The 1-N-(methoxycarbonyl-2-phenylethyl)imino-2,2,2- trifluoroethanephosphonate systems are not stable enols of carboxylic esters

Full text of DOI:10.1016/S0022-1139(03)00189-1

Journal of Fluorine Chemistry 124 (2003) 119–122
Letter to the Editor
The 1-N-(methoxycarbonyl-2-phenylethyl)imino-2,2,2-
trifluoroethanephosphonate systems are not stable enols
of carboxylic esters
compound, no data for it were given. The Arbuzov reaction
of 1 gave 2, which according to Eq. (1) occurs without
structural rearrangement. The microanalysis data for com-
pounds 2/3 fit any isomer of these compounds. The mass
spectra which give either the molecular peak or fragments
þ
1
. Introduction
such as m/z ¼ 91 (C H ) or M-84 (M-CF -Me) were not
7
7
3
applied for obtaining structural information. Only the NMR
and IR data were used for structural assignment. A major
In a recent paper in this journal it was suggested that 1-N-
1-methoxycarbonyl-2-phenylethyl)imino-2,2,2-trifluoro-
discrepancy is shown by the 19F NMR (CDCl , TFA) spectra
(
3
ethanephosphonate systems 2, R: Et, n-Pr, i-Pr, n-Bu,
synthesized according to Eq. (1), tautomerize completely
to their stable carboxylic acid ester tautomers 3 [1]. The
which for all four systems reported signals at d ¼ 3.87–4.01
(t, J ¼ 8:7 Hz, CF ). However, except in the unlikely pos-
3
6
FH
sibility that a long range J coupling with the PhCH
2
1
protons, with no 5JFH coupling from the CH group is
responsible for the CF triplet, the CF should be a doublet
evidence for the enol of ester structures was the H NMR
CDCl ) OMe signals at d ¼ 3.3 ascribed to vinyl-OMe, the
(
3
3
3
3
1
low field signal at d ¼ 8.3 ascribed to the OH signal and the
due to J coupling (neglecting J coupling with the 1.1%
PF
13C). Consequently, the 19F NMR data exclude the suggested
structure for 3.
CO Me
CO Me
2
2
CCl , Ph P
4
3
CF COOH + PhCH CHNH
PhCH CHN=C(Cl)CF
However, the multiplicity of the signal and the J value are
consistent with either the presence of a CF CH moiety with a
3
2
2
2
3
Et N
3
1
3
2
3
3
JFH if JPF is negligible or with a CF CH moiety with similar
3
3
3
JPF and JFH values. How can a CF CH or a CF CH moiety
3
CO Me
C(OH)OMe
2
3
2
P(OR)3
be created by the reaction in Eq. (1)? The paper of Tamura
et al. [4] on which the reaction of PhCH CH(NH )CO Me
PhCH CHN=CCF3
PhCH CN=CCF
2 3
2
2
2
2
PO(OR)2
PO(OR)2
was modeled showed that most compounds investigated
gave the expected product with various amines. However,
the reaction with benzylamine gave a rearranged product
2
3
(
1)
CF CH N¼C(Cl)Ph, JF;H ¼ 9:2 Hz. This was ascribed to
lack of CH signals at d ¼ 5.0 ppm, the IR signals at
3
2
À1
the initial formation of CF CðClÞ¼NCH Ph, the analog
3
2
3
250 cm
(OH) and the loss of optical purity of the
0
of 1, which underwent Cl-rearrangement involving S 2
N
products formed from L-(À)-phenylalanine methyl ester
À
reaction by Cl and prototropy.
Application of a similar scheme for the reaction of
which may be due to racemization to the enols.
Stable enols of carboxylic acid esters are still uncommon
and hence novel. Claims to their observations should be
therefore checked critically. We had refuted earlier some
claims for formation of several enols of carboxylic acid
amides [2] and anhydrides [3] by using data for known
species and computations of the energy of the carboxylic
acid derivative and its enol, as well as by some experimenta-
tion. In this paper, we conclude that the alleged compounds
PhCH CH(NH )CO Me will initially give 1 which will
2
2
2
then rearrange according to Eq. (2) to give 4, which could
CO Me
CO Me
2
2
1
PhCH C=NCH(Cl)CF
PhCH=CNHCH(Cl)CF3
2
3
4
5
2
/3 do not have the suggested enol structures.
CO Me
2
CO Me
2
PhC(Cl)=C
PhCH(Cl)C=NCH CF
2
3
2
. Results and discussion
NHCH CF
2
3
6
7
2
.1. The synthetic method
(
2)
The preparation of compound 1 followed the procedure
of Tamura et al. [4] for the one-pot preparation of trifluoro-
acetimidoyl chlorides. Although 1 is apparently a new
further rearrange to 5, 6 or 7 or to their mixture. Compounds
4 and 5 contain a CHCF moiety and compounds 6 and 7
3
contain a CH CF moiety. Reaction of 4–7 with P(OR) will
2
3
3
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00189-1

120
Letter to the Editor / Journal of Fluorine Chemistry 124 (2003) 119–122
Table 1
give products 8–11, respectively, the isomers of 2 and 3
which contain a CF CH moiety. Compounds 8–11 can be
also formed from 1 in the presence of P(OR)3.
ꢀꢀ
Calculated B3LYP/6-31G free energy differences at 25 8C and KEnol
between ester 2 and its isomers, 3 and 13
3
Compounds
DE (kcal/mol)
K
Enol
CO Me
2
CO Me
2
2
a
0.0
1.2
2
PhCH C=NCHCF3
PhCH=CNHCHCF3
2b
2c
3a
PO(OR)2
PO(OR)2
1.3
À9.2
8
9
12.6
20.8
22.4
12.8
19.1
19.6
10
3
3
b
c
À9.4
CO Me
CO Me
13a
13b
13c
10
2
2
PhC=C
NHCH CF
PO(OR)2
PhCHC=NCH CF3
2
2
3
PO(OR)2
10
11
group in 3. Structure 3 is therefore inconsistent with the
suggested d(OH) value of 8.3.
Regardless of the mechanism we believe that the com-
pound reported by Ding and coworkers as 3 is probably one
of compounds 8–11. In none of them there is a CH(CO Me)
2
2
.3. Computations
moiety and an enol of the ester cannot be formed. The loss
of m/z ¼ 84 or of m/z ¼ 99 fragments from ‘‘2/3’’, R: n-Bu,
i-Pr, respectively, is consistent with the loss of CF CH and
Computations [10] and experiment [11] show that for the
3
3
parent system CH CO R/H C¼C(OH)(OR), R: Me, Et, the
3
2
2
CF CH NH moieties, indicating the likely presence of a
3
2
2
equilibrium constant favors the ester over its enol by 19–22
orders of magnitude. A single EWG is insufficient to over-
come this difference in related amide/enol systems [12], and
alkyl groups increase very little the percentage of the enol
form [2].
CF CHN moiety in the molecule.
3
2
.2. Literature precedents
Several enols of carboxylic esters were suggested as
reaction intermediates on the basis of kinetics [5], but no
NMR data are available. Short-lived but observable enols,
In order to investigate the relative stabilities of the two
ꢀꢀ
isomers, density functional B3LYP/6-31G calculations
[13] were conducted for isomers 2 and 3, R: Me, as well
Ar C¼C(OH)OR were observed [6] and for Ar: 2,4,6-i-
2
as of another isomer, i.e. 13, formed by tautomerization of
the methine hydrogen to the phosphorus oxygen. For each
isomer 5–8 different conformers were examined and con-
firmed to be local minima by frequency calculations. The
relevant data are given in Table 1, and several selected
conformations are given in Fig. 1. By comparing the most
stable conformations of the three isomers we find that 3 and
Pr C H , R: Me, dðOHÞ ¼ 9:25 in CCl [6b]. Other obser-
3
6
2
4
vable stable enols of esters gain stabilization from the
presence of strong b-electron-withdrawing groups (EWGs)
[
7–9]. For five-substituted Meldrum’s acid derivatives
d(OH) of the enol is in the range of 11.0–14.4 ppm [7].
For cyclopentadienes 12a–c dðOHÞ ¼ 19:7À20:1 in
Cl CDCDCl [9].
2
2
1
3 are much less stable, by 12.6 and 12.8 kcal/mol than the
ester form 2. In terms of KEnol (¼[3]/[2] or [13]/[2]) the
O
À9.2
À9.4
and 10 , respectively.
H
MeO
corresponding values are 10
C
The energy differences for the less stable conformers are
mostly much larger, being up to 20 kcal/mol (Fig. 1).
O
R3
C
2.4. Preliminary experiments
OMe
In order to compare the spectra of compounds 1 and 2, the
CO Me
2
first step of Eq. (1) was conducted according to Tamura
et al.’s method [4]. TLC of the reaction mixture showed that
at least three compounds were formed. One of them was
R2
R1
PhCH2C=NCCF3
1
2
3
1
2a: R = R = R = CO Me
P(OH)(OR)2
2
1
2
3
identified as compound 1 according to its H, 13C and 19
1
b: R = R = CO Me, R = H
F
NMR spectra and microanalysis: calcd. for C H ClF NO :
2
2
1
3
c: R = CO Me, R = R = H
13
12 11
3
2
2
C, 49.06; H, 3.75; N, 4.77; found: C, 49.53; H, 3.88; N, 4.66.
Its highest mass spectral peak was at m/z ¼ 257 which is
þ
All these d(OH) values are at a lower field than the alleged
d(OH)valuesfor2/3.Moreover,theextremelowerfieldvalues
are for systems with b-EWGs which are also hydrogen bond
consistent with [M À HCl] . A second compound with
a nearly similar mass spectrum may be a geometrical
(E/Z) isomer of 1. A third compound had a completely
different mass spectrum and was not investigated further.
acceptors, such as the P¼O of the N¼C(CF )P(¼O)(OR)2
3

Letter to the Editor / Journal of Fluorine Chemistry 124 (2003) 119–122
121
Fig. 1. Optimized structures of compounds 2, 3, and 13. Numbers in parentheses are free energies at 25 8C relative to the most stable conformer of 2. For
each compound, three representative conformations are shown.
The CF group of the three compounds appears as a singlet
3
formation of an HDO signal. In the 13C NMR spectrum, the
CF centered at 124.1 is a quartet of doublets due to coupling
in the 19F spectra.
Reaction of the ‘‘1’’ formed with P(OMe) gave several
3
1
3
1
with F and P ( JCF ¼ 282 Hz, JPC ¼ 8:6 Hz), but in the H
3
products according to TLC. The major one was isolated and
displayed the following spectra when impurities of <8%
coupled spectrum each doublet becomes an apparent triplet
with J ¼ ca: 8 Hz. The singlet at d ¼ 117, becomes a
1
1
were neglected. The H NMR spectra showed three 1H
doublet of doublets, J ¼ 160 Hz (J ¼ 3:6 Hz) in the
CH
signals: a triplet of quartets (or overlapping quintets) cen-
tered at d ¼ 4.40 (J ¼ 8 Hz), a doublet of broad doublets
centered at d ¼ 4.71 with J of 4 and 12 Hz, and a singlet at
CH coupled spectrum. The other aliphatic signals partly
overlap so that assignments in the H coupled spectrum are
unsafe. The uncoupled 19F NMR spectrum (d(CF Cl) ¼ 0)
3
3
d ¼ 6.84. The MeO signals are a CO Me singlet at d ¼ 3.87
shows a doublet at d ¼ À69.32, JPF ¼ 8 Hz which becomes
2
3
and two OMe doublets d ¼ 3.80 and 3.84, JPH ¼ 11 Hz and
an apparent triplet in the hydrogen coupled spectrum.
The data indicate that the structure is not similar to that
reported for 2 or interpreted as due to 3. There is no low field
the 5H Ph is a multiplet. The signal at d ¼ 4.71 disappeared
after standing for 12 h with added D O at the expense of
2

122
Letter to the Editor / Journal of Fluorine Chemistry 124 (2003) 119–122
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7
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1
4
17
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4
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3
1
147–1161.
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[
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1
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3
3
JPF and JHF values is reasonable but couplings to the
4
038.
phosphorous, which is known to give larger J’s for couplings
with further away carbons [14] complicate the spectrum and
this structure is regarded as tentative only.
Since the compound itself is of no special interest neither
to us nor to the authors [1] except for its claimed enol
structure 3, which was not formed, we do not plan a further
experimental work.
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Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challa-
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3
. Conclusion
We conclude that the enol of ester 3 is not formed and is
much less stable than enol 2. Moreover, the structure
suggested for 2 is incompatible with the NMR spectra.
[
Acknowledgements
We are indebted to the Israel Science Foundation for
support. The calculations were carried out in part at the
Research Center for Computational Science, Okazaki
National Research Institute.
Jinhua Song
*
Zvi Rappoport
Department of Organic Chemistry and the
Minerva Center for Computational Quantum Chemistry
The Hebrew University, Jerusalem 91904, Israel
Tel.: þ972-2-6585278; fax: þ972-2-6585345
References
*
Hiroshi Yamataka
Institute for Scientific and Industrial Research
Osaka University, Ibaraki, Osaka 567-0047, Japan
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[
*
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E-mail addresses: yamataka@sanken.osaka-u.ac.jp
(H. Yamataka), zr@vms.huji.ac.il (Z. Rappoport)
Received 19 May 2003
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