Haloalkanes

• Haloalkanes are also known as organohalides or alkyl halides are organic compounds with one or more halogen present
• Halogen is always considered as a substituent to a parent organic molecule, therefore the -X is always named as prefix
• Haloalkanes undergoes reaction via two mechanisms: Nucleophilic substitutions and Elimination Reactions
• RX has higher boiling points compared to their corresponding alkanes
• Increase in boiling and melting points is proportional to the size of the alkyl group
• Increase in boiling and melting points is proportional to the size of the halogen atom, from F (smallest) to I (largest)
• Haloalkanes do not exhibit H-bonding, therefore water solubility is limited regardless of the size of the molecule
• Haloalkanes are not miscible with water
• Synthesis of Haloalkanes

  • Radical Substitution
  • Electrophilic Addition
  • Bromination of Allylic Carbon
  • Alcohol Nucleophilic Substitution
• Reactions of Haloalkanes

  • Synthesis of Grignard Reagent
  • SN1
  • SN2
  • E1
  • E2
  • E1cb
• Radical Substitution of alkanes

  • Bromination = Br2/hv
  • Chlorination = Cl2/hv
• Electrophilic Addition of alkenes

  • Hydrohalogenation = HX/ether (M) or peroxide (NM)
  • Halogenation = X2/DCM or CCl4
• Bromination of allylic carbon

  • Alkene = Br2, NBS/hv, CCl4
  • Benzene = Br2, NBS/Ph(CO2)2, CCl4
• Different types of alcohol can be used to synthesize haloalkanes
• Tertiary Alcohol is the most reactive (via Sn1), Secondary and Primary (via Sn2) are less reactive and requires higher temperature
• RX is synthesize via the reaction of Tertiary Alcohol with HX (X= Cl or Br) in ether
• RX is synthesize from Primary and Secondary Alcohol via the reaction between RX and SOCl2 in pyridine or PBr2 in ether.
• Alcohol Nucleophilic Substitution

  • Tertiary Alcohol = HX/ether
  • Primary and Secondary Alcohol = SOCl2/pyridine or PBr2/ether
• Grignard reagents are example of organometallic compounds
• RMgX is synthesize through a heated addition of RX to Mg metal in ether or Tetrahydrofuran (THF) solvent
• RMgX is used to synthesize ROH from carbonyl compounds
• Synthesis of Grignard Reagent

  RMgX = RX + Mg/ether or THF
• Nucleophilic substitutions reaction takes place when a nucleophile reacts with a substrate (RX) and substitutes for a leaving group (-X)
• The general reaction produces a neutral product or a positively charged product
• Bimolecular nucleophilic substitution (SN2) reaction is a 1-step reactionwithout a carbocation intermediate
• It is referred as bimolecular because the rate of reaction is dependenton the concentration of two substances: RX (substrate) and Nü.
• The electron pair from the Nü forces out the leaving group (-X) at exactly 180° angle.
• Stereochemistry is inverted after the new Nü approaches the carbonatom. The reaction takes places opposite the position of the leavinggroup.
• Steric effect affects how the Nü attaches to the halide-bearing carbon.
• Reactivity: 3° Carbon < 2° Carbon < 1° Carbon < Methyl Carbon
• SN2 commonly happens for methyl and 1° carbons.
• Reactivity of leaving group also affects SN2 reactions.• Reactivity: OH, NH2, OR < F < Cl < Br < I
• Most common leaving group are those that give anions of strong acids(ex. HX). Cl, Br, and I are the most commonly used leaving groups.
• Unimolecular nucleophilic substitution (S N 1) reaction is a 2-stepreaction with a carbocation intermediate.
• It is referred as unimolecular because the rate of reaction is dependenton the concentration of one substance: RX (substrate).
• SN1 reactions occur only to 3° carbon substrates because they form themost stable carbocation intermediates.
• Stereochemistry with SN1 reactions has a 50:50 chance to form racemicmixture (S and R).
• SN1 reactions take place only under neutral or acidic conditions using ahydroxyl solvent (e.g. ROH) or water.• Reactivity of leaving group is similar to SN2 reactions• Reactivity: OH < Cl < Br < I ≈ H2O
• If done in acidic condition, -OH becomes a better leaving group in theform of its conjugate acid, water (H2O).
• Elimination reactions can undergo either as a unimolecular (E1 / E1cB) orbimolecular (E2) mechanisms to produce an alkene product.