INTRODUCTION TO ORGANIC REACTIONS @ 2 >0 - & What make chemical reactions happen? What factors determine the reactivity of organic compounds? Prepared by Maria Nora B. del Rossrie Reaction Mechanism During a chemical reaction, two molecules collide in such a way that bonds are broken and bonds are formed leading to the formation of new molecules. In general Substrate + reagent — intermediate(s) + products by-products Reaction mechanism describes the various steps that occur in the conversion of the reactants to products.Reaction Mechanism Mechanism of a reaction © Very important to our understanding of reactions The detailed course of an overall reaction — its sequence and timing of steps and the details of e movement. » Purely theoretical description of all the bond breaking and bond forming processes taking place in a reaction. = Itis based on experimental facts about the reaction; it is valid if it consistently explains many experimental facts. EXERCISE Use curved arrows to show the movement of electrons in each of the following reaction steps oO a cHe—o—H + HOT —- cHd—o + Bt: Br ae b ] +e —(f Cod Co « endon + 1—G—n — crdoun + 1.0 h cH, cn a. cu—d—er — en—é- + or Hy HyReactivity Sites + Basically chemical reactions of organic compounds involve attack of an e‘rich reagent (or nucleophile, Nu’) on an e"poor site on a substrate; or attack of an epoar reagent (or electrophile, E*) on an evrich site in a molecule ® Mainly, attraction of a (—) specie to a (+) site, or of a (+) specie to a (-) site. > Hence, organic reactions take place on the functional group. Example Et Reactivity Sites “+ Functional group — structural unit that acts as y of a molecule the center of reacti cholesterolEXERCISES Predict the sites on each of the following compounds where the reaction can occur: a, CH;CH =CHOCH, + H* ANAS + Be a bh + HO a ON ) + Ht A Reagents Nucleophiles (Nu-) An electron-rich species “Has a pair of electrons it can share > those with excess (—} charge or © those that possess lone pairs or unsaturations. HO CH3gNH2 H2G;| these are nucleophiles because they have a pair of electrons to shareReagents Common nucleophilic reagents: Anions or Neutral compounds with negatively charged species| _ lone pairs of electron HO: {hydroxide jon} HGH (water? 'H=> (hydride ion) ROH (an alcohol) HN (ammonia) RH, {an amine) eee yeh (hydrazines) “NH, (amide ion) x (halides) ee, Ch Ber Reagents + all nucleophiles sre bases. Trend in nucleaphilicity, i.e. reactivity as nucleaphile, parallels base strength: Reactivity: H> R> RjN> HjN> “OR> “OH> @iO> RCOO >X- telative acid strengthsReagents Nueleophile @ Effect of Solvent Tncreaah mucteophilicty || Ofthe i ina imaprotic || halogens: we salen e risthe biggest anion > co i polarizable Be- > eigerron pairieast e shielded > increasing feast cen deophibckty atetes Nucleophilicity in protic solvents: |- > Br- > Cl > F- iue., Strength as 2 nucleophile RS-> RO- Reagents Nucleophile @ Effect of Solvent Solvolysis “ Reaction with a solvent } Solvent also acts as a nucleophile. Example: = Water can serve both as the nucleophile and the solvent.Reagents ~ CHs ° Nucleophile @ Effect of Size - ie Hy tert-butexide ion crc” tenth ethoxide lon better nucleophile, racine pater Nucleophilicity is Affected by Steric Effects Reagents Electrophiles (E*) Electron deficient/poor species — looks for electrons “electron loving” > Species that may possess formal (+) charge, or an atom with an unpaired electron, or incomplete octet or with sites which have greatly reduced & densities. Examples: H*, CH,*, R-C=O, *NO,, SO, = ig Is an slectrophile because tis seeking an electronEXERCISE Which of the following are electrophiles, and which are nucleophiles? H AIC; = CHO CHYC=CH_—CH,CHCH, NH Two Ways Covalent Bonds Can Be Broken Homolytic cleavage + One in which a bond is broken symmetrically. One e- remains to each of the originally bonded atoms giving rise to radicals. XY =o Xe + eY —___— Free radicals [free radicals + have odd numbers of electrons; ——| lack electron > unstable > electron-seeking ale — H+:Two Ways Covalent Bonds Can Be Broken Heterolytic cleavage + One in which the pair of bonded e's stay united and attached to only one of the two originally bonded atoms giving rise to cations and anions. XY = XxX EXERCISE Match the different curves with the different types of reaction given: Areaction where: a, Bonds are broken, no bands are formed b, No bonds are broken, bonds are only formed ef Bonds are broken, bonds are formed, reactions endo d. Bonds are broken, bonds are formed, reaction is exo Reaction coordinateReaction Intermediates Many organic reaction: transient Carbon radicals -¢— = Fragments of niolecules, which are formed by the removal of a group, attached to carbon taking one of the bonding e's with it and leaving one to carbon. It has characteristics between the carbonium ions and the carbanions. Reaction Intermediates Carbon radicals -<— Different Types of Free Radicals ° . R. ee cH, R-CH, RCH R-CR methyl fir. 1° fir. 2° fin 3° fir. In any charged species, the greater the dispersal of charges (i.¢., the greater the no. of atoms. sharing with the charge or the greater the area at which charge is distributed), the more stable the species. Free radicals may be considered as a charged species; electron deficient.Reaction Intermediates Carbon radicals -C— | Compared to aH, R(alkyl) groups are e-—donating, Hence, the order of stability of fir. intermediates: relative stabites ef radicals benzyl ab ‘erty —sacondary primary viny|_—_methy radical rede diel nadie! rachel rade mda Carbonium ions or carbocation = = Fragments of molecules in which a group and the pair of bonding e's are removed from one of the carbon atoms. It is in the sp? state of hybridization.Reaction Intermediates Carbonium or carbocation 7 Relative Stabilities of Carbocations: 2. a ce > ced Rem wt > att = ateriarr —aseconday —asecondory —eptinary a pray citeatien _tabennet__veyirtame _coboamn _vapitenee “eawen™™ Carbon Stability’ 3°> 29> 1° Reaction Intermediates Carbonium or carbocation “c— Relative Stabilities of Carbocations | | set sect Gise-donating groups: GIs e-withdrawing groups: ¥ diminishes (+) charge intensifies (+) charge ® stabilizes Rt ® destabilizes Ri*) “ Electron donating group diminishes (+)charge and therefore stabilizes the carbocation + Electron withdrawing group intensifies (+) charge; therefore, destabilizing carbocation.EXERCISES ing stability | b a, cuctden CH,CH.CHCH cu,cucu,cH, C7 a bay cuguctitt, 3 ? Reaction Intermediates ra Jone-pair electrons anions —C— are In an sp} orbltal s Fragments of | Sorameapy molecules, which are | | sp3s overlap formed by the removal of a group without the pair of TH, bonding e's. It is in methyl anion the sp? state of hybridization.Reaction Intermediates Carbocation stabili is more stable than 1°. Carbanion stability: 1° is more stable than 3° (relative stabilities of carbocations: R R most least pony carbocation carbocation carbocation cation, {atv aber of bles H eebe : of < + < tertiary secondary primary methyl carbanion carbanion eérbanion ‘anion EXERCISE Which reaction intermediate(s) is/are described by the ff: A. Carbocations 8.Carbanions C.Carbon radicals or D.none 1. The reactive carbon is sp hybridized 2. The reactive carbon is sp? hybridized 3. The reactive carbon is sp3 hybridized The reactive carbon has an incomplete octet of electrons in its outermost shell. s formed by homolytic bond cleavage s formed by heterolytic bond cleavage tis a nucleophile oN w tis an electrophile.Classification of Organic Reactions ‘© Emphasizes the changes that occur in the bonding of ¢ atoms | Substitution An atom or group attached to Cis removed and another takes its place. This takes place either at saturated or unsaturated C. At the reactive C, no change in the degree of unsaturation occurs. e.g. CH;Br + Cl = CH,Cl + Br Classification of Organic Reactions | Addition mT attached to C. This takes place among compounds which are unsaturated, | @ associated with C=C, -C=C- & C=O, and es therefore capable of accepting additional atams or groups. \ eg. HC=CH,+Br,H,C-CH, |™ 9 fa Best Tae ee oe | 7Classification of Organic Reactions Elimination YA decrease in the number of groups bound to C. e.g. CH;CH,Cl + “OH & H,C=CH, + H,0 + Cr Classification of Organic Reactions Rearrangement reactions can occur on all three reactions in which the C skeleton of the molecule is internally arranged. e.g. ha fa H3C-C-CH=CH, + HC] = H,C-(-CH-CHs CH; CICH, earrangement i tlClassification of Organic Reactions [Occurrence of Rearrangement | | Rearrangement may be 1,2-hydride -hit, or 1,2emnethyl shift or 1, 2ealky shift ae Zeon 2ealky! e Addition Reactions | oy, ere icH—CH, were — CR CHCHCH; + cadoucn, Seve peda L. he Poromo zmavyibutane 3 bromo.2inetby butane cH, H, Hs 1 pm 1, cutr—oncen, + Ge — ond fe onc ona, sah sey ‘When amore stable Re | a uacentary nen Sa aaa] resrranges by either 3 [terbocaion fr eat cn, hydride (+) oF sn allyl , ant case, IR) shift to an adjacent cudn—cuca, 4 Csuch that the (+) k sor product, charge ean be better se se accommodated EXERCISE Classify the ff reaction as: A. Substitution 8. Addition ¢. Elimination D. Rearrangement CH,CH,CH(OH)CH,CHO <> CH,CH,CH=CHCHO + H.G CH, CH=CHBr + OH = CH,C=CH + H,0 + Br (CH,),C=O + 2 CH,OH + Ht © (CH,),C(OCH,), + H,0 C,H, + 3H, > C,H, C,H, + HNO, = C,H,NO, + H,0 (CH,),CCl + -OH => (CH,),C-OH + Cr PPP YY eThe Orientation Factor (i Eee cats (Metis alse ‘Since orbitals and thelr mutual overian ta form bond have strong siractionalty, there ‘will be 2 geometric constraints on the direction and orientation in which reactants can come together for a successful reaction Orbitals must be aligned along the inter nuclear axis. The Orientation Factor Regioselective reaction One in which two constitutional isomers can be obtained as products but forms more of one constitutional isomer than another. ‘Areaction can be moderately regioselective, highly regioselective, or completely regioselective depending on the relative amounts of the constitutional isomers formed in the reaction.The Orientation Factor Regioselective Reaction Example Cus gis Cy cHcecn, + Hcl cHdécH, CH,CHCHAEI 2-methylpropene fert-betyl chloride tecbutyl chloride cx, cu, cade, = S2 endon, tertebuty! eation i CHs uty! cl r tert-butyl chloride (CHsCe=CH, + HCI only uct formed NL cay City arndaén, 2 ndacuc icobutyl cation isebutyl chleride " not fommed reaction is regioselect The Orientation Factor Stereoselective Reaction & One which forms more of one stereoisomer than another. a stereoselective reaction A—B+CE more B is formed than CThe Orientation Factor Stereoselective Reaction Examples An‘$,2 reaction takes place with inversion of configuration The Orientation Factor In 8 stereospecific reaction each stereoisomer forms 3 different stereoisomeric product ora different set of stereoisomeric products. A stereospecific reaction is also stereoselective but a stereoselective is not necessarily stereospecific stereospecific reactions A — B. (iesiean” SseThe Orientation Factor Stereoselective Reaction 7 ee Soman ean 7 Rox + eth incu, “arvthe-anarruses sia Flacher prelectlens Reaction Coordinate Diagram “Shows the energy changes that take place in each of the steps of the mechanism. "In a reaction coordinate diggram, the totel energy of all species is plotted against the progress of the reaction. A. reaction progresses from left to right as written in the chemical equation, so the energy of the reactants is plotted on the left- hand side of the x-axis and the energy of the products is plotted on the right-hand sid ———___; Peagresof the reactionReaction Coordinate Diagram # In the reactants, bonds are broken (energy- requiring processes) while in the products, bonds are formed (energy- releasing processes). “Curve shows that at the beginning, there are more bonds breaking than bond forming, but towards the end, there are more bond forming than bond breaking. Reaction Coordinate Diagram b Fee eaergy AG? = (free energy of the products) — (Ire energy of the reactants)Reaction Coordinate Diagram Two Fields of Chemistry Involved in Understanding Organic Reactions * Thermodynamics — * Kinetics — deals with the describes a reaction at rates of chemical equilibrium reactions > The relative concentrations of products and reactants at equilibrium depend on their relative stabilities: The more stable the compound, the greater is its concentration at equilibrium Reaction Coordinate Diagram Two Fields of Chemistry Involved in Understanding Organic Reactions Consider a reaction in which Y is converted to Z Y » The thermodynamics of the reaction gives the information regarding the relative amounts of Y and Z that are present when the reaction has reached equilibrium. » The kinetics of the reaction provides an idea on how fast V is converted into Z.Reaction Coordinate Diagram Energy Changes During A Reaction Eset = Es. ~ creactants > E,.,is the minimum amount of energy needed for a reaction to occur. * It determines how readily a reaction will occur. H BA xn = Aproducts ~ It is not the AH, which determines how readily a reaction will occur. reactants The more stable the transition state (t.s.) > the lower the E,, > the lower the E, , > the faster the reaction. Reaction Coordinate Diagram May be use in solving the ff types of problem 1. Comparison of rates of different pathways, which a particular reaction can take path 1 CH,-CH,-CH, + HCl e.g. CH:CH3CH; + *Cl . path 2] CHs-CH-CH, + HCIReaction Coordinate Diagram 2. Comparison of reactivities of different compounds towards the same reagent e.g.H,C=CH, + HCl & (CHg),C=CH, + HCl > Reaction Coordinate Diagram “ For reactions involving two or more step CHCH=CHCH, + H—Br —> SHG SE AOE ole H Br oH avcarbocation ‘2bromebutane analkylhalide a OR CH.CH—CHCH, + H — Car a + Be H CH,CH—CHCH; + :BiT —> CH,CH—CHCH, % | Sf a SHY:Reaction Coordinate Diagram } For reactions involving two or more step CHCH=CHCH, + HBr “ee CHCHCHCH, + Be “h ‘transition state CAGHCHCH, + Be psenen CHLCHCHLCH, be h semesasoe! :Reaction Coordinate Diagram = For reactions involving two or more step, the slowest step (one with the highest E,,) is the rate-determining step. > The 1" step is the rate determining step It determines the rate of overall reaction. EXERCISES For each of the following reaction coordinate diagrams, tell whether the structure of the transition state will be more closely resemble the structure of the reactants or the structure of the products: | | b 4 4,EXERCISE For the reaction: “OH (CHz)3CBr = (CH3)3C+ + Br => (CH3)3C-OH slow fast 3. Draw the energy profile diagram showing that the product is more stable than the reactant. b. In your diagram, show the positions of the initial reactant, transition states, intermediate(s}, and product. c. Draw the structures of the transition states and intermediates. Oxidation- Reduction Reactions Involves changes in oxidation state as a consequence of changes in covalent bonding between atoms of different EN values Oxidation - T in oxid Reduction - ) in oxid state state > Oxidation and reduction are always linked together. Oxidation at carbon signifies decrease in the number of C-H bonds or increase in the number of C-O, C-N, or ‘CX bonds. Reduction at carbon signifies an increase in the number of C-H bonds or decrease in the number of C-Q, C-N, or CX bonds.Oxidation- Reduction Reactions +» Oxidizing agent - compound that brings about oxidation and is reduced. It is represented by the symbol [0]. “> Reducing agent - compound that brings about reduction and is oxidized. It is represented by the symbol [H]. Some common oxidizing agents ‘Strong Mild KMnO, / H? & its neutral soln (CrO3 in pyridine K,Cr,0, / H* & its neutral soln cut, “OH Ag? in Tollen’s reagent Tollen’s A: Ag(NH3)3* Tollen’s B: NaOH 0; /2n /HOAc Oxidation- Reduction Reactions Some common reducing agents sn/ Hcl H, / Pt or Pd or Ni ® reduces both C=O & C=C LIAIH, or NaBH,, H* / H30 ® reduces only C=O not C=COxidation State “* The neutral atom of the element has an oxidation state of zero. © e.g, Oxid. no. -£+=0 Oxid. No. He =0 Oxid, No.*G-=0 “+The possession of the electron pair ina covalent bond is assigned to the more electronegative atom of the two bonded atoms. Oxidation State Example: In the case of C in organic molecules 1. In a carbon-hydrogen bond, the bonding electrons are assigned to C since C is more electronegative than H. The circle loses th HGH The C possesses 8 electrons | "32se5n* H Oxidation state of C=-4 raeena ‘the carbonOxidation State 2. In a carbon-carbon bond, neither C can easily be assigned both bonding electrons and so each is assigned only 1. HH Each C possesses 7 electrons H3t2GZH Oxidation state of C= -3 HH 3. In a carbon-heteroatom bend, the bonding electrons are assigned to the heteroatom since the heteroatom is more electronegative than C. H The C possesses 6 electrons H#C¥O3H Oxidation state of C = -2 H Oxidation State “Hence, the oxidation state for any single C atom is obtained by adding the ff values from each of its four bonds > -1 for each H } OforeachC > +1 for each bond to a heteroatom more electronegative than C.Oxidation States of Carbon in Organic Compounds Oxidation 1c 2°c 3°c ac state 4 CHy 3 RCH; 2 CH;OH ACH) -1 RCH;0H R3CH 0 H,C=0 R,CHOH Rc +1 RCHO R;COH 42 HCOOH RCO 43 RCOOH +4 co, Oxidation- Reduction Reactions Examples H \ (2) HoC-e=c-¢=0 | HHHH Total =-4 HH H,CrOy wd HEGOH => HoH No change in total oxidation state LP mFS H OH Total = 0 “Loss of 4 in total oxidation state (Qxidstion) Gain of 2e"in total oxidation state (Reduction) H H \ f Hegel HHH Total =-8Oxidation- Reduction Reactions (Oxidation Reduction RCH=CH Ha RCHSCH; nese a (f ‘i alkent 5 @ tne of a oro | ee ee A.M con RH RO ~OH R To ‘ aot cant HNN veo te. Ben FA ae noe an alcohol ~aketone Common Oxidation Path 1a 1 Alkenes 1®Alcchols * Aldehydes * Carboxylic acids or [OH 2° Alcohols {2! Ketones 9! No reaction Alkynes 3ealcohals ' No reaction No reaction under mild conditions; several degradation products are ‘obtained under drastic conditions, Examples (0 ] ce (0) H,C=CH,-F HO-CH.CH.-OH® 2 H.G-0 2H.C20-* 00, H Final ProductsEXERCISES Indicate whether each of the following reactions is an oxidation reaction, a reduction reaction, or neither: o a — ey { oy, partially HyCr0, CHE Cl deaatated CH! a chchon —— c bd cu¢ “on Br | » roH=cHe ME, Retuk —e CHAO=N BE CHCHNH: Br ee &. O al) Cr f CHSCKCHBr ——> CHCH:CHDOH.