Ch.10 Alkyl alides Organic halides are valuable as industrial solvents, inhaled anesthetics in medicine, refrigerants, and pesticides. F F C C F Trichloroethylene (a solvent) alothane (an inhaled anesthetic) F C F C Dichlorodifluoromethane (arefrigerant) omoethane (a fumigant)
Ch.10 Alkyl alides a lot of pharmaceutical compounds are organic halides N N 200 times more potent than morphine at blocking pain in animals Epibatidine
10.1 Naming Alkyl alides Ch.10 Alkyl alides named in the same way as alkanes, treat the halogen as a substituent Step 1 Step 2 Name the parent hydrocarbon: Find the longest carbon chain. If a double bond or triple bond is present, parent chain must contain it. Numbering: Begin at the end nearer the first substituent, regardless of whether it is alkyl or halo. 1 2 4 5 2-omo-4,5-dimethylheptane
Ch.10 Alkyl alides (a) di-, tri-, tetra-...: same kind of halogens (b) list in alphabetical order for different halogens 1 2 3 4 2,3-Dichloro-4-methylhexane 1 2 3 4 1-omo-3-chloro-4-methylpentane
Ch.10 Alkyl alides Step 3 Begin at the end nearer the substituent (either alkyl or halo) that has alphabetical precedence. 5 2 2-omo-5-methylhexane common names C 3 I Iodomethane (or Methyl iodide) 2-Chloropropane (or Isopropyl chloride) omocyclohexane (or Cyclohexyl bromide)
Ch.10 Alkyl alides 10.2 Structure of Alkyl alides sp 3, tetrahedral Bond length Bond strength C F C C C I 139 pm 178 193 214 452 kj/mol 351 293 234 108 kcal/mol 84 70 56 Electrophilic carbon in C-X δ - X δ + C electrophilic site
Ch.10 Alkyl alides 10.3 Preparation of Alkyl alides Additions of X, X 2 to alkenes: X 2 X X X X C 3 3 C X=, X=, or I
adical chlorination Ch.5 An Overview of Organic eactions 3 C + hv 3 C + initiation hv (UV) 2 propagation (a) 3 C + C 3 + (b) C 3 + 3 C + (c) epeat steps (a) and (b) until termination
Ch.5 An Overview of Organic eactions C 3 C 3 3 C termination + 2 C 3 + 3 C C 3 + C 3 3 C C 3
Ch.10 Alkyl alides 10.4 adical alogenation of Alkanes a poor method of alkyl halide synthesis: poly-halogenation 3 C + hv 3 C + hv C 2 2 + hv C 3 + hv C 4 +
Ch.10 Alkyl alides hv 2 + + dichloro-, trichloro,... 30 : 70 hv + + dichloro-, trichloro,... 2 35 : 65
Ch.10 Alkyl alides eactivity toward halogenation relative reactivity + 1 o C: 6 2 o C: 4 30% / 6 = 5% 70% / 4 = 17.5% 30 : 70 2 o : 1 o = 17.5 : 5 = 3.5 : 1 + 3 o C: 1 1 o C: 9 35% / 1 = 35% 65% / 9 = 7.2% 35 : 65 3 o : 1 o = 35 : 7.2 = 5 : 1 1 o : 2 o : 3 o = 1 : 3.5 : 5.0
Ch.10 Alkyl alides eactivity toward halogenation C C C primary < secondary < tertiary 1.0 3.5 5.0 reactivity
Ch.10 Alkyl alides Bond dissociation energy: weaker 3 o C- bond is most reactive Table 5.3 Bond dissociation energy (D) 1 o C- bond 2 o C- bond 3 o C- bond 420 kj/mol (100 kcal/mol) 401 kj/mol (96 kcal/mol) 390 kj/mol (93 kcal/mol) bond strength Stability of radicals C C C primary < secondary < tertiary stability
Ch.10 Alkyl alides An explanation of the relationship between reactivity and bond strength in radical chlorination relies on the ammond postulate. - C- abstraction step is slightly exorgonic; developing radical character in the TS - alkyl substituents stabilize the transition state leading the radical intermediate Therefore, the relative rate of formation of radicals is the same as their stability order.
Ch.10 Alkyl alides eaction energy diagram for alkane chlorination C 3 '- + 2 C 2 3 C Energy ' + '- eaction progress (reaction coordinate)
Ch.10 Alkyl alides Alkane brominarion: highly selective hv + 2 >99 : 1 - C- abstraction by. is much less exergonic; the transition state for bromination resembles the alkyl radicals more closely than does the transition state for chlorination, and the stability of that radical is therefore more important for bromination than for chlorination. C 3 C 3 3 C C + X 3 C C + X C 3 C 3 o = -50 kj for X= o = +13 kj for X=
Ch.10 Alkyl alides TS 1 TS 2 (C 3 ) 3 C + (C 3 ) 3 C + TS 1 has much more radical character than TS 2 Selectivity v.s.. eactivity
Ch.10 Alkyl alides 10.5 Allylic omination of Alkenes 1942, Karl Ziegler; allylic bromination - 2 reacts with alkene - use NBS for selective allylic bromination O N (NBS) O O + N allylic position hv, C 4 85% O
Ch.10 Alkyl alides radical mechamism + 2 + O O O N + N + 2 hv O
Ch.10 Alkyl alides Selective bromination: allylic radical is relatively stable alkyl: 400 kj/mol (96 kcal/mol) allylic: 360 kj/mol (87 kcal/mol) vinylic: 445 kj/mol (106 kcal/mol)
Ch.10 Alkyl alides adical stability C C C C C C C C C vinylic < methyl < primary < secondary < tertiary < allylic less stable stability more stable
Ch.10 Alkyl alides 10.6 Stability of the Allyl adical: esonance evisited esonance stabilization C C C The unpaired electron is delocalized over the extended π-orbital: the unpaired electron is equally shared between the two terminal carbons.
Ch.10 Alkyl alides Allylic bromination of unsymmetrical alkene NBS, C 4 unsymmetrical radicals + 83% 17% reaction of less hindered primary end is favored
Ch.10 Alkyl alides Synthesis of conjugated diene: NBS KO hv, C 4
Ch.10 Alkyl alides Example: 3 C 3 C a NBS a 3 C 3 C + 3 C 3 C hv, C 4 b b 3 C 3 C + 3 C 3 C
Ch.10 Alkyl alides 10.7 Preparing Alkyl alides from Alcohols Alcohol to alkyl halide:,, I ; limited to 3 o alcohols (1 o and 2 o alcohols: slow, high temp.) -O + X -X + 2 O (X =,, I) eactivity of alcohols under acidic condition C O C O C O C O methyl < primary < secondary < tertiary less reactive reactivity more reactive
Ch.10 Alkyl alides 3 C O (g) Et 2 O, 0 o C 3 C + 2 O 90%
Ch.10 Alkyl alides 1 o and 2 o alcohols: use SO 2, P 3 O SO 2 O Pyridine O + SO 2 + 86% 3 O P 3 Et 2 O, 0 o C 3 + P(O) 3 86% - less acidic condition: no acid sensitive side reactions
Ch.10 Alkyl alides 10.8 eactions of Alkyl alides: Grignard eagents Victor Grignard: Grignard reagent -X + Mg -Mg-X = 1 o, 2 o, 3 o alkyl, aryl, alkenyl X =,, I - activation of Mg required (I 2, C 2 C 2..) - reactivity: I > > (F is not reactive)
Ch.10 Alkyl alides Mg Et 2 O Mg Mg Et 2 O Mg Mg Et 2 O Mg
Ch.10 Alkyl alides Grignard reagent: strong base and strong nucleophile δ + δ - MgX C basic and nucleophilic Grignard reagents react with weak acids such as 2 O, O, COO, N 2 Convert -X to - - + Mg -Mg- 3 O + -
Ch.10 Alkyl alides 10.9 Organometallic Coupling eactions alkyl lithium reagent + 2 Li pentane Li n-butyllithium copper reagent: Gilman reagent ( 2 CuLi) 2 C 3 Li + CuI Et 2 O (C 3 ) 2 Cu - Li + + LiI Lithium dimethylcuprate (a Gilman reagent)
Ch.10 Alkyl alides Organo copper reagents: undergo coupling reactions with alkyl halides (,, I, but not F) to form C-C bonds (C 3 ) 2 Cu - Li + + Lithium dimethylcuprate -I Et 2 O 0 o C -C 3 + LiI + C 3 Cu
Ch.10 Alkyl alides Coupling reactions with alkenyl halides: vinyl, aryl halides I n-bu 2 CuLi n-bu + n-buli + LiI I Me 2 CuLi Me + MeLi + LiI mechanism - X + ' Cu ' Li + ' Cu ' ' + ' Cu
Ch.10 Alkyl alides 10.10 Oxidation and eduction in Organic Chemistry Oxidation: eduction: Decreases electron density (increase oxidation state) on carbon by: forming one of these: C-O, C-N, C-X or breaking this: C- (addition of C-O bonds) Increase electron density (decrease oxidation state) on carbon by: forming this : C- or breaking one of these : C-O, C-N, C-X (addition of C- bonds) 3 C 2 hv 3 C oxidation: C- bond broken and C- bond formed 3 C 1. Mg 2. 3 O + 3 C reduction: C- bond broken and C- bond formed
Ch.10 Alkyl alides oxidation: two new bonds 2 formed between carbon and a 2 C C 2 2 C C 2 more electronegative element reduction: two new bonds 2 formed between carbon and a 2 C C 2 2 C C 2 less electronegative element 2 C C 2 2 C C 2 neither oxidation nor reduction: one new C- bond and one new C- bond formed
Ch.10 Alkyl alides Oxidation levels C 3 C 3 C 2 =C 2 C C C 3 O C 2 =O COO CO 2 C 3 C 2 2 C 3 C 4 C 3 N 2 C 2 =N C N Low oxidation state igh oxidation state
Chemistry @ Work Naturally Occuring Organohalides organohalogen compounds: drugs, solvents, toxins... N N N O O O N O Jasplakinolide O O disrupts formation of the actin microtubles that make up the skeleton of cellular organelles - many organisms use organohalogen compounds for self-defence - marine organisms produce diverse organohalogen compounds