Organic Reactions Summary For Use as a Study Guide ... - CPP

1 Typical First Year Organic Reactions Beauchamp 1 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Organic Reactions Summary For Use as a Study Guide Beauchamp Typical First Year Organic Reactions Beauchamp 2 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Important acid/base Reactions used in the examples below. Write out every one of these easy mechanisms. OHNathiolates are good nucleophiles,SN2>E2atMe,1oand 2oRX,and strong bases, E2 > hydroxideRH2 CSHthiolsRH2 CSNaKeq=Ka(RSH)Ka(H2O)10-810-16=10+8 Keq= n-BuLiLDA is a very strong base thatis also very sterically hindered,it always acts as a base in = lithium diisopropylamidediisopropylamineLiKeq=Ka (HNR2)Ka(H-C4H9)10-3710-50=10+13 Keq=NHn-butyl lithiumN Typical First Year Organic Reactions Beauchamp 3 y.

2 \files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with NR2 Naenolates are good nucleophiles, SN2 > E2 at Me, 1o and 2o RX, and strong bases, E2 > SN2 at = lithium diisopropylamideestersNaKeq =Ka(ROCOCH3)Ka(HNR2)10-2510-37=10+12 Keq =ester enolatesOCOCR2 HOCOCR2RR NR2 Naenolates are good nucleophiles, SN2 > E2 at Me, 1o and 2o RX, and strong bases, E2 > SN2 at = lithium diisopropylamidecarboxylic acidsNaKeq =Ka( O2 CCH3)Ka(HNR2)10-2510-37=10+12 Keq =acid dianionOCOCR2 HOCOCHR2H2 NR2 Naenolates are good nucleophiles, SN2 > E2 at Me, 1o and 2o RX, and strong bases, E2 > SN2 at = lithium diisopropylamidenitrilesKeq =Ka( O2 CCH3)Ka(HNR2)10-3010-37=10+7 Keq =nitrile enolateCCR2H2 n-BuLin-butyl lithium removes proton from sulfur salt and makes a good nucleophile at ketones and aldehydes, forming =Ka(HCR2 SPh2)Ka(H-C4H9)10-3310-50=10+17 Keq =n-butyl lithiumsulfur salt = ylidRCSPh2 XHRRCSPh2R n-BuLin-butyl lithium removes proton from dithiane and makes a good nucleophile at all of our electrophiles.

3 It can react once or twice in SN2 Reactions . Sulfur acetal forms carbonyl group after hydrolysis using Hg+2. Makes aldehydes and =Ka(dithiane)Ka(H-C4H9)10-3310-50=10+17 Keq =n-butyl lithiumdithianeSCSHH dithiane carbanionSCSH Typical First Year Organic Reactions Beauchamp 4 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Arrow-Pushing schemes for the above Reactions HONacarboxylatesRCOOHRCOON acarboxylic acidsHNaalkoxidessodium hydoxideRH2 COHalcoholsRH2 CONasodium hydrideHOHHH thiolatesRH2 CSHthiolsRH2 CSNaHONaHOHNR2 Nasodium amideterminal alkynesCRCH terminal acetylidesCRCNaLDAlithium diisopropylamidediisopropylamineLiNHn-bu tyl lithiumNCH2H2CH2 CCH3 Liketones / aldehydesNaketone enolatesRCOCH2 HRCOCH2 LDANR2 NaestersNaester enolatesOCOCR2 HOCOCR2 RRLDANR2 Nacarboxylic acidsNaacid dianionOCOCR2 HOCOCHR2H2 enolateCCR2 HNaNCCR2 NbetaineWittig salt = ylidRCPPh3 XHRRCPPh3 Rbetainesulfur salt = ylidRCSPh2 XHRRCSPh2 RLidithianeSCSHH dithiane carbanionSCHSHLDANR2 NaLDANR2 Nan-butyl

4 LithiumCH2H2CH2 CCH3 Lin-butyl lithiumCH2H2CH2 CCH3 Lin-butyl lithiumCH2H2CH2 CCH3 Lisodium hydoxide Organometallics used in our course (Mg, Li and Cu) RBrLiRBrRBrLiLiRLiorganolithium reagentsbromohydrocarbonsdiscardLi RBrRBrRBrRGrignard reagents(organomagnesium reagents)bromohydrocarbonsMgMgMgMg+2 BrR(MgBr) CuBrRLiRCuRLiRCuRLireacts with RBr (SN2)reacts with acid chloridesreacts with , -unsaturated C=Odialkyl cuprates Typical First Year Organic Reactions Beauchamp 5 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with SN2 versus E2 choices at 2oRX. At secondary RX (X= OTs, I, Br, Cl) SN2 and E2 products are in close competition with each other.

5 Anions whose conjugate acids have higher pKa s (stronger bases have weaker acids) generally produce more E2 relative to SN2. The examples that we will emphasize at 2oRX centers are carboxlyates (SN2 > E2) vs hydroxide and alkoxides (E2 > SN2), and cyanide (SN2 > E2) vs terminal acetylides (E2 > SN2), azide (SN2 > E2) vs dialkylamides (E2 > SN2) and metal hydrides (SN2 > E2) vs simple hydride (E2 > SN2). Higher basicity and steric hindrance in either RX or the electron pair donor also favors E2 > SN2. The following examples show similar looking base/nucleophiles (used in our course) that react differently with 2oRX structures. (They all react by SN2 at methyl and 1oRX and they all react by E2 at 3oRX.)

6 It is the Reactions at 2o RX centers that are ambiguous. 2o RX structures are the most basic, so SN2 > basic, so E2 > of conjugate acid = 9pKa of conjugate acid = 25pKa of conjugate acid = 5pKa of conjugate acid = 16-19 RCOOOHOR cyanideterminal acetylidescarboxylateshydroxide and alkoxidesMore basic, so E2 > basic, so SN2 > E2. Less basic, so SN2 > basic, so E2 > of conjugate acid = 5pKa of conjugate acid = 37pKa of conjugate acid = ?pKa of conjugate acid = 37azidedialkyl amidessodium borohydridelithium aluminum hydridehydridesMore basic, so E2 > basic, so SN2 > Typical First Year Organic Reactions Beauchamp 6 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with 1.

7 Making RBr from alkane and alkene hydrocarbons and alcohols a. RBr from alkanes - mechanism using Br2 / h for free radical substitution of alkane sp3 C-H bonds to form sp3 C-Br bonds at the weakest C-H bond. H3CH2 CCH3H3 CCHCH3 BrBrBroverall reactionh BrH1. initiationBrBrh BrBr H = 46 kcal/moleweakest bond ruptures first2b propagationH3 CCCH3 HBrBrH3 CCCH3 HBrBr H = -22 kcal/mole (overall)BE = +46 kcal/moleBE = -68 kcal/mole2a propagationH3 CCCH3 HHBrBrHH3 CCCH3H H = +7 kcal/mole (overall)BE = +95 kcal/moleBE = -88 kcal/mole H = -15both steps3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrationsBrH3 CCCH3HH3 CCCH3 HBrH3 CCCH3 HCH3CH3 CHCHCH3H3 CCHCH3CH3 H = -68 kcal/mole H = -80 kcal/molevery minor product Example Reactions BrBr2 / h CH4Br2 / h BrH3 Cachiralachiral Brenantiomers (R and S)Br2 / h BrachiralBr2 / h can do E2 twice,to make alkynes2 Br2 / h BrBr Typical First Year Organic Reactions Beauchamp 7 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Brallylic substitutionBr2 / h b.

8 RBr from alkenes (anti-Markovnikov addition of HBr using free radical chemistry): mechanism using HBr / ROOR / h for free radical addition to alkane pi bonds (anti-Markovnikov addition = Br adds to less substituted position to form most stable free radical intermediate, and then H adds to more substituted position) H3CH2 CCH2 BrH3 CHCCH2 HBrR2O2 (cat.)h overall reaction1. initiation (two steps)ROORh ROORBrHROROHBr H = 40 kcal/mole H = -23 kcal/moleBE = +88 kcal/moleBE = -111 kcal/mole(cat.)reagent2a propagationH3 CHCCH2 BrH3 CCCH2 BrH H = -5 kcal/moleBE = +63 kcal/mole BE = -68 kcal/mole H = -15both steps(2a + 2b)2b propagationH3 CCCH2 BrHBrHH3CH2 CCH2 BrBr H = -10 kcal/moleBE = +88 kcal/mole BE = -98 kcal/mole3.

9 Termination = combination of two free radicals - relatively rare because free radicals are at low concentrationsBrH3 CCCH2 HBrCH2 CCH3 HCH2CH3 CHCHCH3H2 CCHCH2CH3 H = -68 kcal/mole H = -80 kcal/molevery minor productsH3 CCCH2 BrHBrBrBrBrBr Example Reactions H-Br / h ROOR (cat.)Brachiral Br2 / h ROOR (cat.)Brachiral Typical First Year Organic Reactions Beauchamp 8 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Br2 / h ROOR (cat.)BrR/Senantiomers BrBr2 / h ROOR (cat.)cis and trans c. RBr from alkenes (anti-Markovnikov addition of HBr using borane chemistry): mechanism using 1. BH3 2. Br2 / CH3O-- for anti-Markovnikov addition of H-Br to alkane pi bonds (concerted, syn addition of H-BH2 to alkene pi bond, followed by complex with Br2 and migration of R group to Br) H3CH2 CCH2 BrH3 CHCCH2overall reactionstep 1 BHRR1.

10 (BH3)22. Br2, CH3OH2 CCCHH2 CCH2CH2CH3H2 CCCH2 CCH2CH2H3 CHHBRRsyn addition, with H at more substituted position and B at less substituted 2H2 CCCH2 CCH2CH2H3 CHHBRRBrBrH2 CCCH2 CCH2CH2H3 CHBRRBrBrHH2 CCCH2 CCH2CH2H3 CHBRRBrHBrOH3CH2 CCCH2 CCH2CH2H3 CHBRRBrHOCH3H2 CCCH2 CCH2CH2H3 CHBRRBrHOCH3 Example Reactions Brachiral1. (BH3)22. Br2, CH3O Typical First Year Organic Reactions Beauchamp 9 y:\files\classes\ Organic Chemistry Tool Chest\ Reactions Lists\Org rxns Summary , SN-E, C=O, epoxides chem, with Brachiral1. (BH3)22. Br2, CH3O BrR/Senantiomers1. (BH3)22. Br2, CH3O Br( ) or (dl) enantiomers1. (BH3)22. Br2, CH3O d. RBr from alcohols: i. mechanism using HBr SN2 at methyl and 1o ROH.