Select All Products Obtained When 3 3 6 Trimethylcyclohexene

Unveiling the Products of 3,3,6-Trimethylcyclohexene Reactions: A Comprehensive Guide

3,3,6-Trimethylcyclohexene, a cyclic alkene with three methyl substituents, serves as a fascinating building block in organic synthesis. Its reactivity stems primarily from the presence of the double bond within the ring, which undergoes a variety of addition, oxidation, and rearrangement reactions. Understanding the products formed when this molecule undergoes chemical transformations requires a deep dive into reaction mechanisms and stereochemical considerations. This article will explore the major reaction pathways of 3,3,6-trimethylcyclohexene and detail the resulting products.

Understanding the Reactivity of 3,3,6-Trimethylcyclohexene

Before delving into specific reactions, it's crucial to understand the factors influencing 3,3,6-trimethylcyclohexene's reactivity. The alkene moiety is the site of most reactions, but the methyl groups also play a significant role due to steric and electronic effects.

• Steric Hindrance: The bulky methyl groups at positions 3 and 6 hinder the approach of reagents to the double bond, affecting both the rate and stereochemistry of reactions. This steric crowding can favor certain products over others.

• Electronic Effects: Methyl groups are electron-donating due to the inductive effect. This increases the electron density of the double bond, making it more reactive towards electrophilic reagents.

• Ring Strain: While cyclohexene itself exhibits relatively low ring strain, the presence of substituents can introduce subtle changes in the ring conformation and stability, thereby affecting reaction pathways.

Reaction Pathways and Products

Here we explore several key reactions of 3,3,6-trimethylcyclohexene and the products they yield.

1. Hydrogenation

Hydrogenation involves the addition of hydrogen (H₂) across the double bond in the presence of a metal catalyst (e.g., Pt, Pd, Ni). This reaction reduces the alkene to an alkane.

• Reactants: 3,3,6-Trimethylcyclohexene, H₂, Catalyst (e.g., Pd/C)
• Product: 3,3,6-Trimethylcyclohexane
• Mechanism: The reaction proceeds via syn-addition on the catalyst surface. Both hydrogen atoms are added to the same face of the double bond.
• Stereochemistry: In this case, since the product is achiral, stereochemistry is not a major concern.

2. Halogenation (Addition of Halogens)

The addition of halogens (Cl₂, Br₂) across the double bond is a classic electrophilic addition reaction.

• Reactants: 3,3,6-Trimethylcyclohexene, X₂ (X = Cl, Br)
• Product: trans-1,2-Dihalo-3,3,6-trimethylcyclohexane (racemic mixture)
• Mechanism:
  1. Electrophilic Attack: The halogen molecule (e.g., Br₂) approaches the double bond, and electron density from the π bond attacks one of the bromine atoms. This forms a cyclic halonium ion intermediate (bromonium ion in the case of Br₂).
  2. Halide Attack: The halide ion (e.g., Br⁻) attacks the halonium ion from the opposite side of the ring, leading to anti-addition. This anti-addition is driven by steric hindrance and the need to relieve ring strain in the intermediate.
• Stereochemistry: The anti-addition results in the formation of a trans dihalide. Because the halonium ion can form on either face of the ring, a racemic mixture of enantiomers is obtained.

3. Hydrohalogenation (Addition of Hydrogen Halides)

Hydrohalogenation involves the addition of a hydrogen halide (HX, where X = Cl, Br, I) to the double bond. This reaction follows Markovnikov's rule.

• Reactants: 3,3,6-Trimethylcyclohexene, HX (X = Cl, Br, I)
• Product: 1-Halo-3,3,6-trimethylcyclohexane (with Markovnikov regioselectivity)
• Mechanism:
  1. Protonation: The alkene is protonated by the hydrogen halide, forming a carbocation intermediate. According to Markovnikov's rule, the proton adds to the carbon with more hydrogen atoms already attached (in this case, the carbon at position 2 relative to the methyl group at position 6), resulting in the more stable carbocation. The stability of the carbocation is increased by the electron-donating effect of the adjacent methyl groups.
  2. Halide Attack: The halide ion attacks the carbocation, forming the haloalkane product.
• Regiochemistry: Markovnikov's rule dictates that the halide adds to the more substituted carbon. In 3,3,6-trimethylcyclohexene, this means the halide will primarily add to the carbon at position 1 relative to the methyl group at position 6.
• Stereochemistry: The reaction can proceed with either syn or anti addition, leading to a mixture of stereoisomers. The steric hindrance of the methyl groups will influence the ratio of these isomers.

4. Hydration (Addition of Water)

Hydration involves the addition of water (H₂O) to the double bond, typically catalyzed by a strong acid.

• Reactants: 3,3,6-Trimethylcyclohexene, H₂O, Acid Catalyst (e.g., H₂SO₄)
• Product: 1-Hydroxy-3,3,6-trimethylcyclohexane (with Markovnikov regioselectivity)
• Mechanism:
  1. Protonation: The alkene is protonated by the acid catalyst, forming a carbocation intermediate (similar to hydrohalogenation). Again, Markovnikov's rule applies.
  2. Water Attack: Water acts as a nucleophile and attacks the carbocation.
  3. Deprotonation: A proton is removed from the protonated alcohol, yielding the alcohol product.
• Regiochemistry: The hydroxyl group (-OH) adds to the more substituted carbon, following Markovnikov's rule.
• Stereochemistry: Similar to hydrohalogenation, both syn and anti addition are possible, leading to a mixture of stereoisomers.

5. Oxymercuration-Demercuration

Oxymercuration-demercuration is a two-step process used to hydrate alkenes with Markovnikov regioselectivity without carbocation rearrangements.

• Reactants:
  • Step 1 (Oxymercuration): 3,3,6-Trimethylcyclohexene, Hg(OAc)₂ (mercuric acetate), H₂O
  • Step 2 (Demercuration): NaBH₄ (sodium borohydride)
• Product: 1-Hydroxy-3,3,6-trimethylcyclohexane (with Markovnikov regioselectivity)
• Mechanism:
  1. Oxymercuration: Mercuric acetate reacts with the alkene to form a cyclic mercurinium ion intermediate. Water attacks the more substituted carbon of the mercurinium ion (Markovnikov addition).
  2. Demercuration: Sodium borohydride replaces the mercury atom with a hydrogen atom.
• Regiochemistry: Markovnikov addition is observed, with the hydroxyl group adding to the more substituted carbon.
• Stereochemistry: Oxymercuration-demercuration generally proceeds with anti-addition, but due to the subsequent reduction with NaBH₄, the stereochemistry at the carbon bearing the -OH group is often lost or randomized.

6. Hydroboration-Oxidation

Hydroboration-oxidation is a two-step process that results in the anti-Markovnikov hydration of alkenes.

• Reactants:
  • Step 1 (Hydroboration): 3,3,6-Trimethylcyclohexene, BH₃ (borane) or a borane equivalent (e.g., BH₃•THF, borane-tetrahydrofuran complex)
  • Step 2 (Oxidation): H₂O₂, NaOH (hydrogen peroxide, sodium hydroxide)
• Product: 2-Hydroxy-3,3,6-trimethylcyclohexane (anti-Markovnikov addition)
• Mechanism:
  1. Hydroboration: Borane adds to the alkene in a syn fashion. The boron atom adds to the less substituted carbon of the double bond (steric considerations favor this). The boron and hydrogen add to the same face of the double bond.
  2. Oxidation: Hydrogen peroxide and sodium hydroxide oxidize the carbon-boron bond, replacing the boron with a hydroxyl group (-OH). The stereochemistry is retained during this step.
• Regiochemistry: Anti-Markovnikov addition is observed, with the hydroxyl group adding to the less substituted carbon.
• Stereochemistry: The reaction proceeds with syn-addition of boron and hydrogen in the first step. The overall stereochemistry is syn-addition of H and OH (after oxidation), and the hydroxyl group ends up on the less substituted carbon. The bulky methyl groups at positions 3 and 6 influence the stereochemical outcome, favoring addition from the less hindered side.

7. Epoxidation

Epoxidation involves the addition of an oxygen atom to the double bond, forming an epoxide (oxirane) ring.

• Reactants: 3,3,6-Trimethylcyclohexene, Peroxyacid (e.g., m-CPBA, meta-chloroperoxybenzoic acid)
• Product: 7-Oxa-3,3,6-trimethylbicyclo[4.1.0]heptane (Epoxide)
• Mechanism: The peroxyacid transfers an oxygen atom to the double bond in a concerted, syn-addition manner.
• Stereochemistry: The reaction proceeds with syn-addition. However, because of the steric hindrance of the methyl groups at positions 3 and 6, the oxygen atom will preferably add from the less hindered face of the ring. This leads to a major product with the epoxide ring on the opposite face of the methyl groups.

8. Ozonolysis

Ozonolysis involves the cleavage of the double bond with ozone (O₃), followed by a reductive workup.

• Reactants: 3,3,6-Trimethylcyclohexene, O₃, Reductive Workup (e.g., DMS, dimethyl sulfide; or Zn, H₂O)
• Product: 3,3-Dimethylhexanedial
• Mechanism:
  1. Ozone Addition: Ozone adds to the double bond to form a primary ozonide (molozonide).
  2. Ozonide Formation: The molozonide rearranges to form a more stable ozonide.
  3. Reductive Workup: The ozonide is cleaved by a reducing agent (e.g., dimethyl sulfide or zinc and water) to yield carbonyl compounds. A reductive workup is used to prevent further oxidation to carboxylic acids.
• Regiochemistry: The double bond is cleaved, resulting in two carbonyl groups at the carbons that were originally part of the double bond.
• Stereochemistry: Ozonolysis destroys the stereocenter at position 6.

9. Oxidation with KMnO₄

Potassium permanganate (KMnO₄) can oxidize alkenes, and the outcome depends on the reaction conditions.

• Cold, dilute KMnO₄: Under cold, dilute conditions, syn-dihydroxylation occurs.

  • Reactants: 3,3,6-Trimethylcyclohexene, Cold, dilute KMnO₄, NaOH
  • Product: cis-1,2-Dihydroxy-3,3,6-trimethylcyclohexane
  • Mechanism: Permanganate adds to the double bond in a syn fashion, resulting in the cis-diol.
  • Stereochemistry: Syn-addition of the two hydroxyl groups occurs.

• Hot, concentrated KMnO₄: Under hot, concentrated conditions, oxidative cleavage of the double bond occurs.

  • Reactants: 3,3,6-Trimethylcyclohexene, Hot, concentrated KMnO₄, H⁺
  • Product: 3,3-Dimethylhexanedioic acid and Acetic acid. The initial product is likely 3,3-Dimethyl-6-oxohexanoic acid, which can be further oxidized to 3,3-Dimethylhexanedioic acid. The methyl group at the 6 position can be cleaved to form acetic acid under vigorous oxidizing conditions.
  • Mechanism: The strong oxidizing conditions cleave the double bond and oxidize the resulting fragments to carboxylic acids.

10. Diels-Alder Reaction

The Diels-Alder reaction is a cycloaddition reaction between a conjugated diene and a dienophile to form a substituted cyclohexene. 3,3,6-Trimethylcyclohexene cannot act as a diene because it is not conjugated. It can act as a dienophile, but its reactivity will be affected by the steric hindrance of the methyl groups.

• Reactants: Dienophile: 3,3,6-Trimethylcyclohexene, Diene: (e.g., butadiene)
• Product: Adduct Cyclohexene Derivative
• Mechanism: The reaction involves a concerted [4+2] cycloaddition. The pi electrons of the diene and dienophile rearrange to form a six-membered ring.
• Stereochemistry: The reaction is stereospecific; cis substituents on the dienophile remain cis in the product (syn-addition). The endo rule often dictates the preferred stereochemistry, favoring the approach of the diene such that it maximizes overlap with the pi system of the dienophile. However, the bulky methyl groups in 3,3,6-Trimethylcyclohexene might hinder the endo approach, leading to a preference for the exo product.

Factors Affecting Product Distribution

Several factors influence the distribution of products in these reactions:

• Steric Hindrance: The bulky methyl groups at positions 3 and 6 can significantly affect the stereochemistry and regiochemistry of addition reactions. They can block the approach of reagents from one face of the molecule, favoring addition from the less hindered side.
• Electronic Effects: The electron-donating nature of the methyl groups stabilizes carbocations, influencing the regioselectivity of reactions like hydrohalogenation and hydration (Markovnikov's rule).
• Reaction Conditions: Temperature, solvent, and the presence of catalysts can all influence the reaction pathway and the resulting product distribution. For example, the oxidation of 3,3,6-trimethylcyclohexene with KMnO₄ can yield different products depending on whether the reaction is performed under cold, dilute conditions or hot, concentrated conditions.
• Carbocation Rearrangements: In reactions involving carbocation intermediates, rearrangements (e.g., methyl shifts or hydride shifts) can occur, leading to unexpected products. However, the presence of the methyl groups at the 3 position limits the likelihood of these rearrangements because they will lead to a less stable carbocation.

Conclusion

3,3,6-Trimethylcyclohexene is a versatile molecule that undergoes a wide range of reactions, yielding a variety of products. The steric and electronic effects of the methyl substituents play a critical role in determining the regiochemistry, stereochemistry, and overall product distribution. Understanding the mechanisms of these reactions and the factors that influence them is essential for predicting and controlling the outcome of chemical transformations involving this important building block in organic synthesis. Careful consideration of reaction conditions and the potential for side reactions is also crucial for achieving desired synthetic outcomes.