Cycloaddition - Lecture notes cyclo9 PDF

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Cycloaddition: The Diels-Alder Reaction and Hydrolysis of Anhydrides Introduction: The objective of this lab is to prepare 4-cyclohexene-cis-1,2-dicarboxylic anhydride from 3sulfolene and maleic anhydride through Diels-Alder reaction and hydrolyze the anhydride in water to form 4-cyclohexene-cis-1,2-dicarboxylic acid. The steps include recrystallization to purify both the products which will be characterized by meting point analysis and IR spectroscopy. Finally, the percent yield will be calculated from synthesis reactions. Cycloaddition reaction is also known as Diels-Alder reaction. In this reaction, two or more πsystems join together to form a cyclic adduct to produce two new carbon-carbon σ bonds.As shown in Figure 1, this reaction is pericyclic which means it follows one-step mechanism that involves a cyclic transition state. The reaction has two reactant that are diene and dienophile. To understand the Diels- Alder reaction, the molecular orbitals of diene and dienophile interaction in transition state need to be considered.

Figure 1 As shown in Figure 2, there is a interaction between the highest occupied molecular orbital (HOMO) of the diene and the lowest unoccupied molecular orbital (LUMO) of the dienophile. Diels-Alder reaction is stereoselective so in order to concerted reaction to occur, the dienes must be in the s-cis conformation. Due to less steric hinderence and strain, the s-trans conformation is the more stable for a conjugated diene. Dienes in s-trans conformation with heavy or bulky substituents perform Diels-Alder reaction at a slower rate because they cannot readily rotate around the single bond to adopt the s-cis conformation.The rate of the reaction can be increased by electron withdrawing substituents, such as nitriles, aldehydes, ketones, esters, and anhydrides on the dienophile. These electron withdrawing substituents are strongly electronegative groups that remove electron density from the dienophile and thus lower the energy of the dienophile (LUMO), bringing it closer in energy to the (HOMO) of the diene. On the other hand, an electron donating group such as amino and ether on the diene increases the rate of the reaction and also increases the energy of the diene (HOMO). These electron donating groups pushes the electron density towards the diene, while increasing the energy of HOMO.

Figure 2 The arrangement of the diene and dienophile in the transition state corresponds that the reaction is a syn addition. As shown in Figure 3 the groups that are cis to each other in the reactants will remain cis to each other in the product, and groups that are trans to each other in the reactants will remain trans to each other in the product. Similarly, the groups are cis to each other when they are out on the diene whereas groups that groups that have out relationship to each other on the diene will be trans to each other in the product. The product adduct formed from the cyclic diene is a bridged bicyclic. The major product of this reaction will be the electorn-withdrawing groups facing under the bridge as a endo product. But the minor product will be the exo product in which electron withdrawing groups face towards the bridge because secondary orbital interactions can’t occur in the exo transition state.

Figure 3 In this lab, a two-step synthesis will be performed using Diels-Alder reaction to form an anhydride, which will then be hydrolyzed to form dicarboxyllic acid. Carboxylic acids are not good dienophile substituents as the corresponding anhydride, and therefore it is first more attractive to join with anhydride on to the product via cycloaddition. Then, it is hydrolyze the Diels-Alder adduct versus performing a one-step Diels-Alder reaction with carboxylic acid substituents. The mechanism for the hydrolysis reaction is shown in Figure 4. Hydrolysis of the anhydride is starts by nucleophilic attack of water on the carbonyl function, and then the cleavage of a C-O bond of the anhydride occurs. As shown in Figure 5, this experiment consists of 3-Sulfolene will be used in place of 1,3-butadiene because the latter is a gas at room temperature, but 3-Sulfolene is a solid that quickly decomposes upon heating under reflux to give diene and sulfur dioxide. 3-Sulfolene is heated and then a diene will be formed which will

be added to the dienophile that is Maleic anhydride to form 4-cyclohexene-cis-1,2-dicarboxylic anhydride. 4-cyclohexene-cis-1,2-dicarboxylic anhydride will be added to water to form 4cyclohexene-cis-1,2-dicarboxylic acid.

Figure 4

Figure 5: There are two main techniques used in this lab: heating under reflux and recrystallization. These will help to synthesize and purify the Diels-Alder product. For heating under reflux, the condenser is attached to a drying tube. The drying tube consists of ascarite (sodium hydroxide on silica) to trap any evolved SO2 gas as shown in Figure 6. Recrystallization of the Diels-Alder product will be performed twice: once before hydrolysis of the anhydride and second after the hydrolysis reaction. In recrystallization, the solid is dissolved in an appropriate solvent at an elevated temperature and crystals are allowed to re-form on cooling in ice water in which the impurities remain dissolved in the solution. The recrystallization solvent must meet the following requirements: it must not react with the desired product, the desired product is easily soluble in the solvent at elevated temperatures, but only slightly soluble or insoluble at all or at room temperatures, impurities must be highly soluble at all temperatures, and the solvent must be easily removed from the crystalline product by filtration or evaporation. Vacuum filtration will be also used in order to separate solids from liquids which involve passing a liquid containing a solid material through a filter paper that is permeable by suction. Procedure: Part I: Diels Alder-Reaction and Crystallization Procedure Weighed 2.5 g of 3-Sulfolene and 1.5 g of maleic anhydride and transferred to a 50 mL of round bottom flask. Then, 1 mL of anhydrous xylenes and 1-2 boiling stones were added to the flask.

The solid allowed dissolving for a while. When it was unable to dissolve, the remaining solute was completely dissolved under heat. The apparatus for reflux was assembled in which the condenser was attached to the flask and a drying tube on the top. The joints were greased before assembly. A drying tube with ascarite (sodium hydroxide on silica) was attached to the condenser to avoid SO2 (g) from escaping. The mixture was heated under reflux until the solution for 30 minutes.

Figure 6 After the reaction mixture was cooled from the reflux, 10 ml of xylenes were added to the mixture. The reaction was stirred again to dissolve any solids formed and even heated a little to dissolved any solutes. Then, the hot solution was poured into a clean 50 ml Erlenmeyer flask. To the mixture, more than 5 ml of Petroleum ether was slowly added until it was cloudy. The solution was cooled to room temperature. The crystalline product was vacuum filtered. The final product was weighed and percent yield was calculated. The product was then characterized by melting point analysis and IR spectroscopy. Part II: Hydrolysis Reaction and Crystallization Procedure Out of the final product from the Diels-Alder reaction, 1.0 g of 4-cyclohexene-cis-1,2dicarboxylic anhydride from was measured and transferred to a 25mL of Erlenmeyer flask. Into the solute, 5 mL of distilled water was added to the flask and was heated to boil until the entire solid dissolves. The reaction mixture was cooled in an ice-water bath. The flask was scratched using a spatula to induce crystallization. The crystalline product was vacuum filtered. The product was added to minimum hot water in order to recrystallize. The solute didn’t completely dissolve in the water. The crystalline product was vacuum filtered. The final product was

weighed and percent yield was calculated. The product was then characterized by melting point analysis and IR spectroscopy. Data Acquisition/ Calculation: The percent yield will help in determining the success of this experiment. The formula for calculating the percent yield as follows, Percent Yield = [(Actual Yield) / (Theoretical Yield)] x 100 Table 1: Reaction Table Compound

Molecular Weight

Density or Molarity or Melting Point

Rxn Weight or Volume

3-Sulfolene

118.15 g/mol

n/a

2.5 g

21.16

1.00

Maleic Anhydride

98.06 g/mol

n/a

1.5 g

15.29

0.723

4-cyclohexenecis-1 2dicarboxylic anhydride (1)

152.14 g/mol

103-104 °C

1.0

-

-

4-cyclohexenecis-1 2dicarboxylic acid (2)

170.16 g/mol

168 °C

-

-

-

mmol Equivalents

Reference: http://www.chemicalbook.com Percent Yield Calculation of the Diels-Alder reaction Product: Limiting reactant is Maleic Anhydride Theoretical yield: (0.01529 mol Maleic Anhydride) (1mol 4-cyclohexene-cis-1 2-dicarboxylic anhydride/ 1 mol Maleic Anhydride) (152.14 g/mol (1)) = 2.326 g of (1) Assuming that the mols of Maleic Anhydride is equal to 4-cyclohexene-cis-1,2-dicarboxylic anhydride than all of the Maleic Anhydride must have been changed to 4-cyclohexene-cis-1,2dicarboxylic anhydride, we calculate the mass of 4-cyclohexene-cis-1,2-dicarboxylic anhydride Actual Yield: 2.05 g (1) Percent Yield: (2.05 g/ 2.326 g) 100 = 88.1 % Percent Yield Calculation of the Hydrolyzed Product:

Theoretical Yield: (1.0 g (1)) (1 mol/ 152.14 g (1)) (1 mol (2)/ 1 mol (1)) (170.16g /mol (2)) = 1.11 g (2) Actual Yield: 0.97 g Percent yield: 0.97/1.11) 100 = 87 % Melting Point The melting point was obtained to confirm the purity of the collected crystal and if the Markovnikov rule was carried out by hydration reaction. Table 2: Melting Points of Products Substance 4-cyclohexene-cis-1,2dicarboxylic anhydride 4-cyclohexene-cis-1,2dicarboxylic acid

True melting Point (°C) 103-104 °C

Experimental Melting Point (°C) 94-95 °C

168 °C

168.5-169 °C

Infrared Spectroscopy The infrared spectroscopy was performed to determine the presence of functional groups in the final products. Table 3: IR Data of 4-cyclohexene-cis-1,2-dicarboxylic anhydride (1) Frequency

Intensity

Functional Group(s)

2959.22 cm-1

Strong

Hybridized sp3 C-H bond (alkene)

1838.78cm-1

Strong

C=O stretch of an acid anhydride

1759.27 cm-1

Strong

C=O stretch of an acid anhydride

Table 4: IR Data of 4-cyclohexene-cis-1,2-dicarboxylic acid (2) Frequency

Intensity

3366.19 cm-1 Broad band 1682.36 cm-1

Strong

Functional Group(s) O-H bond stretching C=O stretch of an acid

Conclusion: The objectives of this lab were to prepare 4-cyclohexene-cis-1,2-dicarboxylic anhydride from 3sulfolene and maleic anhydride through Diels-Alder reaction and hydrolyze the anhydride to produce 4-cyclohexene-cis-1,2-dicarboxylic acid. Another goal was to purify both of the

products by recrystallization and then to characterize the products by melting point and IR spectroscopy. The last goal was to calculate the percent yield of both products. For the first part of the lab which was the Diels-Alder reaction consists of the synthesis of 4cyclohexene-cis-1,2-dicarboxylic anhydride was successful. The procedure was followed properly while the percent yield of the anhydride was 88.1% which is significantly high. This mean the procedure was done correctly and the synthesis of anhydride reaction was accurately performed. Similarly, the second part of the lab was to hydrolyze 4-cyclohexene-cis-1,2dicarboxylic anhydride to form 4-cyclohexene-cis-1,2-dicarboxylic acid which was also successfully performed. The percent yield of the hydrolyzed product was 87%. The reason why the entire formed product was not recovered could be that some of the product must have lost while performing recrystallization and vacuum filtration. The IR tests were performed to verify the presence of functional groups in the structure of the final products. The IR graph of 4-cyclohexene-cis-1,2-dicarboxylic anhydride showed three peaks: a strong sp3 hybridized C-H bond peak at 2959.22 cm-1, a strong C=O stretch of an acid anhydride at 1838.78cm-1 and1759.27 cm-1 .Two bands of carbonyl group are present because each band depicts an alteration in the ring size and conjugation in the anhydride. The IR graph of 4-cyclohexene-cis-1,2-dicarboxylic acid showed two peaks: a broad O-H band at 3366.19 cm-1 and a strong C=O stretch of an acid at 1682.36 cm-1. The frequencies of carbonyl stretches of 4cyclohexene-cis-1,2-dicarboxylic anhydride and 4-cyclohexene-cis-1,2-dicarboxylic acid were not the same because the former contains an acid anhydride group whereas the latter contains a carboxylic acid functional group in its structure. In order to determine the purity of the substance, melting points were determined of Diels-Alder and hydrolysis reaction. The melting point range of 4-cyclohexene-cis-1,2-dicarboxylic anhydride was 94–95 °C, which is significantly closer to the true melting point range (103-104 °C). This confirms that the synthesis of 4-cyclohexene-cis-1,2-dicarboxylic anhydride was successfully performed and very few impurities are present in the final product. Similarly, the melting point of 4-cyclohexene-cis-1,2-dicarboxylic acid was 159-165°C that is significantly similar to the true melting point of 4-cyclohexene-cis-1,2-dicarboxylic acid (168 °C). Overall, from the above experiments, the tests from the IR and melting point prove the purity and structure of both final products. Overall experiment was successful because the data for the IR, melting point and percent yield had been carefully calculated to determine the accuracy of the procedure, purity and structure of the products. In conclusion, this experiment had few errors and the experiment was done accurately aiming the objectives. Reference Gilbert, John C., and Stephen F. Martin. Experimental Organic Chemistry. Cengage Learning, Massachusetts, 2011, 5th Ed, pp. 421-425, 93-100....