Propargyl unit can be anchored to phenolic substances via a SN2 type reaction under slightly basic c — Organic Chemistry Chemistry Question
Phenol propargylation: Synthesis of 1-nitro-4-(prop-2-ynyloxy)benzene and (prop-2-ynyloxy)benzene
Propargyl unit can be anchored to phenolic substances via a SN2 type reaction under slightly basic condition. The resultant products can be feasible candidates as substrates for the following Huisgen dipolar cycloaddition reaction. [1, 2]
In this experiment, two parallel experiments, using phenol as a reactant in one of them, and 4-nitrophenol as a reactant in the other, will be performed under the same conditions. Both experiments will be stopped after 3 h as indicated in the following procedure. [2]
Chemicals and reagents [3]
* Phenol, C6H5OH
* 4-Nitrophenol, NO2C6H4OH
* Propargyl bromide, CH≡CCH2Br
* Toluene, C6H5CH3
* DMF, dimethylformamide, (CH3)2NCHO
* Potassium carbonate, K2CO3
* Ethyl acetate, CH3COOC2H5
* Heptane, C7H16
* Ether, C2H5OC2H5
* Brine, saturated NaCl solution
* Anhydrous sodium sulfate Na2SO4
Apparatus and glassware [4]
* Round bottom flask, 50 cm3
* Pipettes
* Magnetic stirrer
* TLC pre-coated silica gel plates (Silica Gel PF-254)
* UV-lamp
* Flash column chromatography, thick-walled glass column filled with a flash grade Silica Gel 60.
Pre-laboratory work
Before starting the experiment, estimate the phenolic substrate that would undergo a faster reaction. Explain the reason. [5]
Procedure
1. Place 1.0 mmol 4-nitrophenol (or phenol) to a 50 cm3 round bottom flask containing 1.0 cm3 DMF. Stir the mixture at room temperature for 5 min and then add 1.2 mmol propargyl bromide (80% weight solution in toluene) and 1.2 mmol of potassium carbonate. [5]
2. Stir the resulting mixture at room temperature for 3 hrs until TLC analysis indicates the completion of the reaction. For TLC, use pre-coated silica gel plates (Silica Gel PF-254) and visualize the spots by UV-light. Use ethyl acetate: heptane 1 : 3 mixture as an eluent. [6]
3. Dilute the reaction mixture with 1.0 cm3 of water and extract with 10.0 cm3 of ether. Wash the organic phase 3 times with 1.5 cm3 of brine, then dry over anhydrous sodium sulfate. [6]
4. Evaporate the solvent to afford the crude corresponding propargyl ether and weigh the product. [7]
5. Purify the crude product of (prop-2-ynyloxy)benzene by flash column chromatography which is performed by using thick-walled glass column with a flash grade Silica Gel 60. [7]
Calculate the Rf values of 4-nitrophenol and 1-nitro-4-(prop-2-ynyloxy)benzene. [VISUAL] Repeat the same calculations for phenol and (prop-2-ynyloxy)benzene. [VISUAL]
Model Answer
Compound | Rf
Phenol | 0.22
prop-2-ynyloxy)benzene | 0.66
4-nitrophenol | 0.20
1-nitro-4-(prop-2-ynyloxy)benzene | 0.46
Note: The retention factor, or Rf, is defined as the distance traveled by the compound divided by the distance traveled by the solvent front. [8, 9]
Calculate the chemical yield of 1-nitro-4-(prop-2-ynyloxy)benzene isolated as a solid substance. Measure the melting point of this substance.
Model Answer
After purification by column chromatography:
- m(1-nitro-4-(prop-2-ynyloxy)benzene) = 0.1312 g
Yield (1-nitro-4-(prop-2-ynyloxy)benzene) = (0.131 g / (0.001 mol * 177.2 g mol-1)) * 100 = 74.1%
Melting point of 1-nitro-4-(prop-2-ynyloxy)benzene = 110.5 - 112.5 °C [8, 9]
Calculate the chemical yield of (prop-2-ynyloxy)benzene.
Model Answer
- m(prop-2-ynyloxy)benzene) = 0.081 g
Yield (prop-2-ynyloxy)benzene) = (0.081 g / (0.001 mol * 132.6 g mol-1)) * 100 = 61.3 % [9]