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J. D. Moseley, J. P. Gilday / Tetrahedron 62 (2006) 4690–4697
ꢀ
sample was analysed in duplicate by LC and gave results
comparable to those in Figure 2.
70 C. The residual gas pressure was released by opening
the caps (care). The tubes were then re-sealed and re-heated
to the set temperature for a further 7 min, then hydrolysed
and isolated as described above. All samples gave a pale
cream solid of good form. Each sample was analysed in du-
plicate by LC and the mean result is used in Table 1. Typical
maximum pressures recorded were initiallyw200–240 psig,
reducing to w50–60 psig residual pressure after the first
7-min heating. Residual pressure after the second period of
heating was typically only 6–18 psig.
4.2.4. Microwave HCl hydrolysis reactions. Seven reac-
tions were conducted in microwave tubes varying the HCl
hydrolysis time and temperature under micꢀrowave heating
as follows: 15, 30, 60 and 120 min at 120 C, and 15 min
ꢀ
at 130, 140 and 150 C. In each tube naphthoic anhydride
(205 mg, 1.00 mmol) was added to 2.5 mL 1.0 M NaOH
(2.50 mmol) in a microwave tube and heated in aluminium
ꢀ
hot block with magnetic stirring at 50–60 C for 15–
20 min. After this time Hg(OAc)2 (374 mg, 1.15 mmol)
was added in one portion to the hydrolysed naphthoic anhy-
dride to give a dense white precipitate, which was shaken up
thoroughly to achieve intimate mixing of the Hg salts. Each
tube was then heated in the microwave with stirring at 80 W
maximum power, to achieve afterw90 s a set-point temper-
4.2.7. Optimised microwave process for naphthoic anhy-
dride. (This optimised procedure is conducted in a single
tube as a ‘one pot’ process by sequential additions of re-
agents.) Naphthoic anhydride (205 mg, 1.00 mmol) was
added to 2.5 mL 1.0 M NaOH (2.50 mmol) in a microwave
tube and heated in a microwave with maꢀgnetic stirring
ꢀ
ꢀ
ature of 180 C, which was maintained for 15 min. After
at 100 C for 1 min. After cooling to 70 C, Hg(OAc)2
compressed air cooling, concentrated HCl (2.0 mL) was
added to each tube and shaken up, and further microwave
heating was applied at the set-point temperature for
15 min or longer as appropriate with stirring. The crude
product was isolated, washed and dried as in previous exam-
ples, except for using 10 mL wash volumes, to yield the
naphthoic acid in typically quantitative yield (0.17–
0.18 g). Each sample was analysed in duplicate by LC aꢀnd
the mean result was used. Samples hydrolysed at 120 C
gave a typically good form of pale cream naphthoic acid,
whilst those hydrolysed at higher temperatures gave darker
coloured solids with fair to poor form, including hard brown
lumps. Yields remained consistently high for all.
(341 mg, 1.05 mmol) was added in one portion, mixed
thoroughly and heated in a microwave with stirring at
ꢀ
200 C (with 90 W maximum power) for 15 min. After
cooling to 70 C, concentrated HCl (2.0 mL) was added,
ꢀ
mixed thoroughly and heated in a microwave with stirring
at 120 C for 15 min. After cooling to rt, the crude product
ꢀ
was isolated on a sinter, slurry was washed twiceꢀwith water
(10 mL each) and dried in a vacuum oven at 45 C to yield
the naphthoic acid product as a pale cream solid (0.17 g,
99%). LC quality 98.9%.
4.2.8. Microwave reactions with substituted naphthoic
anhydrides. (This procedure is conducted in a single tube
as a ‘one pot’ process by sequential additions of reagents.)
The appropriate naphthoic anhydride 4 (1.00 mmol) was
added to 2.5 mL 1.0 M NaOH (2.50 mmol) in a microwave
tubeꢀand heated in a microwave with magnetic stirring at
4.2.5. Microwave Hg stoichiometry reactions. Eight reac-
tions were conducted in microwave tubes varying the
Hg(OAc)2 equivalents as follows: 0.77 equiv (250 mg);
0.86 (281 mg); 0.96 (312 mg); 1.05 (343 mg); 1.15
(375 mg); 1.44 (468 mg); 1.92 (624 mg). In each tube naph-
thoic anhydride (205 mg, 1.00 mmol) was added to 2.5 mL
1.0 M NaOH (2.50 mmol) in a microwave tube and heated
ꢀ
100 C for 1 min. After cooling to 70 C, Hg(OAc)2
(341 mg, 1.05 mmol or 374 mg, 1.15 mmol) was added in
one portion, mixed thoroughly and heated in a microwave
ꢀ
for 15 or 30 min. After cooling to 70 C, concentrated
with stirring at 180 or 200 C (80–90 W maximum power)
ꢀ
ꢀ
in aluminium hot block with magnetic stirring at 50–60 C
for 15–20 min. After this time Hg(OAc)2 was added in one
portion to the hydrolysed naphthoic anhydride to give
a dense white precipitate, which was shaken up thoroughly
to achieve intimate mixing of the Hg salts. Each tube was
then heated in the microwave with stirring at 80 W maxi-
mum power, to achieve after w90 s a set-point temperature
HCl (2.0 mL) was added, mixedꢀthoroughly and heated in
a microwave with stirring at 120 C for 15 min. After cool-
ing to rt, the crude product was isolated on a sinter, slurry
washed twice with water (10 mL each) and dried in a vacuum
oven at 45 C to yield the substituted naphthoic acids (5 and
6) as an unresolved mixture. Exact conditions, yield and
quality for each anhydride are shown in Table 2.
ꢀ
ꢀ
of 180 C, which was maintained for 15 min. After com-
pressed air cooling, concentrated HCl (2.0 mL) was added
to each tube and shaken up, and further microwave heating
4.3. Preparation of methyl naphthoate esters (7/8)
ꢀ
was applied at 120 C for 15 min with stirring. The crude
product was isolated, washed and dried as in previous exam-
ples, except for using 10 mL wash volumes, to yield the
naphthoic acid in typically quantitative yield (0.17–
0.18 g). Each sample was analysed in duplicate by LC and
the mean result is used in Figure 3. The 1.15 equiv reaction
was repeated as above but with a 16 h NaOH hydrolysis time
at rt.
4.3.1. Methyl naphthoate (7a). Six combined naphthoic
acid samples (0.95 g in total with a mean quality of
90% w/w, 4.97 mmol) were slurried in methanol (9.5 mL)
and concentrated H2SO4 was added (150 mL, 2.48ꢀmmol).
The resulting mixture was heated to reflux (65 C) for
20 h, after which time LC analysis showed that the reaction
was 90% complete. A further three drops of H2SO4 were
added and heating continued for a further 10 h, after which
a slight improvement was detected. The reaction mixture
was cooled to rt and water (20 mL) was added, which gave
a milky white suspension. This was extracted with MTBE
(4ꢁ15 mL), the combined organic extracts washed with
saturated brine (1ꢁ15 mL), dried over MgSO4 and
4.2.6. Microwave reactions with gas venting. The standard
procedure described in Section 4.2.5 above was used, but
with 1.15 equiv of Hg(OAc)2 (374 mg, 1.15 mmolꢀ) in every
case. Tubes were heated at 160, 180 and 200 C under
microwave heating at 70–90 W for 7 min before cooling to