4 It is a pain relieverIt is more potent than morphine
5 A. Naming Alkyl HalidesAlkyl halides are named according to the system of nomenclature devised by the International Union of Pure and Applied Chemistry (IUPAC):
6 Steps to naming alkyl halides1 Find the parent hydrocarbonInclude the double or triple bond if presentNumber the atoms in the main chainThe correct sequence is when the substituents have the lowest possible numberUse multiplicity prefixes di-, tri-, tetra-, …Put the substituents in alphabetical order (Do not consider multiplier prefixes)
7 Steps to naming alkyl halides2 If the parent chain can be properly numbered from either end by step 2, begin at the end nearer the substituent that has alphabetical precedence
11 Practice Problem: Give IUPAC names for the following alkyl halides:
12 Practice Problem: Draw structures corresponding to the Practice Problem: Draw structures corresponding to the following IUPAC names:2-Chloro-3,3-dimethylhexane3,3-Dichloro-2-methylhexane3-Bromo-3-ethylpentane1,1-Dibromo-4-isopropylcyclohexane4-sec-Butyl-2-chlorononane1,1-Dibromo-4-tert-butylcyclohexane
13 B. Structure of Alkyl Halides As you go down the periodic table,C-X bond is longerC-X bond is weaker
14 Due to DEN, C-X bond is polarized with: slight positive on carbon andslight negative on halogenThe C-X carbon atom can behave as an electrophile
15 C. Preparing Alkyl Halides Alkyl halide - is synthesized from addition of HCl, HBr, HI to alkenes to give Markovnikov productAlkyl dihalide - is synthesized from anti addition of Br2 or Cl2
16 Reaction of Alkanes with Halogens Alkane + Cl2 or Br2, heat or light, replaces C-H with C-X but gives mixtureshard to controlvia free radical mechanismIt is usually not a good idea to plan a synthesis that uses this method
17 Mechanism of the radical chlorination of methane
18 D. Radical Halogenation of Alkanes Radical halogenation of alkanes is not a good method of alkyl halide synthesis because mixtures of products usually result.
19 If there is more than one type of hydrogen in an alkane, reactions favor replacing the hydrogen at the most highly substituted carbons30% / 6 = 5%70% / 4 = 17.5%Primary H’sSecondary H’s
21 Relative ReactivityBased on quantitative analysis of reaction products, relative reactivity is estimatedOrder parallels stability of radicals
22 Increasing alkyl substitution stabilizes the transition state and radical intermediate The more stable radical forms faster
23 Reaction distinction is more selective with bromine than chlorine
24 Reaction distinction is more selective with bromine than chlorine Reaction with Br. is much less exergonicT.Sbromination resembles the alkyl radical more closely than does T.Schlorination
25 Practice Problem: Draw and name all monochloro products you Practice Problem: Draw and name all monochloro products you would expect to obtain from radical chlorination of 2-methylpentane. Which, if any, are chiral?
26 Practice Problem: Taking the relative reactivities of 1o, 2o, and 3o Practice Problem: Taking the relative reactivities of 1o, 2o, and 3o hydrogen atoms into account, what product(s) would you expect to obtain from monochlorination of 2-methylbutane? What would the approximate percentage of each product be? (Don’t forget to take into account the number of each type of hydrogen)
27 E. Allylic Bromination of Alkenes N-bromosuccinimide (NBS) selectively brominates allylic positionsIt requires light for activationIt is a source of dilute bromine atoms
28 NBS allylic bromination Br. radical abstracts an allylic hydrogenAllylic radical forms as an intermediate and reacts with Br2
29 Bromination with NBS occurs exclusively at an allylic position because: an allylic radical is more stable than a typical alkyl radical by about 40 kJ/mol
30 Stability OrderAllylic radical is more stable than tertiary alkyl radical
31 F. Stability of the Allyl Radical Allyl radical is resonance-stabilizedAllyl radical has two resonance formsAlkyl radical has only one structure
32 The greater the number of resonance forms, the greater the stability
33 Allyl radical is delocalized The unpaired electron is spread out over an extended p orbital networkThe unpaired electron is equally shared between the two terminal carbons
34 Allylic bromination of an unsymmetrical alkene often leads to a mixture of products less hindered
35 Allylic bromination can be used to convert alkenes into dienes by dehydrohalogenation with base.
36 Practice Problem: Draw three resonance forms for the Practice Problem: Draw three resonance forms for the cyclohexadienyl radical
37 Practice Problem: The major product of the reaction of Practice Problem: The major product of the reaction of methylenecyclohexane with N-bromo succinimide is 1-(bromomethyl)cyclohexene Explain.
38 Practice Problem: What products would you expect from the Practice Problem: What products would you expect from the reaction of the following alkenes with NBS? If more than one product is formed, show the structures of all.
39 G. Preparing Alkyl halides from Alcohols Alcohols react with HX to form alkyl halides, but the reaction works well for tertiary alcohols, R3COH
40 Reaction of tertiary C-OH with HX is fast and effective Add HCl or HBr gas into ether solution of tertiary alcoholPrimary and secondary alcohols react very slowly and often rearrange, so alternative methods are used
41 Preparation of Alkyl Halides from Primary and Secondary Alcohols Primary and secondary alkyl halides are normally prepared from alcohols using eitherthionyl chloride (SOCl2)SOCl2 : ROH RClphosphorus tribromide (PBr3)PBr3 : ROH RBrThese reactions use mild conditions – less acidic and less likely to cause rearrangements
43 Practice Problem: How would you prepare the following alkyl Practice Problem: How would you prepare the following alkyl halides from the corresponding alcohols?
44 H. Reaction of Organohalides: Grignard Reagents Alkyl halides react with magnesium in ether solution to form organomagnesium halides, Grignard reagents (RMgX)
45 Reaction of RX with Mg in ether or THF Product is RMgX – an organometallic compound (alkyl-metal bond)R is alkyl 1°, 2°, 3°, aryl, alkenylX = Cl, Br, I
46 The carbon-magnesium bond is polarized The carbon atom is thus both nucleophilic and basic
47 Reactions of Grignard Reagents Many useful reactionsRMgX behaves as R-R- (carbon anions) are very strong basesRMgX react with such weak acids as H2O, ROH, RCO2H and RNH2 to abstract H+RMgX + H3O+ R-H
48 Practice Problem: Just how strong a base would you expect a Practice Problem: Just how strong a base would you expect a Grignard reagent be? Look at Table 8.1, and then predict whether the following reactions will occur as written. (The pKa of NH3 is 35)CH3MgBr H-CΞC-H CH H-CΞC-MgBrCH3MgBr NH3 CH H2N-MgBr
49 Practice Problem: How might you replace a halogen substituent Practice Problem: How might you replace a halogen substituent by a deuterium atom if you wanted to prepare a deuterated compound?
50 I. Organometallic Coupling Reactions Alkyllithium (RLi) forms from RBr and Li metalRLi reacts with copper iodide to give lithium dialkylcopper (Gilman reagents)Lithium dialkylcopper reagents react with alkyl halides to give alkanes
51 Alkyllithium (RLi) forms from RBr and Li metal Alkyllithiums are both nucleophiles and bases
52 RLi reacts with copper iodide to give lithium dialkylcopper (Gilman reagents)
53 Lithium dialkylcopper reagents react with alkyl halides to give alkanes Gilman reagents undergo organometallic coupling reactionswith chlorides, bromides and iodides (but not fluorides)
54 Utility of Organometallic Coupling in Synthesis Coupling of two organometallic molecules produces larger molecules of defined structureAryl and vinyl organometallics are also effective
55 Coupling of lithium dialkylcopper molecules proceeds through trialkylcopper intermediate
56 Practice Problem: How would you carry out the following Practice Problem: How would you carry out the following transformations using an organocopper coupling reaction? More than one step is required in each case.
57 J. Oxidation and Reduction in Organic Chemistry Oxidation is a reaction that results in loss of electron density at carbon either bybond formation between carbon and a more electronegative atom (oxygen, nitrogen, or halogen)bond breaking between carbon and a less electronegative atom (usually hydrogen)Not necessarily defined as loss of electrons by an atom as in inorganic chemistryOxidation: break C-H (or C-C) and: form C-O, C-N, C-X
58 Organic Reduction is the opposite of oxidation Organic Reduction is the opposite of oxidation. It results in increase of electron density at carbon either bybond breaking between carbon and a more electronegative atom (oxygen, nitrogen, or halogen)bond formation between carbon and a less electronegative atom (usually hydrogen)Reduction: form C-H (or C-C) andbreak C-O, C-N, C-X
59 HalogenationConversion of alkyl halide to alkane