To find the optimal reaction conditions for carrying out the Michaelis-Arbuzov reaction

To find the optimal reaction conditions for carrying out the Michaelis-Arbuzov reaction

To find the optimal reaction conditions for carrying out the Michaelis-Arbuzov reaction, we have selected 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea (3a) and diethyl phosphite (4) as model substrates. The progress of the reaction was investigated in the presence of different Lewis acid catalysts (10mol%) such as AlCl3, FeCl3, LaCl3.7H2O, CeCl3.7H2O, ZnCl2, SiO2.ZnCl2, BF3.Et2O and 37% nano-BF3.SiO2 under solvent-free conditions using both conventional as well as microwave irradiation methods (Table 1, entry 1-8). The results revealed that, nano-BF3.SiO2 is a more efficient catalyst for the synthesis of phosphonates under microwave assisted neat reaction conditions with respect to reaction times and yields as compared to the conventional method (Table 1, entry 8).
Table 1. Synthesis of compound 5a under various conditions

Entry Catalyst

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

Conventional methoda Microwave irradiation methodb
Time (h) Yieldc (%) Time (min) Yieldc (%)
1 AlCl3 (10mol%) 6 58 30 63
2 FeCl3 (10mol%) 5 61 28 67
3 LaCl3.7H2O 4 63 26 69
4 CeCl3.7H2O (10mol%) 4 65 24 70
5 ZnCl2 (10mol%) 5 62 27 66
6 SiO2.ZnCl2 (10mol%) 3 68 20 74
7 BF3.Et2O (10mol%) 2 71 19 78
8 37% nano-BF3.SiO2 (0.30g) 1 80 9 95
aReaction of 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea and triethyl phosphite in presence of 37% nano-BF3.SiO2 in solvent-free condition at 70 ºC
bReaction of 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea and triethylphosphite in presence of 37% nano-BF3.SiO2 in solvent-free condition under microwave irradiation at room temperature
c Isolated yield.
On further modification of the reaction conditions, we examined the effect of the amount of the catalyst on the model reaction by altering the loading of catalyst (Table 2, entries 1-8) under solvent-free conditions using microwave irradiation. It was observed that good yield of the product was obtained when used 0.25 g of 37% nano-BF3.SiO2 catalyst. High loading of the catalyst did not lead to the significant variation in the yield of product, but lower yields of the product.
Table 2. The effect of the amount of the catalyst, 37% nano-BF3-SiO2 to promote the Michaelis-Arbuzov reactiona
Entry Amount of Catalyst (gm) Time (min) Yieldb (%)
1 0.05 9 56
2 0.1 9 66
3 0.15 9 75
4 0.2 9 83
5 0.25 9 96
6 0.3 9 95
7 0.35 9 92
8 0.40 9 87

aReaction of 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea and triethylphosphite in presence of 37% nano-BF3.SiO2 in solvent-free condition under microwave irradiation at room temperature
bIsolated yield.
The reusability of the nano-BF3•SiO2 catalyst was also examined. After each run, the product was filtered and the residue of catalyst was washed with CHCl3 to remove stains from the catalyst surface and reused up to three cycles for the synthesis of compound 5a and re-examined these reactions (Table 3, entry 1-5). It is remarkable that the yield was diminished when the catalyst was reused in the forth cycle; hence, we did not reuse the catalyst more than three times for the reaction.
Table 3. Reusability of the catalyst, 37% nano-BF3.SiO2 for the synthesis of compound 5aa
Entry 37% nano BF3.SiO2 (0.30g) Time (min.) Yieldb (%)
1 1st run 8 96
2 2nd run 8 94
3 3rd run 8 94
4 4th run 8 89
5 5th run 8 85

a Reaction of 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea and triethylphosphite in presence of 37% nano-BF3.SiO2 (0.25g) in solvent-free condition under microwave irradiation at room temperature
b Isolated yield.

The model reaction was optimized by screening at 180, 220, 350, 420, 455 and 560 Watts to find out the effect of microwave power on the reaction. A microwave power 420 W was found to be optimal (Table 4).
Table 4. Effect of microwave oven power (Watt) on the yield of the compound 5a.a
Entry Microwave Power (Watts) Yieldb
1 180 70
2 220 85
3 350 86
4 420 96
5 455 87
6 490 84
7 570 76
a Reaction of 1-(4-bromo-3-methylisoxazol-5-yl)-3-(pyridin-3-yl)urea and triethylphosphite in presence of 37% nano-BF3.SiO2 (0.25g) in solvent-free condition under microwave irradiation at room temperature
b Isolated yield.
After optimization of the reaction conditions by various examinations, the scope of the reaction was investigated by changing various urea/thiourea derivatives and the results are summarized in Table 5.
Table 5. Effect of microwave irradiation on the synthesis of phosphonates (5a-j)

Entry Product Time (min) Yieldb (%)
5a
9 96
5b
11 94
5c
16 90
5d
12 91
5e
13 95
5f
12 89
5g 10 92
5h 15 91
5i
17 94
5j
13 93

a Reaction of various urea/thiourea derivatives of 4-bromo-3-methylisoxazol-5-amine (3a-j) and triethylphosphite(4) in presence of 37% nano-BF3.SiO2 (0.25g) in solvent-free condition under microwave irradiation at room temperature
b Isolated yield.

The structures of the synthesized compounds were characterized by NMR (31P, 1H, 13C), IR, mass and elemental analysis. 31P NMR signals appeared in the region d 26.1-18.7 ppm for all the compounds (5a-j). The 1H NMR spectra of the compounds (5a-j) gave signals due to Ar-H in the range of 8.15-6.32 ppm. The proton signal at 11.49-9.25 and 7.36-7.32 ppm are assigned to NH group attached to heterocyclic moiety and isoxazole moiety respectively for the compounds. The methylene protons of P-O-CH2CH3 gave a multiplet and methyl protons of P-O-CH2CH3 resonated as a triplet in the region ? 4.09-4.05 and ? 1.27-1.23 respectively for the compounds (5a-j). In the 13C NMR spectra of compounds (5a-j), the P-O-CH2-CH3 and P-OCH2-CH3 were resonated at ? 63.8-63.1 and 16.7-16.2 respectively. 13C NMR chemical shift for C=O of compounds (5a-e) and C=S of compounds (5f-j) were observed in the region ? 154.5-154.1 and 175.8-175.2 ppm. The compounds (5a-j) showed characteristic infrared absorption bands in the region 3345-3221, 1229-1220 and 1021-1013 cm-1 for NH, P=O and P-O-Calip stretching frequencies. The compounds (5a-e) exhibited characteristic absorption bands for C=O functional group in the region 1743-1702 cm-1. The compounds (5f-j) showed characteristic infrared absorption bands in the region 1098-1092 cm-1 for C=S stretching frequencies. In their mass spectra, M+. ions were observed in the expected m/z values.
3.2. Antibacterial activity

x

Hi!
I'm Alfred!

We can help in obtaining an essay which suits your individual requirements. What do you think?

Check it out