In organic chemistry, understanding synthetic techniques is crucial for manipulating molecular structures. This overview highlights three essential rules for synthesis that serve as a foundational cheat sheet for the chapter.
The first technique is alkane halogenation. Alkanes are generally unreactive, so to introduce a functional group, halogenation is necessary. This process typically involves radical reactions, such as using bromine (Br2) in the presence of heat. Once halogenated, the alkane can undergo various reactions, including substitution (SN2), elimination, or addition. It’s important to note that addition reactions occur after elimination, as they require the presence of double bonds.
The second technique is organometal alkylation. Organometal compounds, which consist of carbon bonded to a metal, act as strong nucleophiles. A common example is sodium alkynide, where a carbon carries a negative charge. When synthesizing longer carbon chains, alkyl halides serve as electrophiles, allowing for the formation of carbon-carbon bonds through alkylation. Carbonyls can also act as electrophiles, but they are less frequently used in this context. The key takeaway is to think of organometals when adding carbon to a chain.
The third technique involves moving functionality. Often, a functional group needs to be relocated within a molecule. This is achieved through alternating elimination and addition reactions. By creating double bonds through elimination, and then adding to the desired carbon, functional groups can be effectively repositioned. The direction of these reactions can be influenced by the choice of reagents. For example, Zaitsev's rule applies when favoring more substituted eliminations, while Markovnikov's rule applies to additions towards more substituted carbons. Conversely, less substituted reactions can be achieved through Hoffman eliminations and anti-Markovnikov additions.
When considering reagents for these reactions, small strong bases favor Zaitsev eliminations, while bulky bases are used for Hoffman eliminations. For Markovnikov additions, acid-catalyzed hydration or oxymercuration can be employed, while hydroboration is used for anti-Markovnikov alcohol additions. Radical reactions with peroxides can also facilitate anti-Markovnikov halogen additions.
Ultimately, this cheat sheet serves as a guide for determining the appropriate synthetic pathway based on the starting materials and desired outcomes. By understanding these fundamental techniques, students can approach organic synthesis with a structured mindset, making the process more intuitive and less reliant on guesswork.