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CH221 CLASS 18 CHAPTER 10: ALKYL HALIDES Synopsis. This is an introductory class dealing with nomenclature, structure, radical halogenation, allyl and benzyl radicals, formation and uses of some organometallic compounds and oxidation/reduction. Introduction Halogenated organic compounds are widespread throughout nature and are very important in industry and in the laboratory as synthetic intermediates. Some examples of natural and commercially important organohalogen compounds are given below, but see also p. 335 in the textbook for other examples from nature. CH3Cl Chloromethane (methyl chloride) - secreted by various organisms from certain species of worms (acorn worm of Okinawa) to kelp, a variety of seaweed Cl Epibatidine, from the South American frog, Epipedobates tricolor. This compound is a powerful pain killer N NH H CH2Cl2 dichloromethane (methylene chloride) ClCH=CCl2 Trichloroethylene CH3-CCl3 1,1,1-Trichloroethane CH2=CHCl vinyl chloride, an important monomer all useful solvents E.tricolor The major types of organohalogen compounds are illustrated below, where it can be seen that the classification depends on the type of carbon atom to which the halogen is attached. Furthermore, it will be shown that the group alkyl halides, which are especially emphasized in this course, can be subdivided into primary, secondary and tertiary halides. CH3 CH3CH2Br an alkyl halide Br CH2=CHCl a vinyl halide an aryl halide CH2Br CH2=CHCH2Br an allyl halide special kinds of alkyl halides a benzyl halide Naming Alkyl Halides To name alkyl halides, carry out the following steps. 1. Find the longest chain and name it as the parent (if a double or triple bond is present, it must be included in this chain). 2. Number the carbon atoms of the parent chain beginning at the end nearer the first substituent, irrespective of whether it is alkyl or halogen. E.g. CH3 CH3 CH3CHCH2CHCHCH2CH3 The longest carbon chain has 7 carbons = heptane Br CH3 Number from the left (first substituent at 2) gives 5-bromo-2,4-dimethylheptane CH3 5 6 7 CH3CHCH2CHCHCH2CH3 1 2 3 4 Br Note the following special situations. (a) If more than one of the same halogen is present, name as follows. Cl Cl 4 5 6 CH3CHCHCHCH2CH3 1 2 3 2,3-dichloro-4-methylhexane CH3 (b) If different halogens are present, list them in alphabetical order: Br 4 5 ClCH2CH2CHCHCH3 1 2 3 3-bromo-1-chloro-4-methylpentane CH3 (c) If the parent can be properly numbered from either end, begin at the end nearer the substutuent that has alphabetical precedence. CH3 Br CH3CHCH2CH2CHCH3 6 5 4 3 2 1 2-bromo-5-methylhexane (NOT 5-bromo-2-methylhexane) (d) For simple (linear) unsaturated halogen compounds, the halogen-containing carbon atom is given the lower number. E.g. CH2 CHCH2Br 1-bromo-2-propene Otherwise the numbering is devised to give the lowest total. E.g. Br CH2 Cl 2-bromo-1-propene CH3 CHCH3 1-methyl-2-chloro-4-bromocyclohexane Br Note that many halogen compounds are better known by their trivial names, including methyl bromide (bromomethane), methylene chloride (dichloromethane), allyl chloride (1-chloro-2-propene) and benzyl bromide (bromophenylmethane). Structure of Alkyl Halides: Polarity and Strength of the C-Hal (C-X) Bond From Table 10.1 on p. 319 of the textbook, it is possible to make the following generalizations for the halomethanes, CH3-X. CH3F CH3Cl CH3Br CH3I C-X bond strength increases C-X bond length increases C-X bond polarity increases Polarizability of X increases The same generalizations are true for all alkyl halides. These factors make the halogen-containing carbon atom electrophilic in nature, which in turn is responsible for much of the important chemistry of alkyl halides (SN and E reactions – Chapter 11, see class 19). Preparation of Alkyl Halides We have seen already that alkyl halides can be prepared by the halogenation or hydrohalogenation of alkynes and alkenes (see classes 12, 13 and 15). We have also seen that light-initiated radical halogenation of alkanes and cycloalkanes yields alkyl halides (class 9). It is now time to time to consider the last method in a bit more detail, noting particularly the range of reactivities and the synthetic limitations of the method. Radical Halogenation of Alkanes using Elemental Halogens: Chlorination The one big limitation of this method (especially chlorination) is that it almost inevitably leads to a (often complex) mixture of products. Even chlorination of methane gives a mixture: light CH4 + Cl2 CH3Cl, CH2Cl2, CHCl3 and CCl4 The situation is even worse for the chlorination of alkanes that have more than one kinds of hydrogen: light (h) CH3CH2CH2CH3 + Cl2 CH3CH2CH2CH2Cl 30% CH3CH2CHCH3 Butane 1-chlorobutane 2-chlorobutane 70% + other (polychlorinated) products CH3 CH3CCH3 35% CH3 light (h) + CH3CHCH3 Cl2 2-chloro-2-methylpropane Cl CH3 Methylpropane CH3CHCH2 Cl 65% 1-chloro-2-methylpropane + other (polychlorinated) products In the first example, 30% of primary halide means that each one of the six primary hydrogens (CH3) is responsible for 30%/6 = 5% of product, whereas 70% of secondary alkyl halide means that each one of the four secondary hydrogens (CH2) is responsible for 70%/4 = 17.5% of the product. Hence, chlorination at secondary carbon occurs about 3.5 times the rate of chlorination at primary carbon. Similarly, in the second example, chlorination occurs at the single tertiary carbon (CH) at about 5 times the rate of chlorination at the primary carbons. The order of reactivity toward radical chlorination is rel. rate R-CH3 1o 1 < R2CH2 < 2o 3.5 R3CH 3o 5 This order reflects the relative order of the C-H bond strengths: 3o < 2o < 1o. Since less energy is needed to break a tertiary C-H bond than either a 2o or a 1o C-H bond, the resulting tertiary radical is more stable than either a secondary or primary radical, as we have already noted (see class 10). However, although the rates of chlorination at different carbon atoms are different, the difference is not great, so that in practice, some chlorination occurs at all sites. Radical chlorination has poor selectivity Bromination, on the other hand, is much more selective, mainly because of the lesser reactivity of the halogen species (in particular Br.): CH3 Br2 CH3CHCH3 CH3 CH3 CH3CCH3 h and CH3CHCH2Br Br >99% <1% Bromination at Allylic and Benzylic Carbon Atoms Compounds with allylic and benzylic hydrogen atoms can be brominated readily using the mild brominating agent N-bromosuccinimide (NBS): O Br NBr (NBS) O allylic initiator O + O benzylic CH3 NBr CH2Br O initiator The reaction is thought to proceed via the following type of radical chain mechanism: NH O O O initiator N Br N . + Br . e.g. light O O H H . H + Br . + HBr an allyl radical O N O Br + N HBr O H + Br2 O H . H + Br Br2 + . Br etc Bromination occurs preferentially at the allylic carbon because the allyl radical is more stable than any other possibility (vinylic and alkyl), a fact that is reflected by the relative bond energies: allylic 360 kJ/mol alkyl 400 kJ/mol H H H vinylic 445 kJ/mol Thus, it is possible to extend the previous radical stability sequence: Vinyl < 1o alkyl (CH3) < 2o alkyl (CH2) < 3o alkyl (CH) < allyl (benzyl) Resonance Stabilization of Allyl and Benzyl Radicals The enhanced stability of allyl and benzyl radicals is best explained by the influence of resonance or delocalization. One important synthetic consequence of the delocalized allyl radical is that more than one bromination product is often obtained: NBS initiator C5H11CH2CH CH2 . C5H11CH CH CH2 1-octene C5H11CH . CH CH2 Br2 thermodynamic control Br C5H11CH CH 17% CH2 3-bromo-1-octene C5H11CH CH CH2 83% 1-bromo-2-octene Preparing Alkyl Halides from Alcohols Just as alkyl halides are often key synthetic intermediates, so are alcohols and carbonyl compounds and hence a useful sequence is >C=O reduction >CHOH oxidation >CHX Br Alkyl halides can be formed from alcohols by three basic methods, as summarized below. C PBr3 Br best for 3o alcohols HX C OH C diethyl ether X X = I, Br, Cl diethyl ether SOCl2, pyridine good for 1o and 2o alcohols C Cl E.g. Cl OH SOCl2 CH3CH2CHCH3 CH3CH2CHCH3 pyridine 2-chlorobutane Br 1/3 PBr 3 2-butanol ether 35oC CH3CH2CHCH3 2-bromobutane Reactions of Alkyl Halides: Formation of Grignard Reagents and Other Organometallic Compounds Victor Grignard discovered that a dry alkyl halide will react with dry magnesium metal in a dry ether solvent to produce an organometallic compound with that behaves as if it has the structure R-Mg-X It is now called an alkylmagnesium halide or Grignard reagent: ether R X + Mg R Mg X dry R = alkyl (all types) or vinyl or alkynyl or aryl X = I, Br, Cl In common with other organometallic compounds the metal-bound carbon atom is highly nucleophilic, CH3 Mg I methylmagnesium iodide This carbon atom is also highly basic and hence Grignard reagents must be prepared in the absence of both water and acidic groups such as –COOH, -OH or –NH2 in the molecule. Organometallic Coupling Reactions Other organometallic compounds, like alkyllithiums, can be made in a similar manner to Grignard reagents, although many of these are even more sensitive to the presence of water. 2Li nC4H9BLi + LiBr nC4H9Br pentane n-butyllithium dry! These organolithium compounds can be used to make lithium diorganocopper compound (LiR2Cu), known as Gilman reagents, 2 CH3Li + methyllithium CuI ether - + (CH3)2Cu Li + LiI dry! lithium dimethylcopper Gilman reagents are useful coupling agents – they undergo alkylation reactions with alkyl halides: dry ether + nC9H19CH2I nC9H19CH2CH3 + LiI + CH3Cu (CH3)2Cu Li iododecane 0oC undecane These are versatile reactions, occurring at vinyl and aryl carbon atoms, as well as alkyl carbons, nC7H15 H nC7H15 H + (n-C H ) Cu Li C C C C 4 92 C4H9-n H I H + n-C4H9Cu + LiI A Note on Oxidation and Reduction in Organic Chemistry Oxidations and reductions (redox reactions) have been met already at several points on this course (e.g. the perhydroxylation and hydrogenation of alkenes in class 14 and the hydrogenation of alkynes in class 15). At this point, it is worth noting qualitative ways (i.e. those that don’t involve the determination of oxidation numbers) of describing organic oxidation/reduction reactions. OXIDATION – a reaction that results in loss of electron density at carbon, by either C-O, C-N or C-X (X = halogen) bond formation or by C-H bond breaking REDUCTION – a reaction that results in gain of electron density at carbon, by either C-H bond formation or by C-O, C-N or C-X bond breaking Examples A list of common compounds (and corresponding functional groups) is given below, with alkanes being the most reduced and CO2, CCl4 being the most oxidized. Any conversion left right is an oxidation, whereas any conversion right left is a reduction. CH3CH3 alkanes CH2=CH2 alkenes CH3OH alcohols CH3Cl Alkyl halides CH3NH2 amines LOWEST OXIDATION LEVEL CHCH alkynes CH2=O aldehydes and ketones CH2Cl2 dihalogen compounds CH2=NH imines HCOOH carboxylic acids CHCl3 trihalogen compounds HCN nitriles CO2 CCl4 HIGHEST OXIDATION LEVELS