Cyano-, Nitro-, and Alkoxycarbonyl-Activated Observable Stable Enols of Carboxylic Acid Amides

Article abstract of DOI:10.1021/jo000293e

A search for the enol structures of several amides YY′CHCONHPh with Y,Y′ = electron-withdrawing groups (EWGs) was conducted. When Y = CN, Y′ = CO₂Me the solid structure is that of the enol (8b) MeO₂CC(CN)=C(OH)NHPh, whereas in soluti

Full text of DOI:10.1021/jo000293e

6856
J . Org. Chem. 2000, 65, 6856-6867
Cya n o-, Nitr o-, a n d Alk oxyca r bon yl-Activa ted Obser va ble Sta ble
En ols of Ca r boxylic Acid Am id es
J ayanta Kumar Mukhopadhyaya, Stepan Sklenak, and Zvi Rappoport*
Department of Organic Chemistry and the Minerva Center for Computational Quantum Chemistry,
The Hebrew University, J erusalem 91904, Israel
zr@vms.huji.ac.il
Received March 2, 2000
A search for the enol structures of several amides YY′CHCONHPh with Y,Y′ ) electron-withdrawing
groups (EWGs) was conducted. When Y ) CN, Y′ ) CO2Me the solid structure is that of the enol
(8b) MeO2CC(CN)dC(OH)NHPh, whereas in solution the NMR spectrum indicate the presence of
both the amide MeO2CCH(CN)CONHPh (8a ) and 8b. When Y ) NO2, Y′ ) CO2Et the main
compound in CDCl3 is the amide, but <10% of enol(s), presumably EtO2CC(NO2)dC(OH)NHPh
(9b), are also present. When Y ) COEt, Y′ ) CO2Me or Y ) COMe, Y′ ) CO2Et (10 and 11)
enolization in solution and of 11 also in the solid state occurs at the carbonyl rather than at the
ester site. With Y ) Y′ ) CN a rapid exchange between the amide (NC)2CHCONHPh (12a ) and a
tautomer, presumably the enol, take place in several solvents on the NMR time scale. With YY′ )
barbituric acid moiety the species in DMSO-d6 is an enol of an amide although which CONH group
enolizes is unknown. B3LYP/6-31G** calculations showed that the enol (NC)2CdC(OH)NH2 (13b)
is more stable by ∆G of 0.4 kcal/mol than (NC)2CHCONH2 (13a ) due to a combination of stabilization
of 13b and destabilization of 13a and both are much more stable than the hydroxyimine and ketene
imine tautomers. The effect of Y,Y′ and the solvent on the relative stabilization of enols of amides
is discussed.
In tr od u ction
cally sufficiently long-lived to be observed by UV and
NMR spectroscopies. A recent approach generated a
simple enol of an amide by solvolysis of a chloroenamine.5
However, in none of these methods KEnol was found to be
sufficiently high (i.e., g0.05) to enable observation of the
enols at equilibrium.
The low stabilities and KEnol values (eq 1) are attributed
to a strong stabilization of the acid structure by a
significant resonative electron donation of the heteroatom
X in hybrid 2b, which locate the negative charge on the
electronegative oxygen. We reasoned that the enol will
be similarly stabilized if the negative charge on Câ of the
dipolar hybrid 1b will be delocalized by â-electron-
withdrawing groups (EWGs) R1 and R2.2,6
Enols of carboxylic acids and their derivatives (esters,
amides, anhydrides, and acyl halides, 1, X ) OH, OR,
NRR′, OCOR, halogen) are usually unstable compared
with the acid derivative 2 itself. Consequently, only a few
systems with X ) OH, OR, NRR′ were observed and
investigated in recent years, although others were sug-
gested as reaction intermediates.1 Recent literature
references including those to calculations of the relative
stabilities of these species and several examples are given
in our recent paper.2
Most approaches used until recently to generate ob-
servable enols of acid derivatives include nucleophilic
addition to ketenes. The groups of Wirz,3a Kresge,3b-f and
recently Lusztyk3g photochemically generated short-lived
ketenes and studied their rapid hydration to 1 and the
rapid 1 f 2 isomerization by fast detection methods. The
groups of Hegarty4a and Rappoport4b-d used bulky di-
aryl substituted ketenes to generate sterically hindered
Ar2CdC(OH)X (X ) OH, OR, NRR′), which were kineti-
(1) For reviews on carboxylic acid enols and derivatives, see: (a)
Hegarty, A. F.; O’Neill, P. In The Chemistry of Enols; Rappoport, Z.,
Ed.; Wiley: Chichester, 1990; Chapter 10, p 639. (b) Kresge, A. J .
Chem. Soc. Rev. 1996, 25, 275.
Indeed, nitromalonamide O2NCH(CONH2)2, few cyclic
amides and three tetracyclines having an amide group
(2) Mukhopadhyaya, J . K.; Sklenak, S.; Rappoport, Z. J . Am. Chem.
Soc. 2000, 122, 1315.
(4) (a) O’Neill, P. J .; Hegarty, A. F. J . Chem. Soc., Chem. Commun.
1987, 744; Allen, B. M.; Hegarty, A. F.; O’Neill, P.; Nguyen, M. T. J .
Chem. Soc., Perkin Trans. 2 1992, 927; Allen, B. M.; Hegarty, A. F.;
O’Neill, P. J . Chem. Soc., Perkin Trans. 2 1997, 2733. (b) Frey, J .;
Rappoport, Z. J . Am. Chem. Soc. 1995, 117, 1161; 1996, 118, 5169,
5182. (c) Frey, J .; Rappoport, Z. J . Am. Chem. Soc. 1996, 118, 3994.
(d) Rappoport, Z.; Frey, J .; Sigalov, M.; Rochlin, E. Pure Appl. Chem.
1997, 69, 1933.
(5) Hegarty, A. F.; Enstace, S. J .; Relihan, C. 7th European
Symposium on Organic Reactivity (ESOR 7), Ulm, Germany, Aug 22-
27, 1999, Abstr. A8, p 68.
(6) Lei, Y. X.; Cerioni, G.; Rappoport, Z. J . Org. Chem. 2000, 65,
4028.
(3) (a) Urwyler, B.; Wirz, J . Angew. Chem., Int. Ed. Engl. 1990, 29,
790; Almstead, J .-I. K.; Urwyler, B.; Wirz, J . J . Am. Chem. Soc. 1994,
116, 954. (b) Andraos, J .; Chiang, Y.; Huang, C.-G.; Kresge, A. J .;
Scaiano, J . C. J . Am. Chem. Soc. 1993, 115, 10605. (c) Andraos, J .;
Chiang, Y.; Kresge, A. J .; Popik, V. V. J . Am. Chem. Soc. 1997, 119,
8417. (d) Chiang, Y.; Kresge, A. J .; Pruszynski, P.; Schepp, N. P.; Wirz,
J . Angew. Chem., Inter. Ed. Engl. 1990, 29, 1972. (e) Andraos, J .;
Chiang, Y.; Kresge, A. J .; Pojarlieff, I. G.; Schepp, N. P.; Wirz, J . J .
Am. Chem. Soc. 1994, 116, 73. (f) Chiang, Y.; J efferson, E. A.; Kresge,
A. J .; Popik, V. V.; Xie, R.-Q. J . Phys. Org. Chem. 1998, 11, 610. (g)
Wagner, B. D.; Arnold, B. R.; Brown, G. S.; Lusztyk, J . J . Am. Chem.
Soc. 1998, 120, 1827.
10.1021/jo000293e CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/16/2000

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6857
which carry â-EWGs have the enol of amide structures
H2NCO(O2N)CdC(OH)NH2,7 3a -d 8 and 4a -c,9 respec-
tively, in the solid state. This encourages us to start a
systematic study of this topic, and we had already
showed2 that a 5-CONHPh-substituted Meldrum acid
(MA) is enolic (cf. 5) both in the solid state and in
solution. The open chain analogue 6 has the amide
structure 6a in the solid, but in CDCl3 solution it appears
as ca. 95% 6a in equilibrium with an enolic structure
which may be either 6b or a mixture of 6b and 6c. The
diketo-activated six-membered analogues of 5 are enolic
on a ring oxygen, having structures 7.2
there are trends, which are corroborated by calcula-
tions,2,12 at present we do not see any systematic behav-
ior. Hence, our first stage in a more systematic search of
the enol of amide structure is to screen various anilides
with different EWGs.
Syn th esis. In analogy with the preparation of 5-7,2,13
we prepared the anilides in the present work by reaction
of active methylene compounds with phenyl isocyanate
(eq 2). The combination of EWGs involve CN and CO2-
Me (8), NO2 and CO2Et (9), MeCO and CO2Et (10) and
EtCO, CO2Me (11), CN, CN (12) and the barbituric acid
moiety 14.
We had also shown that cyclopentadienes substituted
by at least two vicinal CO2Me groups, one of which on
the formally sp3-hybridized carbon, exist in the solid state
and in chlorinated solvents as the enol of the tautomeric
ester.6
In the present work we extend these works to carbox-
ylic acid anilides activated by various combinations of
the two EWGs, CN, CO2R, NO2, and CONHR.
Resu lts a n d Discu ssion
Gen er a l Con sid er a tion s. The two ester groups in the
anilides 5 and 6 are sufficient to generate observable
enols of anilides, whereas most diketo-activated systems
(e.g., 7) enolize on the nonamidic keto groups, although
compounds 4 exist as solid enols of amides. Solid nitro-
malonamide7 is enolic but ethyl dinitroacetate is fully in
the ester form.10 Likewise, tri(methoxycarbonyl)methane
is completely in the ester form.11 Consequently, although
Also prepared was the dicyanoamide 13, where the
N-Ph of 12 is replaced by N-H, since there is literature
claim that it has the enol structure, 13b.14 For conven-
ience, structures 8-11 and 14 are written in the amide
form with the suffix a , and enols of amides are written
with the suffix b. Other structures, including isomeric
enolic ones are written with the suffixes c, d , and e. The
discussion below reveals the observed structures.
(7) Simonsen, O.; Thorup, N. Acta Crystallogr. Sect. B 1979, 57,
1177.
(8) (a) de Mester, P.; J ovanovic, M. V.; Chu, S. S. C.; Biehl, E. R. J .
Heterocycl. Chem. 1986, 23, 337; Gavuzzo, E.; Mazza, F.; Carotti, A.;
Casini, G. Acta Crystallogr. Sect. C 1984, 40, 1231; Bolton, W. Acta
Crystallogr. 1963, 16, 950. (b) Bideau, J .-P.; Bravic, G.; Filhol, A. Acta
Crystallogr. Sect. B 1977, 33, 3847; Bideau, J . P.; Huong, P.; Toure, S.
Acta Crystallogr. Sect. B 1976, 32, 481. (c) Tranqui, D.; Vicat, J .;
Thomas, M.; Pera, M. N.; Fillion, H.; Duc, C. L. Acta Crystallogr. Sect.
B 1976, 32, 1724. (d) For a discussion see Gilli, G.; Bertolasi, V. In
The Chemistry of Enols; Rappoport, Z., Ed.; Wiley: Chichester, 1990;
Chapter 13, pp 713-764, especially pp 736-740.
(9) (a) de C. T. Carrondo, M. A. A. F.; Matias, P. M.; Heggie, W.;
Page, P. R. Struct. Chem. 1994, 5, 73. (b) Bordner, J . Acta Crystallogr.
Sect. B 1979, 35, 219. (c) Glatz, B.; Helmchen, G.; Muxfeldt, H.;
Porcher, H.; Prewo, R.; Senn, J .; Stezowski, J . J .; Stojda, R. J .; White,
D. R. J . Am. Chem. Soc. 1971, 101, 2171.
Str u ctu r e Deter m in a tion . Our previous work2,6 had
shown that the structure of the systems depends strongly
(12) Sklenak, S.; Apeloig, Y.; Rappoport, Z. J . Am. Chem. Soc. 1998,
120, 10359.
(13) Lee, H. K.; Lee, J . P.; Lee, G. H.; Pak, C. S. Synlett 1996, 1209.
(14) Trofimenko, S.; Little, T. L.; Mower, H. F. J . Org. Chem. 1962,
27, 433.
(10) Kissinger, L. W.; Ungnade, H. E. J . Org. Chem. 1958, 23, 1340.
(11) Guthrie, J . P. Can. J . Chem. 1979, 57, 1177.

6858 J . Org. Chem., Vol. 65, No. 21, 2000
Mukhopadhyaya et al.
on the medium. Whereas the solid-state structure fre-
quently coincides with those deduced from the spectrum
in solution, there are differences in the species observed
or predominate in low dielectric solvents such as CDCl3
and in dipolar aprotic solvents, e.g., DMSO-d6. Hence,
whenever possible the solid-state structure was deter-
mined by X-ray crystallography, and the structure in
several solvents was examined by NMR spectroscopy.
Indeed, the amides of the present study had shown a
variety of behaviors, depending on the phase (solid or
solution), the substituents and the solvent, as detailed
below.
A. Th e Cya n oa ceta te An ilid e 8. (a ) Th e Solid Sta te
Str u ctu r e. All the three different groups on the central
CH of the cyanoester 8, i.e., CO2Me, CONHPh, CN are
potential tautomerisation sites; i.e., two enols (8b, 8c),
one amide (8a ), and one imine (8d ) are possible tau-
tomers. The solid-state structure was determined by
X-ray crystallography. The ORTEP drawing (Figure 1),
shows a dimeric structure of an enol of amide 8b in which
two molecules are doubly hydrogen bonded. The amido
hydrogen of one unit is hydrogen bonded to the cyano
nitrogen of the other and the same applies to the other
PhN-H‚‚‚NC‚‚‚ group. Structure 8b generally resembles
the Meldrum acid anilide 5 which also forms an enol of
amide (but structural differences between 8b and 5 are
given below). The structure differs from that of 6, the
noncyclic analogue of 8 which has the amide structure
6a in the solid. Consequently, 8b is our second example
of a solid enol of amide activated by EWG.
Selected bond lengths and angles are given in Table
1. General X-ray data, other bond lengths and angles,
positional and thermal parameters and the stereoview
are given in Tables S1-S4 and Figure S1 of the Sup-
porting Information. The enolic hydrogens and H(N2),
H(O1) were found in the difference Fourier map. The
N(2)-H bond length is 0.97 Å and the N(1)-H hydrogen
bond length is 2.07 Å, the hydrogen bond is nonlinear,
the N(1)-H-N(2) angle being 146.6°. The other hydrogen
is located on the “amido” oxygen O(1) in the enol form
8b and is unsymmetrically hydrogen bonded to the
CdO of a cis ester group. The O(1)-H and O(2)-H
bond lengths are 1.15 and 1.48 Å and the O(1)-H-O(2)
angle is 139.5°. The shorter distance of the enolic
F igu r e 1. ORTEP drawing of 8b.
Ta ble 1. Bon d Len gth s a n d An gles in Solid 8b
bond
length, Å
angle
deg
C1-C2
1.394 (4)
C1-C2-C5
C1-C2-C3
C3-C2-C5
N2-C1-O1
N2-C1-C2
C2-C1-O1
C2-C3-O3
C2-C3-O2
C1-N2-C6
O1-H-O2
N1-H-N2
121.0 (3)
118.5 (3)
120.5 (3)
116.4 (3)
123.2 (3)
120.4 (3)
114.7 (3)
122.7 (3)
123.8 (2)
139.5
C1-O1
C1-N2
C3-O2
C3-O3
C5-N1
C4-O3
C2-C5
C2-C3
6 C-C in Ph
O1-H
1.311 (3)
1.336 (4)
1.237 (4)
1.324 (2)
1.136 (4)
1.443 (4)
1.418 (4)
1.436 (4)
1.363 (5)-1.385 (5)
1.15
146.6
O2-H
1.48
0.97
2.07
N2-H
N1-H
hydrogen to O(1) than to O(2) indicate structure 8b
rather than the enol of ester 8c, but a small displacement
of the hydrogen concerted with a single/double bonds
exchange in the formal cyclo-1,3-dioxadiene ring will
convert 8b to 8c. Both 8b and 5 are stabilized by an
intramolecular O-H‚‚‚O hydrogen bond, but in 8b the
solid enol is also stabilized by two intermolecular
N-H‚‚‚NtC hydrogen bonds giving a “dimeric” structure
whereas in 5 the N-H is weakly hydrogen bonded
intramolecularly to the ester oxygen. This reflects a
favorable distance and geometry for the inter-, rather
than the intramolecular hydrogen bond to a more distant
cyano nitrogen in 8b.
Other differences between the two enols are: (a) the
C(1)dC(2) bond is shorter (i.e., of higher double bond
character) in 8b than in 5 whereas the former amido
carbonyl C-O bond is slightly shorter in 5. (b) The C(2)-
C(3) bond is somewhat longer in 8b than in 5 but
corresponding bond angles are not much different in 5
and in 8b.

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6859
F igu r e 2. 1H NMR spectrum of 8 in DMSO at room temper-
ature: (A) solvent; (B) OMe; (C) exchanging CH/OH; (D-F)
Ph; (G) NH.
The polar electron-withdrawal effect of CN is higher
than that of a methoxycarbonyl (CO2Et: σI 0.30, σR- 0.34,
-
CN: σI 0.56, σR 0.34)15 but this effect is too small to
account for the difference in the solid-state structures of
6 and 8. This difference can be due to a stereoelectronic
effect. The smaller and linear cyano group enables both
â-substituents to be simultaneously in the double bond
plane and thus to exert their maximal resonance effect
in stabilizing the enol. The X-ray data support this
assumption. The dihedral angles between the plane of
the CdC group and its substituents and the OdC-C(2),
NC-C(22), HO-C(1) and NH-C(1) planes are respec-
tively, 0.02°, 6.6°, 1.0°, and 0.03°, i.e., the system is nearly
planar. Note, however, that in the calculated structure
of enol 6b both ester groups are also nearly in the CdC
plane.
F igu r e 3. 13C NMR spectrum of 8 in DMSO-d6 at room
temperature: (A) solvent; (B) Me; (C-F) Ph + CN. Note the
trace of a very low intensity signal at δ of ca. 163.
observed and the CR signal at 164 ppm is barely observed.
The only observed significant signals are for Ph and CN
at δ 119.65-138.05 (Figure 3). In D2O/H2O the signals
at δ 124.5 and for Cipso broaden. This is not inconsistent
with structure 8a as the main component of a rapidly
exchanging mixture. At 366.8K the spectrum fits a
decomposition process since signals at 23.56, 25.96 (new)
and 48.02, 52.18, 160.22, and 163.89 ppm are observed.
The 1H NMR spectrum in CD3CN resembles that in
DMSO-d6 in the Me and Ph region, but there are three
broad signals at δ 4.86, 8.30, and 8.85. The compound
precipitates on cooling, and the only reliable information
is that no new OH signal is observed at 230K im-
mediately after cooling. On warming to 340 K, the signal
at δ 8.30 disappears, the other two broad signals remain
broad and other signals, mainly aliphatic, appear. Again,
this may be due to decomposition.
(b) Th e Str u ctu r e in Solu tion . In contrast with the
unequivocal enolic structure of solid 8, the structural
assignment in solution is not obvious and is solvent-
dependent.
(i) In Solu tion s of th e P ola r Solven ts DMSO-d 6
a n d CD3CN. In DMSO-d6 8 displays Me (at δ 3.70) and
Ph (at δ 7.07) signals but also a broad signal at δ 5.60
(CH) and at δ 10.68 (NH), and no signal at a lower field
than 15 ppm (Figure 2). The two latter signals disappear
on addition of D2O. Similar features were observed for
the major species of 6 (i.e., 6a ), and hence, the structure
is either mainly 8a , or in view of the broad signal at δ
5.60, there is an exchange process involving the CH or
the OH groups in a mixture in which 8a predominates.
To find out if an enol signal is not lost at room temper-
ature due to an exchange, a DMSO-d6 solution of the
sample was heated during 30 min to 366.8 K. The
The rt 13C NMR spectrum in CD3CN shows four
aliphatic signals at 46.76-57.47 ppm, seven signals at
117.30-137.40 ppm, and three very weak signals at 158-
162.5 and 171 ppm (see the Experimental Section). The
coupled spectrum shows the aliphatic signals as a doublet
at δ 46.76 (J ) 135 Hz), two Me quartets at δ 52.36,
53.96, and a singlet at δ 57.47. These are consistent
with a mixture of 8a (CH at δ 46.76, and a Me) and 8b
(>Cd at δ 57.47 and a Me). In the aromatic region the
signals are for CD3CN (strongest) and for Ph + CN of 8;
i.e., there is only one extra signal over those expected
for a single species. The low field signals are too weak to
give reliable information, although their low intensity
may indicate an exchange process.
1
solution became light orange and its H NMR spectrum
became more complex showing aliphatic signals at δ
3.21, 3.63, 3.72, 3.80, 3.89 and ca. 5.2 (broad), 6.9-7.6
(aromatic multiplet), 10.0 (singlet) and 10.4 (broad
singlet), but no new signal at δ 15-18. Most of these
signals were retained on re-cooling to room temperature,
and we conclude that an irreversible reaction occurred
on warming. This could be a cleavage reaction but it was
not investigated further.
In the 13C spectrum in DMSO-d6 at room temperature
there are very weak and broad CR, Câ signals and a broad
Me signal (at δ 53.0). For example, in Figure 3, Câ is not
(ii) In Ch lor in a ted Solven ts. In CDCl3 at room
temperature, the H NMR spectrum is deceptively simple.
A CH signal is not observed at ca. 4.7 whereas a lower
(15) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry, 3rd ed.; Harper and Row: New York, 1987; pp
154 and 157.
1

6860 J . Org. Chem., Vol. 65, No. 21, 2000
Mukhopadhyaya et al.
F igu r e 5. 13C NMR spectrum of 8 in CDCl3 at 220 K: (A)
OMe; (B) C(CN)CO2Me; (C) solvent; (D-H) Ph + CN; (I,J ) CR
and CO.
spectrum at 220 K, which differs only slightly (∆CRâ
113.28 ppm) is given in Figure 5.
)
A single CdO signal appears in the IR spectrum in
CDCl3 at 1642 cm-1
.
F igu r e 4. 1H NMR spectrum of 8 in CDCl3 (A) at room
temperature and (B) 220 K: (A) OMe; (B,C) Ph; (D) NH; (E)
OH.
The enol 8b is also observed in CCl4 and Cl2CDCDCl2
where the 1H NMR spectra at room temperature re-
semble that in CDCl3. In CCl4 the signals are at δ 3.03,
4.83 and a very weak OH signal appears at 16.25 ppm.
In Cl2CDCDCl2 the room temperature 1H NMR spectrum
shows Me, Ph and NH signals, a broad OH signal at δ
15.40 and a narrower signal at 7.72 ppm.
The solid state 13C spectrum shows Me signals at ca.
36.50, Ph + CN signals at 123.7-132.8 and signals at
ca. 171 ppm.
field signal at ca. 15.4 ppm is mostly (but not always)
observed in addition to a Me singlet at 3.88 ppm, a Ph
multiplet at 7.23-7.48 and a broad 0.8H signal at 7.88
(N-H). A broad signal may be hidden below the aromatic
signal (Figure 4A). On adding D2O, an HDO signal at δ
4.73 replaces the δ 7.75 signal. The lack of characteristic
signals for the amide form 8a and the weak OH signal
suggests that enol 8b is present, but the broadening of
the latter signal suggest that 8b exchanges with another
isomer (possibly with catalysis by impurities in the
solvent). However, addition of traces of HCl as a catalyst
for the exchange, did not change the appearance of the
spectrum. To slow a possible exchange the spectra were
therefore measured at 243 and 220 K. Most signals were
slightly shifted, but the small signal at δ 7.88 was
replaced by two new signals at δ 8.70 and 15.27 (243 K)
[or 8.95 and 15.15 ppm at 220 K]. These sharper signals
were ascribed to the NH and OH protons, respectively,
of enol 8b (Figure 4B). Since no CH signal was observed
at 220 K we conclude that at room temperature 8b is
the main component of the mixture and it rapidly
exchanges with a small amount of 8a , 8c, or 8d . This is
supported by the single carbonyl signal in the IR at 1642
cm-1, which is consistent with the highly conjugated ester
group of the push-pull alkene 8, and with the OH signal
B. Th e Nitr o Ester Activa ted An ilid e 9. The be-
havior of ethyl anilidoacetate 9 in CDCl3 at room tem-
perature resembles that described for the diester 6. The
main signals are CH (δ 5.91), NH (δ 8.99), Et (δ 1.38,
4.43), and Ph (δ 7.23-7.56) signals. However, a very
weak (<0.1H) signal at δ 16.66, which is the only one
disappearing rapidly in D2O is also sometimes (but not
always) observed. When a solution which does not show
this signal is cooled to 220 K four very small singlets
appear: two are of nearly the same intensity at δ 19.32
and 12.03 and somewhat more intense signals are at
16.84 and 11.94. The signal at δ 9.43 (presumably the
N-H of 9a ) which is ca. 35-50-fold more intense than
these signals, becomes sharper. Expansion shows also a
very broad signal centered at ca. 15 ppm. Small Ph
multiplets and Me signals accompany the major corre-
sponding signals and the CH2 signal is broadened. We
conclude that the main compound in CDCl3 is the amide,
9a . The IR peaks at 1754, 1677 cm-1 are consistent with
the CdO stretching vibrations of 9a . However, the
appearance of a <0.1 H signal at δ 16.66 which rapidly
disappears on addition of D2O, suggests the presence of
an additional minor enolic species at room temperature.
Moreover, the observation at 220 K of two signals at δ
<16.84 (OH) and two signals at ca. 12 ppm (NH) and
additional small Me and Ph signals, superimposed on
these of 9a indicate the presence of two enols of amides,
consisting together <10% of the mixture. There is no
further data to decide if these are 9b and 9c (or even
9d ) or two geometrical isomers of either of these species.21
Exchange between 9a and enol forms is slower than for
5.
at 3192 cm-1
.
The coupled 13C NMR spectrum in CDCl3 shows a Me
at δ 52.59(q), a CN at δ 116.22(s) and Ph signals at δ
112.69-134.91 and signals at 57.74(s), 171.11 and 173.75
ppm. The former is a singlet in the coupled spectrum and
can be assigned to the CH of 8a only if the associated
proton exchanges rapidly on the NMR time scale. Alter-
natively, the structure could be 8b, if δ 57.74 is assigned
to Câ in Câ(CN)CO2Me in the push-pull ethylene. Since
this signal is still a singlet at 220 K, when the OH group
is observed and exchanges much more slowly, this
assignment is more likely. The low field signals are then
CR at 171.11 ppm and an ester carbonyl at 173.35 ppm,
and ∆CRâ ) 113.37 ppm. This large value is consistent
with the high ∆CRâ found for 5. On adding 1:1 D2O/H2O
the Câ, Co, Cipso and CR signals split by 25, 8.3, 1.5, and
7 Hz, due to isotope induced shifts. The uncoupled
Ethyl dinitroacetate was reported before sensitive
NMR spectrometers were available, to be in the ester
form.10 It seems worthwhile to reinvestigate this system

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6861
Ta ble 2. Bon d Len gth s a n d An gles for 11d
bond
C1-C2
length, Å
1.473 (4)
1.251 (3)
1.377 (4)
1.461 (4)
1.320 (4)
angle
deg
C(2)-C(12)-O(4) 120.7(3)
C(2)-C(12)-C(13) 128.0 (3)
O(4)-C(12)-C(13) 111.3 (3)
C(1)-C(2)-C(9)
C(1)-C(2)-C(12) 117.6 (3)
C(1)-O(1)
C(2)-C(12)
C(2)-C(9)
C(12)-O(4)
119.4 (2)
6 Ph C-C bonds 1.369 ( 0.010a C(9)-C(2)-C(12) 123.1 (2)
C(9)-O(2)
C(12)-C(13)
C(1)-N(1)
C(3)-N(1)
O(4)-H
1.208 (3)
1.483 (4)
1.335 (4)
1.411 (3)
0.98
1.47
0.91
1.83
O(1)-C(1)-C(2)
O(1)-C(1)-N(1)
6 Ph CCC
120.7 (3)
120.5 (3)
120.0 ( 1.0
161.3a
O(1)-H-O(4)
O(2)-H-N(1)
O(4)C(12)C(13)/
C(1)C(2)C(9)b
C(1)C(2)C(9)/
C(2)C(1)O(1)b
N(1)C(1)O(1)/
C(9)C(2)O(1)
140.5a
O(1)‚‚‚H
2.25
N(1)-H
O(2)‚‚‚H
0.46
0.46
F igu r e 6. ORTEP drawing of 11d .
although we noted here and earlier2 that enolization on
an ester is less probable than on an amide. Crystals of 9
suitable for X-ray crystallography were not obtained and
the enols concentrations are too small to draw further
conclusions.
a
b
The shorter bond is C(6)-C(7): 1.345 (6) Å. Dihedral angle.
eters are in Tables S5-S8 and the stereoview is in Figure
S2 of the Supporting Information.
The following features are relevant: (a) An almost
normal C(1)-C(2) bond (1.473 Å) for an sp2-sp2 bond.
(b) The C(2)-C(12) bond length of 1.377 Å is somewhat
longer than a normal CdC bond and shorter than the
C(2)-C(9) bond of 1.461 Å. (c) An O(4)-H bond of
0.98 Å, a C(12)-O(4) bond of 1.320 Å and a C(1)-O(1)
bond of 1.251 Å and a O(1)-H distance of 1.47 Å. The
O(1)-H-O(4) angle is 161.3°. (d) N(1)-H and O(2)-H
bonds of 0.91 and 1.83 Å and an N(1)-H-O(2) angle
of 140.5°.
Again, there is less enol in DMSO-d6 where the spectra
1
are consistent with structure 9a . In the H NMR spec-
trum no OH signal is observed, but the relative intensity
of the CH proton is <1. In the 13C NMR spectrum both
carbonyls are relatively upfield (154.44, 161.84). The
situation resemble that for 6.
C. Th e Keto Ester Der iva tives 10 a n d 11. The
isomers 10 and 11 differ in the locations of the Me and
1
Et groups on the acyl and ester moieties. The H NMR
spectra in CDCl3 of both contain in addition to the
aliphatic and Ph signals N-H signals at δ 11.2-11.5 and
temperature-dependent O-H signals at δ 8.2-18.4,
which disappear rapidly on shaking with D2O. These
spectra are not an unequivocal structural probe. The
CdO group of 10 and 11 is a much more favorable
enolization site than the amido or the ester group, and
the very low field OH signal and the IR spectrum which
display OH stretching absorptions are accounted for by
the enol structures of amide (10b, 11b), of ester (10c,
11c) or of a ketone (10d , 11d ), but not by structures
10a /11a .
The 13C NMR spectra of either 10 or 11 in CDCl3
display signals for two Me, one CH2, four C-Ph carbons,
one at ca. δ 94, a singlet and a narrow multiplet at the
168.8-171 region and a single CdO signal (quintet, J )
5-6 Hz) at δ 92 (10) or 196.2 (11) (see Experimental
Section). The structures are 10b/11b or 10c/11c if CR is
at the δ 70 region or 10d /11d if CR appears at a lower
field than 190 ppm. Since CR of 5 is at the δ 170 region,
but δ C(OH) of 7 is at the δ 190 region, the assignment
is difficult. Analogies with the solid-state structure of 11,
which is the amido-substituted carbonyl enol, 11d , and
with the derivative 7, and the calculated much higher
pKEnol values for simple carbonyls than for simple amides
and esters suggest that the structures are 10d /11d . C-H
correlation spectra of 11 had shown long-range corre-
lations between the OH and the CH2, Câ, CO and the
δ 170 signal.
D. Th e Ma lon on itr ile Der iva tives 12 a n d 13. (a )
N-P h en ylca r ba m id om a lon on itr ile 12. In the absence
of a solid-state structure of 12 only the situation in
solution was investigated. Compound 12 displays only
Ph and NH protons in the 1H NMR spectra in both CDCl3
and DMSO-d6 (Figure 7). The absence of either a CH or
an OH signal can reflect an ionization-dissociation of
the carbon acid or a broadening due to exchange of the
amide 12a and the enol 12b. The coupled 13C NMR
spectrum in DMSO-d6 (Figure 7) displays singlets at
34.38 and 167.61 ppm. Since the low field carbon, which
should be due to Câ of the CâH(CN)2 group of the amide
form 12a , is a singlet, a rapid exchange, a dissociation
of Hâ or structure 12b are possible interpretations. Since
the cyano groups appear as a singlet at 121.01 ppm, the
signal at δ 167.61 may be either a CdO (of 12a ) or CR (of
12b) or an average of both if CR is involved in a rapid
exchange. The low solubility in CDCl3 and the high mp
of DMSO prevented a study under conditions of a slower
exchange achieved by cooling. However, the 1H NMR
spectrum in CD3CN, where the solubility is higher shows
at room temperature NH and Ph signals, but also a broad
signal at 5.15 ppm, indicating that an exchange process
takes place. On cooling the CD3CN solution to 233 K, the
signal (now at 5.22 ppm) sharpens. On addition of D2O
the NH and the δ 5.15 signals disappear immediately,
and hence the latter is ascribed to the exchanging CH/
OH proton of 12a /12b. Assuming that the δ(OH) of the
proton of 12b is at δ 15-18 as with 6b, 8b, and 9b and
the δ(CH) signal of 12a is at δ 3-5, the observed δ
suggests that 12a is the major component of the mixture
in CD3CN. Consequently, the trend found for 12 re-
sembles that for 9, i.e., in a higher dielectric constant
solvent the amide/enol equilibrium is shifted in the amide
direction.
Solid Sta te Str u ctu r e of 11. To unequivocally de-
termine the structure of 11, its X-ray diffraction was
determined. The ORTEP structure (Figure 6), shows that
the solid-state structure is 11d . Selected bond lengths
and angles are in Table 2 and general X-ray data, other
bond lengths and angles, positional and thermal param-

6862 J . Org. Chem., Vol. 65, No. 21, 2000
Mukhopadhyaya et al.
gave differing microanalysis results and the HRMS
showed the presence of one water molecule. The com-
pound is slightly soluble in DMSO-d6 and its 1H NMR
spectrum shows a broad, concentration-dependent signal
at δ 5.58 (which shifts to δ 7.94 on dilution), a small
signal at δ 7.93 and very small signals at δ 2.71 and 2.94.
The coupled 13C spectrum [singlets at 33.96 (C(CN)2),
119.02 (CN) and 175.58 (CR or CONH2)], is consistent
with the enol structure 13b. These δs shift somewhat
with different batches of solvents (cf. Experimental
Section) which we ascribe mainly to temperature-
dependence of the δs and different amounts of water. Due
to the difficulties mentioned, the structural assignment
is only tentative and the data were supplemented by
theoretical calculations.
E. Th e Ba r bitu r ic Acid An ilid e 14. Due to low
solubility in CDCl3, the spectra of 14 were taken only in
1
DMSO-d6 at room temperature. The H NMR spectrum
displays major Ph protons at δ 7.20, 7.42, and 7.51 and
signals at δ 11.51 and 11.96 which disappear on shaking
with D2O and are ascribed to the NH protons. There are
additional small (ca. 0.06H) Ph proton signals at 7.45,
7.26 (t), and 6.94 (t) ppm. The 13C NMR spectrum (cf.
Experimental Section) displays 10 signals including
seven aromatic protons at 117.97-135.80 of which three
are small, having 0.05-0.07 of the intensity of the main
signal. The highest field signal is at δ 80.26, ascribed to
Câ and the two lower field signals than Cipso are at δ
148.47 and 168.70, ascribed to NHCO signals.
In addition to the amide (14a ) and enol (14b) tau-
tomers, enolization of a ring amide is another option,
especially since a triple enolization, two of the ring NHCO
moieties and one of the keto-enol type will give the
aromatic 4-anilido-2,4,6-pyrimidinetrione 14d .
F igu r e 7. NMR spectrum of 12 in DMSO-d6 at room tem-
perature. (Bottom) 1H spectrum: (A) CH(CN)2; (B-D) Ph; (E)
NH. (Top) 13C spectrum: (A) C(CN)2; (B) solvent; (C-F) Ph +
CN; (H) CO.
There are too many signals for a single compound in
1
the H and 13C NMR spectra which indicate the presence
Compounds 15a and 15b were considered as 13C NMR
models for enol 12b. In CDCl3 15a displays signals at δ
24.05 (Me), 84.38 (Câ), 112.58, 112.68 (CN), 127.16,
of two Ph rings. The major compound displays signals
for a Ph, a CONH and a carbon (Câ), which is formally
substituted by three EWGs and uncoupled to a proton.
The absence of coupling and the appearance of at most
two CONHR carbonyls exclude the tetra-amide structure
14a , whereas the absence of an observable OH signal
suggests that if an enol is present it exchanges rapidly
with an isomeric species. The enols could be 14b and 14c,
both having two types of amide NH groups. In view of
the trioxo structure of barbituric acid17 we believe that
the ureido moiety does not enolize and exclude 14d . In
5,5-diethylbarbituric acid the C2 and C4 CO groups are
displayed at 149 and 173 ppm, respectively,18 and in
analogy we ascribe the signals at δ 148.47 and 168.70 to
the C2 and C4 carbonyls of 14. Without further experi-
ments we can only conclude that an enol of an amide,
either 14b and 14c, is present in DMSO-d6 solution.
Th eor etica l Ca lcu la tion s. The relative energies of
the four isomers of 13, i.e., the amide 13a , the enol 13b,
the ketenimine 13c and the hydroxyimine 13d were
calculated by using the density functional theory hybrid
method B3LYP/6-31G**.19,20 Full optimization was per-
formed, and zero point energies and vibrational frequen-
cies were calculated. The ∆H and ∆G values for the
interconversion of the most stable conformer of each
128.89, 132.05, 135.70 (C-Ar) and 175.47 (CR); ∆CRâ
)
ca. 91 ppm. 15b which is little soluble in CDCl3 displays
signals in DMSO-d6, at 50.23 (C(CN)2), 55.26 (Me),
114.39, 114.46, 116.68, 119.53, 132.43 (Ar + CN), 155.58
(d, J ) 176 Hz, CR), 156.82 (Cipso to OMe); ∆CRâ ) 105.35
ppm. Although δ Câ values are at a very low field, Câ in
12 is at a much higher field (δ 34.38 in DMSO-d6) and
hence ∆CRâ ) 133.23 ppm is higher than in 15a and 15b.
This reflects the much higher zwitterionic character of
12b than of 15.
The compound decomposes on standing in solution
since the relative intensity of the two small signals
observed at δ 2.09 and 2.20 on dissolution increase
consistently with time on standing for several days.
(b) Dicya n oca r ba m id om eth a n e, 13. The literature
hints that solid 13 is enolic (13b).14 Moreover, the
corresponding esters (NC)2CHCO2R display 13C NMR
signals for both the ester and enol species.16 On the basis
of the enolic structure of solid 8b, the presence of enol
12b in an exchanging mixture in solution, the larger
tendency of amides to enolize compared with esters and
the ability of two cyano groups to be simultaneously
accommodated in the C-CdC plane, an enolic structure
for 13 is expected. However, the sample of 13 obtained
from its salt by ion exchange according to the literature14
(17) (a) J effrey, G. A.; Ghose, S.; Warwicker, J . O. Acta Crystallogr.
1961, 14, 881. (b) Katritzky, A. R. Handbook of Heterocyclic Chemistry;
Pergamon Press: New York, 1985; p 196.
(16) Neidlein, R.; Kikelj, D.; Kramer, W.; Sui, Z.; Boese, R.; Bla¨ser,
D.; Kocjan, D. Chem. Ber. 1989, 122, 1341.
(18) Kalinowski, H.-O.; Berger, S.; Braun, S. Carbon-13 NMR
Spectroscopy; Wiley: Chichester, 1988; p 377.

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6863
Ch a r t 1
Ch a r t 2
isomer (i.e., their relative stabilities) are given in Chart
1 and absolute energies of the isomers and other species
used in the calculation are given in Table S9 of the
Supporting Information.
Calculation of the structures of dicyano(carbonyl-
amido)methane 13a and its isomers had given several
minima. The most stable structure is the enol of the
amide 13b, whose syn conformer (Cs) is more stable than
the gauche conformer by 7.3 (∆G) and 7.1 (∆H) kcal/mol.
The gauche (H/CO) “amide” structure 13a (which is more
stable than the anti H/CO conformer 13a ′ by 4.3 (∆G) or
3.1 (∆H) kcal/mol), is 0.4 (∆G) and 1.1 (∆H) kcal/mol less
stable than 13b. Both isomers are much more stable than
the two stable keteneimine structures 13c and 13c′. Of
these, 13c having the keteneimino moiety anti to the NH2
group is more stable than the syn conformer 13c′ by 3.9
(∆G or ∆H) kcal/mol, and 6.0 (∆G) and 6.2 (∆H) kcal/
mol less stable than 13b. The least stable is the enol
imine form 13d , which is 15.9 (∆G) and 16.1 (∆H) kcal/
mol less stable than the planar 13b (with dihedral angles
of 0° or 180°). The geometries of 13a -d are given in
Chart 2 and the structures and relative energies of all
the stable conformers of 13a -c and the two more stable
conformers of 13d vs the most stable conformer of each
species are given in Chart 3.
Ch a r t 3
Eight stable conformers were found for 13d . Their
designations involve two descriptors. The first one relates
to the conformation of the O-H group in relation to
the single bond, and the second to the conformation of
the C-CdN-H moiety. The most stable conformer is
13d -anti-syn-1 which differs from 13d -anti-syn-2 in the
conformation at the CH(CN)2 group. Likewise, there are
two anti-anti, two syn-anti, and two syn-syn conformers.
Their structures and relative energies are given in Chart
4. The order of stabilities is anti-syn-1 > anti-syn-2 >
(19) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, A.; Cheeseman, J . R.; Keith, T. A.; 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.; Andress, 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 C.2; Gaussian Inc.: Pittsburgh, PA, 1995.
(20) (a) Becke, A. D. J . Phys. Chem. 1993, 98, 5648. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(21) Note a d d ed in p r oof: Based on analogy with the enols
ArNHC(OH)dC(CO2R)CO2R′ where R and/or R′ contain fluorine sub-
stituents (Lei, Y. X., unpublished results), the species observed at 220
K are the E- and Z-isomers of 9b.
anti-anti-2 > syn-anti-2 > anti-anti-1 > syn-anti-1 >
syn-syn-1 > syn-syn-2. The energy difference between the
more stable and least stable conformers is 8.1 kcal/mol

6864 J . Org. Chem., Vol. 65, No. 21, 2000
Mukhopadhyaya et al.
Ch a r t 4
methane as the reference and 3b-5b with ethylene as
the reference. Analogous isodesmic reactions are not
available for 13c.
(NC)2CdC(OH)NH2 + CH4 h
H2CdC(OH)NH2 + H2C(CN)2
∆H ) 27.7 kcal/mol (3a)
(NC)2CH-C(NH2)dO + CH4 h
H3C-C(NH2)dO + H2C(CN)2
∆H ) -1.0 kcal/mol (4a)
(NC)2CH-C(OH)dNH + CH4 h
H3C-C(OH)dNH + H2C(CN)2
∆H ) -3.1 kcal/mol (5a)
(NC)2CdC(OH)NH2 + H2CdCH2 h
H2CdC(OH)NH2 + H2CdC(CN)2
∆H ) 17.0 kcal/mol (3b)
(NC)2CH-C(NH2)dO + H2CdCH2 h
H3C-C(NH2)dO + H2CdC(CN)2
∆H ) -11.7 kcal/mol (4b)
and steric effects play an important role in this difference.
In the most stable conformer the CR-O-H is anti, i.e.,
remote from the small Câ-H substituent and the C-O
bond bisect the HCCN angle. In the least stable con-
former the C-O bond bisects the NCCCN angle and the
syn-OH is close to a larger cyano group.
(NC)2CH-C(OH)dNH + H2CdCH2 h
H3C-C(OH)dNH + H2CdC(CN)2
∆H ) -13.8 kcal/mol (5b)
From the pair of isodesmic reactions 3b and 4b (∆H )
17 and -11.7 kcal/mol, respectively), the stabilization by
â-(NC)2 of the enol over the amide is 28.7 kcal/mol,
sufficient to overcome the 27.6 kcal/mol destabilization
of the parent acetamide/1-aminoethenol system.12 This
large effect is mainly due to stabilization of the enol by
the dipolar interaction shown in 1b, but also to a
significant destabilization of the amide form, presumably
due to a repulsive interaction between the electronegative
CN and CO dipoles. This destabilizing effect of the
â-substituents is superimposed on the carbonyl stabiliza-
tion by the substituent X. Hence, introduction of two
â-cyano groups increase KEnol by simultaneously stabiliz-
ing the enol (60% of the effect) and destabilizing the
amide form (40% of the effect). A combination of effects
was previously calculated for the 6a /6b system except
that the relative contribution of the enol stabilization
effect was higher (86%).
Another conclusion from the isodesmic reactions is
that the reactions with CH4 as a reference are more
convenient for comparison with both 13a and 13d
because all the four species of these equilibria have an
sp3 carbon. In contrast, for 13b ethylene is a more
convenient model since all four species in these reactions
have an sp2 carbon.
The hydroxyimine 13d formally resembles the amide
13a by having a double bond to an heteroatom and a
single bond to a resonatively electron-donating hetero-
atom. It is therefore not surprising that the ∆H of eqs
4a and 5a or of 4b and 5b differ by only ca. 2 kcal/mol,
accounting for the small substituent effect.
In the two dC(OH) structures, 13b and 13d , the O-H
and N-H hydrogens are too far from the cyano group to
form hydrogen bonds. In 13b the O-H points in the
direction of the CN but its distance from the nitrogen is
2.64 Å. In 13d the distance between the imino hydrogen
and the corresponding cyano nitrogen is 2.86 Å. More-
over, the orientation of the cyano nitrogen lone pairs in
relation to the O-H and N-H bonds do not enable the
formation of hydrogen bonds.
The qualitative order of stability of the isomers of 13
resembles that calculated for 5: enol > amide > hydroxy-
imine. However, the 13b-13a energy difference of ∆G
) 0.4 kcal/mol is much smaller than that for 5, despite
the planarity of 13b. This result is consistent with our
conclusion that both species of 12 coexist in solution; i.e.,
on accepting an error of a few kcal/mol the calculations
on the parent compound 13 reflect the behavior of
the corresponding anilide 12 in solution. Again, the syn
CdC-O-H conformers are appreciably stabilized com-
pared with the gauche conformers.
The difference between systems 5 and 13 may mainly
reflect the absence of intramolecular hydrogen bonding
in 13b, where the enolic hydrogen is too far away from
the cyano nitrogen even in the favored syn-CdC-O-H
conformation. In contrast with the amide/enol differences,
the amide/imine (anti-H, OH) differences in the two
systems are large but not differ much, being ∆G ) 15.6
kcal/mol for 13a /13d and 13.9 kcal/mol for the corre-
sponding two species of 5. Proton transfer to the cyano
nitrogen to give 13c is 6.0 kcal/mol more expensive than
to the oxygen.
Str u ctu r a l Effects a n d KEn ol Va lu es. The present
data extend the scope of the enols of carboxanilides which
we started to screen previously.2 There is one new solid
enol (8), and in solution we have the same multitude of
To evaluate the effect of the cyano groups on the
equilibria of isomers 13a , 13b and 13d we calculated
∆H values for the isodesmic reactions 3a-5a with

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6865
the broad peaks at 4.88 and 8.68 remained and a broad signal
at 3.77 overlaps the main MeO signal. 13C NMR (uncoupled,
CDCl3) δ: 52.59 (CH3, q), 57.74 (s, Câ), 116.22 (s, CN), 122.69
(d of d, Cm), 126.31 (d of d), 129.16 (d), 134.91 (m, Cipso), 171.11
(CR, d, J ) 4.7), 173.75 (CO2Me, m). Except for small shifts
the same spectrum was obtained at 220 K. In the presence of
a 1:1 D2O/H2O mixture the four italicized signals were split
to 57.66 + 57.70; 122.63 + 122.74; 134.87 + 134.89; 170.90 +
170.99. 13C NMR (DMSO-d6, rt) δ: 52.71 (br, vw, sometimes
unobserved), 119.66 (d of m, Co), 123.90 (br), 128.85 (d of d,
Cm), 138.05 (Cipso), 164 (br, vw, sometimes unobserved). On
adding a 1:1 D2O/H2O solution the signals at δ 123.90, 138.97
broadened. When heated for 30 min at 366.8 K signals were
observed at δ 23.56, 25.96, 40.02, 52.18, 114.51, 119.21, 123.68,
128.19, 137.77, 160.22, 163.88. 13C NMR (CD3CN, coupled) δ:
46.76 (d, J ) 136 Hz), 52.36 (d, J ) 148 Hz), 53.96 (d, J ) 148
Hz), 57.47 (s) [all small], 120.09 (d, J ) 162 Hz), 124.17 (d, J
) 163 Hz), 125.13 (d of t, J ) 162 Hz), 126.58 (Ph), 129.02
(large, CN), 137.40 (m, Cipso). Smaller signals are observed at
δ ca. 158, 162.5, 171. At 340 K small signals at ca. 48, 53.91,
120.89 and 125.70 and an intense signal at 129.25 (CD3CN)
were observed. IR (νmax, cm-1, CHCl3): 3193 (m, OH), 2218 (s,
CN), 1642 (s, CdO). (b) When a mixture containing the ester
(1 g, 10.1 mmol), PhNCO (1.65 mL, 15.14 mmol) and Et3N (3.54
mL, 25.23 mmol) was heated at 50 °C for 3 h without a solvent
and then worked up as above, 3.9 g of a crude solid was
obtained. Column chromatography on silica gel gave two
fractions. The first one, 0.92 g, mp 141-3 °C was identical
with that described above except for the absence of a signal
at 7.88. The second one (1.34 g) showed a complex NMR
spectrum.
behavior. The enol is the observable major component
in a tautomeric mixture (8 in CDCl3 at 220 K), it is the
minor component of an amide/enol mixture (9 in CDCl3),
it is in a rapid equilibrium with an isomeric species, (12,
14, and perhaps 13), and it is not observed and is much
less favorable than an enol on a keto function (10 and
11). The number of known (i.e., observed as pure species
or in an equilibrium mixture) enols of amides, activated
by â-EWGs is now close to dozen and they cannot be
regarded anymore as esoteric species.
The data are still mostly qualitative. The range of
experimental KEnol values is limited by the NMR tech-
niques, sometimes by the lower solubility in nonpolar
solvents where KEnol is higher than in polar ones, by the
several potential enolization sites which are not easily
distinguishable when the enol is present in a small
percentage, by the exchange of the enol with a tautomer
which cannot be always frozen, and by the slow decom-
position of some of the compounds in solution.
In the present work, for ethyl anilidonitroacetate 9 0.09
> KEnol > 0.05 in CDCl3 provided that the minor species
is indeed 9b. For methyl anilidocyanoacetate 8, KEnol in
CDCl3, at 220K, where an OH was observed is g9. The
percentage of enol (i.e., KEnol values in CDCl3) derived
from the varied data for YY′CHCONHPh is qualitatively
in the following order of YY′: c-(RCO2C)2 [meldrum acid]
> NC, CO2Me > NC, NC . CO2Me, CO2Me ∼ NO2,
CO2Me.
Qualitatively, the percentage of enol for 8 and 9, as
well as for 5 and 6, is lower in DMSO-d6 or CD3CN than
in CDCl3, CCl4 or Cl2CDCDCl2. This is explained by the
higher polarity of the amide form, which is more favored
in the more polar solvent.
Microanalysis: Calcd for C11H10N2O3: C, 60.55; H, 4.62; N,
12.84. Found: C, 60.24; H, 4.69; N, 12.54.
Cr ysta llogr a p h ic Da ta : C11H10N2O3, space group P21/n;
a ) 22.561(5) Å, b ) 5.856(1) Å, c ) 8.048(2) Å; â ) 93.66(2)°,
V ) 1061.1(8) Å3, Z ) 4, Fcalcd ) 1.37 g cm-3, µ (Mo KR) )
0.95 cm-1, no. of unique reflections 2063, no. of reflections with
I g 3σI 1326, R ) 0.059, Rw ) 0.086.
Rea ction of Eth yl Nitr oa ceta te w ith P h en yl Isocya n -
a te. A solution of ethyl nitroacetate (1 g, 7.5 mmol), phenyl
isocyanate (0.81 mL, 7.5 mmol), and Et3N (2.2 mL, 15 mmol)
in DMF (7 mL) was heated with stirring for 4 h at 60 °C and
then stirred for additional 16 h at room temperature. The
mixture was poured into ice-cold 2 N aqueous HCl solution,
the aqueous phase was extracted with EtOAc, the organic layer
was washed with water and dried (Na2SO4), and the solvent
was evaporated. The crude residue (1.74 g, 97%) was chromato-
graphed over silica gel using a 1:4 EtOAc-petroleum ether
eluent, giving 0.95 g (50%) of pure 9, which after recrystal-
lization from ether-petroleum ether has a mp of 98-9 °C.
1H NMR (CDCl3) δ: 1.38 (3H, t, J ) 7.2 Hz, Me), 4.36-4.50
(2H, q, J ) 7.2 Hz, CH2), 5.91 (1H, s, CH), 7.23 (1H, t, p-
Ph-H), 7.37 (2H, t, m-Ph-H), 7.56 (2H, d, o-Ph-H), 8.99 (ca.
1H, br s, NH). A weak singlet (<0.1H) was also observed at δ
16.66 and on shaking with D2O it disappeared. At 243 and at
220 K there are four signals of 0.02-0.03H intensity at δ 19.32,
16.84, 12.03 and 11.94, a very broad small signal at δ 15.86,
Exp er im en ta l Section
Gen er a l Meth od s. Melting points, FT IR spectra, NMR
spectra and low- and high-resolution mass spectra were
recorded as described previously.4b
Solven ts a n d Ma ter ia ls. The active methylene compound,
phenyl isocyanate, and commercial deuterated solvents (CDCl3,
DMSO-d6, CD3CN) were purchased from Aldrich and were
used without further purification.
R ea ct ion of Met h yl Cya n oa cet a t e w it h P h en yl Iso-
cya n a te. (a) A mixture containing methyl cyanoacetate (1 g,
10.1 mmol), phenyl isocyanate (1.0 mL, 10.1 mmol), and Et3N
(2.80 mL, 20.2 mmol) in dry DMF (7 mL) was stirred for 4 h
at 60 °C and then for 16 h at room temperature. The mixture
was poured into a cooled 2 N aqueous solution, extracted with
EtOAc, washed with water, dried (Na2SO4), and evaporated.
The crude solid was crystallized from EtOAc/petroleum ether,
1
giving 1.14 g (52%) of 8 as a white solid, mp 144-145 °C. H
1
NMR (CDCl3, rt) δ: 3.88 (3H, s, CO2Me), 7.23-7.41 (5H, m,
Ph), 7.88 (<1H, br, NH), 15.40 (<1H, OH, not always ob-
served). On shaking with D2O the signals at δ 7.88 and 15.40
disappeared. The spectra at 243 and 220 K are similar except
for a minor shift and a sharper OH signal at δ 15.15. δ (DMSO-
d6, rt): 3.70 (3H, s, CO2Me), 5.60 (ca. 1.5H, br, exchanging
CH), 7.07 (1H, t, p-Ph-H), 7.31 (2H, t, m-Ph-H), 7.50 (2H, d,
o-Ph-H), 10.68 (0.7H, br s, NH). The signals at δ 5.60 and 10.68
disappear on shaking with D2O. 1H NMR (CCl4, with external
C6D6, low solubility) δ: 3.03 (1H, CH), 4.83 (3H, CO2Me), 8.11
(1H, p-Me), 8.28 (2H, Ph-H), 8.35 (2H, Ph-H), 9.43 (ca. 1H,
1H signals at δ 9.51 and 6.10 and the Ph and Et signals. H
NMR (CCl4, with external (CD3)2CO, low solubility) δ: 1.38
(3H, t, Me) signal), 4.36 (2H, t, CH2), 7.10 (1H, t, p-H), 7.25
1
(2H, m, m-H), 7.49 (2H, t, o-H), 8.84 (1H, s, NH). H (DMSO-
d6) δ: 1.24 (3H, t, J ) 7.1 Hz, Me), 4.30 (2H, q, J ) 7.1 Hz,
CH2), 6.57 (0.5H, s, CH ?), 7.15 (1H, t, p-Ph-H), 7.42 (2H, t,
m-Ph-H), 7.54 (2H, d, o-Ph-H), 10.77 (0.25H, br s, NH). 13C
NMR (uncoupled, CDCl3) δ: 13.76 (q of t, Me), 64.73 (t of q,
CH2), 89.35 (d, CH), 120.48 (d of m, Co), 125.84 (d of t, Cp),
129.22 (d of d, Cm), 136.08 (t, J ) 7.5 Hz, Cipso), 155.44 (d, J )
3.3 Hz, CONHPh), 161.84 (q, J ) 3.3 Hz, CO2Et). In the
presence of a 1:1 D2O/H2O mixture the signals at δ 120.48 and
155.44 split to δ 120.38 + 120.48 and 155.42 + 155.54. At 220K
all signals were somewhat shifted, and a few Hz to a lower
field of most aromatic signals, signals of the same multiplicity
having 3-4% of the intensities of the corresponding major
signals had appeared. 13C NMR (uncoupled, DMSO-d6) δ:
13.60 (q, Me), 19.49 (d, J ) 4 Hz), 63.13 (t, CH2), 89.83 (d,
1
NH), 16.25 (0.7H, OH). H NMR (CD3CN, rt) δ: 3.83 (3H, s,
CO2Me), 4.86 (ca. 0.5H, br s), 7.16-7.55 (5H, m, Ph), 8.30
(0.15H, br s), 8.85 (ca. 0.5H, br s). At 230 K the compound
started to precipitate. The proton spectrum showed broad
signals at δ 2.2, 3.7, 3.80 (3H, CO2Me), 4.87 (small), 7.35 (5H,
Ph), 8.50 (small) and 9.08 (small). At 340 K the number of
signals is smaller. Except for the MeO and the 5-Ph-H signals

6866 J . Org. Chem., Vol. 65, No. 21, 2000
Mukhopadhyaya et al.
CH), 119.46 (d of m, Cm), 124.68 (d of t, Cp), 129.01 (d of d,
Co), 137.45 (t, J ) 10 Hz, Cipso), 156.75 (d of d, J ) 5, 1.7 Hz,
CONHPh), 160.94 (2 overlapping t, J ) 3.3 Hz, CO2Et). IR
(νmax, cm-1, CHCl3): 3326 (s), 3214 (m), 3158 (m), 3108 (m),
1754 (s, CdO), 1677 (s, CdO).
3499 (s), 3428 (s), 3326 (s), 3216 (s), 2800-2400 (br, including
peak at 2629), 2233 (s, CN), 2203 (s, CN), 1654 (s). HRMS:
127.0373 (94), 109.0289 (47), calcd for C4H5N3O2 127.0382, for
C4H3N3O 109.088.
Anal. Calcd for C4H3N3O: C, 44.05; H, 2.77; N, 38.52.
Found: C, 42.40; H, 3.00; N, 37.85%.
Microanalysis: Calcd for C11H12N2O5: C, 52.38; H, 4.79; N,
11.10. Found: C, 52.78; H, 4.83; N, 10.90.
Rea ction of Meth yl P r op a n oyl Aceta te w ith P h en yl
Isocya n a te. To a stirred solution of methyl propanoyl acetate
(2 g, 15.36 mmol) and Et3N (4.26 mL, 30.74 mmol) in DMF
(16 mL) was added phenyl isocyanate (1.68 mL, 15.36 mmol)
with stirring. Workup was identical with that described below
for the reaction of ethyl acetoacetate, and the crude product
(3.5 g, 92%) was crystallized from petroleum ether (40-60 °C),
giving 10 as a white solid (2.4 g, 63%), mp 40-41 °C. 1H NMR
(CDCl3) δ: 1.22 (3H, t, J ) 7.5 Hz, Me), 2.84 (2H, q, J ) 7.5
Hz, CH2), 3.83 (3H, s, Me), 7.15 (1H, t, J ) 7.5 Hz, p-H), 7.35
(2H, t, J ) 8.1 Hz, m-H), 7.53 (1H, d, J ) 7.8 Hz, o-H), 11.22
(0.9H, s, NH), 18.34 (1H, s, OH). On addition of D2O the signal
at δ 18.34 disappears almost completely after a short time.
13C NMR (CDCl3) δ: 10.61 (q of t, J ) 129 Hz, J ) 5.0 Hz,
Rea ction of Ma lon on itr ile w ith P h en yl Isocya n a te.
This reaction was conducted several times under different
conditions: (a) A mixture of malononitrile (1 g, 15.15 mmol),
phenyl isocyanate (1.64 mL, 15.15 mmol), and Et3N (5 mL,
36.07 mmol) in dry DMF (7 mL) was heated at 70 °C for 30
min and then stirred at room temperature for 20 h. It was
poured into 2 N aqueous HCl, and the solid obtained was
filtered, washed with water, dried, and crystallized from
EtOAc/CH2Cl2, giving 1.85 g (66%) of solid 12, mp 168-170
°C (sublimed). 1H NMR (CDCl3) δ: 7.26-7.55 (5H, m, Ph), 8.06
1
(1H, br s, NH); H (DMSO-d6) δ: 6.26 (2H, v br, not always
observed), 6.85 (1H, t, p-Ph-H), 7.15 (2H, t, m-Ph-H), 7.48 (2H,
d, o-Ph-H), 8.02 (∼0.1H, very b, NH). 13C NMR (uncoupled,
DMSO-d6) δ: 34.38 (s), 120.06 (d of q, Co or Cm), 121.01 (s,
CN), 122.24 (d of t, Cp), 128.35 (d of m, Co or Cm), 139.61 (d, J
) 9 Hz, Cipso), 167.61 (s). On shaking the solution with 1:1
D2O/H2O the signal at 122.24 is split to two very close signals.
1H NMR (CD3CN, rt) δ: 5.15 (0.8H, br, CH), 7.20 (1H, t, p-H),
7.41 (2H, t, m-H), 7.49 (2H, d, o-H), 8.82 (1H, s, NH). At 233K
the two broad signals (now at δ 5.22 and 9.05) sharpen and
each integrates to 0.8-0.9H. When D2O (0.6 mL) was added
to the solution (10 mg) in CD3CN (0.5 mL) at room tempera-
ture, the signals at δ 5.15 and 8.82 were absent immediately
after mixing. In another experiment without D2O at room
temperature, small signals at δ 2.09 and 2.20 (br) were
observed on dissolution, but their intensities increase on
standing and after 5-9 days they were the major signals. We
1
CH2Me), 31.57 (t of quintets, J ) 131 Hz, J ) 4.5 Hz, CH2),
51.50 (q, J ) 147 Hz, MeO), 94.04 (5 lines m, J ) 4.2 Hz, Câ),
1
1
121.41 (d of m, J ) 163 Hz, Co), 124.76 (d of t, J ) 162 Hz,
1
2
J ) 7.5 Hz, Cp), 128.90 (d of d, J ) 162 Hz, J ) 8.4 Hz, Cm),
136.90 (t of m, Cipso), 169.59 (d, J ) 4 Hz, CR or CONH), 170.97
(s, CO2Me), 196.19 (quintet, J ) 5.0 Hz, CdO). After shaking
with D2O, the lowest field signal is unsymmetrical quintet at
δ 194.91, CR is an unsymmetrical q, and the quintet at 31.57
is now a quartet at δ 31.24.
A long-range C-H correlation exists between the OH and
CH2, with Câ, and with the δ 170, 196.19 signals. IR (Nujol,
ν
max, cm-1): 3194 (w), 2900-2500 (H bonded OH), 1676 (CO);
IR (CHCl3): 3238 (m), 3194 (m), 2886, 1668 (CO).
Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62.
Found: C, 62.56; H, 6.10; N, 5.32%.
ascribe this behavior to decomposition of 12. IR (νmax:, cm-1
,
CHCl3): 3467 (vw, OH), 3242 (m, OH), 2232 (m, CN), 2204 (s,
CN), 1642 (m, CdO). IR (νmax:, cm-1, Nujol): 3432 (vw), 3242
(w), 2239 (m, CN), 2197 (s, CN), 1712 (s), 1635 (s).
Microanalysis: Calcd for C10H7N3O: C, 64.86; H, 3.81; N,
22.69. Found: C, 64.62; H, 4.01; N, 22.44
Rea ction of Eth yl Acetoa ceta te w ith P h en yl Isocya n -
a te. To a stirred solution containing ethyl acetoacetate (2 g,
15.4 mmol) and Et3N (4.26 mL, 30.7 mmol) in DMF (14 mL)
was added phenyl isocyanate (1.68 mL, 15.4 mmol), and
stirring was continued for 1 h at room temperature and then
for 45 min at 40-45 °C. The mixture was cooled to room
temperature, poured into a cold 13% solution of aqueous HCl
and extracted with EtOAc. The organic phase was washed with
water (50 mL), dried (Na2SO4), and the solvent was removed
yielding a solid (4 g, ca. 100%). Crystallization from petroleum
ether (40-60 °C) gave 11 as a white solid (2.83 g, 74%), mp
(b) Malononitrile (1 g, 15.2 mmol), phenyl isocyanate (2.74
g, 22.7 mmol), and Et3N (5.3 mL, 37.9 mmol) were kept without
a solvent at 58 °C for 130 min. The complex mixture (by TLC
and NMR) obtained was purified by column chromatography
over silica gel using 25% EtOAc/petroleum ether as eluent.
One fraction (1.10 g) displayed the following 1H NMR (CDCl3)
δ: 7.11-7.59 (H, m, Ph), 8.93 (1H, br s), which was not
changed on shaking with D2O. (c) Malononitrile (1 g, 15.2
mmol), PhNCO (3.6 g, 30.3 mmol) and Et3N (7.44 mL, 53
mmol) were heated for 4 h at 88 °C. Chromatography gave a
mixture and one fraction which was eluted with 30-35%
CH2Cl2/petroleum ether (1.31 g) has a mp of 206-236 °C and
is probably crude N,N′-diphenylurea, mp 238 °C. 1H NMR
(CDCl3) δ: 7.14-7.49 (H, m, Ph).
1
57-8 °C. H NMR (CDCl3, 223 K [and room temperature]) δ:
1.31 [1.33] (3H, t, J ) 6.9 Hz, Me) 2.17 (e0.1 H, small s), 2.42
[2.48] (3H, s, Me), 4.17 [4.31] (2H, t, CH2, J ) 6.6 Hz), 7.13
[7.14] (1H, t, J ) 7.2 Hz, p-Ph-H), 7.34 [7.35] (2H, t, J ) 7.8
Hz, m-Ph-H), 7.53 [7.53] (2H, d, J ) 8.4 Hz, o-Ph-H), 11.49
[11.28] (1H, s, NH), 18.43 [18.17] (1H, s, OH). On shaking with
D2O at room temperature the signal at 18.17 ppm disappears.
13C NMR (CDCl3, coupled, 223K [rt]) δ: 13.80 [14.07] (q of t,
J ) 130 Hz), 26.79 [26.17] (q of d, J ) 130 Hz, J ) 5.1 Hz),
60.81 [60.70] (t of q, J ) 148 Hz, J ) 4.5 Hz), 94.19 [94.86]
(m), 120.66 [121.11] (d of br m), 124.34 [124.53] (d of t J )
163 Hz, J ) 7.5 Hz), 128.64 [128.75] (d of d, J ) 162 Hz, J )
8 Hz), 136.34 [136.88] (t of m), 168.81 [168.94] (br, s), 170.30
[170.69] (s), 192.26 [191.88] (quintet, J ) 6 Hz). In D2O the δ
26.79 signal is a q of s and the 168.81 signal is a t and δ 190.72
is a q + s. IR (CHCl3, νmax, cm-1): 3238 (m, O-H), 3000-2830
(m, O-H), 1720 (m), 1668 (CdO, s). IR (Nujol): 3157 (m), 1720
(m), 1685 (s).
Microanalysis: Calcd for C13H12N2O: C, 73.56; H, 5.70; N,
13.20. Found: C, 73.07; H, 5.55; N, 12.59.
Rea ction of Ma lon on itr ile w ith P ota ssiu m Cya n a te.
This is a modification of the literature method.14 To a solution
of malononitrile (4 g, 60.61 mmol) in DMF (30 mL) was slowly
added finely powdered potassium cyanate (4.91 g, 60.61 mmol)
with vigorous stirring during 1 h. The mixture was refluxed
with stirring for 1 h, cooled to room temperature, and diluted
with ether (50 mL), and the solid formed was filtered and
washed with water, giving the pure yellowish potassium salt
(8.4 g, 94%), mp 276-278 °C (with decomposition). IR (Nujol,
Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62.
Found: C, 62.84; H, 6.12; N, 5.45%.
ν
max, cm-1): 3472 (m), 3311 (m), 3201 (m), 2204 (s), 2182 (s),
1661 (s), 1588 (s).
Cr ysta llogr a p h ic Da ta . 11: C13H15NO4, space group P21/
n; a ) 14.349(3) Å, b ) 14.107(3) Å, c ) 6.319(1) Å; â ) 98.83-
(2)°, V ) 1263.9(7) Å3, Z ) 4, Fcalcd ) 1.31 g cm-3, µ (Mo KR) )
0.98 cm-1, no. of unique reflections 3813, no. of reflections with
I g 3σI, R ) 0.067, Rw ) 0.093.
Rea ction of Ba r bitu r ic Acid w ith P h en yl Isocya n a te.
To a solution of barbituric acid (1 g, 7.8 mmol) in dry DMF (8
mL) was added Et3N (2.16 mL, 15.6 mmol), and after the
solution was stirred for 5 min phenyl isocyanate (0.85 mL, 7.8
Anal. Calcd for C4H2N3OK: C, 32.7; H, 1.5; N, 28.6. Found:
C, 32.86; H, 1.43; N, 28.90%.
The salt was converted to carbamoyldicyanomethane, a
gray-white solid, mp >300 °C dec in 94% yield, by exchange
on an ion exchange (Amberlite IR 120(H)) resin.14 1H NMR
(DMSO-d6) δ: 5.58 or 7.94 (br s) and very small signals at
2.71, 2.94. 13C NMR (coupled, DMSO-d6, rt) δ: 34.65 (s, Câ),
117.87 (s, CN), 172.69 (s, CR). IR (Nujol, νmax, cm-1): 3582 (m),

Stable Enols of Carboxylic Acid Amides
J . Org. Chem., Vol. 65, No. 21, 2000 6867
mmol) was added and the reaction mixture was stirred for 90
min at room temperature. The mixture was poured into ice-
cold 1:9 concentrated HCl/H2O mixture, the crude solid
obtained was filtered and washed with H2O, and the wet solid
was heated with 1:4 EtOAc/petroleum ether (40-60 °C) (50
mL) and filtered, giving 14 as a white solid (1.45 g, 75%), mp
292-96 °C dec.
found 247.0605 (rel abundance (18%): base peak 93.0585, calcd
for PhNH2 93.1293.
Anal. Calcd for C11H9N3O4: C, 53.45; H, 3.67; N, 16.99.
Found: C, 53.36; H, 3.92; N, 16.77%.
+
Ack n ow led gm en t. We are indebted to Prof. M.
Kaftory for his help with the CSDB, to Dr. Shmuel
Cohen for the crystallographic determination, to
Mr. Y. X. Lei for a few experiments, and to the Israel
Science foundation for support.
1H NMR (DMSO-d6) δ: 7.20 (1H, t, p-Ph-H), 7.42 (2H, t,
m-Ph-H), 7.51 (2H, d, o-Ph-H), 11.51 (1H, s, NH), 11.96 (vw, v
br, NH). There are additional overlapping small signals (<0.07
H) in the Ph region at 7.45, 7.26 (t) and 6.94 (t) ppm. The
signals at δ 11.51 and 11.96 disappear on shaking the solution
with D2O. 13C NMR (DMSO-d6, coupled) δ: 80.26 (CR, narrow
m), 117.97, 120.93 (both small, with intensity 5-6% of main
signal), 121.06 (d of m, J ) 163 Hz), 125.11 (d of t, J ) 163
Hz), 128.62 (small, intensity 7% of the main signal), 129.08 (d
of d, J ) 162, J ) 8 Hz, most intense signal), 135.80 (t, J ) 6
Hz, Cipso), 148.47, 168.70 (NHCO). IR (Nujol, νmax, cm-1): 3282
(w, OH), 3252 (w, OH), 3157 (w), 2365 (w), 1808 (w), 1764 (s),
1690 (s, CdO), 1639. HRMS: calcd for C11H9N3O4 247.212,
Su p p or tin g In for m a tion Ava ila ble: Tables S1-S8 of
general X-ray data, bond lengths and angles, and position and
thermal parameters, and Table S9 of energies of the species
used in the calculations and Figures S1 and S2 of stereoviews
of 8 and 11. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O000293E