Stereoselectivity of additions to N-methyl acetonitrilium fluorosulfonate

Article abstract of DOI:10.1021/jo301983s

Alkoxy-N-methyl-acetiminium salts were prepared by addition of CH ₃OH and C₂H₅OH to N-methyl acetonitrilium fluorosulfonate at low temperature. Analysis of the ⁵J_HH and ³J¹³_C-H coupling constants in the NMR spectra showed an anti addition with a diastereoselectivity of >95%. Deprotonation of these salts with (Z)-configuration gave the corresponding N-methyl-alkoxyacetimines with very high (E)-configuration. Upon protonation at -78 °C, these iminoesters gave the corresponding alkoxy-N-methyl-acetiminium salts with (E)-configuration. Computational analyses of the iminoesters and the corresponding iminium cations including the conformations give insight into the relative stability. Nitrilium salts can be used as reagents, exemplified by some esterifications between simple acids and alcohols.

Full text of DOI:10.1021/jo301983s

Article
pubs.acs.org/joc
Stereoselectivity of Additions to N‑Methyl Acetonitrilium
Fluorosulfonate
Reinhart Keese,* Franco̧ is Berdat, and Piero Macchi
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
S
* Supporting Information
ABSTRACT: Alkoxy-N-methyl-acetiminium salts were prepared by
addition of CH3OH and C2H5OH to N-methyl acetonitrilium
5
3
13C−H
fluorosulfonate at low temperature. Analysis of the JHH and J
coupling constants in the NMR spectra showed an anti addition with a
diastereoselectivity of >95%. Deprotonation of these salts with (Z)-
configuration gave the corresponding N-methyl-alkoxyacetimines with
very high (E)-configuration. Upon protonation at −78 °C, these
iminoesters gave the corresponding alkoxy-N-methyl-acetiminium salts
with (E)-configuration. Computational analyses of the iminoesters and
the corresponding iminium cations including the conformations give
insight into the relative stability. Nitrilium salts can be used as reagents,
exemplified by some esterifications between simple acids and alcohols.
Scheme 1
INTRODUCTION
■
Nitrilium salts were first prepared by Meerwein by reaction of
trialkyloxonium salts and aryl diazonium fluoroborates with
nitriles or by reaction of N-substituted chloroimines with
strong Lewis acids.1 Methylation with FSO3CH3 is a very
convenient method for methylation of alkyl- and aryl-nitriles
−
−
because the FSO3 salts are less hygroscopic than the BF4
salts.2−4 The N-methylation of nitriles by treatment with
FSO3CH3 occurs at lower temperature and provides higher
yields of these hygroscopic salts.
Also, N-alkylation is readily achieved by reaction of nitriles
with Lewis acids and alkylhalides.5,6 Furthermore, nitrilium
cations are intermediates in Beckmann rearrangements,7,8 in
the Schmidt-9 and the Ritter-reaction,10 as well as in the Ugi
reaction.11 Nitrilium salts are highly reactive and can undergo a
variety of reactions. Addition of nucleophiles leads to reactive
intermediates which can undergo a wide variety of further
reactions.5,6 According to the X-ray structure analysis of N-(2,6-
RESULTS AND DISCUSSION
■
The assignment of the E-configuration to (E)-10 and (E)-11 is
based on 5JHH coupling constants. Protonation under controlled
conditions led to the acetiminium salts (E)-8 and (E)-9. The
5JHH coupling constants measured were compared with those
obtained for the acetiminium cations prepared by addition of
alcohols to the nitrilium salt 7.
−
dimethyl)phenyl acetonitrilium BF4 (1), the nitrilium moiety
is linear with a CN bond length of 1.13 Å, slightly shorter
than that in nitriles (1.16 Å; Scheme 1).12,13 A detailed analysis
by advanced ab initio calculations has appeared.14
We report here our results about the stereoselectivity of
additions of simple alcohols to N-methyl-acetonitrilium
fluorosulfonate 7. Reaction of CH3OH and C2H5OH to 7 at
−20° gave the alkoxy-N-methyl-acetiminium salts (Z)-8 and
(Z)-9, respectively, from which the corresponding N-methyl-
alkoxy-acetimines (E)-10 and (E)-11 were obtained by
deprotonation (Scheme 2).15
The key information for the assignment of the configuration
in N-methyl alkoxyacetimines is due to Weinberger, who
1
reported that the H NMR spectrum of 2-methyloxazolin (2),
where the CH3 and the CH2 group are trans to each other,
showed a JHH coupling constant of 1.38 Hz.18
5
5
Kandel used this information to assign the JHH coupling
constant of 1.25 Hz in phenoxy-N-methyl-acetimine to the (Z)
Treatment of the alkoxyacetimines (E)-10 and (E)-11 with
FSO3H at −70° gave stereoselectively the N-methyl-alkox-
yacetiminium salts (E)-8 and (E)-9, respectively (Scheme
2).16,17
Special Issue: Howard Zimmerman Memorial Issue
Received: September 12, 2012
Published: October 31, 2012
© 2012 American Chemical Society
1965
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The Journal of Organic Chemistry
Article
excluded, the N-CH3-alkoxyacetiminium cations of (E)-8 and
(E)-9 should have preserved the (E)-configuration (Table 3).
When (E)-N-CH3-methoxyacetimine (E)-10 was slowly
added to FSO3H in CD2Cl2 at −78 °C, the 1H NMR spectrum
Scheme 2
5
showed the expected signals for (E)-8 with JHH = 0.46 Hz. In
addition, signals of minor intensity were observed at 2.58, 3.07,
5
and 4.28 ppm including the coupling constant JHH = 1.0 Hz.
These signals correspond to those observed in the product (Z)-
8, formed by addition of CH3OH to the nitrilium salt 7.
Addition in the inverse sequence, i.e. treatment of N-CH3-
methoxyacetimine (E)-8 with FSO3H at rt, gave the two sets of
signals for the (E)- and (Z)-isomers of N-CH3-methoxy-
acetiminium cations 8 in the ratio Z:E = 5:2. The mechanistic
pathways for the formation of this diastereomeric mixture have
not been determined.20
These results are to be compared with the appropriate N-
CH3-alkoxyacetiminium cations (Z)-8 and (Z)-9 obtained by
addition of alcohols to N-CH3-nitrilium salts (Scheme 2)
(Table 4). It is apparent that the addition of alcohols to N-
CH3-acetonitrilium cation proceeds preferentially, if not
exclusively, in an anti fashion to give the (Z)-isomers (Z)-8
and (Z)-9.
isomer and the smaller one of 0.25 Hz to the (E)-isomer, where
the two CH3 groups are cis to each other.19 Walter analyzed
several open chain alkoxyimines, such as 4−6, and associated
the 5JHH coupling constants of 1.25 Hz and 0.3−0.5 Hz with the
(Z)- and (E)-isomers, respectively (Table 1).20 Measurement
Olefins with one vinylic H show 3J
coupling
13C−C−C−H
5
Table 1. Coupling Constants JHH (Hz) of the N-Methyl-
constants of ca. 7 Hz in the case where the C atom of the
alkoxyimines 4−6 with Their E:Z Ratios20
13CCCH
allylic substituent is trans to the vinylic H and a J
coupling constant of 11 Hz for a cis relationship.23,24 A similar
iminoester
solvent
5JHH (Z)
5JHH (E)
ratio E:Z
3
13C−H
result has been reported for acetamide where the J
in
4
CCl4
0.4 q
0.4 q
0.3 t
0.3 t
0.5 q
0.5 q
100:0
95:5
(H3CCO)H3CC−NH2 is 7.1 Hz for the trans- and <1 Hz for
CD3OD
CCl4
1.2
the cis relationship.25,26 In view of these results it was of interest
5
6
100:0
95:5
3
+
to analyze the J
in the (R)3CCNH+(CH3)
13CCNH
CD3OD
CCl4
1.0 t
1.3 q
1.3 q
substructure for the stereoisomers of the N-methyl-methoxy-
acetiminium cations. As shown in Tables 2 and 3, the (E)
isomer with a trans H3CCN+H arrangement shows a
larger coupling constant than the (Z) isomers prepared from
the nitrilium salts directly. Although we have only a few
examples in hand, it was tempting to use these observations for
analyzing the configuration in N-methyl-alkoxy-iminium
69:31
56:44
CD3OD
of dipole moments of 2-substituted oxazolines with (Z)-
configuration, being smaller, and cyclic 2 methoxyimines ((E)-
configuration), being larger, are compatible with the config-
uration determined by NMR measurements.21
5
cations, where a JHH is absent.
In a first example, the N-methyl-methoxy-2,4,6-trisisopro-
Thus, it is evident that N−CH3-alkoxyacetimines such as 4−
6 have preferentially, if not exclusively, (E) configuration, with
the 2 alkylgroups of the CN double bond being cis to each
other. The X-ray structure of 3 with the ethoxyimine-
substructure shows this stereochemistry.22 It should be noticed
that the adjacent N-methyl-iminium substructure has (Z)
configuration (cf. Scheme 5 for computational results). In our
case, the N-methyl-alkoxyacetimines (E)-10 and (E)-11 were
prepared by deprotonation of the adducts obtained by addition
of alcohols to the nitrilium salt 7.
−
pylbenzonitrilium FSO3 salt 13, prepared from 12c, was
submitted to the same reaction sequence as described above for
the acetiminium salts (Scheme 3).
Addition of CH3OH at low temperature gave the N-methyl-
iminium cation (Z)-14 with (Z)-configuration, from which the
imine (E)-15 was obtained by base treatment (Scheme 3).
Reaction of this imine with FSO3H gave the (E)-N-methyl-
iminium cation (E)-14. On the basis of the (E)-configuration,
shown for the N-methyl-alkoxy-acetimines (E)-10 and (E)-11,
it is reasonable to assume that the imine 15 also has the (E)-
The 5JHH coupling constant for (E)-10 closely corresponds to
that of (E)-4, whereas we measured a slightly larger coupling
constant for (E)-11 than that reported for (E)-5 (cf. Table 2);
4 and 5 are identical with 10 and 11, respectively). Upon
protonation under conditions where an isomerization can be
configuration. Protonation under mild conditions should
3 13
Cipso-CN+H
preserve this configuration: Consequently, the J
of ∼5.4 Hz is assigned to the (E)-isomer (E)-15. The
3J
coupling constant of 1.5 Hz found for the
13Cipso‑CN+H
iminium salt (Z)-14, prepared by addition of CH3OH to the
nitrilium salt 13 is compatible with an anti addition and
formation of the (Z)-isomer (Z)-14. The 3J coupling constants
were extracted from selective decoupling experiments (cf. the
Experimental Part).
1
Table 2. H-NMR Results (ppm; J(Hz)) for the N-CH3-
Alkoxyacetimines (E)-10 and (E)-11 Prepared by
Deprotonation of the N-CH3-Alkoxyacetiminium Salts 8 and
9 in CD2Cl2 (Scheme 2)
The mechanism of the highly stereoselective additions of
alcohols to the nitrilium salts 7 and 13 leading to the (Z)-
isomers via an anti addition may be discussed in terms of a
reaction at a stereoelectronically optimal angle.27 The
concomitant addition of H+ terminates the reaction.
R
RO
NCH3 H3CCN
5JHH
(E)-10
(E)-11
H3C
H3C−CH2
3.62 s
4.03 q
3.00 q
2.98 q
1.88 q
1.87 q
0.51
0.49
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Article
1
Table 3. H-NMR Results (ppm; J(Hz)) for the N-CH3-Alkoxyiminium Salts Prepared by Protonation of the (E)-N-CH3-
Alkoxyimines (E)-8 and (E)-9 in CD2Cl2 at −78 °C (Scheme 2)
13C−H
R
RO
NH+CH3
H3CCNH+
5JHH
3J
(E)-8
(E)-9
H3C
H3CCH2
4.19 s
4.48 q
3.29 dxq
3.27 d
2.44 m
2.41 m
0.46
0.3
5.0
4.72
1
Table 4. H-NMR Results (ppm; J(Hz)) for the N-CH3-Alkoxyiminium Salts Prepared by Addition of Alcohols to N-CH3-
−
Acetonitrilium FSO3 7 at −20 °C in CD3CN (Scheme 2)
R
RO
NH+CH3
H3CCNH+
5JHH
3J
13C−H
(Z)-8
(Z)-9
H3C
H3C−CH2
4.26 s
4.55 q
3.23 dxq
2.98 dxq
2.49 m
1.0
0.9
2.44 dxq
1.7
Scheme 3
Upon deprotonation the (Z)-alkoxyiminium salts (Z)-8, (Z)-
9, and (Z)-14 isomerize to the (E)-N-methylalkoxyimines (E)-
10, (E)-11, and (E)-15, respectively. According to detailed
NMR analyses by Kessler and others, the (Z)- to (E)-
isomerization occurs via in-plane inversion at the N center.28,29
Computational Aspects. The structures of the stereo-
isomers of the (Z/E)-alkoxyimine 10 and of the (Z/E)-
alkoxyiminium cations of 8 are to be discussed in terms of the
two configurations, including the syn(peri)- and anti(peri)-
planar conformations of the methoxy group (Scheme 4).
Table 5. Relative Energies (kcal/mol) for the Z/E
Diastereomers of Hydroxyformimine 16, the Iminoester (Z/
E)-10, the N-CH3-methoxyacetiminium Cation (Z/E)-8, and
Their Antiperiplanar (ap)/Synperiplanar (sp)
Conformations (in parentheses, the results from ref 30 for
16)
Z sp
Z ap
E sp
E ap
16
10
8
3.1 (6.7)
7.8
3.8 (3.8)
4.1
0.0
0.0
2.3
6.6 (8.3)
8.8
7.0
0.0
2.1
Scheme 4. The Z/E Configurations Including the Synplanar/
Antiplanar Conformations of Hydroxyformimine 16 and N-
Methyl-methoxyacetimine 10
16, with Esp being the most stable isomer and Eap being the
least stable structure, thus supporting the experimental results
for 4,20 discussed above. In the protonated series, 8, the stable
structure is Zap with an antiplanar conformation. Zsp (8) is
associated with the highest energy as for 10. This configuration
has been observed in the substucture of 3. Interestingly, all the
synplanar conformers are associated with stationary points in C1
symmetry, slightly distorted out of Cs. The antiplanar
conformers are stable in Cs symmetry, with the exception of
Eap 10, which has C1 symmetry. The reason of distortion from
planar symmetry in 10, at variance from 16, must be due to the
larger steric hindrance of the methyl groups.
Nitrilium Salts as Reagent. It is well-known that nitrilium
salts, most often prepared in situ, are useful building blocks in
preparations of a variety of compounds.3,5,6,32,33 We have
explored reactions where a nitrilium salt serves as reagent for
esterifications under mild conditions (Scheme 5).
First we repeated Pople’s ab initio calculations30 on
hydroxyformimine (16) at the B3LYP/6-31+G(2d,2p) level
of theory using Gaussian09.31 Our computational results
confirm that Esp is the stable isomer although Zsp and Zap are
inverted (Table 5). All isomers have Cs symmetry.
We calculated the diastereomeric structures including the
conformations of N-CH3-methoxyacetimine (E/Z)-10 and their
protonated congeners (E/Z)-8 at the same level of theory (see
Table 5). The iminoester 10 has a similar order of stabilities as
Addition of an acid to the nitrilium salt 13 leads to an
intermediate, which is an iminium analogue of a protonated
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The Journal of Organic Chemistry
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Computations. All calculations were carried out with Gaussian
09,30,31 at density functional level (with hybrid B3LYP functional),
using the 6-31G+(2d,2p) basis set. For some compounds, the results
were compared against those at MP2 level, to detect possible
ambiguities of DFT calculations.
Scheme 5
For the two conformations of each of the (Z)- and (E)-
configurations of 8 and 10, molecular geometry optimizations were
carried out, searching for true minima on the potential energy surface
(PES) by calculation of the frequencies. An initial guess was obtained
from molecular mechanics simulations. All simulations do not include
temperature effects.
anhydride and may thus show an enhanced reactivity. (The
configuration of this intermediate salt has not been
determined.) Reaction of an alcohol at rt for 2 h led to the
appropriate ester; the reactions were not optimized (Table 6).
N-Methyl-acetonitrilium Fluorosulfonate 7. To freshly distilled
FSO3CH3 (11.4 g, 0.1 mol) was added 1.37 g (33.3 mmol) of CH3CN
in one batch under N2. After stirring the mixture for 1 h at 50 °C, the
excess of FSO3CH3 was removed in high vacuo to give 4.05 g (79%) of
a clean, white salt, which was stable for several weeks at −20 °C.
Mp 84−90 °C (sealed tube); IR (cm−1; Nujol, 10% suspension):
3290m, 3190 (sh), 2640 (sh), 2410, 1280, 1155, 1105, 1075, 735, 655,
580; additional signals at 1680 and 1635; probably CN stretch
vibrations. 1H NMR (60 MHz, CD3CN): 2.82 (m, 3H), 3.75 (m, 3H)
Table 6. Nitrilium Salt 13 as Reagent for Formation of Esters
from Acids and Alcohols (Scheme 5)
exp
acid 17 R =
R′OH
yield 18 (%)
a
CH3-
butan-2-ol
phenol
39
94
30
61
47
b
c
CH3-
H5C6-
H5C6-CH2-
CH3-
phenol
d
e
geraniol
geraniol
[2.67, 3.66 and coupling constants;34b 2.78, 3.7134 both for the BF4
−
salt); additional signal at 2.43 (ca. 0.3 H). 13C NMR (CD3CN): 8.33
4
1
(q, J = 140.6 Hz) broadend by J ∼ 1.0 Hz), 39.46 (qxt, J = 150.89
Hz; J (13C−15N) = 7.35 Hz), 113.47 (t, J (13C N) = 47.47 Hz);
C3H6FNO3S; calc. C 23.22, H 3.90, N 9.03, found: C 23.01, H 3.73, N
8.85.
1
1
15
CONCLUSIONS
■
Addition of Alcohols to N-Methylacetonitrilium Fluorosul-
fonate 7. General procedure. A weighted amount of the nitrilium salt
7 in a flame-dried NMR tube was dissolved in CD3CN and treated
with an equivalent amount of the alcohol at −30 °C. The tube was
Detailed NMR-analyses were used to determine the stereo-
selectivity of additions of simple alcohols to the nitrilium salts 7
and 13. It is concluded that these additions proceed
preferentially via an anti addition to N-methyl-alkoxy-
acetiminium salts with Z-configuration. These assignments are
1
attached to a vibromixer and vibrated for 5 min at −20 °C. The H-
and 13C NMR spectra were subsequently recorded at rt.
5
(Z)-N-Methyl-methoxyacetonitrilium Fluorosulfonate [(Z)-8].
based on JHH coupling constants reported for N-methyl
3
1H NMR (CD3CN) (100 MHz): 2.49 (m, 3H), 3.23 (dxq, J (H−
alkoxyacetimines which were transferred to the iminium cations
CH2−N+−H) 5.0, 3H), 4.26 (s, 3H) for further data, see Table 2; 13
C
prepared by protonation of these iminosters and addition of
NMR: 17.6, 29.5, 60.7, 177.6.
3
13C−H
alcohols to the nitrilium salts, respectively. J
coupling
1
(Z)-N-Methyl-ethoxyacetonitrilium Fluorosulfonate (Z)-9. H
constants ((R)3CCNH+(CH3)) were correlated with the
5JHH coupling constants to show that the addition of methanol
to the nitrilium salt 13 also occurs with a high stereoselectivity.
Finally it should be mentioned that N-alkyl-methoxy-
acetiminium salts can also be generated by alkylation of N-
methylacetamide with FSO3CH3. Since it is known that N-
methylacetamide exists exclusively in the “peptide” config-
uration ((Z)-arrangement),26 it is not surprising that this
compound gives exclusively the N-methylmethoxy-acetiminium
(Z)-8.
NMR (CD3CN) (100 MHz): 1.44 (t, J = 7.2 Hz, 3H), 2.44 (dxq, 5JHH
4
5
= 0.95, J (H−CH2−CN+−H) = 0.78, 3H), 2.98 (dxq, JHH = 0.9
Hz, 3JHH = 5.0 Hz, 3H), 4.55 (J = 7.2 Hz, 2H), 11.80 (br); 13C NMR
(CD3CN): 14.41 (qxt, J = 128 Hz, J(13C−C−H) = 3 Hz, 18.12
1
2
(qxm), 1J = 132 Hz, 3J(13CCN+H) = 1.7 Hz, 29.37 (qxm, 1J =
1
2
142 Hz), 71.66 (txqxm), J = 150 Hz, JCH = 4 Hz) 178.1; additional
couplings are not resolved.
N-CH3-Alkoxyacetimines 10 and 11 by deprotonation of the N-
CH3-alkoxyacetonitrilium salts 8 and 9.
(E)-N-Methyl-methoxyacetimine [(E)-10].35 In a 25 mL three-
necked flask equipped with a N2 valve and a stirring bar, 1.9 g (12.3
mmol) of nitrilium salt (7) was dissolved in 50 mL of CH3CN and
cooled to −20 °C. The solution of an equimolar amount of the alcohol
in acetonitrile was slowly added. After removal of CH3CN under N2 at
the rotary evaporator, the residue was taken up in CH2Cl2 and cooled
to 0 °C. After addition of an equimolar amount of (i-Pr)2NH in
CH2Cl2, the solution was stirred for 1 h. The soluble compounds were
distilled off into a cooling trap at 300 Torr and fractionated under
normal pressure. The residue was purified by GC. Yield: 0.27 g (25%),
GC-purity 99.7% [GC: Carbowax 1900, 5% on Chromosorb, 60°, 20
mL of N2/min] tR: 6.3 min.] IR (cm−1): 2950 s, 2910, 1685 (1675
EXPERIMENTAL PART
■
General. All experiments were conducted under N2. Solvents: the
most relevant solvents were distilled prior to use. FSO3CH3: Fluka
pract. distilled under Ar; FSO3H: Fluka pract. distilled under Ar;
DMAP: Fluka purum; Cu(I)CN: Siegfried purum; CH2Cl2: distilled
over P2O5; (n-Bu)4N+Cl−: Fluka techn. crystallized from CCl4. Other
reagents were used as obtained. For work up sat. NaHCO3, 2 N
NaHCO3, NaCl sat., and 2 N HCl were used. The solutions were dried
over MgSO4. For CC silica gel 60 (Merck) was used. GC: analytical:
column length 2 m, diameter 2 mm; preparative: column length 3.6 m,
diameter 10 mm. Mp. were measured in an open capillary and are
uncorrected. Bp. are not corrected, for Kugelrohr distillations the
temperature of the oven is given. IR spectra (cm−1) were measured in
CHCl3; only the most intensive signals are reported, sh (shoulder). 1H
NMR spectra (δ in ppm) were recorded in CDCl3; otherwise, the
solvent is given. The coupling constants J are given in Hz, with the
following abbreviations: s(inglet), d(oublet), t(riplet), q(uartet),
S(eptet), m(ultiplet), br (broad). 13C NMR spectra were recorded
at 25.2 MHz. MS were measured at 70 eV, direct inlet, source temp.
250°. The temp. of the sample is given in brackets. The peaks are
reported as m/z %; intensities relative to the strongest peak.
1
5
[33]), 1435, 1370, 1265, 1050; H NMR (100 MHz): 1.88 (q, JHH
=
0.51, 3H), 3.00 (q, JHH = 0.51, 3H), 3.62 (s, 3H); 13C NMR: 14.3,
5
36.05, 52.08, 162.7.
(E)-N-Methyl-ethoxyacetimine (E)-11. This Alkoxyimine Was
Prepared Analogously. Yield after GC-separation [Carbowax 20M,
20% on Chromosorb A, 60 °C, 254 mL N2/min] tR 34 min: 0.006 g
(5%); IR (cm−1): 2960, 1670, 1370, 1265, 10.50; 1H NMR (CD2Cl2):
1.26 (t, J = 7, 3H), 1.87 (q, 5JHH = 0.49, 3H), 2.98 (q, 5JHH = 0.49 Hz,
3H), 4.03 (q, J = 7 Hz, 2H); 13C NMR: 14.37, 14.42. 35.96, 60.17,
161.97; MS (20°): 101(14, M+), 86 (11), 73(58), 58(44), 57(100),
56(92), 43(53), 42(86); C5H11NO: calc. 59.37, H 10.96. N 13.85;
found: C 59.43, H 11.18, N 13.72.
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Addition of FSO3H to (E)-Alkoxyacetimines (E)-10 and (E)-11.
General procedure. A weighted amount of FSO3H in a dried NMR
tube under N2 was dissolved in CD2Cl2 and cooled to −78 °C. A
solution of the iminoesters (E)-10 and (E)-(11) (∼99% of 1 mol
equiv) in CD2Cl2 was slowly added, and the mixture was vibrated for 5
min at −78 °C. The protonated iminoesters (E)-8 and (E)-9 were
Esterification with the N-Methyl Nitrilium Salt (13) as
Reagent. Method A for exp. a−e: To a solution of the acid and
DMAP (ca. 20 mol %) in CH2Cl2 was dropped a solution of 13 in
CH2Cl2 at 0 °C. After addition of the alcohol (2 mol equiv) at rt, the
mixture was left for 20 h. Diluted with CH2Cl2, the organic phase was
washed 2× each with 0.5 N HCl and sat. NaHCO3 solution. Work up
gave the appropriate ester, which was purified and identified by
1
characterized by their H and 13C spectra.
38
1
comparison of its H NMR spectrum with the published one.
(E)-N-Methyl-methoxyacetonitrilium Fluorosulfonate [(E)-8].
1H NMR (CD2Cl2) (80 MHz): 2.44 (m, 3H), 3.29 (dxq, 3JHH = 5 Hz,
5JHH = 0.46 Hz, 3H), 4.19 (s, 3H, 10.12 (br), coupling constants were
extracted from an experiment with inverse addition at rt); 13C NMR
(CD2Cl2) (80 MHz): 18.1, 32.4, 59.1. 177.6.
(a) The crude product was distilled in a Kugelrohr apparatus at
1
normal pressure. bp 112°, H NMR identical with Sadtler, Nr. 6787.
1
(b) The crude product was distilled at 100 °C (15 Torr); H NMR:
identical with Sadtler 6777. (c) Purified via CC (pentane−ether =
4:1); 1H NMR: identical with Sadtler 3173. (d) 1H NMR corresponds
(E)-N-Methyl-ethoxyacetonitrilium Fluorosulfonate [(E)-9].
1
to Sadtler 4240; (e) H NMR corresponds to Sadtler Nr. 9479.
5
1H NMR (CD2Cl2) (80 MHz): 1.50 (t, J = 7.2, 3H), 2.41 (m, JHH
(Z)-N-Methylmethoxyacetonitrilium Fluorosulfonate ((Z)-8)
from N-Methylacetamide. To FSO3CH3 (0.04 g, 0.35 mmol) in a
NMR tube was added a solution of 0.026 g (0.35 mmol) N-CH3-
acetamide in CD3CN, and the reaction mixture was kept for 24 h. The
1H NMR spectrum was identical to that obtained by addition of
≤ 0.3 Hz, 3H), 3.28 (dxq, 3JHH = 5 Hz, 5JHH ≤ 0.3 Hz, 3H), 4.48 (q, J
= 7 Hz, 2H), 9.96 (br); 13C NMR (CD2Cl2) (80 MHz): 13.4 (qxt, 1J =
2
1
3
128.8 Hz, J(13C-CH-H) = 3.1 Hz), 17.8 (qxd, J = 132.6 Hz, Jtrans
(13CCN+H = 4.7)), 32.2 (q, J = 143.4 Hz), 69.4 (txq, J =
1
1
2
150.1 Hz, J(13CH2−CH2−H) = 4.3 Hz), 176.8.
CH3OH to 7.
N-Methyl-2,4,6-trisisopropylbenzonitrilium Fluorosulfonate
13. 2,4,6-Trisisopropyl-benzonitril (18c) was prepared from 1,3,5-
trisisopropylbenzene (12a) in two steps via (12b).36,37 The reaction
mixture, prepared from 18.32 g (80 mmol) (12c) and 27.28 g (0.24
mol) of FSO3CH3 was stirred at 45° for 45 h. The excess of FSO3CH3
was pumped off in high vacuo and the colorless salt left under high
vacuo for 20 h.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H spectra and Cartesian coordinates and absolute energies.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Yield: 25.04 g (91%). Mp: 86−90° (sealed tube). IR (Nujol, cm−1):
1
2960, 2320, 2250, 1595, 1275, 1215, 1065, 575; H NMR (60 MHz):
AUTHOR INFORMATION
Corresponding Author
*E-mail: reinhart.keese@ioc.unibe.ch.
■
1.28 (d, J = 7.2 Hz, 6H), 1.37 (d, J = 7.2 Hz, 12H), 3.13 (S, J = 7.2 Hz,
3H), 4.33 (s, 3H), 7.17 (s, 2H); 13C NMR: 23.2 q, 23.5 q, 32.7 q, 33.4
d, 35.2 d, 98.7 s, 105.7 s (br), 122.7 d, 158.3 s, 161.1 s.
(Z)-N-Methyl-methoxy-2,4,6-trisisopropylbenziminium Flu-
orosulfonate (Z)-14. This product was prepared as described
above for 8 and 9; CDCl3 was used as solvent for better solubility.
1H NMR (60 MHz): 1.20−1.31 (d, J = 7.5 Hz, 18H), 2.34 (∼S, J = 7.5
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Hz, 1H), 3.33 (d, J = 5.0 Hz, 3H), 3.97 (s, 3H), 7.15 (s, 2H), 11.30
(bro); disturbing signal at 4.30. 13C NMR: 23.3 q, 23.6 q, 24.7 q, 30.2
q, 32.2 d, 34.4 d, 61.3 q, 118.9 s, 122.4 d, 146.1 s, 154.5 s, 177.1 s;
Coupling constants after selective decoupling of the o-CH(C3H7)2
This work was supported by the Swiss National Science
Foundation, a stipend of the Foundation of the Chemical
Industry Basel, and the Canton of Bern. We thank Dr. U.
Voegeli for many detailed NMR analyses.
3
3
1
13
+
13
signals: Cipso: J
≈ 1.5, J
ca. 4.9, Cmeta dxd: J =
CCN H
C−CC(meta)H
3
2
+
98 Hz, J = 4.1 Hz, Ciminium: JCN H 3.62.
(E)-N-Methyl−methyloxy-2,4,6-trisisopropylbenzimine [(E)-
15]. To a solution of the N-methyl-nitrilium salt (Z)-14 (5.37 g,
15.66 mmol) in CH2Cl2, cooled to −78°, was dropped 0.5 g (15.66)
mmol) of CH3OH. The organic phase was shaken 3× with 2 N
Na2CO3 and was dried over Na2SO4. CC with n-pentane−Et2O = 1:1
as eluent gave 2.75 g (64%) of (E)-15, which was crystallized from
pentane at −20 °C and sublimed at 6 × 10−5 Torr to give GC pure
product. Mp 37−39 °C. Rf (n-pentane−Et2O = 1:1): 0.48; GC (anal.),
tR: 12.8 min; XF-1150, 5% on chromosorb, 100 °C, 30 mL N2/min; IR
(cm−1): 2960, 2870, 1670, 1460, 1285, 1255, 1040, 870; 1H NMR (80
MHz): 1.19 (d, J = 7, 12H), 1.24 (d, J = 7, 6H), 2.74 (∼S, J = 7, 3H),
2.78 (s, 3H), 3.73 (s, 3H, 7.00 (s, 2H)); 13C NMR: 23.7 q, 23.9 q, 24.7
q, 31.25 d, 34.3 d, 37.2 q, 52.3 q, 120.7 d, 128.5 s, 145.1 s, 149.5 s,
163.8 s; MS (20°) 276(7), 275 (35, M+), 274(3), 261(21), 260(100),
245(18), 244(11), 229(16); EA C18H29NO: calc. C 78.49, H 10.61, N
5.09; found: C 78.48, H 10.60, N 5.06.
DEDICATION
■
In memoriam: Howard E. Zimmerman, dedicated scientist with
great enthusiasm and achievements.
REFERENCES
■
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13
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