Nomenclature and Uses of Alkyl Halides: Nomenclature, Industrial Uses, and Reactions, Study notes of Organic Chemistry

Download Nomenclature and Uses of Alkyl Halides: Nomenclature, Industrial Uses, and Reactions and more Study notes Organic Chemistry in PDF only on Docsity! Chapter 6 1 A. Nomenclature 1. IUPAC - add flouro- chloro- bromo- iodo- to alkane name examples: CH3 CH CH3 CH Cl CH2CH3 2-methyl-3-chlorohexane I Br trans-1-bromo-3-iodocyclobutane Chapter 6 2 2. common names CH3Cl CH Cl CH3 CH3 CH3CH2Cl CH2Cl2 CHCl3 CCl4 methyl chloride ethyl chloride i-propyl chloride methylene chloride chloroform carbon tetrachloride 3. special names C X X C C X X geminal dihalide vicinal dihalide Chapter 6 5 d. Anesthetics CHCl3 - chloroform carcinogenic CH3CH2Cl - ethyl chloride topical use CF3CHBr-Cl - halothane - general e. polymers H H Cl H F F F F * C H H C Cl H C H H C Cl H * * C F F C F F C F F C F F * polyvinyl chloride (PVC) teflon Chapter 6 6 C. structure/properties X = F = Cl = Br = I increasing electronegativity Chapter 6 7 D. Preparation - we will see many other ways in the future! 1. Free radical halogenation- R H R X + HX or hn X2 BUT • poor selectivity 1° versus 2° versus 3° • little control often di, tri, etc. proctucts formed BUT 2. allylic bromination - a special case •We need only a small amount of Br2 so N Br O O N H O O + HBr (trace) + Br2 (small amts) N- bromosuccinimide (NBS) Chapter 6 10 E. Reactions of alkyl halides - substitution 1. general reaction C X d d + - Lewis acid acidic character - electron deficient N = nucleophile - electron rich - Lewis base R-L = electrophile - electron poor - Lewis acid L = leaving group - must form a stable species (weak base e.g. X-) Chapter 6 11 general examples: (L is not always X- in these examples) Chapter 6 12 specific examples: Cl CH2CH2 S CH2CH2 Cl + H2O + 2HCl HO CH2CH2 S CH2CH2 HO mustard gas WW1 Chapter 6 15 H C CH3 CH3 ClCH3 O - + H C CH3 CH3 CH3O + Cl - H C CH3 H IN C - + H C CH3 H NC + I- Chapter 6 16 Experimentally - always get inversion - backside attack 3. stereochemistry in SN2 mechanism: CH3 C CH3CH2CH2 H INaI* + I* CH3 CH2CH2CH3 H + NaI Ingold - 1935 R-2-iodopentane S-2-iodopentane Chapter 6 17 4. Effect of nucleophile - The stronger the base - in general - the stronger the nucleophile. Examples: H2O: versus HO:- CH3O:- versus HO:- H2N:- versus HO:- Bascity factors - see Chapter 1.F.2 in class notes - a. electronegativity of atom that contains the lone pair b. inductive effects of substituents on lone pair c. resonance effects - delocalization of lone pair There is one major exception to this rule: The size of the orbital and polarizability - Nucleophilicity increases going from bottom to top row in Periodic Table. Chapter 6 20 6. Leaving group effects: The R-L bond should be as weak as possible, therefore,L should be as stable as possible. In other words, L should have: a. an electron withdrawing group or atom connected to L b. a polarizable atom connected to R c. as weakly basic as possible Chapter 6 21 7. Effects in R - the alkyl group - primarily steric: R Relative rates CH3- 1.0 CH3CH2- 0.033 CH3CH2CH2- 0.013 (CH3)2CH- 8.3 x 10-4 (CH3)3CCH2- 2 x 10-7 (CH3)3C- <<10-7 H C H H Br CH3 C CH3 CH3 Br Space-filling model Chapter 6 22 So for any R-L compound, the relative rates of SN2: CH3- > 1° > 2° > 3° 3. stereochemistry - racemization iF ionization aR er R H R lo (slow) & H,0: | 4/ deprotonation . R—C— Br CL «R28 ——$— RA c—tH + HO: | 7 R R addition | “Bri or HO: j * R _ (fast) R H a 2 R ‘Bri OCH,CH, CH,CHOH — _py | oT sa oe from the top H.C" \ ‘Bri (CH,),CH CH,CH, . () my retention of configuration — Hoy <—_ HSE aC * —CH,CHy (CH,),CH CH,CH, (CH,),CH HC, & HCH, (S) CH,CHLOH ge (CH32.CHN —_—— . (R) | trom the bottom OCH,CH planar carbocation (achiral) 2 3 inversion of configuration 25 Chapter 6 26 4. effect of nucleophiles - to a first approximation - none Chapter 6 27 5. solvents - we need a very polar solvent to stabilize the carbocation - water and alcohols are good R O H d- d+ 6. Leaving group effects - same as for SN2 (weak R-L, stable L-) Chapter 6 30 CH2 CHCH3 Cl NaCN DMF CH2 CHCH3 CN CH CH2CH3 X CN 8. Rearrangements from a carbocation - Primarily a 1,2-H shift to form a more stable carbocation. Another mystery!! Chapter 6 31 CH2 CHCH3 Cl NaCN DMF CH2 CHCH3 CN CH CH2CH3 X CN mechanism: CH2 CHCH3 Cl C CHCH3 + CL-+ H H reg. 2° carbocation C CHCH3 + H H benzyl carbocation - stabilized by resonance -CNCH CH2CH3 CN C CHCH3 + H H C CHCH3+ H H 1,2 -H shift Chapter 6 32 9. Difference between SN1 and SN2 - PRIMARILY the structure of R •solvent polarity •strength of R-L bond Chapter 6 35 In GENERAL E1 is favored by a strong base, e.g. Chapter 6 36 2. orientation - generally follows Saytzeff rule - the most substituted(most stable) olefin is formed Chapter 6 37 J. E2 - elimination bimolecular - one step just like SN2 1. mechanism: NS 5 The favored hasksida alsplacementin the Sy2 reaction Nua The 180° F2 reaction: the electrons In the C-H bond displac2 the leaving group trom the rear Tho 0° E2n the alectran: the leaving group from the front 1 frontside S2 reaction y the C-H bond displace o—So; CH; Tosylate, an excellent CaHs leaving group (see Fig. 6.48) H,C CH, CH; CH; on—}—4 go hd anti = 180° Chapter 6 41 3. Orientation - mainly follows the Saytzeff rule (most substituted olefin) - HOWEVER - there is another pattern! The Hofmann orientation - the least substituted olefin is formed: Saytzeff rule Hofmann rule The difference in orientation here is (obviously) due to the nature of the leaving group, L… Chapter 6 42 The orientational preference for the Hofmann rule is derived from a change in the nature of the E2 mechanism. Let us first look at the third mechanism - E1cB - elimination unimolecular carbon base: rate determining slow stepfast step Chapter 6 45 K. Substitution versus eleimination - general patterns: 1. Strong bases - favor SN2 or E2. 2. Weak bases - favor SN1 or SN2. 3. Bulky bases (Me3C-O- etc.) favor elimination. 4. Polarizable bases (Me3P, etc) favor substitution. 5. Primary halides - usually undergo SN2 - except if we are using a very, very strong base, then E2. 6. Tertiary halides - usually undergo E2 with a strong base but a combination of SN1/E1 with a weak base. 7. Good leaving groups (form stable bases) favor SN1 or E1. 8. High temperatures promote elimination (-TDS term). Chapter 6 46 J. Summary 1. Nomenclature of R-X. 2. Preparation - a. allylic halogenation -NBS. 3. Nucleophilic substitution a. mechanisms of SN1 and SN2 b. rate laws and stereochemistry c. variation of nucleophile, structure of R group, solvent and leaving group, L on reaction rates d. rearrangements in carbocations 4. Elimination reactions a. mechanisms of E1, E2 and E1cB b. stereochemistry and rate laws c. orientation - Saytzeff versus Hofmann d. effect of base, leaving group and alkyl group 5. Factors favoring substitution versus elimination