Question

Write detailed, reaction mechanism of guaifensin synthesis. Must include arrows, electron flow and lone pairs.

100 Pre-lab preparation BREE In your lab notebook, prepare the following (see lab notebook guide for details): Jl. Write all procedures required for this experiment. Prepare it so that it can be used as a sole source of your experimental procedures 2. In your notebook, draw structures of both enantiomers of 3-chloro-1.2-propanediol 3. In few sentences summarize main factors that have influence on Sw2 type reactions: • the reactivity of the macleophile • the nature of the leaving group • the structure of the alkyl portion of the substrate • the nature of the solvent 4. Write detailed, reaction mechanism of guaifenesin synthesis. Must include wrows, electron flow and lone pairs. 5. Write written table of chemicals that include physicochemical data for all chemicals used (see chapter 6). 6. Write the theoretical yield calculations for this reaction. In the laboratory The essential reactants guaifenesin synthesis are provided in Table 1. Table 1. Compound 2-methoxyphenol bp ("C) Reactants used amount used mmol 550 L calculate MW 124.14 d (g/mL.) 1.13 NaOH (25% soln.) 40 1 mL b ethanol 46.07 18 water Sodium sulfate (1)-3-chloro-1,2- propanediol 142.04 110.54 1.32 500L calculate 164

Answer 1

Guaifenesin Synthesis

S.No Bp (°C) Density mmol 5.0064 1.13 | 2 40 Calculation for conducting the reaction: Name of chemicals M.Wt Amount Used 2-methoxy phenol 124.14 550 ML (621.5 mg) NaOH (25% Soln) | 1 mL Ethanol 46.07 Water Sodium Sulfate 142.04 (+)-3-Chloro-1,2- 110.54 500 UL (660 mg) propanediol 18 5.9706 1.32

Procedure:

            2-methoxy phenol (550 uL), NaOH (25% Soln) (1 mL) and (±)-3-Chloro-1,2-propanediol (500 uL) charge into single neck round bottomed flask with magnetic stirring bar and then placed the reaction mass flask on heating magnetic stirrer with oil bath. Heat the reaction mass up to 50°C, maintained the reaction under stirring for 1 hour at 50°C condition. Cool the reaction mixture and then extracted the product with ethyl acetate two times each 2ml. The organic layer dried with Sodium Sulfate and evaporated the ethyl acetate till dryness. The crude product recrystallized by ethanol and water system then isolate the product by filtration. The solid product dried.

Enantiomer of 3-Chloro-1,2-propanediol

HO Y HO V HOY voor de motor OH OH OH (+)-3-Chloro-1,2-propanediol (2R)-3-chloropropane-1,2-diol (2S)-3-chloropropane-1,2-diol racemic mixture

Mechanism for Guaifenesin Synthesis:

HO WO ö: Na BHO -CHz 0-CH3 TO-CH3 (+)-3-Chloro-1,2-propanediol + - Na OH SN? Guaifenesin M.Wt = 198.21 phenoxide ion 2-methoxyphenol (Guaiacol) M.Wt = 124.14 Naci

Yield:

Theoretical yield calculation

621.5 × 198.21 = 992.33 mg   so the theoretical yield is 992.33 mg

        124.14

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