Lecture 2 Alkenes & Alkynes_BMC 2022 PDF

20/03/2022 Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Science KNUST SMS 151 BASIC MEDICAL CHEMISTRY [ALKENES & ALKYNES 2022] PROF. ISAAC AY...

20/03/2022 Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Science KNUST SMS 151 BASIC MEDICAL CHEMISTRY [ALKENES & ALKYNES 2022] PROF. ISAAC AYENSU KNUST COVID-19 AWARENESS COVID-19: Ca used by a vi rus known a s Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2). Spreads very easily from person to person. Signs and symptoms: Fever or chi lls, cough, difficulty i n breathing, cold, headache, di a rrhoea, loss of taste/smell, a nd several non-specific s ymptoms. Transmission: Res piratory droplets, airborne, contaminated surfaces. Prevention: Us e both Pharmaceutical a nd Non-Pharmaceutical measures. Pharmaceutical measures: Va cci nes a re safe a nd a vailable. Speak to a Professional i f you ha ve a ny questions Non-Pharmaceutical measures: Res piratory hygiene: Wear a nose mask, cough etiquettes Ha nd hygiene: Frequent hand washing, hand sanitizing Ma i ntain ‘safe’ physical distancing Avoi d crowds and confined/poorly ventilated s paces Virus is changing itself with even more serious ramifications, so it is important we all adhere to the safety protocols www.knust.edu.gh 3/20/2022 BMC 2022 2 1  20/03/2022 Bonding Basics for Hydrocarbons Hybrid Orbitals The valence shell electron configuration of carbon is 2s2, 2px1, 2py1 & 2pz0. The tetrahedral structures of methane and carbon tetrachloride demonstrate that carbon can form four equivalent bonds, leading to the desired octet. 3/20/2022 BMC 2022 3 sp3 hybrid orbitals In order to explain the structure of methane (CH 4), the 2s and three 2p orbitals are converted to four equivalent hybrid atomic orbitals, each having 25% s and 75% p character, and designated sp3. A single 2s AO is combined with three 2p AOs on the same carbon atom to form four new sp3 hybrid orbitals. The total number of orbitals is conserved (stays the same). Four AOs (one 2s and three 2p) combined to give four new sp3 hybrid orbitals. 3/20/2022 BMC 2022 4 2  20/03/2022 These hybrid orbitals have a specific orientation, and the four are naturally oriented in a tetrahedral fashion. Thus, the four covalent bonds of methane consist of shared electron pairs with four hydrogen atoms in a tetrahedral configuration, 3/20/2022 BMC 2022 5 Ground state Excited state sp3 Hybridized state 3/20/2022 BMC 2022 6 3  20/03/2022 sp3 hybrid orbitals 3/20/2022 BMC 2022 7 sp2 hybrid orbitals Since carbon atoms involved in double bonds have only three bonding partners, they require only three hybrid orbitals to contribute to three sigma bonds. 3sp2 3/20/2022 BMC 2022 8 4  20/03/2022 sp2 A mixing of the 2s-orbital with two of the 2p orbitals gives three sp2 hybrid orbitals, leaving one of the p-orbitals unused. Two sp2 hybridized carbon atoms are then joined together by sigma and pi-bonds (a double bond) 3/20/2022 BMC 2022 9 3/20/2022 BMC 2022 10 5  20/03/2022 sp hybrid orbitals Finally, in the case of carbon atoms with only two bonding partners only two hybrid orbitals are needed for the sigma bonds, and these sp hybrid orbitals are directed 180º from each other. 3/20/2022 BMC 2022 11 Two p-orbitals remain unused on each sp hybridized atom, and these overlap to give two pi-bonds following the formation of a sigma bond (a triple bond), as shown below. 3/20/2022 BMC 2022 12 6  20/03/2022 Alkenes and Alkynes This section concerns the chemistry of some simple hydrocarbons (alkenes and alkynes) 3-methylene-7, 11-dimethyl 1,6,10-dodecatriene ethylene (An aphid alarm pheromone) Neocembrene (A termite trail marker) 6-methoxy-α-(5-vinyl-2-quinuclidinyl)-4- 3/20/2022 quinoline-methanol BMC 2022 14 7  20/03/2022 Calicheamicin is one of the most potent antitumour agents known, derived from bacteria Calicheamicin 3/20/2022 BMC 2022 15 Alkenes: 3/20/2022 BMC 2022 16 8  20/03/2022 Alkenes These compounds involve a carbon - carbon DOUBLE bond. Alkenes. CnH2n H H C C H H 3/20/2022 BMC 2022 17 Alkenes The double bond is stronger than a single bond. It is however, also the source of the reactivity of these molecules. 3/20/2022 BMC 2022 18 9  20/03/2022 Nomenclature Replace alkane –ane with -ene propene 1,3-butadiene ethene cyclohexene 1,3,5-hexatriene 2-methyl-1,3-butadiene 2-methyl-2-pentene (a pent-2-ene) 3-buten-1-ol 3/20/2022 2-butenoic BMC 2022 acid 19 Trivial names of some alkenyl groups Methylene cyclohexane CH2= Vinyl chloride CH2=CHCl Allyl bromide CH2=CHCH2Br 3/20/2022 BMC 2022 20 10  20/03/2022 Properties Because of exposed pi electrons in alkenes, there is some slight interaction with water molecules. This is absent in alkanes. Alkenes are therefore, more soluble in water than alkanes. Alkenes are however considered nonpolar. Physical properties, eg bp identical to their alkane parents. 3/20/2022 BMC 2022 21 Preparation of alkenes Na + -OCH 2CH 3 wa rm 2-bromopentane Trans-2-pentene (51%) Cis –isomer (18%) May also use elimination reactions of alcohols. Whether with 1o, 2o or 3o halides or alcohols, mixtures of 1-pentene (31%) products result. 3/20/2022 BMC 2022 22 11  20/03/2022 Alkenes: Overview These compounds involve a carbon - carbon DOUBLE bond. This double bond is the source of the reactivity of these molecules. One of the major types of reactivity is ADDITION. 3/20/2022 BMC 2022 23 Alkenes: Addition reactions Addition reactions have the following general form: 3/20/2022 BMC 2022 24 12  20/03/2022 Reactions Pt H2 Cl 2 HCl 1. Addition reactions, reagents add to pi-bond, rehybridization, no loss of atoms. Note: hydrogenation 3/20/2022 BMC 2022 of fats/oils - margarine 25 Addition Reactions Y C C + X Y C C X 3/20/2022 BMC 2022 26 13  20/03/2022 Addition of H-X H H H H H H X C C C C H H H H X H X H H H X H H 3/20/2022 BMC 2022 27 Addition of Water H H H H+ catalyst H O H C C H H C C H H H H OH H OH H+ catalyst H O H H H H H 3/20/2022 BMC 2022 28 14  20/03/2022 MECHANISM STEP-BY-STEP ACCOUNT OF WHAT HAPPENS :X- X s tep 1 s tep 2 C C C C C C + E E + E i ntermediates are Intermediate formed during a rea ction but are not products 3/20/2022 BMC 2022 29 Electrophilic Addition to a Double Bond CH2 CH2 + X Y X CH2 CH2 Y 3/20/2022 BMC 2022 30 15  20/03/2022 Addition of Hydrogen Halides: Markovnikov’s rule CH3 Br C H major H3C C product CH3 H H-Br H C H3C CH2 CH3 H minor C product H H3C C H Br 3/20/2022 BMC 2022 31 Markovnikov’s Rule In the ionic addition of an acid to the carbon- carbon double bond of an alkene, the hydrogen of the acid attaches itself to the carbon atom which already holds the greater number of hydrogens. –“Them that has, gets!” –“The richer get richer!” (V. W. Markovnikov -- 1838 - 1904) 3/20/2022 BMC 2022 32 16  20/03/2022 MARKOVNIKOV RULE When adding HX to a double bond the hydrogen of HX goes to the carbon which already has the most hydrogens CH 2 CH 3 Cl + HCl..... conversely, the anion X adds to the most highly substituted carbon ( the carbon with most alkyl groups attached). 3/20/2022 BMC 2022 33 REGIOSELECTIVE REACTION C H3 C H3 C H3 HCl C H3 C C H2 C H3 C C H 3 + C H 3 C H C H2 Cl Cl major minor one of the possible products is formed in larger amounts than the other one Compare REGIOSPECIFIC only one of the possible products is formed (100%). 3/20/2022 BMC 2022 34 17  20/03/2022 Mechanism (Markovnikov) + slow 1) R CH CH2 + H R CH-CH2 H Secondary C+ + Electrophile _ fast 2) R CH-CH2 H + Br R CH CH2 H + Br Nucleophile Ma jor product 3/20/2022 BMC 2022 35 Mechanism (anti-Markovnikov) CH CH2+ + slow 1) R CH CH2 + H R H Pri ma ry ca rbocation + _ fast 2) R CH CH2 + Br R CH CH2 Br H H Minor! 3/20/2022 BMC 2022 36 18  20/03/2022 Addition of Sulfuric Acid to an Alkene R CH CH2 + H2SO4 R CH CH2 H (cold, concentrated) O O S O OH an alkyl hydrogen sulfate 3/20/2022 BMC 2022 37 Addition of Bromine to an Alkene Br CCl4 R CH CH R + Br2 R CH CH R or CH2Cl2 Br 3/20/2022 BMC 2022 38 19  20/03/2022 ADDITION OF BROMINE Br Br C C l4 C C C C C C SLOW + Br Br Br Br d+ d- : Br Br a l kene polarizes bromine 3/20/2022 BMC 2022 39 Bromination of an Unsymmetrical Alkene + Br 1) _ slow R CH CH2 + Br Br R CH CH2 + Br + Br H 2) Br H C C R CH CH2 R H Br. _ anti-addition + : Br: (stereospecific). 3/20/2022 BMC 2022 40 20  20/03/2022 Carbocation Rearrangements CH3 CH3 CH3 H H HCl CH3 C CH CH2 CH3 C CH CH2 + CH3 C CH CH2 CH3 CH3 Cl CH3 Cl major minor rearranged!! not rearranged!! 3/20/2022 BMC 2022 41 ADDITION OF HBr conc. HBr Markovnikov Addition CH2 CH3 Br conc. HBr CH2 CH2Br Oxygen H Anti-Markovnikov Addition 3/20/2022 BMC 2022 42 21  20/03/2022 Hydrogenation of Alkenes Pt, Pd, R CH CH R + H2 R CH CH R or Ni H H syn-addition (stereospecific) Also PtO2 -- sometimes Ru, Rh, or Re 3/20/2022 BMC 2022 43 Oxidation Epoxi de Col d KMnO4 / OH - (O) 1,2-di ol or glycol Hot KMnO4 (O) Ca rboxyl ic acids a nd ca rbonyls (aldehydes & ketones) 3/20/2022 BMC 2022 44 22  20/03/2022 Alkenes : cis / trans isomerism We represent these structures via: 3/20/2022 BMC 2022 45 Alkenes : cis / trans isomerism The reason such isomers exist is that unlike single bonds the C - C double bond cannot rotate. 3/20/2022 BMC 2022 46 23  20/03/2022 Alkenes: Conjugation Sequential double bond/single bonds have increased stability. 3/20/2022 BMC 2022 47 Alkenes: Conjugation Sequential double bond/single bonds have increased stability. 3/20/2022 BMC 2022 48 24  20/03/2022 Alkenes: Conjugation Sequential double bond/single bonds have increased stability. 3/20/2022 BMC 2022 49 Alkenes: Conjugation Alternating double bond and single bonds have increased stability. The double bonds are said to be “conjugated”. 3/20/2022 BMC 2022 50 25  20/03/2022 Alkenes: Conjugation The double bonds can be conjugated within a ring. 3/20/2022 BMC 2022 51 Alkenes: Conjugation The double bonds can be conjugated within a ring. 3/20/2022 BMC 2022 52 26  20/03/2022 Alkenes: Conjugation The double bonds can be conjugated within a ring. This is 1,3-cyclohexadiene. 3/20/2022 BMC 2022 53 Alkenes What happens when there are three double bonds within a six-membered ring? 3/20/2022 BMC 2022 54 27  20/03/2022 Alkenes What happens when there are three double bonds within a six-membered ring? 3/20/2022 BMC 2022 55 Alkenes What happens when there are three double bonds within a six-membered ring? The compound is called benzene. 3/20/2022 BMC 2022 56 28  20/03/2022 Benzene Benzene can be made to react with Br2, but only in the presence of a catalyst. 3/20/2022 BMC 2022 57 Benzene Benzene can be made to react with Br2, but only in the presence of a catalyst. And the reaction is a substitution and not an addition! 3/20/2022 BMC 2022 58 29  20/03/2022 Benzene Benzene can be made to react with Br2, but only in the presence of a catalyst. And the reaction is a substitution and not an addition! 3/20/2022 BMC 2022 59 Benzene Benzene is only one example of a class of compounds called aromatics. They are all stabilised by aromaticity. The term originally referred to their pleasant smell. Non-aromatics were called aliphatic. 3/20/2022 BMC 2022 60 30  20/03/2022 What is aromaticity? They are cyclic. They are conjugated all around the ring. The molecule must have (4n+2) Pi electrons. (2,6,10,14, 18, etc. )**. Huckel’s Rule states that all aromatic molecules must satisfy this condition. The molecule must be flat/planar 3/20/2022 BMC 2022 61 ALKYNES Alkynes. CnH2n-2 C2 H2 H:C:::C:H H—C  C—H sp => linear, 180o acetylene ethyne C3 H4 CH3 CCH methylacetylene propyne 3/20/2022 BMC 2022 62 31  20/03/2022 Alkynes in nature There are only a few naturally occurring alkynes. Examples include capillin, which has fungicidal activity, and ichthyothereol, a convulsant used by the Amazon Indians for poisoned arrowheads. A class of naturally occurring compounds called enediynes has been found to have powerful antibiotic and anticancer properties. These compounds all have a nine- or ten-membered ring that contains two triple bonds separated by a double bond. Some 3/20/2022 enediynes are currently BMC 2022 in clinical trials. 63 Alkynes in nature 3/20/2022 BMC 2022 64 32  20/03/2022 Esperamicin is a potent antitumour agent known, derived from bacteria 3/20/2022 BMC 2022 65 Synthetic Drugs Some drugs contain alkyne functional groups, but they are not naturally occurring compounds. They exist only because chemists have been able to synthesize them. Their trade names are shown in green. 3/20/2022 BMC 2022 66 33  20/03/2022 Synthetic alkyne drugs 3/20/2022 BMC 2022 67 Properties Pi bond prevents free rotation of groups around the double bond. Geometric isomerism_Not possible for the alkene or alkyne Electronegativity : sp carbon has more s character, orbital closer to C nucleus than in sp2 or sp3. Alkyne sp C is therefore more e-ve than the others. Alkynyl C-H bond is more polar than alkane CH or alkene CH bond. 3/20/2022 BMC 2022 68 34  20/03/2022 Properties Terminal alkynes can therefore, lose the hydrogen to very strong bases. Are however, weaker acids than water The resulting anion, RC≡C: - , called acetylide ion CH3C≡C-H + Na+ -NH2 liq NH3 CH3C≡C:- Na+ + NH3 Alkanes and alkenes do not react under these conditions. 3/20/2022 BMC 2022 69 Alkynes Ethyne acetylene 2-pentyne ethylmetylyacetylene Phenyl ethyne Phenyl acetylene 3/20/2022 BMC 2022 70 35  20/03/2022 nomenclature: common names: “alkylacetylene” IUPAC: parent chain = longest continuous carbon chain that contains the triple bond. alkane drop –ane add -yne prefix locant for the triple bond, etc. CH3 CH2 CCCH3 2-pentyne ethylmethylacetylene 3/20/2022 BMC 2022 71 “terminal” alkynes have the triple bond at the end of the chain: CH3 CH3 CH2 CCH HCCCHCH2 CH3 1-butyne 3-methyl-1-pentyne ethylacetylene sec-butylacetylene 3/20/2022 BMC 2022 72 36  20/03/2022 physical properties: weakly or non-polar, no H-bonding relatively low mp/bp water insoluble 3/20/2022 BMC 2022 73 Synthesis, alkynes: 1. dehydrohalogenation of vicinal dihalides H H H | | | —C —C— + KOH  — C = C — + KX + H2 O | | | X X X H | —C =C— + NaNH2  — C  C — + NaX + NH3 | X 3/20/2022 BMC 2022 74 37  20/03/2022 H H | | —C—C— + 2 KOH  — C  C — + KX + H2 O | | heat X X CH3 CH2 CHCH2 + KOH; then NaNH2  CH3 CH2 CCH Br Br “ + 2 KOH, heat 3/20/2022 BMC 2022 75 X2 1. KOH alkene vicinal dihalide alkyne 2. NaNH2 Br2 1. KOH CH3 CH=CH2 CH3 CHCH2 CH3 CCH 2. NaNH2 Br Br 3/20/2022 BMC 2022 76 38  20/03/2022 3/20/2022 BMC 2022 77 2. coupling of metal acetylides with 1o /CH3 alkyl halides R-CC-Na+ + R´X  R-CC-R´ + NaX a) SN2 b) R´X must be 1o or CH3 X CH3 CC-Li+ + CH3 CH2 -Br  CH3 CCCH2 CH3 3/20/2022 BMC 2022 78 39  20/03/2022 note: R-X must be 1o or CH3 to get SN2! CH3 CH3 CH3C C Na + CH3CCH3 CH3C CH2 Br + 3o alkyl halide CH3C CH E2 elimination! 3/20/2022 BMC 2022 79 alkynes acids  bases  some terminal only metals  terminal only oxid.  reduct.  halogens  3/20/2022 BMC 2022 80 40  20/03/2022 Reactions, alkynes: 1. addition of H2 (reduction) 2. addition of X2 3. addition of HX 4. addition of H2 O, H+ 5. as acids 6. Ag+ 7. oxidation 3/20/2022 BMC 2022 81 1. Addition of H2 H H | | —C C — + 2 H2 , Ni  —C—C— | | H H alkane requires catalyst (Ni, Pt or Pd) 3/20/2022 BMC 2022 82 41  20/03/2022 HCCH + 2 H2 , Pt  CH3 CH3 [ HCCH + one mole H2 , Pt  CH3 CH3 + CH2 =CH2 + HCCH ] H \ / Na or Li C=C anti- NH3 (liq) / \ H —CC— \ / H2 , Pd-C C =C syn- Lindlar catalyst / \ H H 3/20/2022 BMC 2022 83 CH3 H \ / Na or Li C=C anti- NH3 (liq) / \ H CH3 trans-2-butene CH3 CCCH3 H H \ / H2 , Pd-C C =C syn- Lindlar catalyst / \ CH3 CH3 cis-2-butene 3/20/2022 BMC 2022 84 42  20/03/2022 2. Addition of X2 X X X | | | — C C— + X2  — C = C — + X2  — C — C — | | | X X X Br Br Br CH3 CCH + Br2  CH3 C=CH + Br2  CH3 -C-CH Br Br Br 3/20/2022 BMC 2022 85 3. Addition of hydrogen halides: H H X | | | — C C— + HX  — C = C — + HX  — C — C — | | | X H X a) HX = HI, HBr, HCl b) Markovnikov orientation Cl CH3 CCH + HCl  CH3 C=CH2 + HCl  CH3 CCH3 Cl Cl 3/20/2022 BMC 2022 86 43  20/03/2022 4. Addition of water. Hydration. O — C  C — + H2 O, H+, HgO  — CH2 — C— H OH —C=C— “enol” keto-enol tautomerism Markovnikov orientation. 3/20/2022 BMC 2022 87 CH3 CH2 CCH + H2 O, H2 SO4 , HgO  1-butyne O CH3 CH2 CCH3 2-butanone 3/20/2022 BMC 2022 88 44  20/03/2022 5. As acids. terminal alkynes only! a) with active metals CH3 CCH + Na  CH3 CC-Na+ + ½ H2  b) with bases CH3 CCH + CH3 MgBr  CH4 + CH3 C CMgBr SA SB WA WB 3/20/2022 BMC 2022 89 acid strength: CH4 < NH3 < HCCH < ROH < H2 O < HF HC CH + NaOH  NR ( H2 O = stronger acid! ) CH3 CH2 CCH + LiNH2  NH3 + CH3 CH2 CC-Li+ SA WA 3/20/2022 BMC 2022 90 45  20/03/2022 6. Ag+ terminal alkynes only! CH3 CH2 CCH + AgNO3  CH3 CH2 CC-Ag+  CH3 CCCH3 + AgNO3  NR (not terminal) formation of a precipitate is a test for terminal alkynes. 3/20/2022 BMC 2022 91 7. Oxidation KMnO4 R-CC-R´ hot KMnO 4 RCOOH + HOOCR´ carboxylic acids O3 ; then Zn, H2 O 3/20/2022 BMC 2022 92 46  20/03/2022 CH3 CH2 CCCH3 + KMnO4  CH3 CH2 COOH + HOOCCH3 CH3 CCH + hot KMnO 4  CH3 COOH + CO 2 CH3 CCCH3 + O3 ; then Zn, H2 O  2 CH3 COOH 3/20/2022 BMC 2022 93 Alkynes Nomenclature Syntheses 1. dehydrohalogenation of vicinal dihalide 2. coupling of metal acetylides with 1o /CH3 X 3/20/2022 BMC 2022 94 47  20/03/2022 Reactions, alkynes: 1. addition of H2 (reduction) 2. addition of X2 3. addition of HX 4. addition of H2 O, H+ 5. as acids 6. Ag+ 7. oxidation 3/20/2022 BMC 2022 95 POST-TEST https://forms.gle/8xxEncxn9xCxwg6R9 www.knust.edu.gh 3/20/2022 BMC 2022 96 48