Grignard addition to δ-valerolactone
October 04, 2021
Introduction: The purpose of this experiment is to introduce the techniques of inert atmospheric
synthetic manipulation and column chromatography purifications by adding excess MeMgBr to
δ-valerolactone through a grignard addition reaction. This specific reaction is important because
lactones provide valuable building blocks in the synthesis of many other compounds from
pharmaceuticals all the way to monomers for the preparation of polyesters.
Reaction Scheme:
Chemical Table:
Reagent:
Molecular
Formula:
Molar
Mass
(g/mol):
Density
(g/mL):
Amount:
(*Adjusted:)
δ-valerolactone
C5H8O2
100.116
1.08
1.9 mL
mmol:
Mol.
(*Adjusted:) equiv.:
20
(1.51 mmol)
1 eq.
(0.140 mL)
Methylmagnesium
bromide
CH3MgBr
119.25
1.035
8.1 mL
8.3 g
(0.608 mL)
70
(5.28 mmol)
3.5 eq.
Tetrahydrofuran
C4H8O
72.11
0.889
40 mL
(3.00 mL)
490
(37.0 mmol)
24.5 eq.
Ammonium
chloride
NH4Cl
53.491
1.53
10 mL
(0.766 mL)
290
(21.9 mmol)
14.5 eq.
Ethyl Acetate
C4H8O2
88.11
0.902
45 mL
(3 x 15mL)
3.39 mL
(3 x 1.13mL)
460
(34.7 mmol)
23 eq.
Safety:
●
●
●
●
●
δ-valerolactone: Corrosive.
Methylmagnesium bromide: Flammable and Corrosive.
Tetrahydrofuran: Flammable, Irritant, and Health Hazard
Ammonium chloride: Irritant
Ethyl Acetate: Flammable and Irritant.
Calculations:
Procedure:
1. Set up N2 atmosphere.
a. Attach connector, open regulator, moderate flow, connect to flask, vent, flow for
3-5 mins, remove needle, add balloon, and then remove line.
2. Set up solution:
a. Add 1.6 mL of MeMgBr to valerolactone dropwise, bring up to room temp and mix
overnight.
b. Add 0.766 mL of sat. NH 4Cl w/ water slowly
c. Remove THF under pressure w/ rotovap
d. Extract with AcOEt
e. Dry with MgSO4
3. Set up TLC
4. Set up Column Chromatography
a. Find best eluent
i.
Combination of hexanes or toluene (apolar solvents) and ethyl acetate,
diethyl ether or dichloromethane (polar solvents) will be the optimal eluent
mixture.
b. Prepare column
c. Add reaction mixture
d. Collect 20 test tubes and run TLC on all of them
e. Run a H-NMR
Observations:
●
●
●
Solution
○ Added:
■ 1.4 uL of δ-valerolactone
● color - clear
■ 3.0 mL THF
● color - clear
■ 1.6 mL MeMgBr
● color - grey
Extracted residue
○ Yellowish Oily substance
Performed Column Chromatography and TLC
○ Collected 16 test tubes
○ Product was found in test tubes 8-11
● TLC (Test Tube 8)
○ H = 3.78 cm
○ 1 dot formed
■ Dot8 = H = 1.40 cm
● RF8 = 0.37
● TLC (Test Tube 9)
○ H = 3.80 cm
○ 1 dot formed
■ Dot9 = H = 1.46 cm
● RF9 = 0.38
● TLC (Test Tube 10)
○ H = 3.78 cm
○ 1 dot formed
■ Dot10 = H = 1.45 cm
● RF10 = 0.38
● TLC (Test Tube 11)
○ H = 3.68 cm
○ 1 dot formed
■ Dot11 = H = 1.31 cm
● RF11 = 0.36
● Test tubes 8-11 combined and evaporated to yield 0.079 g of product.
Analysis of Results:
1. Calculate the product yield obtained.
Final product = 0.079 g = 79 mg
Percent yield =
79 𝑚𝑔
200 𝑚𝑔
* 100% = 39.5 % yield
2. Assign all the peaks of the 1H NMR spectrum and describe the multiplicity
observed. If peaks are overlapping, describe what multiplicity would be expected.
● Peak A (1.51): Corresponds to atoms 3, 4, 5, and 6 the multiplicity expected
would be a quintet; Integration should be 8.
● Peak B (1.22): Singlet corresponds to atoms 1 and 8 (methyl groups)
● Peak C (3.66): Triplet corresponds to atoms 7 and 9 (hydroxyl groups)
● Peak D (7.26): Chloroform reference peak
● Unlabeled Peaks: The three unlabeled peaks with arrows correspond to AcOEt
Post-Lab Questions:
1. At the end of the reaction a saturated NH4Cl in water was added, what is the purpose of
this step?
a. NH4Cl is used as the work-up reagent that retains the intermediate product of the
grignard reaction while the proton transfer takes place between water. Since
Ammonium Chloride is a weak acid we can avoid any elimination steps from
occurring.
2. Why is the THF removed prior to the extraction?
a. The THF is removed so that it doesn’t not interact with the ethyl acetate in the
next step. The purpose of the extractions and column chromatography is to purify
the sample as much as possible and because THF is highly soluble it would be
hard to remove during/after the separation leading to an impurities in the sample.
3. The experiment includes a column chromatography purification of the final product.
Explain how you identify the best eluent and what requirement does the eluent used
need to fulfill to allow the product to be obtained in high purity?
a. TLC is used to identify the best eluent by finding a mixture that generates an RF
value between 0.25 - 0.30. Based on this Ethyl Acetate was found to be the best
eluent for separating the product from solution.
4. An excess of the MeMgBr was used, what is the minimum amount required to
get the desired product?
a. 1.75 mL of MeMgBr is the minimum amount required to obtain the desired
product.
5. What would you expect as product or product mixture if 1 equivalent of the MeMgBr was
used? Explain why.
a. Either the product, 5-Methyl-1,5-hexanediol, would not form and instead the
product would be 1,5-Hexanediol because there would not be enough MeMgBr to
add the second methyl group, or, the reaction would only produce 0.286 mmol of
product instead of 1.51 mmol.