Comparison of iodination of methoxylated benzaldehydes and related compounds using iodine/silver nitrate and iodine/periodic acid

Article abstract of DOI:10.1080/00397910701569080

Iodination of the three methoxybenzaldehydes, four dimethoxybenzaldehydes, vanillin, and piperonal by two methods were compared. Iodine and periodic acid gave better yields for iodination for the methoxybenzaldehydes, whereas iodine and silver nitrate generally gave better yields for the rest of the compounds. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701569080

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Comparison of Iodination of Methoxylated
Benzaldehydes and Related Compounds using
Iodine/Silver Nitrate and Iodine/Periodic Acid
a
a
a
Bruce A. Hathaway , Kristen L. White & Mark E. McGill
a
Department of Chemistry , Southeast Missouri State University , Cape
Girardeau, Missouri, USA
Published online: 19 Oct 2007.
To cite this article: Bruce A. Hathaway , Kristen L. White & Mark E. McGill (2007) Comparison of Iodination
of Methoxylated Benzaldehydes and Related Compounds using Iodine/Silver Nitrate and Iodine/Periodic Acid,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:21, 3855-3860, DOI: 10.1080/00397910701569080
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Synthetic Communications , 37: 3855–3860, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701569080
Comparison of Iodination of Methoxylated
Benzaldehydes and Related Compounds
using Iodine/Silver Nitrate
and Iodine/Periodic Acid
Bruce A. Hathaway, Kristen L. White, and Mark E. McGill
Department of Chemistry, Southeast Missouri State University,
Cape Girardeau, Missouri, USA
Abstract: Iodination of the three methoxybenzaldehydes, four dimethoxybenzalde-
hydes, vanillin, and piperonal by two methods were compared. Iodine and periodic
acid gave better yields for iodination for the methoxybenzaldehydes, whereas iodine
and silver nitrate generally gave better yields for the rest of the compounds.
Keywords: benzaldehydes, iodination, periodic acid, silver nitrate
Previously, we reported a high-yield iodination of 2,5-dimethoxybenzalde-
hyde, 1d, to produce 4-iodo-2,5-dimethoxybenzaldehyde, 2d, using iodine
[
and silver nitrate. In contrast, iodination with iodine and periodic acid
1]
[2]
gave a mixture of iodinated products. We decided to compare these two
methods of iodination for other methoxylated benzaldehydes and related
compounds. The reaction is shown in Scheme 1.
As can be seen in Table 1, both methods succeeded well for the methox-
ybenzaldehydes, 1a–1c, although the iodine and periodic acid method gave
somewhat higher yields. For the dimethoxybenzaldhydes, 1d–g, iodine and
silver nitrate gave fair to good yields, whereas iodine and periodic acid
gave variable results: In some cases, mixtures of the desired product and iodo-
deformylated product, as shown in Scheme 2. Iododeformylation has been
Received in the USA March 30, 2007
Address correspondence to Bruce A. Hathaway, Department of Chemistry,
Southeast Missouri State University, MS 6400, One University Plaza, Cape
Girardeau, MO 63701, USA. E-mail: bahathaway@semo.edu
3
855

3
856
B. A. Hathaway, K. L. White, and M. E. McGill
Scheme 1.
[
3]
previously reported for some related benzaldehydes. The iododeformylation
reaction is being investigated further.
The iodination of 2,3-dimethoxybenzaldehyde, 1e, to form 5-iodo-2,3-
dimethoxybenzaldehyde, 2e, in 51% yield is notable, because the previously
reported synthesis of 2e required five steps from 2-hydroxy-3-methoxybenzalde-
[
4]
hyde. Iodination of vanillin, 1h, proceeded in fair yield using iodine and silver
nitrate, although the yield is not as good as using sodium iodide, iodine, and
[
sodium hydroxide. The yield for iodination of piperonal, 1i, was also low,
5]
but this procedure is simple and has one step to form a single product, 6-iodopi-
[6]
peronal, 2i, as opposed to the three-step procedure previously reported.
In conclusion, iodine and silver nitrate can be used to iodinate a wide
variety of methoxylated benzaldehydes in fair to excellent yields. For mono-
methoxybenzaldehydes, however, iodine and periodic acid gives somewhat
higher yields. In all cases, except for iodination of some dimethoxybenzalde-
hydes with iodine and periodic acid, monoiodination products free of other
isomers were obtained.
EXPERIMENTAL PROCEDURES
NMR spectra were recorded on a Bruker DPX-300, using CDC1 as a solvent.
3
GC-mass spectra were obtained with a Thermo-Electron/Finnigan Trace GC
Ultra-Polaris Q GC-MS. IR spectra were recorded on a Thermo-Electron
Nexus 670 FT-IR with a Smart Endurance ATR accessory. Melting ranges
are reported in degree Celsius.
Example Procedure for Iodination with Periodic Acid (H IO ) and Iodine
5
6
To 100 mL of acetic acid, 5.77 g (40 mmol) m-anisaldehyde, 4.71 g
18 mmol) of iodine, and 1.40 g (6 mmol) of periodic acid were added,
(
followed by 20 mL of water and 3 mL of sulfuric acid. A dark purple
solution resulted. The mixture was heated and stirred at 65–708C overnight.
After the reaction was cooled, saturated sodium bisulfite solution was added
to remove the dark color. A yellow precipitate formed upon pouring the
solution into ice water. The precipitate was filtered off and recrystallized in
95% ethanol to yield 6.53 g (67%) of 2-iodo-5-methoxybenzaldehyde.

Comparison of Iodination Methods
Table 1. Yields of iodinated products under two different iodination conditions
3 2
Starting material Product /H IO AgNO /I
3857
I
2
5
6
1a
2a
97%
95%
1
1
b
c
2b
2c
67%
83%
47%
66%
1
d
e
2d
2e
Mixture of
products
84%
51%
1
6%
1
1
1
f
2f
2g
2h
Mixture of
products
78%
42%
35%
g
h
81%
a
NR
1i
2i
NR
16%
a
NR-means no solid product formed upon workup of the reaction.
Example Procedure for Iodination with Silver Nitrate and Iodine
A mixture of 1.68 g (10 mmol) of 3,4-dimethoxybenzaldehyde, 1.71 g
10 mmol) of silver nitrate, and 2.80 g (11 mmol) of iodine in 65 mL of
(
methanol was stirred overnight at room temperature under nitrogen. The
yellow precipitate of silver iodide that formed was filtered off and washed

3
858
B. A. Hathaway, K. L. White, and M. E. McGill
Scheme 2.
with methanol. Excess iodine was reduced with sodium bisulfite solution. The
methanol was removed on a rotary evaporator; the solid was suspended in
30 mL water for several minutes and then filtered. The product was recrystallized
in 95% ethanol to yield 2.30 g (78%) of 2-iodo-4,5-dimethoxybenzaldehyde.
Data
5-Iodo-2-methoxybenzaldehyde, 2a
[7] 1
Mp 140–141, literature mp 140–142. H NMR (ppm): 10.3 (1H, s), 8.1 (1H,
d, J ¼ 2.4 Hz), 7.8 (1H, dd, J ¼ 8.8 Hz & 2.4 Hz), 6.8 (1H, d, J ¼ 8.8 Hz), 3.9
1
3
3H, s). C NMR (ppm): 188.3, 161.4, 144.1, 137.0, 126.4, 114.2, 83.0, 55.9.
(
EI-GCMS (relative abundance): 262 (M , 100), 63 (38), 263 (34), 244 (28),
þ
2
1
1
18 (15), 62 (12), 77 (12), 92 (11), 64 (10), 75 (10). IR (cm ): 3071,
009, 2874, 1666, 1584, 1267, 1243, 1176, 817.
3
2-Iodo-5-methoxybenzaldehyde, 2b
[8] 1
Mp 105–106, literature mp 112–113. H NMR (ppm): 10.0 (1H, s), 7.8 (1H,
d, J ¼ 8.7 Hz), 7.4 (1H, d, J ¼ 3.2 Hz), 6.9 (1H, dd, J ¼ 8.7 Hz & 3.2 Hz), 3.9
1
3H, s). C NMR (ppm): 195.7, 160.2, 141.0, 135.6, 123.5, 113.5, 89.9, 55.7.
3
(
EI-GCMS (relative abundance): 262 (M , 100), 63 (60), 134 (47), 261 (30), 62
þ
2
15), 64 (12), 74 (11), 262 (10), 92 (10). IR (cm ): 3003, 2947, 2860, 1667,
1
(
1593, 1276, 1243, 932, 817.
3-Iodo-4-methoxybenzaldehyde, 2c
[9] 1
Mp 101–102, literature mp 106–107.
H NMR (ppm): 9.8 (1H, s), 8.3 (1H,
d, J ¼ 2.0 Hz), 7.9 (1H, dd, J ¼ 8.5 & 2.0 Hz), 6.9 (1H, d, J ¼ 8.5 Hz), 4.0
1
3H, s). C NMR (ppm): 189.4, 162.7, 141.0, 132.1, 131.4, 110.5, 86.5,
3
(
þ
56.8. EI-GCMS (relative abundance): 262 (M , 100), 261 (77), 63 (22), 77
(
(
16), 119 (16), 51 (14), 76 (13), 62 (12), 92 (12), 76 (12), 105 (12). IR
21
cm ): 3004, 2936, 2829, 1669, 1591, 1562, 1274, 1243, 1196, 818.

Comparison of Iodination Methods
-Iodo-2,3-dimethoxybenzaldehyde, 2d
3859
5
[4] 1
Mp 97–98, literature mp 101–102. H NMR (ppm): 10.3 (1H, s), 7.7 (1H, d,
1
3
J ¼ 2.0 Hz), 7.4 (1H, d, J ¼ 2.0 Hz), 4.0 (3H, s), 3.9 (3H, s). C NMR (ppm):
188.6, 153.7, 152.6, 130.9, 128.2, 126.6, 87.0, 62.4, 56.3. EI-GCMS (relative
abundance): 292 (M , 100), 293 (37), 51 (31), 274 (29), 245 (23), 94 (22), 121
þ
2
20), 79 (19), 63 (17), 66 (16). IR (cm ): 3078, 2936, 2864, 1680, 1567, 1237,
1
(
1
170, 988, 827.
2
-Iodo-4,5-dimethoxybenzaldehyde, 2e
[
10] 1
Mp 140–141, literature mp 145–146.
H NMR (ppm): 9.9 (1H, s), 7.4 (1H,
s), 7.3 (1H, s), 4.0 (3H, s), 3.9 (3H, s). C NMR (ppm): 194.9, 154.5, 149.7,
1
3
1
28.4, 121.8, 111.1, 92.8, 56.5, 56.1. EI-GCMS (relative abundance): 292
þ
(M , 100), 164 (38), 136 (37), 291 (34), 51 (31), 94 (18), 293 (14), 121
2
(14), 79 (14), 66 (13). IR (cm ): 3006, 2936, 2850, 1671, 1579, 1498,
1
1
261, 1212, 1016, 861.
4
-Iodo-2,5-dimethoxybenzaldehyde, 2f
[
11] 1
Mp 137–139, literature mp 136–137.
1H, s), 7.2 (1H, s), 3.90 (3H, s), 3.88 (3H, s). C-NMR (ppm): 189.1,
H NMR (ppm): 10.4 (1H, s), 7.5
1
3
(
1
abundance): 292 (M , 100), 246 (40), 274 (33), 276 (31), 53 (24), 51 (23),
56.2, 152.7, 125.0, 123.7, 108.0, 95.9, 56.9, 56.4. EI-GCMS (relative
þ
2
1
6
3 (20), 79 (20), 77 (19), 107 (19). IR (cm ):2938, 2876, 2843, 1670,
591, 1569, 1380, 1268, 1213, 1041, 711.
1
5
-Iodo-2,4-dimethoxybenzaldehyde, 2g
[
12] 1
Mp 172–173, literature mp 172–173.
(
H NMR (ppm): 10.2 (1H, s), 8.2
1
1H, s), 6.4 (1H, s), 3.97 (3H, s), 3.95 (3H, s). C NMR (ppm): 187.0,
3
1
abundance): 292 (M , 100), 274 (58), 148 (41), 246 (40), 275 (40), 291
64.1, 163.8, 139.2, 120.3, 94.8, 75.6, 56.7, 55.9. EI-GCMS (relative
þ
2
1
21), 293 (11), 135 (10). IR (cm ): 2966, 2937, 2871, 2831, 1654, 1590,
(
1
455, 1271, 1210, 1024, 810, 683.
4
-Hydroxy-3-iodo-5-methoxybenzaldehyde, 2h
[
13] 1
Mp 175–177, literature mp 180.
H NMR (ppm): 9.8 (1H, s), 7.9 (1H, d,
3
1
J ¼ 1.7 Hz), 7.4 (1H, d, J ¼ 1.7 Hz), 6.7 (1H, br s), 4.0 (3H, s). C NMR
(
ppm): 189.6, 151.4, 146.5, 136.2, 131.1, 108.6, 80.5, 56.5. EI-GCMS
þ
(
relative abundance): 278 (M , 100), 277 (58), 51 (21), 235 (15), 135 (15),
2
9 (13), 279 (11), 53 (10), 107 (9), 136 (9). IR (cm ): 3151 (broad), 2845,
664, 1571, 1415, 1256, 1142, 1039, 852, 782, 669.
1
7
1

3
860
-Iodopiperonal, 2i
Mp 108–110, literature mp 108–110. H NMR (ppm): 9.9 (1H, s), 7.37 (1H,
B. A. Hathaway, K. L. White, and M. E. McGill
6
[6] 1
1
3
s), 7.34 (1H, s), 6.1 (2H, s). C NMR (ppm): 194.5, 153.6, 149.2, 129.7,
þ
1
1
6
9
19.5, 108.9, 102.7, 93.4. EI-GCMS (relative abundance): 276 (M , 100),
48 (60), 120 (52), 275 (37), 62 (35), 63 (21), 119 (18), 61 (16), 149 (14),
21
9 (12). IR (cm ): 2894, 2857, 1661, 1608, 1592, 1383, 1247, 1166, 1110,
25, 872, 847, 783.
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