Question

Preamble This experiment involves the synthesis of target molecules using Q-substitution chemistry. You are assigned two target molecules, one of which is best synthesized by an alkylation approach, while the other is best synthesized by an addition or condensation approach. You must do the following: 1. Perform a retrosynthetic analysis on the two target molecules assigned to you. In each case the organic starting material (what you have to work backwards toward) depends upon the target. For targets 1-10, the starting material is either malonic ester or acetoacetic ester and any halide. For targets 11-16, the starting material is any four carbon halide. Draw a retrosynthetic scheme; use the rightwards double arrow to show functional group transformations and disconnections. 2. Propose the forward synthesis (based upon the retrosynthetic analysis) for each molecule. Include important reagents over the reaction arrows. 3. Provide a paragraph where you explain how each of the chemical reactions required for ONE of the two syntheses will be carried out. The conditions for each step and anticipated purification procedures must be included. You will write up a short paper (no more than 400 words) including 1) the two retrosynthetic and synthetic schemes and 2) A short paragraph outlining the conditions for each step. (One short paragraph per step). The report format should be as follows: a-Substitution Synthesis (bold, centered on first line) Name (bold, centered on second line) Retro Synthetic Analysis (bold, centered on third line) Proposed Synthesis (bold, centered on the fourth line) Proposal (bold, right/left justified on the fifth line) Save as a pdf file and upload to BlackBoard Learn. Use the following formatting; font: Garamond, 12 pt margins: 1 inch (top and bottom) spacing: double The example below is for a similar exercise. Note that the aldol/Claisen target is based on five-carbon alkyl bromides rather than the 4-C starting materials that are specified in your assignment.

**(left structure)****(right structure)**

The two structures for the assignment are above and the task is:

1. Perform a retrosynthetic analysis on the two target molecules assigned to you. In each case the organic starting material (what you have to work backwards toward) depends upon the target. For the structure given above (structure on left), the starting material is either malonic ester or acetoacetic ester and any halide. For the structure given above (structure on right), the starting material is any four carbon halide. Draw a retrosynthetic scheme; use the rightwards double arrow to show functional group transformations and disconnections.

2. Propose the forward synthesis (based upon the retrosynthetic analysis) for each molecule/structure given above. Include important reagents over the reaction arrows.

3. Provide a paragraph where you explain how each of the chemical reactions required for ONE of the two syntheses will be carried out. The conditions for each step and anticipated purification procedures must be included.

**that is not the answer above! the one posted above is an EXAMPLE of what the assignment should look like! i have to use the two structures given above!**

Answer 1

Solution:

1. Retrosynthetic Analysis:

Refer the below image for the retrosynthetic analysis of compound of left structure as well as right structure.

2. Proposed forward synthesis:

Left structure: The starting materials are diethyl malonate, (bromo methyl)cyclohexane and ethyl bromide. Other reactants are NaOEt, HCl, water and NaOH.

Right structure: The starting material is isobutyl bromide. Other reagents are NaOAc, HCl, water, PCC (Pyridinium chloro chromate) and Dil. NaOH.

Refer the below image for the proposed synthesis analysis of compound of left structure as well as right structure.

3. Paragraph on the synthesis of left structure:

Step 1 - Diethyl malonate reacts with NaOEt in ethanol and forms a carbanion which further reacts with (bromo methyl)cyclohexane and forms the compound I. The compound I is extracted with ether and the inorganics are washed with enough water. The ether layer containing I is dried over anhydrous Na₂SO₄, filtered and the ether is evaporated to get the crude compound I. This compound is purified by vacuum distillation.

Step 2 - Compound I reacts with NaOEt in ethanol and forms a carbanion which further reacts with ethylbromide and forms the compound II. The compound II is extracted with ether and the inorganics are washed with enough water. The ether layer containing II is dried over anhydrous Na₂SO₄, filtered and the ether is evaporated to get the crude compound II. This compound is purified by vacuum distillation.

Step 3 - Compound II is heated with dilute HCl to effect the hydrolysis of ester as well as decarboxylation. The TM1 is extracted into the basic aqueous solution and washed with ether to remove unreacted starting materials and other neutral compounds. The aqueous layer is separated, acidified using dilute HCl, the product is extracted with ether. The ether extract is washed with water to eliminate inorganics. The ether layer containing TM1 is dried over anhydrous Na₂SO₄, filtered and the ether is evaporated to get the crude TM I.  Crude TM1 can be purified either by recrystallization or by column chromatography.

Left structure: 1. Retro synthetic Amlysis? FGI c-c I Ficoar CO2H CORR CORR le-c H 2. Proposed synthesis: ROC A (1) NADET (1) NADEE teact a coget Et Of COZEE (2) IZ OLC Coget (2) •Br 1 Hal { coat TM1 Right Stoncture - 1. Retrosynthetic Analysis C-c Fes FGT H مد و پارت ال => OH 1 FG I LB 2. Proposed synthesis: hay Hoy Low Pay & L Br NADAL Iy o I Dil NaOH, m D: H OH TM 2