single bond

Biological Chemistry 1A: Singly Bonded Functional Groups

Overview

This series of lectures, conducted by Dr. Joshua Levinsky, covers the chemistry of singly bonded functional groups (FGs). This discussion will focus on their formation, interconversion, and relevant biological significance. The four main functional groups highlighted are:

  • Alkyl Halides

  • Alcohols

  • Ethers

  • Amines
    All of these functional groups are characterized by polarity, which plays a significant role in their chemical behavior.

Lecture Content

Lecture 1: Introduction to Singly Bonded Functional Groups

  • Key Functional Groups:

    • Alkyl Halides: Noted as the most significant of the single bonded functional groups.

    • Alcohols: Compounds containing hydroxyl (-OH) groups.

    • Ethers: Compounds with an R-O-R configuration.

    • Amines: Organic compounds derived from ammonia by replacement of one or more hydrogen atoms with alkyl or aryl groups.

Alkyl Halides Classification

  • Alkyl halides can be classified based on substitution:

    • Primary (1ry, 1o)

    • Secondary (2ry, 2o)

    • Tertiary (3ry, 3o)

  • They can be generally represented as:
    R−XR - X where R is alkyl and X is the halogen (F, Cl, Br, I).

  • Importance: Alkyl halides serve as versatile building blocks in organic synthesis due to their reactivity in various reactions.

Synthesis of Alkyl Halides

Alkyl halides can be synthesized via several methods:

  • From alkenes

  • From alcohols using thionyl chloride (SOCl₂)

  • From alcohols using phosphorus tribromide (PBr₃), driven by the strong affinity of phosphorus for oxygen.

Reactivity of Alkyl Halides

  • Alkyl halides exhibit polarization due to the difference in electronegativity between carbon and halogen (d+ and d-), making the carbon atom susceptible to attack by nucleophiles.

  • The effectiveness of leaving groups follows the order: F < Cl < Br < I (increasing atomic size).

Nucleophilic Substitution Mechanism

Nucleophilic substitution reactions involve the following:

  • Reaction proceeds at the carbon atom (d+).

  • Due to tetravalency of carbon, when a nucleophile attacks, a bond must break simultaneously (this is usually an equilibrium situation).

  • Curly arrows represent the electron pair movement, indicating where the electrons originate and their new destination.

  • The nucleophile, typically electron-rich, donates a pair of electrons to form a bond with an electrophile.

Nucleophiles and Electrophiles

  • Nucleophiles: Negatively charged or neutral species with a pair of electrons in a high energy filled orbital (e.g., ammonia, dimethylsulfide).

  • Electrophiles: Neutral or positively charged species with an empty atomic orbital (e.g., carbonyls, aluminum trichloride).

Retrosynthetic Analysis

  • This is a method used to plan a synthesis in reverse, visualizing the desired product and working backwards to identify starting materials.

Synthesis of C-C Bonds

  • Generating a new C-C bond can be done from alkyl halides using carbon-based nucleophiles, which involves deprotonating a suitable source (like an alkyne) and using sodium amide as a strong base.

  • Subsequent reactions can generate further alkynes and facilitate additional organic transformations.

Reaction with Nitrogen-Based Nucleophiles

  • A primary amine can be synthesized using an azide through sequential steps involving the reduction of the alkyl azide.

Reactions with Oxygen-Based Nucleophiles

In reaction scenarios with nucleophiles such as hydroxide (OH-):

  • Alkyl halides can be converted into alcohols, although processed rarely due to the availability of alcohols.

Williamson Ether Synthesis

  • A strategic synthesis involves forming a nucleophile (typically an alkoxide) that reacts with an alkyl halide, yielding ethers or thioethers.

Elimination Reactions

  • Elimination reactions occur alongside substitution reactions and typically form alkenes, especially in cases involving strong bases.

  • Favorability for E1 versus E2 depends on the substrate and reaction conditions, relating to the producing structure's stability (Zaitsev’s rule).

  • Elimination processes often lead to the formation of a conjugated double bond, usually more substituted and stable than para-substituted alkenes due to sterics and molecular stability.

Alkyl Halides Reactivity Summary

  • Two key mechanisms are:

    • SN1 (unimolecular nucleophilic substitution)

    • Involves two steps; requires a stable carbocation formation.

    • SN2 (bimolecular nucleophilic substitution)

    • Involves direct attack, featuring inversion of configuration around the carbon center.

Solvent Effects on Nucleophilic Substitution

  • Polar solvents favor SN1 by stabilizing reaction intermediates. Transition rates differ significantly between solvent types (e.g., protic vs. aprotic).

Conclusion

  • Understanding the chemistry of singly bonded functional groups is essential for a strong foundation in biological chemistry.

  • The lecture series concludes with important takeaways about synthetic pathways and functionalization of biomolecules, emphasizing their practical implications in pharmacology and organic synthesis.

Final Notes

  • Reach out to Dr. Joshua Levinsky for any questions regarding these lectures at j.levinsky@ed.ac.uk.