Aggregation of Amide and Oxazoline Enolates in THF
J . Org. Chem., Vol. 64, No. 7, 1999 2285
by a dialkylaminocarbonyl than by a 2-oxazolinyl sub-
stituent. The difference in acidity between the two
systems is substantial, especially on the lithium scale
the pure product (2.28 g, 8.33 mmol, 60.8%): mp 173 °C from
1
i-PrOH; H NMR (CDCl
3
) δ 7.63-7.56 (m, 4H), 7.47-7.32 (m,
5
H), 5.90 (s broad, 1H), 3.64 (s, 2H), 3.62-3.53 (m, 4H). Anal.
Calcd for C16H16NOCl: C, 70.20; H, 5.89; N, 5.12. Found: C,
(carbonyl vs imino functions).
7
0.06; H, 6.05; N, 5.00.
2
-(4-Bip h en ylylm eth yl)oxa zolin e, 6. N-(2-Chloroethyl)-
Con clu sion s
The spectra of the lithium salts of the amides 1-5 and
oxazolines 6 and 7 indicate that they are contact ion pairs
in THF as are the corresponding cesium salts. The
lithium ion pair acidities have pK’s ranging from 20 to
biphenylylacetamide (1.00 g, 3.65 mmol) was dissolved in 30
mL of 1 M MeONa in MeOH and the solution was refluxed.
After being stirred for 2 h, the solution was poured onto water
(100 mL) and the precipitate was collected by filtration. The
crude oxazoline (750 mg) was chromatographed on silica gel
(
1:1 CH
2 2
Cl /AcOEt) to afford the pure compound as a white
solid (340 mg, 1.43 mmol, 39.2%): mp 87 °C (after sublima-
2
2 units. These values are 4-5 pK units lower than the
corresponding cesium ion pair pK’s, indicating that the
1
tion); H NMR (CDCl
3
) δ 7.63-7.51 (m, 4H), 7.48-7.30 (m,
H), 4.27 (t, J ) 9.3 Hz, 2H), 3.87 (t, J ) 9.2 Hz, 2H), 3.66 (s,
H). Anal. Calcd for C16 15NO: C, 80.97; H, 6.38; N, 5.90.
5
2
lithium enolates have dissociation constants to the free
H
-
4
-5
ions 10 -10 that of the cesium compounds. Both the
cesium enolates Cs-(1-5) and the corresponding lithium
compounds Li-(1-5) show low tendencies to aggregate;
only for the biphenylyl enolates 1 and 2 were small
Found: C, 81.00; H, 6.41; N, 5.89.
(
E)-(4S,5R)-2-(4-Bip h en ylylm eth yl)-4-m eth oxym eth yl-
5-p h en yloxa zolin e, 7. Dry hydrogen chloride was passed into
a solution of biphenylylacetonitrile (300 mg, 1.55 mmol) and
EtOH (75 mg) in dry toluene (8 mL). After one night at 0 °C,
dry ether (15 mL) was added and ethyl iminobiphenylyl acetate
hydrochloride precipitated (420 mg, 1.52 mmol, 98.2%):
NMR (DMSO-d
q, J ) 6.9 Hz, 2H), 3.98 (s, 2H), 1.28 (t, 3H). The white solid
was washed twice with ether and used in the following step
without further purification.
(1S,2S)-1-Phenyl-2-amino-3-methoxy-1-propanol (250 mg,
1.38 mmol) was added in one portion to a solution of the imino
ether hydrochloride (420 mg) in dry methylene chloride (5 mL)
at 0 °C. After being stirred for 7 h at 0 °C, the white turbid
mixture was poured into ice-water (10 mL). The methylene
chloride layer was separated, and the aqueous solution was
extracted twice with methylene chloride (20 mL), dried (Mg-
-
4
amounts of dimer found at concentrations of about 10
M. Similar studies of the lithium enolates of 3-5 showed
that their dimerization constants are too low to be
accurately detected using our UV-vis method.
1
H
6
) δ 7.69-7.57 (m, 4H), 7.48-7.32 (m, 5H), 4.37
(
Two new 2-(4-biphenylyl)oxazolines 6 and 7 have been
synthesized, and the ion pair acidities of their lithium
and cesium enolates were determined. Their pK’s are
about 20-21 and 24-25 on the lithium and cesium scale,
respectively. These ion pair acidities are almost invariant
with concentration, showing that the enolates of 6 and 7
are essentially monomeric. The results show that a
dialkylaminocarbonyl group is more acidifying than a
2
-oxazolinyl group. Internal coordination of the alkali
4
SO ), and concentrated to give a brown oil (0.501 g). Flash
chromatography on silica gel (1:1 Et O/ETP) gave 7 as a
cation by the methoxy group in 7 provides stabilization
2
-
1
of about 2 kcal mol for both the lithium and cesium
derivatives.
colorless oil (330 mg, 0.92 mmol, 66.9%). Kugelrohr distillation
gave a pure sample for the glovebox studies: 1H NMR (CDCl
)
3
δ 7.65-7.15 (m, 9H), 5.38 (d, J ) 6.6 Hz, 1H), 4.17 (m, 1H),
.84 (s, 2H), 3.68-3.47 (m, 2H), 3.42 (s, 3H); HRMS mass calcd
for C24 357.1729, found 357.1734.
Eth yl 1,3,5-Cycloh ep ta tr ien e-7-ca r boxyla te. 7-Cyano-
,3,5-cycloheptatriene (3 g, 25.61 mmol) was refluxed under
nitrogen in methanol (45 mL) containing concentrated H
9 g) for 35 h. The bulk of the solvent was removed in vacuo,
and the residue was poured into water (120 mL). The solution
3
Exp er im en ta l Section
H
23NO
2
1
9
Gen er a l P r oced u r es. Melting points (Pyrex capillary)
were determined on a Buchi melting point apparatus and are
uncorrected. Elemental analysis and HRMS were by Analytical
Services, College of Chemistry, University of California,
1
2 4
SO
(
Berkeley. Spectral measurements were with the glovebox-
spectrometer facility described previously.8
was extracted with petroleum ether (3 × 20 mL), the extract
4
was dried over MgSO , and the solvent was evaporated to give
Ma ter ia ls. Starting materials for synthesis were obtained
from commercial suppliers and were purified by crystallization
or distillation prior to use. All of the amides 1-5 are known
compounds and were available from our previous study. The
purity of these compounds was monitored by combination of
the crude ester (3.03 g). Two distillations under reduced
pressure afforded the pure ester as a colorless oil (1.78 g, 11.85
mmol, 46.3%): 1H NMR (CDCl
) δ 6.70-6.61 (m, 2H), 6.33-
.26 (m, 2H), 5.41-5.34 (m, 2H), 3.34 (s, 3H), 2.59 (t, J ) 5.5
Hz, 1H).
,3,5-Cycloh ep ta tr ien e-7-ca r boxylic Acid .19 A solution
of ethyl 1,3,5-cycloheptatriene-7-carboxylate (1.00 g, 6.65
mmol) in methanol (8 mL) was added to a solution of NaHCO
0.76 g, 9.05 mmol) in water (6 mL). The reaction mixture was
3
6
1
H NMR, GLC, mp, and elemental analysis.
1
N-(2-Hyd r oxyeth yl)-4-bip h en ylyla ceta m id e. A mixture
of biphenylylacetic acid (3.5 g, 16.49 mmol) and thionyl
chloride (25 mL) was stirred at 60 °C for 3 h. The excess thionyl
cloride was removed in vacuo to yield the crude chloride as a
brown oil (3.4 g). A solution of the acid chloride in methylene
chloride (30 mL) was added dropwise to a solution of 2-ami-
noethanol (1.66 g, 27.16 mmol) in the same solvent (6 mL) at
3
(
refluxed for 2 h and then poured into water (25 mL). The
alkaline solution was washed with petroleum ether (2 × 25
mL) to remove the unreacted ester, acidified (pH ) 1) with
H
2
2
SO
4
(30%, ca. 1 mL) and finally extracted with ether (3 ×
0
°C. After being stirred overnight at room temperature, the
0 mL). The organic layer was dried over MgSO
solvent was removed under reduced pressure to afford the pure
acid as a colorless oil that crystallized on standing in the
refrigerator (0.67 g, 4.92 mmol, 74.0%): H NMR (CDCl
4
, and the
solution was filtered and washed with water (50 mL) and the
solvent was evaporated to give the amide as a white solid (3.57
1
g, 13.98, 84.8%): mp 184 °C from MeOH; H NMR (acetone-
1
3
) δ
d
8
3
6
) δ 8.56 (broad, 1H), 7.63 (d, J ) 8.7 Hz, 2H), 7.57 (d, J )
.1 Hz, 2H), 7.48-7.38 (m, 4H), 7.32 (t, J ) 7.2 Hz, 1H), 3.59-
.50 (m, 4H), 3.31-3.22 (m, 2H). Anal. Calcd for C16
6
(
.70-6.60 (m, 2H), 6.35-6.22 (m, 2H), 5.46-5.27 (m, 2H), 2.59
t, J ) 5.7, 1H).
H
2
17NO :
N,N-Dim eth yl-1,3,5-cycloh ep ta tr ien e-7-ca r boxa m id e.10
C, 75.25; H, 6.72; N, 5.49. Found: C, 75.34; H, 6.61; N, 5.22.
N-(2-Ch lor oeth yl)-4-bip h en ylyla ceta m id e. A solution of
N-(2-hydroxyethyl)biphenylylacetamide (3.50 g, 13.70 mmol)
in thionyl chloride (5 mL) was stirred at room temperature
for 20 h. The solution was then poured into dry ether (30 mL),
and the chloride was precipitated and collected by filtration.
The white solid was washed twice with ether (20 mL) to afford
A mixture of 1,3,5-cycloheptatriene-7-carboxylic acid (0.5 g,
.67 mmol) in thionyl chloride (4 mL) was stirred at room
temperature for 42 h. The excess of thionyl chloride was
removed at 60 °C under reduced pressure, leaving the acid
3
(19) Betz, W.; Daub, J . Chem. Ber. 1972, 105, 1778