Arenediazonium Ion in Aqueous Acetamide Solutions
J. Am. Chem. Soc., Vol. 120, No. 39, 1998 10053
have been prepared previously, and literature references are given. All
aqueous solutions were prepared by using distilled water which was
passed over activated carbon and deionizing resin and then redistilled.
prepared and characterized compounds. One significant new peak
consistently appeared in the HPLC chromatograms. Product mixtures
+
from reaction of 1-ArN
extracted with Et
2
in neat liquid N-methylacetamide were
60
Methyl 2,4,6-Trimethylphenyl Ether, 1-ArOMe. The ether was
2
O, and GC/MS analysis showed that this peak was
prepared by alkylation of 1-ArOH with MeI according to the procedure
of Miller et al. The crude product was purified by column chroma-
tography on alumina eluted with n-pentane giving a colorless liquid;
1-ArOAc. This assignment was confirmed by isolating 1-ArOAc from
the product mixture by column chromatography and characterizing it
6
1
1
13
by H and C NMR, and by a spiking experiment with independently
synthesized 1-ArOAc. In previous work, we found that some products,
particularly aryl halide products, have significant vapor pressures and
that their yields decrease on standing.1 This problem was solved by
layering small amounts of cyclohexane on the top of the solutions to
dissolve volatile products. The cyclohexane method was used here to
check for product loss; small increases in the total yield were found,
but the product ratios were unchanged.
-
1
6
1
2
6
5% yield: IR (neat) νmax (cm ) 2938, 1599, 1484, 1451, 1225, 1144,
1
019, 853, 762; H NMR (CDCl ) δ (ppm) 6.92 (2H, s), 3.82 (3H, s),
.31 (3H, s), 2.38 (6H, s); GC/MS 150 (m/e), 135, 119, 105, 91, 79,
3
5.
N-(2,4,6-Trimethylphenyl)acetamide, 1-ArNHAc.62 The aryl amide
was prepared by acylation of 2,4,6-trimethylaniline, 1-ArNH
2
, with
acetyl chloride according to a procedure for the preparation of
63
benzanilide. The crude product was recrystallized twice from EtOH/
O to give white crystals; 80% yield (mp 215-216 °C): IR (film in
Several other products (not shown in Scheme 1) are observed in the
HPLC chromatograms. All have been identified previously and
H
CH
2
-
1
1
2
Cl
2
) νmax (cm ) 3425.5, 3019.1, 1668.7, 1215.9, 770.2; H NMR
:DMSO-d 1:1) δ (ppm) 8.99 (1H, s), 6.81 (2H, s), 2.21 (3H,
1,3
synthesized, if not available commercially: 2,4,6-trimethylbenzene,
(CDCl
3
6
1
1
-ArH, 2,4,6-trimethylfluorobenzene, 1-ArF, and 2,4,6-trimethylanisole,
-ArOMe. The observed yields of these products are small and variable.
s), 2.10 (6H, s), 2.04 (3H, s); GC/MS 177 (m/e), 135, 120, 91, 77, 65,
3, 39.
N-(2,4,6-Trimethylphenyl)-N-methylacetamide, 1-ArNMeAc.64
4
Typical yields are as follow: 1-ArH, <2%; 1-ArF, <2%; and 1-ArOMe,
67
<
2 4
3%. 1-ArF is formed via the Schiemann reaction from 1-ArN BF
The aryl methyl amide was prepared by the phase-transfer catalysis
3
in the solid state or in solution. 1-ArOMe is formed in the MeOH
procedure of Kalkote et al. for the N-alkylation of aryl amides.65
stock solutions and possibly in the reaction mixture. Formation of these
1
-ArNHAc was methylated with dimethyl sulfate in a stirred mixture
of aqueous NaOH/K CO and toluene at ca. 30 °C for ca. 2 h using
tetra-n-butylammonium hydrogen sulfate as the catalyst. The white
flat crystals were recrystallized from EtOH/H O and further purified
by chromatography on silica (eluting solvent PE:EA:Et O 1:1:1) and
by preparative HPLC (C-18 reversed-phase, 40% H O/60% MeOH,
+
two products reduces the amount of 1-ArN
2
available to react but
2
3
does not affect the relative yields of 1-ArOH, 1-ArNAc, and 1-ArOAc.
+ 3
1
-ArH is formed by reaction of 1-ArOH with unreacted 1-ArN , but
2
2
its effect on the total phenol yield is small, and it was ignored in all
calculations. Typical retention times in minutes for dediazoniation
products are as follow: 1-ArNHAc, 6-7; 1-ArOH, 11-12; 1-ArN-
MeAc, 12-13; 1-ArOAc, 17-18; 1-ArOMe, 25-26; 1-ArH, 45-48;
and 1-ArF, 52-54. Concentrations of products were obtained from
peak areas using standard calibration curves obtained from independ-
ently prepared or commercial products. Percent yields reported in the
Supporting Information are based on the concentration of added
2
2
64
2
5
1
20 nm). The overall yield was 80% (mp 53-54 °C, lit. mp 52-
-1
2 2
2.5): IR (film in CH Cl ) νmax (cm ) 3053.6, 1650.3, 1264.9, 1064.9,
1
034.2, 896.0, 738.0; H NMR (CDCl ) δ (ppm) 6.93 (2H, s), 3.11
3
(
1
3H, s), 2.30 (3H, s), 2.16 (6H, s), 1.73 (3H, s); GC/MS 191 (m/e),
76, 148, 134, 119, 105, 91, 77, 65, 56, 43.
,4,6-Trimethylphenyl Acetate, 1-ArOAc.6 The ester was pre-
pared from 1-ArOH and acetyl chloride using a procedure based on
6
2
1
2 4
-ArN BF . Normalized yields based on the total yields of phenol,
ester and amide products were used in the calculations of selectivities.
6
3
the preparations of phenyl acetate and phenyl benzoate. Vacuum
distillation gave an impure product (GC/MS), which was further purified
by column chromatography on silica (eluting solvent EA:hexane 1:6
The Search for N,N-Dimethylaniline. Dediazoniations were carried
W
out in two different aqueous N,N-dimethylacetamide solutions with N /
-
3
N
A
molar ratios of 2 and 4 containing 4.71 × 10 M 1-ArN
2.5% MeOH v/v) at 40 °C for 24 h. No peak was observed at the
retention time for 1-ArNMe , but the areas of all other peaks were
2 4
BF (ca.
or CH
2
Cl
2
:PE 1:3). The overall yield of the colorless liquid was 90%
-
1
(
1
bp 85-90 °C, 3-4 mmHg): IR (neat) νmax (cm ) 3011.5, 1754.6,
1
2
607.1, 1370, 1222.7, 1191.0, 1137.1, 910.6, 854.5, 733.0; H NMR
) δ (ppm) 6.91 (2H, s), 2.36 (3H, s), 2.30 (3H, s), 2.15 (6H, s);
C NMR, broad-band decoupled (CDCl ) δ (ppm) 169.6, 146.4, 135.8,
consistent with earlier results (see Table 3). In a separate set of
(
CDCl
3
+
1
3
experiments, 0.05, 0.1, and 1 equiv (compared to 1-ArN
2
) of
3
-
3
+
1
-ArNMe
2
were added to 5 × 10 M 1-ArN
O:N,N-dimethylacetamide at 40 °C. Increasing the amount of
did not affect the total product yield or the 1-ArOH:1-ArOAc
2
in a 2:1 molar ratio of
1
30.1, 129.7, 21.3, 21.0, 16.7; GC/MS 178 (m/e), 136, 121, 91, 77,
H
2
6
5, 43.
1
-ArNMe
2
HPLC Experiments/Product Yields. Products were identified and
their yields obtained by the following general procedures. Reaction
was initiated by injecting small amounts, ca. 20 µL, of freshly prepared,
2 4
ice cold, stock solutions of 0.1 M 1-ArN BF in MeOH into aqueous
amide solutions of varying molar ratios in 5-10-mL volumetric flasks
thermostated at 40 °C. Note that MeOH was used as the solvent for
product yield ratio significantly within experimental error, i.e., (5%.
A special gradient eluting system was used to minimize broadening of
the 1-ArNMe
7
8
2
peak: 0-7 min, 0.05% TFA/80% H
-37 min, the ratio was changed linearly to 0.05% TFA/20% H
0% MeCN and held constant for 5 min, followed by wash cycles,
2
O/20% MeCN;
2
O/
and returned to the original condition. Typical retention times were
1
-ArN
2 4
BF instead of MeCN because the peak in the chromatograms
+
as follow: 1-ArNMe , 10 min; 1-ArOH, 30 min; 1-ArOAc, 36 min;
for amide product formed from reaction of 1-ArN
2
with MeCN has
2
and 1-ArOMe, 39.5 min. The smallest peak observable by our detector
the same retention time as that of some products from reaction with
3
has an area of ca. 5 × 10
3
µV‚s, which is equivalent to ca. 2.49 ×
the amides. MeOH concentations in the reaction mixtures varied from
-4
-3
+
2
,
10-6 M 1-ArNMe2 or about 0.05% of the initial concentration of
a low of 0.5% (v/v) at 5 × 10 M to 8.2% at 7.81 × 10 M 1-ArN
see Tables 1-3. After 24-72 h (the half-life for dediazoniation is ca.
5 min at 40 °C), products were separated by HPLC.
-ArOH, 1-ArNAc, and other products (see below) were identified
in HPLC chromatograms by spiking experiments using independently
1-ArN BF in the aqueous N,N-dimethylacetamide reaction mixture.
2
4
Isotopic Labeling Experiments. Experiments using 43.85% H218O
were prepared by adding successively to 500-µL cone-shaped flasks
(Weaton), 45 µL of H218O, sufficient weight or volume (based on
densities) of the amide, i.e., acetamide, N-methylacetamide, or N,N-
3
1
(
(
(
60) Miller, B. J. Org. Chem. 1977, 42, 1402.
61) Miller, J. M.; So, K. H.; Clark, J. H. Can. J. Chem. 1979, 57, 1887.
62) Bradshaw, J. S.; Knudsen, R. D.; Loveridge, E. L. J. Org. Chem.
dimethylacetamide, to give the needed N
W A
/N molar ratio (see Table
4
), and sufficient volume of a freshly prepared stock solution of
1
970, 35, 1219.
63) Furniss, B. S.; Hannaford, A. J.; Rogers, V.; Smith, P. W. G.;
1-ArN
10 M 1-ArN
2
BF
4
in MeOH (0.05 M) to give a final concentration of 5 ×
-
3
+
(
. The final concentration (by volume) of MeOH in
2
Tatchell, A. R. Vogel’s Textbook of Practical Organic Chemistry, 4th ed.;
Longman: London, 1979; p 1368.
the solutions was about 10%. The solutions were thermostated at 40
C overnight and then analyzed by GC/MS. Reported peak abundances
°
(
(
64) Volz, H.; Ruchti, L. Justus Liebigs Ann. Chem. 1972, 763, 184.
65) Kalkote, U. R.; Choudhary, A. R.; Natu, A. A.; Lahoti, R. J.;
were average values of triplicate injections.
Ayyangar, N. R. Synth. Commun. 1991, 21, 1889.
66) Baciocchi, E.; Rol, C.; Mandolini, L. J. Org. Chem. 1977, 42, 3682.
(
(67) Swain, C. G.; Rogers, R. J. J. Am. Chem. Soc. 1975, 97, 799.