Alkynes: Structure and organic synthesis

• Alkynes


  Hydrocarbons that contain carbon-carbon triple bonds

  
• Alkynes


  • Provide an introduction to organic synthesis - the preparation of organic molecules from simpler organic molecules
  • The triple bond is known as the 'acetylenic bond'
  • Acetylene, the simplest alkyne, is produced industrially from methane and steam at high temperature

  
• Electronic structure of alkynes


  • The triple bond is shorter and stronger than single or double bonds
  • Breaking a pi bond in acetylene requires 318 kJ/mole, while in ethylene it is 268 kJ/mole
  • The close proximity of the electrons in this geometry orientation creates a molecule with less stability
  • The structure of the carbon-carbon triple bond strongly influences the chemical reactivity of alkynes and the acidity of the terminal alkynes
  • Because of its linear configuration, a ten-membered carbon ring is the smallest that can accommodate this function without excessive strain

  
• Naming of alkynes


  • Apply "yne" as a suffix indicating a triple bond
  • Numbering of chain with triple bond is set so that the smallest number possible includes the triple bond
• Compounds with multiple triple bonds

  • Diyne (two triple bonds)
  • Eneyne (one double bond and one triple bond)
  • Triyne (three triple bonds)
• Numbering of compounds with multiple double/triple bonds


  • Number from chain that ends nearest a double or triple bond
  • Double bonds are preferred if both are present in the same relative position
• Preparation of alkynes


  1. Elimination reaction of dihalides - treatment of a 1,2-dihaloalkane with KOH or NaOH produces a two-fold elimination of HX

  2. Vicinal dihalides are available from addition of bromine or chlorine to an alkene

  3. Intermediate is a vinyl halide

  
• Addition of HX and X2 to alkynes

  1. Addition reactions of alkynes are similar to those of alkenes

  2. Intermediate of alkene reacts further with excess reagent

  3. Regiospecificity according to Markovnikov

  4. Initial addition gives trans intermediate

  5. Product with excess reagent is tetrahalide

  6. Secondary vinyl carbocation form less readily than primary alkyl carbocation

  7. Primary vinyl carbocations probably do not form at all

  
• Hydration of alkynes


  1. Addition of H-OH in alkenes - Mercury (II) catalyzes Markovnikov oriented addition

  2. Hydroboration-oxidation gives the non-Markovnikov product

  3. Mercuric ion (as the sulfate) is a Lewis acid catalyst that promotes addition of water in Markovnikov orientation

  4. The immediate product is a vinylic alcohol, or enol, which spontaneously transforms to a ketone

  
• Keto-enol tautomerism


  • Keto-enol tautomerism is a chemical equilibrium between a keto form (a ketone or an aldehyde) and an enol in organic chemistry (alcohol)
  • Tautomers are isomers that differ solely in moving a hydrogen atom from one atom to another
  • The keto tautomer is often significantly more stable than the enol form
  • Enols rearrange to the isomeric ketone by the rapid transfer of proton from the hydroxyl to alkene carbon

  
• Hydration of unsymmetrical alkynes

  1. If the alkyl groups at either end of the C-C triple bond are not the same, both products can form

  2. Hydration of a terminal alkyne always gives a methyl ketone

  
• Hydroboration/oxidation of alkynes


  1. BH3 (borane) adds to alkynes to give vinylic borane

  2. Oxidation with H2O2 produces an enol; that converts to the ketone or aldehyde: anti-Markovnikov

  3. Hydroboration/oxidation converts terminal alkynes to aldehydes because the addition of water is non-Markovnikov

  
• Reduction of alkynes


  1. Addition of H2 over a metal catalyst (such as palladium on carbon, Pd/C) converts alkynes to alkanes (complete reduction)

  2. The addition of the first equivalent of H2 produces an alkene, which is more reactive than the alkyne so the alkene is not observed

  3. Addition of H2 using chemically deactivated palladium on calcium carbonate as a catalyst (the Lindlar catalyst) produces a cis alkene

  4. Alkynes are reduced to trans alkenes with sodium or lithium in liquid ammonia

  
• Alkyne acidity: formation of acetylide anions


  • Terminal alkynes are weak Bronsted acids
  • Reaction of strong anhydrous bases with terminal acetylene produces acetylide ion
  • The sp-hybridization of carbon holds negative charge relatively close to the positive nucleus, stabilizing the anion

  
• Alkylation of acetylide anions


  1. Acetylide ions can react as nucleophiles as well as bases

  2. Reaction with a primary alkyl halide produces a hydrocarbon that contains carbon from both partners providing a general route to larger alkynes

  
• Limitations of alkylation of acetylide ions

  
• Introduction to organic synthesis

  • Organic synthesis creates molecules by design
  • Synthesis can produce new molecules that are needed as drugs or materials
  • Syntheses can be designed and tested to improve the efficiency and safety of making known molecules
  • Highly advanced syntheses are used to test ideas and methods, confirm structures, and demonstrate methods
• Synthesis as a tool for learning organic chemistry

  • In order to propose a synthesis you must be familiar with reactions - what they begin with, what they lead to, how they are accomplished, and what the limitations are
  • A synthesis combines a series of proposed steps to go from a defined set of reactants to a specified product
• Strategies for synthesis


  1. Compare the target and the starting material

  2. Consider reactions that efficiently produce the outcome. Look at the product and think of what can lead to it (retro-synthetic method)

  3. Example: Prepare octane from one-pentyne - use acetylide coupling

  
• Organo Halide


  Compound that contain one or more halogen atom
• Organo halides


  • Halogen bonded to an alkynyl group (C=C-X)
  • Halogen bonded to a vinylic group (C=C-X)
  • Halogen bonded to an aromatic ring
  • Halogen bonded to an alkyl group
• Naming of Alkyl Halide


  1. Find the longest chain, and name it as the parent

  2. Number the carbons of the parent chain beginning at the end nearer the first substituent

  3. If the parent chain can be properly numbered from either end, begin at the end nearer the substituent that has alphabetical precedence
• Alkyl Halide


  Systematic name is haloalkanes, treating the halogen as a substituent on a parent alkane chain
• Structure of Alkyl Halide


  • As the halogen size increases, the length of the corresponding carbon-halogen bonds also increase
  • The C-X bond strength decrease going down the periodic table
  • The C-X bond is polar
  • The polarity results in a substantial dipole moment and implies the alkyl halide carbon atom should behave as an electrophile in polar reactions
• Preparing Alkyl Halide from Alkene


  1. Reaction of an alkane with Cl2 and Br2

  2. Radical substitution mechanism with initiation, propagation, and termination steps

  3. Alkane halogenation is a poor synthetic method as mixtures of products invariably result

  4. Tertiary radical is weaker than secondary and primary, and the more stable radical forms faster
• Alkane bromination is more selective than chlorination
• Allylic bromination


  Reaction of an alkene with N-bromosuccinimide in the presence of light to substitute hydrogen with bromine at the allylic position
• Allylic C-H bonds are weaker than any sp3 hybridized C-H bond, so allylic bromination occurs exclusively at the allylic position
• Trend in stability of C-H bonds: Vinylic < Methyl < Primary < Secondary < Tertiary < Allylic
• Stability of Allyl Radical


  • The radical carbon atom can adopt sp2 hybridization, placing the unpaired electron in a p orbital and giving a structure that is electronically symmetrical. This allows the p orbital to overlap equally well with p orbitals on neighboring carbons.
  • The allyl radical has two resonance forms, making it more stable than a typical alkyl radical
  • Delocalization of the unpaired electron over the pi orbital network has other chemical consequences, like allylic bromination often leading to a mixture of products
• Preparing Alkyl Halides from Alcohols

  1. Treat the alcohol with HCl, HBr, HI

  2. Primary and secondary alcohols are best converted using thionyl chloride (SOCl2) or phosphorus tribromide (PBr3)
• Grignard Reagents


  • Alkyl halides react with magnesium metal in ether or THF to yield alkylmagnesium halides, RMgX
  • Grignard reagents are organometallic compounds with a polarized carbon-magnesium bond, making the carbon both nucleophilic and basic
  • Grignard reagents can be reduced to hydrocarbons by protonation
• Organometallic Coupling Reactions


  • Alkyllithiums and lithium diorganocopper (Gilman) reagents undergo coupling reactions with organohalides to form new carbon-carbon bonds
  • Palladium-catalyzed reactions of organotin reagents with organohalides also form new C-C bonds
• Oxidation and Reduction


  • Oxidation results in loss of electron density by carbon, e.g. bond formation to a more electronegative atom
  • Reduction results in gain of electron density by carbon, e.g. bond formation to a less electronegative atom
  • Any reaction that converts a compound to a higher oxidation level is an oxidation, and vice versa for reductions
• The chlorination of methane to chloromethane is an oxidation reaction
• Alkanes are at the lowest oxidation level as they have the maximum C-H bonds per carbon
• Converting an alkyl chloride to an alkene via a Grignard reagent followed by protonation is a reduction reaction
• Naturally Occurring Organohalides


  • As of 1970, only about 30 naturally occurring organohalogen compounds were known
  • Now, more than 5000 naturally occurring organohalogen compounds have been found, with tens of thousands more likely to exist
  • Many naturally occurring organohalogen compounds are produced in large quantities by organisms for self-defense, as feeding deterrents, irritants, or natural pesticides