Alkyl Halides Part 1 - Organic Chemistry Lecture Notes PDF

Organic Chemistry Part 1 Year 2 - Lecture 1 1 Dr. Ahmed Abudken 1. What Is an Alkyl Halide? An organic compound containing at least one carbon-halogen bond (C-X) X (F, Cl, Br, I) replaces H Can contain many C-X bonds Properties and some uses: Fi...

Organic Chemistry Part 1 Year 2 - Lecture 1 1 Dr. Ahmed Abudken 1. What Is an Alkyl Halide? An organic compound containing at least one carbon-halogen bond (C-X) X (F, Cl, Br, I) replaces H Can contain many C-X bonds Properties and some uses: Fire-resistant solvents Refrigerants Pharmaceuticals and precursors 2  2. Structure of Alkyl Halides Alkyl halides are compounds in which one or more hydrogen atoms in an alkane have been replaced by halogen atoms (fluorine, chlorine, bromine or iodine). Because the neutral bonding pattern for halogens is one bond and three lone pairs, the carbon and halogen always share a single bond. Carbon halogen bond is polarized in nature as halogen atoms are electronegative due to carbon have a partial positive charge and halogen have a partial negative charge. 3 3. Structure of Alkyl Halides 4  4. IUPAC Name Name as haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s. Use lowest possible numbers for position. CH3 CH CH2CH3 CH2CH2Br Cl CH3(CH2)2CH(CH2)2CH3 2-chlorobutane 4-(2-bromoethyl)heptane Problem. Draw structures corresponding to these IUPAC names - 2-Chloro-3,3-dimethylhexane - 3-Bromo-3-ethylpentane - 1,1-Dibromo-4-isopropylcyclohexane 6 5. Preparing Alkyl Halides 5.1 Preparing Alkyl Halides from Alkanes Alkane + Cl2 or Br2, heat or light replaces C-H with C-X but gives mixtures – Hard to control – Via free radical mechanism It is usually not a good idea to plan a synthesis that uses this method - multiple products 7 5.1.1 Radical Chain Mechanism 8 5.1.2 Radical Halogenation: Selectivity If there is more than one type of hydrogen in an alkane, reactions favor replacing the hydrogen at the most highly substituted carbons 9 65:35 5.1.3 Relative Reactivity Based on quantitative analysis of reaction products, relative reactivity is estimated for Cl2: (5 : 3.5 : 1 for 3o : 2o : 1o) Order parallels stability of radicals Reaction distinction is more selective with bromine than chlorine (1600 : 80 : 1) for (3o : 2o : 1o) 10 Relative Reactivity 11  5.2 Preparing Alkyl Halides from Alkenes Alkyl halide can be prepared from addition of HCl, HBr, HI to alkenes to give Markovnikov product. 12 5.2.1 Preparation of Alkyl dihalide from anti addition of bromine or chlorine. Bromine and chlorine undergoes anti-addition through halonium ion intermediate to give 1,2-halogenated product. Trance additions 13 5.2.2 Allylic Bromination Another method for preparing alkyl halides from alkenes is by reaction with N- bromosuccinimide (NBS) in the presence of light to give products resulting from substitution of hydrogen by bromine at the position next to the double bond—the allylic position. Cyclohexene, for example, gives3-bromocyclohexene. NBS is just a source of dilute bromine radicals (Br▪) 14  Allylic Bromination Activation energy for radicals formation from cyclohexene Allyl radical is delocalized—radical is shared over 2 carbons More stable than typical alkyl radical by 40 kJ/mol (9 kcal/mol) Allylic radical is more stable than tertiary alkyl radical 15  Radicals Stability Order We can thus expand the stability ordering to include vinylic and allylic radicals. 16  Use of Allylic Bromination Allylic bromination 1-Octene gives a mixture of 3-bromo-1-octane and 1- bromo-2 octane. The two products Are not formed in equal amounts, However, because the intermediate allylic radical is not symmetrical and reaction at the two ends is not equally likely. Reaction At the less hindered, primery end is favored. 17  Use of Allylic Bromination Reaction of an allylic bromide with base produces a conjugated diene (by elimination), useful in synthesis of complex molecules 18 5.3 Preparing Alkyl Halides from Alcohols Reaction of tertiary alcohol with HX is fast and effective. 19  Preparing Alkyl Halides from Alcohols For example: H.W/ Give the major product for the following reaction? 20  Preparing Alkyl Halides from Alcohols Primary and secondary alcohols react very slowly, so alternative methods are used: SOCl2 (thionyl chloride) or PBr3 (phosphorus tribromide) 21 6. Reactions of Alkyl Halides Amine Ether NH2 Nitrile R N C O R R R' SN SN SN R' C C Alkyl iodide SN R SN X Alkyne I R R Alkyl halide E SN R Mg / ether Alcohol Alkene Li OH Mg R R X Li R Organomagnesium halide (Grignard reagent) Organolithium 22 6.1 Formation of Grignard Reagents Alkyl halides, RX, react with magnesium metal in ether or tetrahydrofuran (THF) solvent to yield alkylmagnesium halides, RMgX. The products, called Grignard reagents 23  Formation of Grignard Reagents Grignard reagent is formally the magnesium salt, R3C-+MgX, of a carbon acid, R3C-OH, and is thus a carbon anion, or carbanion. But because hydrocarbons are such weak acids, with pKa’s in the range 44 to 60, carbon anions are very strong bases. 24  6.2 Organometallic Coupling Reactions Alkyllithium reagents (Gilman reagents), RLi, can be prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiums are both nucleophiles and strong bases. R2CuLi, is prepared by reaction alkyllithiums with copper(I) iodide in diethyl ether as solvent. This reaction are useful because they undergo a coupling reaction with organochlorides, bromides, and iodides. One of the alkyl groups from the Gilman reagent replaces the halogen of the organohalide, forming a 25 new C-C bond and yielding a hydrocarbon product. 6.2.1 Applications in Organic Synthesis Lithium dialkylcopper reagents react with alkyl halides to give alkanes Coupling of two organometallic molecules produces larger molecules of defined structure Aryl and vinyl organometallics also effective. 26 7. Alkyl Halides React with Nucleophiles and Bases Alkyl halides are polarized at the carbon-halide bond, making the carbon electrophilic. Nucleophiles will replace the halide in C-X bonds of many alkyl halides (reaction as Lewis base). Nucleophiles that are Brønsted bases produce elimination. 27