WS 3 Assignment: Grignard Chemistry
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WS 3 Assignment: Grignard Chemistry
A chemist attempts the reaction shown below using a 1 M commercially purchased solution of methyl magnesium bromide in tetrahydrofuran (THF).
A solution of methyl magnesium bromide (1 M THF; 7.40 mL, 7.40 mmol) was placed in an oven-dried flask. Under magnetic stirring, a solution of 4-(dimethylamino) benzaldehyde (1.00 g, 6.70 mmol) in anhydrous THF (5 mL) was added slowly, before heating the reaction mixture at 40 oC for 1 hour. Upon cooling, the reaction mixture was diluted with diethyl ether (30 mL). An ammonium chloride solution (saturated aqueous; 30 mL) was added to the stirred reaction mixture. Next, sulfuric acid (aqueous; 2 M) was added slowly until pH = 2 (two clear layers were observed). The biphasic mixture was transferred to a separatory funnel, and the aqueous phase was discarded. The organic phase was washed with deionised water (30 mL) and a sodium bicarbonate solution (saturated aqueous; 30 mL), before being dried over magnesium sulfate. After filtration, the organic phase was concentrated under reduced pressure … but … didNOTafford anyproduct. |
1. Based on the material safety data sheets (internet search) for 4-(dimethylamino)benzaldehyde, methyl magnesium bromide (1 M THF), and tetrahydrofuran, identify three principal hazards associated with each ofthese compounds. [4.5]
2. Considering the polarity and density of the organic solvents used, THF and diethyl ether, explain the purpose of diluting the reaction mixture (THF) with diethyl ether before the aqueous work-up. [1.5]
3. Assuming the “Grignard reaction” (C–C bond formation) proceeded smoothly, explain why the intended product was not obtained using the above “quenching”/isolation procedure. Suggest a modified work- up to address this issue (to successfully isolate the product). [2]
4. The same reaction was repeated with an amended work-up procedure. The product isolated from the reaction mixture was found –without further purification– to have a melting point of 52–54 oC.
a. Search the literature to find a previously reported value for the melting point of the product. Include the citation in your answer (see workshop 1; SciFinder & Reaxys). [2]
b. By comparing the literature and experimentally determined melting point values, draw a conclusion on the purity ofthe product. [1]
Unlike aldehydes and ketones (reaction via nucleophilic addition–protonation), carboxylic acid derivatives such as amides, esters, anhydrides, and acyl chlorides do react in a distinct mode (reaction via nucleophilic addition–elimination), due to the presence of a leaving group at the carbon centre in the tetrahedral intermediate. In turn, these substrates can react with two equivalents of a Grignard reagent.
Using your lecture & tutorial notes, please answer questions 5– 7 (p. t. o.).
5. According to the scheme below, draw the structures of all organic reaction intermediates / final products after: (a) step 1, (b) step 2, and (c) step 3. [3]
O
Ph Cl
(1) Bu–MgCl (1 equiv)
(3) H3O+
6. According to the scheme below, draw the structures of all organic reaction intermediates / final products after: (a) step 1, (b) step 2, and (c) step 3. [4]
O
Ph OPh
(1) Ph–Li (1 equiv)
(3) H3O+
7. Assess the electrophilicity ofthe acyl–pyridinium species (left) compared with the acyl anhydride (right) by comparing the p* (LUMO) energy level of the corresponding C=O group [factors: (a) formal charge; (b) atomic size & electronegativity]. [2]
O
Ph N
O O
vs.
2022-03-12