1、Alkyl HalidesR-X (X = F, Cl, Br, I)Classification of alkyl halides according to the class of the carbon that the halogen is attached to.RCH2-X R2CH-X R3C-X1o 2o 3o,Nomenclature:common names: “alkyl halide”(fluoride, chloride, bromide, iodide)IUPAC names: use rules for alkaneshalogen = halo (fluoro,
2、chloro, bromo, iodo)Cl CH3CH2CH2CH2-Br CH3CHCH3 n-butyl bromide isopropyl chloride 1-bromobutane 2-chloropropane1o 2o,CH3 CH3 CH3CHCH2CHCH3 CH3CCH3Br I 2-bromo-4-methylpentane tert-butyl iodide2-iodo-2-methylpropane2o 3oCH3 Cl-CHCH2CH3sec-butyl chloride 2-chlorobutane2o,Physical properties:polar + n
3、o hydrogen bonding= moderate boiling/melting pointswater insolubleUses: pesticides, refrigerants (freons), solvents, synthetic intermediates.CH3Br CClF3 CCl4,Synthesis of alkyl halides: 1. From alcoholsa) HX b) PX3 Halogenation of certain hydrocarbons3. (later)4. (later)5. Halide exchange for iodide
4、,From alcohols. #1 synthesis!With HXR-OH + HX R-X + H2Oi) HX = HCl, HBr, HIii) may be acid catalyzed (H+)iii) ROH: 3o 2o CH3 1oiv) rearrangements are possible except with most 1o ROH,CH3CH2CH2CH2-OH + NaBr, H2SO4, heat CH3CH2CH2CH2-Brn-butyl alcohol (HBr) n-butyl bromide1-butanol 1-bromobutaneCH3 CH
5、3 CH3CCH3 + HCl CH3CCH3OH Cltert-butyl alcohol tert-butyl chloride2-methyl-2-propanol 2-chloro-2-methylpropaneCH3-OH + HI, H+,heat CH3-Imethyl alcohol methyl iodidemethanol iodomethane,from alcohols: b) PX3i) PX3 = PCl3, PBr3, P + I2ii) ROH: CH3 1o 2oiii) no rearragementsCH3CH2-OH + P, I2 CH3CH2-Iet
6、hyl alcohol ethyl iodideethanol iodoethaneCH3 CH3 CH3CHCH2-OH + PBr3 CH3CHCH2-Brisobutyl alcohol isobutyl bromide2-methyl-1-propanol 1-bromo-2-methylpropane,Halogenation of certain hydrocarbons.R-H + X2, or h R-X + HX(requires or h; Cl2 Br2 (I2 NR); 3o2o1o)yields mixtures! In syntheses, limited to t
7、hose hydrocarbons that yield only one monohalogenated product.CH3 CH3 CH3CCH3 + Cl2, heat CH3CCH2-ClCH3 CH3neopentane neopentyl chloride2,2-dimethylpropane 1-chloro-2,2-dimethylpropane,Halide exchange for iodide.R-X + NaI, acetone R-I + NaX i) R-X = R-Cl or R-Brii) NaI is soluble in acetone, NaCl/Na
8、Br are insoluble.CH3CH2CH2-Br + NaI, acetone CH3CH2CH2-I n-propyl bromide n-propyl idodide 1-bromopropane 1-idodopropane,ROH,RX,RH,HX,PX3,X2, or h,NaI acetone,Outline a possible laboratory synthesis for each of the following alkyl halides using a different synthesis for each compound:1-bromobutane n
9、eopentyl chloriden-propyl iodide tert-butyl bromide,CH3CH2CH2CH2-OH + PBr3 CH3CH2CH2CH2-BrCH3 CH3 CH3CCH3 + Cl2, heat CH3CCH2-ClCH3 CH3CH3CH2CH2-Br + NaI, acetone CH3CH2CH2-ICH3 CH3 CH3C-OH + HBr CH3C-BrCH3 CH3,R-H R-X,Acids Bases Active Metals Oxidants Reductants Halogens,Reactions of alkyl halides
10、: Nucleophilic substitution Best with 1o or CH3!R-X + :Z- R-Z + :X- 2. (later) Preparation of Grignard ReagentR-X + Mg RMgX ReductionR-X + Mg RMgX + H2O R-HR-X + Sn, HCl R-H,nucleophilic substitutionR-W + :Z- R-Z + :W-substrate nucleophile substitution leavingproduct groupgood nucleophile strong bas
11、egood leaving group weak base,R-X + :OH- ROH + :X- alcohol R-X + H2O ROH + HX alcohol R-X + :OR- R-O-R + :X- ether R-X + -:CCR R-CCR + :X- alkyne R-X + :I- R-I + :X- iodide R-X + :CN- R-CN + :X- nitrile R-X + :NH3 R-NH2 + HX primary amine R-X + :NH2R R-NHR + HX secondary amine R-X + :SH- R-SH + :X-
12、thiol R-X + :SR R-SR + :X- thioether Etc. Best when R-X is CH3 or 1o!,CH3CH2CH2-Br + KOH CH3CH2CH2-OH + KBrCH3CH2CH2-Br + HOH CH3CH2CH2-OH + HBrCH3CH2CH2-Br + NaCN CH3CH2CH2-CN + NaBrCH3CH2CH2-Br + NaOCH3 CH3CH2CH2-OCH3 + NaBrCH3CH2CH2-Br + NH3 CH3CH2CH2-NH2 + HBrCH3CH2CH2-Br + NaI, acetone CH3CH2CH
13、2-I + NaBr,Mechanism for nucleophilic substitution:“substitution, nucleophilic, bimolecular” “curved arrow formalism” uses arrows to show the movement of pairs of electrons in a mechanism.,Kinetics study of the effect of changes in concentration on rates of reactions.CH3Br + NaOH CH3OH + NaBrrate =
14、k CH3-Br OH- Tells us that both CH3-Br and OH- are involved in the rate determining step of the mechanism. “bimolecular”,Relative rates of RXR-I R-Br R-Cl“element effect” CX bond is broken in the rate determining step of the mechanism.,SN2 stereochemistryCH3 CH3H Br + NaOH HO H(SN2 conditions)C6H13
15、C6H13(S)-(-)-2-bromooctane (R)-(+)-2-octanol100% optical puritySN2 proceeds with 100% inversion of configuration! (“backside attack” by the nucleophile),SN2 100% backside attack by the nucleophile Evidence: stereochemistry = 100% inversion of configurationReasonable? incoming nucleophile and negativ
16、ely charged leaving group are as far apart as they can get. 2) there is more room on the backside of the carbon for the incoming nucleophile to begin to bond to the carbon.,Relative rates for alkyl halides in SN2:CH3-X 1o 2o 3o37 : 1.0 : 0.2 : 0.0008The transition state has five groups crowded aroun
17、d the carbon. If the substrate is CH3X then three of the the five groups are Hydrogens. If the alkyl halide is 3o then there are three bulky alkyl groups crowded around the carbon in the transition state. “Steric factors” explain the relative reactivity of alkyl halides in the SN2 mechanism.,CH3 CH3
18、 CH3CCH3 + OH- CH3CCH3 + Br- + alkeneBr OHrate = k tert-butyl bromide The rate of this reaction depends on only the concentration of the alkyl halide. Therefore the nucleophile is not involved in the RDS here, cannot be SN2 mechanism!? “unimolecular”,Substitution, nucleophilic, unimolecular (SN1) me
19、chanism:Kinetics: rate = k R-W ; only R-W is involved in the RDS!,1)2),SN1 stereochemistryCH3 CH3 CH3H Br + NaOH HO H + H OH(SN1 conditions)C6H13 C6H13 C6H13(-)-2-bromooctane (+)-2-octanol (-)-2-octanolSN1 proceeds with partial racemization. The intermediate carbocation is sp2 hybridized. The nucleo
20、phile can attack the carbocation from either the top or the bottom and yield both enantiomeric products.,SN1 reactivity: 3o 2o 1o CH3RBr R+ + Br-CH3Br H = 219 Kcal/mole CH3+ CH3CH2Br H = 184 Kcal/mole 1o CH3CHBr H = 164 Kcal/mole 2oCH3CH3 CH3CBr H = 149 Kcal/mole 3oCH3,SN1 order of reactivity = 3o 2
21、o 1o CH3Stability of carbocations = 3o 2o 1o CH3+RDS in SN1: RW R+ + :W-RX R-X R+ + X-+ -,Rearrangement of carbocations. Carbocations can rearrange by 1,2-hydride or 1,2-methyl shifts: 1,2-H -CC- -CC + +H H 1,2-CH3 -CC- -CC + +CH3 CH3,Carbocations can rearrange by 1,2-hydride or 1,2-methyl shifts bu
22、t only do so when the resultant carbocation is more stable.1o carbocation will rearrange to 2o1o carbocation will rearrange to 3o2o carbocation will rearrange to 3o (only goes “down hill”),CH3 CH3 CH3CHCHCH3 + NaCN (SN1 conditions) CH3CCH2CH3 ?Br CN CH3 1,2-H shift CH3 CH3CHCHCH3 CH3CCH2CH3 + CN-+ +
23、2o carbocation 3o carbocation,SN2 SN1,R-X + Z- R-Z + X- which mechanism? SN2 -CH3 1o 2o 3o- SN1 SN2 “steric factors” CH3 1o 2o 3oSN1 carbocation stability 3o 2o 1o CH3,Effect of solvent polarity on SN1/SN2:water = polar ethanol = less polar Solvent: mixture of ethanol/water Add more water = more pol
24、ar; add more ethanol = less polar.SN1: R-W R+ + W-ionization favored by polar solventsSN2: Z:- + R-W Z-R + :X-solvent polarity does not affect rate,Alkyl halide + base ?SN2: best with CH3 or 1o RX, concentrated, strong base(SN1: 2o or 3o, dilute, weak base, polar solvent; rearrangements are possible
25、 , alkene by-products ),Synthesis of alkyl halides: 1. From alcoholsa) HX b) PX3 Halogenation of certain hydrocarbons3. (later)4. (later)5. Halide exchange for iodide,Reactions of alkyl halides: Nucleophilic substitution Best with 1o or CH3!R-X + :Z- R-Z + :X- 2. (later) Preparation of Grignard ReagentR-X + Mg RMgX ReductionR-X + Mg RMgX + H2O R-HR-X + Sn, HCl R-H,
