1. Introduction. Cis-Trans System Useful for 1,2-disubstituted alkenes Examples: Alkynes Hydrocarbons containing C C Common name: acetylenes

Transcription

1 hapter 7 Alkenes and Alkynes I: Properties and Synthesis. Elimination eactions of Alkyl alides reated by Professor William Tam & Dr. illis hang h. 7-1 About The Authors These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. illis hang. Professor William Tam received his B.Sc. at the University of ong Kong in 1990 and his.d. at the University of Toronto (anada) in e was an NSE postdoctoral fellow at the Imperial ollege (UK) and at arvard University (USA). e joined the Department of hemistry at the University of Guelph (ntario, anada) in 1998 and is currently a Full Professor and Associate hair in the department. Professor Tam has received several awards in research and teaching, and according to Essential Science Indicators, he is currently ranked as the Top 1% most cited hemists worldwide. e has published four books and over 80 scientific papers in top international journals such as J. Am. hem. Soc., Angew. hem., rg. Lett., and J. rg. hem. Dr. illis hang received her B.Sc. at New York University (USA) in 1994, her M.Sc. and.d. in 1997 and 001 at the University of Guelph (anada). She lives in Guelph with her husband, William, and their son, Matthew. h Introduction Alkenes ydrocarbons containing = ld name: olefins Vitamin A 3 Alkynes ydrocarbons containing ommon name: acetylenes l F 3 N I l l l 3 holesterol h. 7-3 Efavirenz (antiviral, AIDS therapeutic) aloprogin (antifungal, antiseptic) h The (E) - (Z) System for Designating Alkene Diastereomers is-trans System Useful for 1,-disubstituted alkenes Examples: (1) l vs trans -1-omo- -chloroethene l cis -1-omo- -chloroethene h. 7-5 Examples () vs trans -3-exene (3) vs trans -1,3- Dibromopropene cis -3-exene cis -1,3- Dibromopropene h. 7-6

2 (E) - (Z) System Difficulties encountered for trisubstituted and tetrasubstituted alkenes e.g. l 3 cis or trans? The ahn-ingold-prelog (E) - (Z) onvention The system is based on the atomic number of the attached atom The higher the atomic number, the higher the priority l is cis to 3 and trans to h. 7-7 h. 7-8 The ahn-ingold-prelog (E) - (Z) onvention (E) configuration the highest priority groups are on the opposite side of the double bond E stands for entgegen ; it means opposite in German (Z) configuration the highest priority groups are on the same side of the double bond Z stands for zusammer ; it means together in German h. 7-9 Examples l 1 3 n carbon : Priority of > n carbon 1: Priority of l > highest priority groups are (on carbon ) and l (on carbon 1) h Examples 3 l (E )--omo-1-chloropropene l 3 (Z )--omo-1-chloropropene h (1) l ther examples 1 l (E )-1,-Dichloroethene [or trans-1,-dichloroethene] 1: l > : l > () l (Z )-1-omo-1,-dichloroethene 1 l 1: > l : l > h. 7-1

3 (3) ther examples (Z )-3-omo-4-tert-butyl-3-octene 3: > 4: t Bu > n Bu 3. elative Stabilities of Alkenes is and trans alkenes do not have the same stability crowding Less stable More stable h h A. eat of eaction Pt eat of hydrogenation -10 kj/mol Enth halpy 7 kj/mol = -17 kj/mol 5 kj/mol = -10 kj/mol = -115 kj/mol h h B. verall elative Stabilities of Alkenes The greater the number of attached alkyl groups (i.e., the more highly substituted the carbon atoms of the double bond), the greater the alkene s stability. elative Stabilities of Alkenes > > > > > > tetrasubstituted trisubstituted disubstituted monosubstituted unsubstituted h h. 7-18

4 Examples of stabilities of alkenes (1) > 4. ycloalkenes ycloalkenes containing 5 carbon atoms or fewer exist only in the cis form () > cyclopropene cyclobutene cyclopentene h h. 7-0 Trans cyclohexene and trans cycloheptene have a very short lifetime and have not been isolated Trans cyclooctene has been isolated and is chiral and exists as a pair of enantiomers cyclohexene ypothetical trans - cyclohexene (too strained to exist at r.t.) cis - cyclooctene trans - cyclooctenes h. 7-1 h Synthesis of Alkenes via Elimination eactions Dehydrohalogenation of Alkyl alides X base -X 6. Dehydrohalogenation of Alkyl alides The best reaction conditions to use when synthesizing an alkene by dehydrohalogenation are those that promote an E mechanism Dehydration of Alcohols, heat - h. 7-3 E B: X B: X h. 7-4

5 6A. ow to Favor an E Mechanism Use a secondary or tertiary alkyl halide if possible. (Because steric hinderance in the substrate will inhibit substitution) When a synthesis must begin with a primary alkyl halide, use a bulky base. (Because the steric bulk of the base will inhibit substitution) Use a high concentration of a strong and nonpolarizable base, such as an alkoxide. (Because a weak and polarizable base would not drive the reaction toward a bimolecular reaction, thereby allowing unimolecular processes (such as S N 1 or E1 reactions) to compete. h. 7-5 h. 7-6 Sodium ethoxide in ethanol (EtNa/Et) and potassium tertbutoxide in tertbutyl alcohol (t-buk/t- Bu) are bases typically used to promote E reactions Use elevated temperature because heat generally favors elimination over substitution. (Because elimination reactions are entropically favored over substitution reactions) h B. Zaitsev s ule Examples of dehydrohalogenations where only a single elimination product is possible (1) () (3) ( ) n EtNa o Et, 55 o EtNa Et, 55 o t -BuK t -Bu, 40 o (79%) (91%) ( ) n (85%) h. 7-8 ate = k 3 B a b 3 a b Et ( nd order overall) bimolecular -methyl--butene -methyl-1-butene h. 7-9 When a small base is used (e.g. Et or ) the major product will be the more highly substituted alkene (the more stable alkene) Examples: (1) () a b NaEt Et 70 o KEt Et 69% 31% (eliminate a ) (eliminate b ) 51% 18% 31% 69% h. 7-30

6 Zaitsev s ule In elimination reactions, the more highly substituted alkene product predominates Stability of alkenes Me Me Me Me Me Me > Me Me Me > Me > Me > Me h Mechanism for an E eaction Et 3 β 3 α 3 Et removes a β proton; breaks; new π bond forms and begins to depart Et 3 δ 3 3 δ Partial bonds in the transition state: and bonds break, new π bond forms Et = is fully formed and the other products are Et and h. 7-3 Energy Free δ Et 3 Et δ G 3 3 G δ eaction oordinate δ Et Et 3 3 Et - 3 h Formation of the Less Substituted Alkene Using a Bulky Base ofmann s ule Most elimination reactions follow Zaitsev s rule in which the most stable alkenes are the major products. owever, under some circumstances, the major elimination product is the less substituted, less stable alkene h ase 1: using a bulky base Et 3 3 (small) 3 (80%) (0%) ase : with a bulky group next to the leaving halide less crowded β- 3 3 Et (small base) t Bu (bulky) t Bu (30%) (70%) (bulky base) h Me Me Et 3 3 Me Me Me Me (mainly) more crowded β- h. 7-36

7 Zaitsev ule vs. ofmann ule Examples (1) Examples b a () b a (eliminate a ) (eliminate b ) NaEt, Et, 70 o 69% 31% K t Bu, t Bu, 75 o 8% 7% (eliminate a ) (eliminate b ) NaEt, Et, 70 o 91% 9% K t Bu, t Bu, 75 o 7% 93% h h D. The Stereochemistry of E eactions The 5 atoms involved in the transition state of an E reaction (including the base) must lie in the same plane The anti coplanar conformation is the preferred transition state geometry The anti coplanar transition state is staggered (and therefore of lower energy), while the syn coplanar transition state is eclipsed h B LG Anti coplanar transition state (preferred) B LG Syn coplanar transition state (only with certain rigid molecules) h rientation equirement and have to be anti periplanar (trans-coplanar) Examples 3 Et 3 since: Et 3 nly is anti periplanar to h E Elimination where there are two axial β hydrogens Et 3 4 Et b 3 l a 1 ( 3 ) Both a and b hydrogens are anti to the chlorine in this, the more stable conformation (a) (b) 3 4 ( 3 ) Menthene (78%) (more stablealkene) 3 4 ( 3 ) 3 1 -Menthene (%) (less stable alkene) h. 7-4

8 E elimination where the only axial β hydrogen is from a less stable onformer 3 1 ( 3 ) l Menthyl chloride (more stable conformer) Elimination is not possible for this conformation because no hydrogen is anti to the leaving group l ( 3 ) Menthyl chloride (less stable conformer) Elimination is possible for this conformation because the green hydrogen is anti to the chlorine h l ( 3 ) -Menthene (100%) The transition state for the E elimination is anti coplanar 3 Et l ( 3 ) 3 ( 3 ) h Acid-atalyzed Dehydration of Alcohols Most alcohols undergo dehydration (lose a molecule of water) to form an alkene when heated with a strong acid A heat h The temperature and concentration of acid required to dehydrate an alcohol depend on the structure of the alcohol substrate Primary alcohols are the most difficult to dehydrate. Dehydration of ethanol, for example, requires concentrated sulfuric acid and a temperature of 180 conc. S o Ethanol (a 1 o alcohol) h Secondary alcohols usually dehydrate under milder conditions. yclohexanol, for example, dehydrates in 85% phosphoric acid at yclohexanol 85% 3 P o yclohexene (80%) h Tertiary alcohols are usually so easily dehydrated that extremely mild conditions can be used. tert-butyl alcohol, for example, dehydrates in 0% aqueous sulfuric acid at a temperature of tert-butyl alcohol 0% S 4 85 o 3 3 -Methylpropene (84%) h. 7-48

9 The relative ease with which alcohols will undergo dehydration is in the following order: > > 3 o alcohol o alcohol 1 o alcohol h Some primary and secondary alcohols also undergo rearrangements of their carbon skeletons during dehydration ,3-Dimethyl--butanol ,3-Dimethyl--butene (80%) 85% 3 P 4 80 o 3 3 3,3-Dimethyl-1-butene (0%) h Notice that the carbon skeleton of the reactant is while that of the product is h A. Mechanism for Dehydration of o & 3 o Alcohols: An E1 eaction onsider the dehydration of tert-butyl alcohol Step protonated alcohol h. 7-5 Step Step a carbocation 3 3 -Methylpropene h B. arbocation Stability & the Transition State ecall > > > 3 o > o > 1 o > methyl most stable least stable h. 7-54

10 h A Mechanism for Dehydration of Primary Alcohols: An E eaction 1 o alcohol protonated alcohol fast A A acid catalyst slow r.d.s alkene A conjugate base h arbocation Stability & ccurrence of Molecular earrangements 8A. earrangements during Dehydration of Secondary Alcohols 3 Step ,3-Dimethyl--butanol 85% 3 P 4 heat protonated alcohol ,3-Dimethyl--butenol,3-Dimethyl-1-butene (major product) (minor product) h h Step Step a o carbocation h δ δ o carbocation transition state (less stable) The less stable o carbocation rearranges to a more stable 3 o carbocation o carbocation (more stable) h. 7-60

11 Step 4 (a) A (b) (a) or (b) (a) (major) 3 3 A 3 3 less stable alkene (b) (minor) 3 A 3 3 more stable alkene h ther common examples of carbocation rearrangements Migration of an allyl group a o carbocation methanide migration o carbocation h. 7-6 Migration of a hydride 3 3 hydride migration a o carbocation 3 o carbocation h B. earrangement after Dehydration of a Primary Alcohol A A E A A protonation A A deprotonation h The Acidity of Terminal Alkynes Acetylenic hydrogen sp sp sp 3 pk a = 5 pk a = 44 pk a = 50 elative basicity of the conjugate base omparison of acidity and basicity of 1 st row elements of the Periodic Table elative acidity > > > N > > 3 pk a elative basicity < < < N < < 3 3 > > h h. 7-66

12 10. Synthesis of Alkynes by Elimination eactions Synthesis of Alkynes by Dehydrohalogenation of Vicinal Dihalides Mechanism N E NaN heat N h h Examples NaN (1) heat (78%) Synthesis of Alkynes by Dehydrohalogenation of Geminal Dihalides Pl 5 l l () l 4 NaN heat 3 0 o 3 gem-dichloride 1. NaN (3 equiv.), heat. A h h eplacement of the Acetylenic ydrogen Atom of Terminal Alkynes The acetylide anion can be prepared by Acetylide anions are useful intermediates for the synthesis of other alkynes ' X ' X NaN liq. N 3 Na N 3 nd step is an S N reaction, usually only good for 1 o o and 3 o usually undergo E elimination h h. 7-7

13 Examples 3 I NaN liq. N 3 Na I 13. ydrogenation of Alkenes Pt, Pd or Ni solvent heat and pressure S N 3 E Pt, Pd or Ni solvent heat and pressure NaI I h ydrogenation is an example of addition reaction h Examples h(p 3 ) 3 l 14. ydrogenation: The Function of the atalyst ydrogenation of an alkene is an exothermic reaction -10 kj/mol hydrogenation Pd/ heat h h A. Syn and Anti Additions An addition that places the parts of the reagent on the same side (or face) of the reactant is called syn addition X Y X Y syn addition Pt atalytic hydrogenation is a syn addition. h h. 7-78

14 15. ydrogenation of Alkynes An anti addition places parts of the adding reagent on opposite faces of the reactant Pt or Pd X Y X Y anti addition h Using the reaction conditions, alkynes are usually converted to alkanes and are difficult to stop at the alkene stage h A. Syn Addition of ydrogen: Synthesis of cis-alkenes Semi-hydrogenation of alkynes to alkenes can be achieved using either the Ni B (P-) catalyst or the Lindlar s catalyst Nickel boride compound (P- catalyst) Ni 3 Lindlar s catalyst Pd/a 3, quinoline NaB 4 Et Ni B (P-) h Semi-hydrogenation of alkynes using Ni B (P-) or Lindlar s catalyst causes syn addition of hydrogen Examples Ni B (P-) (cis) 3 Pd/a 3 3 quinoline (97%) (86%) h B. Anti Addition of ydrogen: Synthesis of trans-alkenes Alkynes can be converted to transalkenes by dissolving metal reduction Anti addition of dihydrogen to the alkyne Example 1. Li, liq. EtN, -78 o. N 4 l ' 1. Li, liq. N 3, -78 o. aqueous work up ' anti addition h h. 7-84

15 Mechanism Li radical anion NEt vinyl radical 16. An Introduction to rganic Synthesis 16A. Why Do rganic Synthesis? To make naturally occurring compounds which are biologically active but difficult (or impossible) to obtain trans alkene EtN Li vinyl anion BzN TAXL Ac Ac Anti-tumor, anti-cancer agent h h TAXL Isolated from Pacific Yew tree Leaves ones and Fruit seed pollen cones usually appear on separate male and female trees h TAXL Approved by the U.S. Food & Drug Administration in 199 for treatment of several types of cancer, including breast cancer, lung cancer, and melanoma An estimation: a 100-year old yew tree must be sacrificed in order to obtain 300 mg of Taxol, just enough for one single dose for a cancer patient bviously, synthetic organic chemistry methods that would lead to the synthesis of Taxol would be extremely useful h B. etrosynthetic Analysis target molecule 1st precursor nd precursor starting compound When doing retrosynthetic analysis, it is necessary to generate as many possible precursors, hence different synthetic routes, as possible 1st precursor A nd precursor a nd precursor b target molecule 1st precursor B nd precursor c nd precursor d h st precursor nd precursor e nd precursor f h. 7-90

16 16. Identifying Precursors Synthesis of etrosynthetic Analysis S N on 1 o alkyl halide: good disconnection 1 δ X δ (target molecule) disconnection δ δ X h S N on o alkyl halide: poor will get E as major pathway h. 7-9 Synthesis NaN liq. N 3 Na (S N ) I NaI 16D. aison d Etre Summary of Methods for the Preparation of Alkenes (Dehydrohalogenation of alkyl halides) X base, heat, Ni B (P-) or Lindlar's catalyst (give (Z)-alkenes) heat (Dehydration of alcohols) Li, liq. N 3 (give (E)-alkenes) h (Semihydrogenation of alkynes) (Dissolving metal reduction of alkynes) h Summary of Methods for the Preparation of Alkynes X X ' NaN heat (Dehydrohalogenation of vicinal dihalide) (Dehydrohalogenation of geminal dihalide) ' l NaN heat l ' END F APTE 7 (Deprotonation of terminal alkynes and S N reaction of the acetylide anion) 1. NaN, liq. N 3. '-X (' = 1 o alkyl group) h h. 7-96