J ϭ 7.7 Hz, p-Carom.), 122.6 (1J ϭ 159.5,
(br. s, 1 H, 10-H), 7.43 (m, 2 H, m-Harom.), 7.32 (m, 2 H, o-Harom.),
3
3
3
3
3
3J ϭ J ϭ 6.8 Hz, o-Carom.), 122.1 (1J ϭ 159.2, J ϭ 3J ϭ 10.6 Hz, 7.23 (m, 1 H, p-Harom.), 6.90 [dd, J(3-H,4-H) ϭ 10.2 Hz, 1 H, 3-
C-5), 114.9 (1J ϭ 155.1, 3J ϭ 3J ϭ 10.3 Hz, C-3 and C-7) ppm. H], 6.86Ϫ6.79 (m, 2 H, 4-H and 6-H), 6.76 [dd, 3J(7-H,6-H) ϭ
15N NMR (CDCl3): δ ϭ Ϫ193.7 (N-1 and N-9) ppm. Compound 12.0 Hz, 1 H, 7-H], 6.71 (m, 2 H, 2Ј-H and 5Ј-H), 6.42 [tdd, J(5-
3
2-2H1 was prepared directly in the NMR sample tube by agitating
the CDCl3 solution with D2O, only 10-H exchange. The NMR
spectroscopic data for the corresponding 10-D deuterated deriva-
H,4-H) ϭ 8.0, J(5-H,6-H) ϭ 10.0, J(5-H,3-H) ϭ J(5-H,7-H) ϭ
1.0 Hz, 1 H, 5-H], 6.26 (m, 2 H, 3Ј-H and 4Ј-H) ppm. 13C NMR
(CDCl3): δ ϭ 159.4 (3J ϭ 3J ϭ 9.9 Hz, C-8), 146.9 (3J ϭ 3J ϭ
9.8 Hz, i-Carom.), 139.1 (3J ϭ 3J ϭ 9.8 Hz, C-2), 134.5 (1J ϭ 155.3,
3
4
4
2
tive; H NMR (CDCl3 ϩ D2O): δ ϭ 9.09 (10-D) ppm. C19H16N2
(272.13): calcd. C 83.79, H 5.92, N 10.29; found C 83.67, H 5.97, 3J ϭ 10.9 Hz, C-4), 134.1 (1J ϭ 156.3, 3J ϭ 9.4 Hz, C-6), 129.6
N 10.23.
(1J 162.6, 3J 8.7 Hz, m-Carom.), 125.5 (1J
ϭ ϭ ϭ 163.0,
p-Carom.),124.4 (1J ϭ 160.5, 3J ϭ 3J ϭ 6.7 Hz, o-Carom.), 123.5 (1J ϭ
159.9, 3J ϭ 3J ϭ 9.9 Hz, C-5), 119.4 (1J ϭ 158.6, 3J ϭ 10.0 Hz, C-
7), 117.0 (1J ϭ 186.7, C-2Ј and C-5Ј), 109.9 (1J ϭ 153.4, 3J ϭ 3J ϭ
11.0 Hz, C-3), 106.8 (1J ϭ 171.6, C-3Ј and C-4Ј) ppm. 15N NMR
(CDCl3): δ ϭ Ϫ271.6 (N-1), Ϫ187.0 (N-1Ј), Ϫ114.4 (N-9) ppm.
Compound 4-2H1 was prepared directly in the NMR sample tube
by agitating the CDCl3 solution with D2O, only 10-H exchange.
The NMR spectroscopic data for the corresponding 10-D deuter-
[15N2]-N-Phenyl-2-(phenylamino)troponimine (2-15N2): Triethyl-
oxonium tetrafluoroborate (960 mg, 4.80 mmol) in dry dichloro-
methane (6 mL) was slowly added to a solution of 7-15N (940 mg,
4.73 mmol) in dry dichloromethane (6 mL) at room temperature
under argon. After stirring for 3 h, labelled aniline (5.95 g,
60.1 mmol) was slowly added to the solution. The mixture was then
stirred for 43 h. The solvent was evaporated, and the crude product
was purified by column chromatography (EtOAc/hexane, 1:30) to
afford 2-15N2 (390 mg, 30%). 1H NMR ([D6]DMSO): δ ϭ 9.25 [br.
t, 1J(10-H, N-1/N-9) ϭ 44.6 Hz, 1 H, 10-H], 7.41 (m, 4 H, m-
Harom.), 7.14 (m, 2 H, p-Harom.), 7.11 (m, 4 H, o-Harom.), 6.82 [dd,
2
ated derivative; H NMR (CDCl3 ϩ D2O): δ ϭ 8.72 (10-D) ppm.
HRMS [Mϩ] m/z: C17H15N3 (436.96): calcd. 261.12732; found
261.12660.
3J(4-H/6-H,5-H) ϭ 9.2 Hz, 2 H, 4-H and 6-H], 6.73 [d, J(4-H/6-
[2-15N]-N-(Pyrrol-1-yl)-2-(phenylamino)troponimine (4-15N): Com-
3
H,3-H/7-H) ϭ 10.6 Hz, 2 H, 3-H and 7-H], 6.37 (t, 1 H, 5-H) ppm. pound 4-15N was synthesised according to a procedure described
1
1
13C NMR (CDCl3): δ ϭ 151.9 [1J(C,N) ϭ 14.0 Hz, C-2 and C-8],
for 4. H NMR ([D8]THF): δ ϭ 9.01 [d, J(10-H,N-1) ϭ 89.9 Hz,
145.2 [1J(C,N) ϭ 10.4 Hz, i-Carom.], 133.4 (C-4 and C-6), 129.5 (m- 1 H, 10-H], 7.41 (m, 2 H, m-Harom.), 7.33 (m, 2 H, o-Harom.), 7.19
Carom.), 123.9 (p-Carom.), 122.6 (o-Carom.), 122.1 (C-5), 114.9 (C-3 (m, 1 H, p-Harom.), 6.86 [dd, 3J(3-H,4-H) ϭ 10.2 Hz, 1 H, 3-H],
and C-7) ppm. 15N NMR (CDCl3): δ ϭ Ϫ193.2 (N-1, N-9) ppm. 6.85Ϫ6.78 (m, 2 H, 4-H and 6-H), 6.69 [dd, 3J(7-H,6-H) ϭ 12.0 Hz,
3
Compound 2-15N2-2H1 was prepared directly in the NMR sample
tube by agitating the CDCl3 solution with D2O, only 10-H ex-
change. The NMR spectroscopic data for the corresponding 10-D
deuterated derivative; 2H NMR (CDCl3 ϩ D2O): δ ϭ 9.14 (10-
D) ppm.
1 H, 7-H], 6.63 (m, 2 H, 2Ј-H and 5Ј-H), 6.37 [tdd, J(5-H,4-H) ϭ
8.0, 3J(5-H,6-H) ϭ 10.0, 4J(5-H,3-H) ϭ 4J(5-H,7-H) ϭ 1.0 Hz, 1
H, 5-H], 6.11 (m, 2 H, 3Ј-H and 4Ј-H) ppm. 13C NMR (CDCl3):
δ ϭ 159.4 (C-8), 146.9 [1J(C,N) ϭ 16.3 Hz, i-Carom.], 139.1
[1J(C,N) ϭ 15.6 Hz, C-2], 134.6 (C-4), 134.0 (C-6), 129.6 (m-
Carom.),125.5 (p-Carom.), 124.4 [2J(C,N) ϭ 2.0 Hz, o-Carom.], 123.0
(C-5), 119.4 (C-7), 117.0 (C-2Ј and C-5Ј), 109.9 (C-3), 106.9 (C-3Ј
and C-4Ј) ppm. 15N NMR (CDCl3): δ ϭ Ϫ271.8 (N-1) ppm.
N-(p-Bromophenyl)-2-(p-bromophenylamino)troponimine (3):
A
solution of 19 (1.75 g, 4.5 mmol) and p-bromoaniline (4.66 g,
26.8 mmol) in ethanol (75 mL) was stirred for 24 h at room tem-
perature. Dichloromethane (85 mL) was then added to the reaction N-(Pyrrol-1-yl)-2-(pyrrol-1-ylamino)troponimine (5): A solution of
mixture, and the mixture was allowed to stir for an additional four 20 (788 mg, 2.25 mmol) and N-aminopyrrole (402 mg, 4.90 mmol)
days at 40 °C. The solvent was evaporated, and the crude product
in dry methanol (20 mL) was stirred for 4 days at room temperature
under argon. The solvent was evaporated, and the crude product
was purified by column chromatography (EtOAc/hexane, 1:30) to
afford 3 (1.92 g, 73%). M.p. 195.6 °C. 1H NMR (CDCl3): δ ϭ 9.04 was purified by column chromatography (EtOAc/hexane, 1:30) to
(br. s, 1 H, 10-H), 7.50 (m, 4 H, m-Harom.), 7.00 (m, 4 H, o-Harom.),
afford 5 (247 mg, 44%). M.p. 137.6 °C. 1H NMR (CDCl3): δ ϭ
3
6.81Ϫ6.72 (m, 4 H, 3-H, 4-H, 6-H and 7-H), 6.39 [tt, J(5-H,4-H/ 8.96 (br. s, 1 H, 10-H), 6.78 (m, 2 H, 4-H and 6-H), 6.75 (m, 4 H,
4
6-H) ϭ 8.3, J(5-H,3-H/7-H) ϭ 1.7 Hz, 1 H, 5-H) ppm. 13C NMR 2Ј-H and 5Ј-H), 6.44 [tt, 3J(5-H,4-H/6-H) ϭ 9.4, 4J(5-H,3-H/7-
3
(CDCl3): δ ϭ 151.8 (3J ϭ J ϭ 9.2 Hz, C-2 and C-8), 144.1 (3J ϭ H) ϭ 0.7 Hz, 1 H, 5-H], 6.35 [dd, 3J(3-H/7-H,4-H/6-H) ϭ 10.8 Hz,
3
3J ϭ 8.6 Hz, i-Carom.), 133.8 (1J ϭ 155.0, J ϭ 9.3 Hz, C-4 and C-
2 H, 3-H and 7-H], 6.27 (m, 4 H, 3Ј-H and 4Ј-H) ppm. 13C NMR
6), 132.6 (1J ϭ 165.7 Hz, m-Carom.), 124.3 (1J ϭ 162.1 Hz, o-Carom.), (CDCl3): δ ϭ 153.5 (3J ϭ 3J ϭ 10.0 Hz, C-2 and C-8), 134.3 (1J ϭ
3
3
3
3
3
122.9 (1J ϭ 159.3, J ϭ J ϭ 9.5 Hz, C-5), 116.8 (p-Carom.), 115.3
155.7, J ϭ 10.7 Hz, C-4 and C-6), 124.5 (1J ϭ 159.9, J ϭ J ϭ
(1J ϭ 154.8, 3J ϭ 10.6 Hz, C-3 and C-7) ppm. 15N NMR (CDCl3): 10.4 Hz, C-5), 119.0 (1J ϭ 187.4 Hz, C-2Ј and C-5Ј), 115.3 (1J ϭ
δ ϭ Ϫ196.3 (N-1 and N-9) ppm. Compound 3-2H1 was prepared
156.4, J ϭ J ϭ 10.1 Hz, C-3 and C-7), 107.6 (1J ϭ 172.2 Hz, C-
3
3
directly in the NMR sample tube by agitating the CDCl3 solution 3Ј and C-4Ј) ppm. 15N NMR (CDCl3): δ ϭ Ϫ202.4 (N-1Ј), Ϫ188.4
with D2O, only 10-H exchange. The NMR spectroscopic data for
(N-1 and N-9) ppm. Compound 5-2H1 was prepared directly in the
the corresponding 10-D deuterated derivative; 2H NMR (CDCl3 ϩ NMR sample tube by agitating the CDCl3 solution with D2O, only
D2O): δ ϭ 8.99 (10-D) ppm. C19H14Br2N2 1/2 H2O (436.96): calcd. 10-H exchange. The NMR spectroscopic data for the correspond-
C 51.98, H 3.44, N 6.38; found C 52.08, H 3.26, N 6.47.
ing 10-D deuterated derivative; 2H NMR (CDCl3 ϩ D2O): δ ϭ
4464
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 4452Ϫ4466

Solid-State Structure and Tautomerism of 2-Aminotroponimines
FULL PAPER
Table 6. Crystal and refinement data for 2, 3, 4 and 5
2
3
4
5
Formula
Mr
C19H16N2
272.34
C19H14Br2N2
430.14
C17H15N3
261.32
C15H14N4
500.60
Temperature K
Crystal system
Space group
293(2)
monoclinic
P21/c
14.569(4)
20.710(6)
10.159(3)
Ϫ
100.166(5)°
Ϫ
293(2)
293(2)
293(2)
monoclinic
P21/c
13.934(5)
19.770(5)
10.129(5)
Ϫ
103.765(5)
Ϫ
triclinic
triclinic
¯
¯
P1
P1
˚
a (A)
9.6533(9)
10.2638(9)
19.302(2)
96.335(2)
99.005(2)
114.689(2)
1683.0(3)
4
10.492(1)
11.839(2)
13.082(2)
72.928(2)
89.832(2)
65.217(2)
1396.7(3)
4
˚
b (A)
˚
c (A)
α (°)
β (°)
γ (°)
3
˚
V (A )
3017(2)
8
2710 (2)
8
Z
F(000)
1152
848
552
1056
Crystal size (mm3)
0.38 ϫ 0.18 ϫ 0.12
1.199
0.071
0.24 ϫ 0.14 ϫ 0.10
1.698
4.817
0.23 ϫ 0.16 ϫ 0.14
1.243
0.076
0.18 ϫ 0.13 ϫ 0.07
1.227
0.077
Dcalcd. (g·cmϪ3
µ (mm
)
Ϫ1
)
Scan technique
Data collected (h,k,l)
ω and ϕ
(Ϫ16,Ϫ19,Ϫ12) to
(17,24,11)
1.42 to 25.0
15347
5305 (Rint ϭ 0.26)
5305/0/385
953
ω and ϕ
ω and ϕ
ω and ϕ
(Ϫ16,Ϫ23,Ϫ11) to
(16,19,12)
1.50 to 25.0
14069
4766 (Rint ϭ 0.090)
4766/0/344
1364
(Ϫ11,Ϫ11,Ϫ20) to
(5,12,22)
1.09 to 25.0
8833
(Ϫ12,Ϫ9,Ϫ15) to
(12,14,15)
1.64 to 25.0
7346
θ (°)
Reflections, collected
Reflections, independent
Data/restraints/parameters
Reflections, obsd.
[(I) Ͼ 2σ(I)]
5838 (Rint ϭ 0.047)
5838/0/415
2937
4846 (Rint ϭ 0.045)
4846/0/364
2075
R (Reflections, obsd.)[a]
RwF (all reflections)[b]
0.11
0.41
0.043
0.099
0.043
0.101
0.052
0.140
[a]
[b]
2
2 2
2 2
Σ||Fo| Ϫ |Fc ||/Σ|Fo|. {Σ[w(Fo Ϫ Fc ) ]/Σ[w(Fo ) ]}1/2
.
8.93 (10-D) ppm. C15H14N4 (250.12): calcd. C 71.98, H 5.64, N
22.38; found C 70.88, H 5.598, N 21.92.
and their coordinates refined for 2, refined riding on the respective
nitrogen atoms for 4 and fixed for 5. In compound 3, only the H11
atom has been located in a Fourier synthesis, included and fixed,
and the other hydrogen atom, H12, was included in calculated posi-
tion and refined riding on N12 atom. Largest peaks and holes in
the final difference map were 0.504 and Ϫ0.265, 0.434 and Ϫ0.285,
X-ray-Diffraction Studies: Suitable crystals for X-ray experiments
were obtained from chloroform/ethanol for 2, from chloroform for
3, and from hexane for 4 and 5.
Ϫ3
˚
0.122 and Ϫ0.123, 0.115 and Ϫ0.301 e·A for 2, 3, 4, and 5,
respectively.
For compound 2, the poor quality of the crystals made it necessary
to repeat the data collection and refinement procedure several times
with different crystals. Finally, a crystal of sufficient quality to
properly solve the structure was obtained.
CCDC-230113 (for 2), -230114 (for 3), -230115 (for 4) and
-230116 (for 5) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cam-
bridge Crystallographic Data Centre, 12, Union Road, Cam-
bridge CB2 1EZ, UK; Fax: ϩ44-1223-336-033; E-mail:
deposit@ccdc.cam.ac.uk].
Data collection was carried out at room temperature on a Bruker
Smart CCD diffractometer using graphite-monochromated Mo-Kα
˚
radiation (λ ϭ 0.71073 A) operating at 50 kV and 25 A or 20 A.
In all cases, data were collected over a hemisphere of the reciprocal
space by combination of three exposure sets. Each exposure of 20
s covered 0.3 in ω. The cell parameters were determined and refined
by a least-squares fit of all reflections collected. The first 50 frames
were recollected at the end of the data collection to monitor crystal
decay, and no appreciable decay was observed. A summary of the
fundamental crystal and refinement data is given in Table 6. The
Acknowledgments
structures were solved by direct methods (SHELXS-97)[32] and We are very grateful to Dr. Ibon Alkorta from Instituto de Quımica
´
Sir,[33] and refined by full-matrix-block least- squares on F2 for 2,
and full-matrix least-squares on F2 for 3, 4 and 5.[32] Anisotropic
parameters were used in the last cycles of refinement for all non-
Medica, CSIC, and Dr. Concepcion Foces-Foces from Instituto de
´
´
´
´
Quımica Fısica Rocasolano, CSIC, for their invaluable help. M.P-
T. thanks the UNED for a postdoctoral fellowship. We also
hydrogen atoms. All hydrogen atoms were included in calculated acknowledge Dr. F. Aguilar-Parrila from Schering AG for warm
positions and refined riding on the respective carbon atoms, except
H11 and H12 bonded to nitrogen atoms. For 2, 4 and 5, these
hydrogen atoms have been located in a Fourier synthesis, included,
and helpful discussions. Financial support was provided by the
MCyT/DGI of Spain (Project Numbers BQU2000Ϫ0252 and
BQU2003Ϫ00976).
Eur. J. Org. Chem. 2004, 4452Ϫ4466
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4465

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