4A. Results and Discussions
4.2 Borax and phosphate catalyzed selective oxidation of organic sulfides
The selection of borax as catalyst was originated from its reaction with H2O2, enabling H2O2 to be more reactive. Thus, borax bocomes the catalyst of choice for sulfide oxidation. In order to ascertain the optimum conditions, several reaction runs were carried out at the out set on methyl phenyl sulfide as the model substrate each time with 2 mmol of the substrate, 6 mmol of H2O2 (45%
aqueous solution), 10 mol% of borax in 2 mL of MeOH at different pH, as shown in Table 4.2.1. pH of the reaction solution was adjusted by careful addition of 0.1M NaOH solution. The solution pH of 6 or 7 appeared suitable for sulfoxidation. Use of four or five molar equivalents of H2O2, instead of three molar equivalents, at pH 6 or 7 reduces the reaction time by ca 1 h, however, 15-20% of sulfone was formed along with the sulfoxide thereby reducing the selectivity. The selective oxidation to sulfone, if desired, can be best done at pH 10 or 11 (Table 4.2.1).
Table 4.2.1. Optimization of pH and solvent for selective oxidation of methyl phenyl sulfide with borax–H2O2
A perusal of the distribution diagram of peroxo-borate system presented by Pizer and Tihal,65 makes it evident that at pH 6 or 7 mono and diperoxoborates, (HO)3BOOH– and
Entry Catalyst Time (h)
mol% pH H2O2
equiv.
Sulfoxide Sulfone (%) (%) 1
2 3 4 5 6 7 8 9 10 11 12
10 10 10 10 10 10 10 10 5 0 10 10
5 6 6 7 6 6 2.5 2.5 12 12 5 5 6
6 7 7 8 9 10 11 7 7 7 7
3 3 3 3 3 3 3 3 3 3 5 6
80 90 92 85 75 35 -- -- 55 45 75 62
-- --
-- 10 25 65 93 93 -- -- 20 35
R R'
S O
R R'
S
R R'
S O O
H2O2, CH3OH H2O2, CH3OH Borax (10 mol%)
pH 6 or 7
Borax (10 mol%) pH 10 or 11
Scheme 4.2.1
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(HO)2B(OOH)2–, respectively, occur in equal but relatively lower concentrations along with a very minute amount of inactive peroxoboric acid, (HO)2BOOH. With the increase in pH to 10 or 11, peroxoboric acid disappears while both the peroxoborates occur in relatively higher concentrations, with the concentration of (HO)2B(OOH)2– being much higher. This may be indicative of the fact that a higher concentration of diperoxoborates favours sulfone formation over the corresponding sulfoxide.
In order to generalize the reactions, a series of structurally diverse sulfides were subjected to oxidation under the optimized reaction conditions and the results are presented in Table 4.2.2. The reactions went on well affording the products in high yields. It is notable that sulfides were
Table 4.2.2. Borax catalyzed sulfide oxidation in MeOH by H2O2 at room temperature pH=6 or 7 pH=10 or 11 Run Substrate
Time (h) Sulfoxide (%)a Time (h) Sulfone (%)a 1 PhSCH3 6 92, 83b (1a) 2.5 93, 85,b 95c (1b) 2 PhSC4H9 8 82 (13a) 4 90 (13b) 3 PhSC6H13 24 65 (4a) 24 87 (4b) 4 C12H25SC4H9 5 82 (8a) 3 84 (8b) 5 C4H9SC4H9 8 78 (14a) 3.5 78 (14b) 6 PhSCH2CH=CH2 8 85 (3a) 6 90 (3b) 7 PhSCH2CH2CN 7 85 (15a) 6 88 (15b) 8 PhCH2SCH2CH2OH 5 90 (9a) -- --
9 PhCH2SPh 8 90 (2a) 3 94 (2b) 10 p-NO2PhCH2SPh 6 88 (16a) 2.5 95 (16b) 11 Dibezothiophene (DBT) 10 55 + 42d (10a) 6 75 (10b) 12 4-Methyl -DBT 24 45+ 58d (11a) 24 75 (11b) 13 4,6-Dimethyl-DBT -- -- 24 10 (12b)
aIsolated yields,
bYield after 7th cycle,
cYield at 5 g scale,
d % of sulfone
chemoselectively oxidized in presence of some oxidation prone functional groups such as C=C, –CN, –OH (entries 6-8, Table 4.2.2). Dibenzothiophene (DBT) and substituted DBT oxidations are rather difficult with the generally practiced oxidation procedures. However, upon treatment with
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112
borax-H2O2 system some of these were converted to the corresponding sulfoxides and sulfones (entries 11 and 12, Table 4.2.2). Although we succeeded in oxidizing DBT and 4-methyl-DBT, our protocol did not work well for 4,6-dimethyl-DBT. Only 10% oxidation has been achieved in 24 h.
The result is not too surprising because this is the most difficult among the refractory sulfides to oxidize. Owing to steric crowding by the methyl groups on DBT, it is rather difficult to approach the sulfur by the oxidant thereby causing the problem, as encountered (entry 13, Table 4.2.2). It may be mentioned that with the increase in alkyl chain length of the sulfides, the rate of reaction becomes slower. This may probably be due to the orientation of hydrophobic alkyl chain around the sulfur atom.
Recyclability of the catalyst was examined through a series of reactions with methyl phenyl sulfide by using the aqueous phase containing borax, obtained after extraction of the reaction mixture with EtOAc. This was charged with a fresh substrate and 3 equivalents of H2O2 and pH was adjusted at either 6 or 7 or at 10 or 11. Interestingly, the catalyst could be reused for at least seven reaction cycles with consistent activity. It is also important to note that the reaction can be performed on a relatively larger scale (5 g) giving good yields (entry 1, Table 4.2.2) showing its potential for scaled-up applications.
While working on borax catalyzed sulfide oxidations and the knowledge gathered from the present experience, we anticipated that phosphate can also bring about this types of reactions.
Accordingly, [(NH4)2HPO4] was used as catalyst with H2O2 being the oxidant for sulfide oxidations (Scheme 4.2.2). The goal was to achieve sulfoxidation.
Here again the work began with optimization of reaction conditions. The results of this exercise are summarized in Table 4.2.3. It is evident that the reaction takes place in each case with the best performance being with 3 equiv. H2O2 containing 10 mol% of the catalyst at pH 7 or 8.
Accordingly, all the subsequent reactions were conducted with this combination.
R R'
S O
R R'
S
H2O2, H2O or CH3OH (NH4)2HPO4 (10 mol%)
pH 7 or 8
Scheme 4.2.2
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Table 4.2.3. Optimization of pH for selective oxidation of methyl phenyl sulfide to the corresponding sulfoxide with [(NH4)2HPO4]–H2O2in MeOH at room temperature
Entry Catalyst Time (h)
mol% pH H2O2
equiv.
Sulfoxide Sulfone (%) (%) 1
2 3 4 5 6 7 8
20 10 10 10 10 5 2 0
2.5 3 4 5 5 12 12 12 9
9 8 8 7 7 7 7
5 3 3 1.5 3 3 3 3
60 72 85 55 82 80 55 45
25 12 -- -- -- -- -- --
Table 4.2.4. (NH4)2HPO4 catalyzed sulfide oxidation in MeOH by H2O2 at room temperature using 0.1 equivalent of catalyst
Entry Substrate Time (h) Sulfoxide Yield(%)a
SCH3 SCH3
O
SC6H13 O S O
S O
SC6H13 S S
S MeO
S MeO
O
S C11H23 C11H23 S O 1
2 3 4 5 6 7 8
9
85 89
88 65 85 89
85 79
82 4
8 8 9 12 8 3 3 6
H7C3 S C3H7 H7C3 S C3H7 O
C4H9
S CN C4H9
S CN
O
S CN S CN
O
1a
2a
3a 4a
5a 6a
14a 17a
15a
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H7C3 S C11H23 H7C3 S C11H23 O
S OH S OH
O
S S
O
S S
O
13 12 11a 00
10
11
12
4.5 4
12
8a
9a
10a
88
84
00
aIsolated yields
A variety of sulfides such as alkyl, aryl and allyl sulfides were subjected to oxidation by (NH4)2HPO4 (10 mol%) in MeOH at room temperature to afford the corresponding sulfoxides in high to very high yields (Table 4.2.4). The facility of the reaction was dependent on the nature of the substituents. Thus, alkyl sufides were more reactive in comparison to aryl and allyl sulfides.
Under these conditions, allylic double bonds, –CN and –OH did not undergo any oxidation.
Though we were successful in oxidizing a variety of organic sulfides, this protocol did not work well for dibenzothiophenes (DBTs). Finally, upon completion of the reaction, the aqueous phase containing phosphate was reused for several cycles with consistent activity (5 cycles).
A comparison of the results of sulfide oxidations with borax-H2O2 and [(NH4)2HPO4]-H2O shows that the former performs relatively better under the given experimental conditions.