Microwave-Assisted Neat Reaction Technology for Regioselective Thiocyanationꢀ
1
13C NMR chemical shift ranging between δ116-113 ppm
indicated that the thiocyano group is present in the products
obtained by the microwave assisted solid supported reaction.
We examined the role of acidic alumina for conversion of
anilines or indoles to corresponding thiocyano products.
Therefore, we carried out reaction in presence and absence of
acidic alumina under solvent-free microwave irradiation. Here
we observed in absence of acidic alumina, the reaction
required longer times and gave low yields, compared to the
presence of acidic alumina reactions. The results are listed in
Table 1. These findings showed acidic alumina enhanced the
rate of the reaction and yield of products.
In the reactions performed on the solid surface of alumina
under microwave conditions, the yields of mono-thiocyanated
desired products were excellent. The comparison of yields
between para and meta substituted anilines or methyl-
substituted and unsubstituted amino groups in anilines did not
show any significant change. In case of indoles, 2-
methylindole 3c reacts with ammonium thiocyanate to give
yield with 64% of 4c (Table 1, entry 14). As expected, a steric
factor was pronounced to lower yield in this case. Para-methyl
aniline 1k and 3-cyanoindole 3f did not react with ammonium
thiocyanate (Table 1, entry 11 and 17), which conforms the
-SCN group attacks regioselective to anilines and indoles.
On the basis of the mechanism proposed by A.-N. Ko, et
al. for the alumina supported selective N-alkylation of anilines
1
C
252, 1154, 610; H NMR (CDCl ) δ (ppm): 7.0-6.6 (3H, m,
3
1
3
6
H
3
), 4.2 (2H, brs, NH
δ (ppm): 151.5, 140.2, 127.2, 126.8, 121.8, 115.6, 109.9, 21.3.
-Amino-2-methoxyphenyl thiocyanate 2g (Table 1,
2
), 2.9 (3H, s, CH
3
); C NMR (CDCl )
3
4
-1
entry 7).ꢀm.p.: 99-100 °C, IR (cm ): 3344, 2966, 2150, 1625,
1
1
584, 1298, 615; H NMR (CDCl ) δ (ppm): 7.2-6.7 (3H, m,
3
1
3
C H ), 4.1 (2H, brs, NH ), 3.4 (3H, s, CH ); C NMR (CDCl3)
δ (ppm): 149.8, 143.8, 130.3, 126.8, 122.5, 118.9, 115.1, 52.1.
H-Indol-3-yl thiocyanate 4a (Table 1, entry 12). m.p.:
6
3
2
3
1
-1
1
6
03-105 °C, IR (cm ): 3333, 3001, 2145, 1548, 1519, 1274,
1
41; H NMR (CDCl
3
) δ (ppm):11.4 (1H, brs, NH), 7.68-6.51
N); 13C NMR (CDCl
) δ (ppm): 139.4, 131.6,
25.1, 124.0, 122.5, 117.0, 113.1, 100.7.
-Methyl-1H-indol-3-yl thiocyanate 4c (Table 1, entry
(
5H, m, C
8
H
5
3
1
2
-1
1
1
4). m.p.: 100-101 °C, IR (cm ): 3341, 3010, 2140, 1580,
1
519, 1281, 632; H NMR (CDCl ) δ (ppm): 11.1(1H, brs,
3
1
3
NH), 7.9-7.2 (4H, m, C H N), 2.4 (3H, s, CH ); C NMR
CDCl ) δ (ppm): 142.4, 139.5, 129.1, 124.0, 121.8, 118.2,
13.4, 105.6, 91.4, 15.4.
-Methyl-1H-indol-3-yl thiocyanate 4d (Table 1, entry
5). m.p.: 127-128 °C, 3324, 3012, 2146, 1519, 1106, 654; H
NMR (CDCl3) δ (ppm): 11.2 (1H, brs, NH), 7.4-6.9 (4H, m,
C H N), 2.8 (3H, s, CH ); C NMR (CDCl ) δ (ppm): 140.1,
8
5
3
(
1
3
4
1
1
1
3
8
5
3
3
1
39.5, 129.1, 125.0, 124.5, 119.1, 113.2, 110.8, 92.4, 17.9.
RESULTS AND DISCUSSION
[
9], we suggest that the possible mechanism for thiocyanation
Our preliminary studies were focused on the reaction
conditions for the synthesis of thiocyano anilines and indoles.
A variety of anilines or indoles, ammonium thiocyanate and
acidic alumina were mixed and placed in a microwave oven
for the time specified in the Table 1. The reaction was
monitored by TLC and complete disappearance of the starting
material was observed during this period. Elution of the
mixture with dichloromethane followed by evaporation of
solvent furnished the crude product, which was purified by
column chromatography. The obtained products were
characterized by comparing their melting points, IR and NMR
spectroscopic data with those reported in literature.
of anilines and indoles occurred by the formation of following
intermediates (I) and (II), respectively. However, to establish
the mechanism for this thiocyanation needs further
investigation.
H
0
NH
A l
H
N
0
A l
ꢀ
ꢀꢀꢀꢀ
ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
(I)
(II)
The occurrence of thiocyanation in anilines and indoles
was examined by IR and NMR studies. The formation of SCN
group in the product was confirmed by IR peaks obtained
CONCLUSIONS
-1
-1
between 2064-2150 cm (-SCN) and 632-748 cm (-C-S-).
Acidic alumina effectively promotes the regioselective
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