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Revision Notes, Chemistry 2, complete

Chemistry 2 (University of Melbourne)

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9 The acidity of ketones is due to the conjugate base resulting from loss of a proton is stabilised by resonance. This is called homolytic.i. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 9 A bond can break in an electronically symmetrical way so that one electron remains with each product fragment. 9 Acids donate protons.e. Nitrogen containing compounds are most common. 9 Considers which bonds are broken an in what order.e. 9 pKa=-logKa 9 A stronger acid has a smaller pKA and a weaker acid has a larger pKa. 9 Organic bases are characterized by the presence of an atom with a lone pair of electrons that can bond to protons. 9 Stronger acids have their equilibria more towards the right and have larger acidity constants. The strength is indicated by the acidity constant. 2. lOMoARcPSD|2416048 2. 5. It is additionally stabilized by resonance. 9 There is an inverse relationship between the acid strength of an acid and base strength of its conjugate base.2 How Organic Reaction Occur: Mechanisms 9 A reaction mechanism is an overall description of how a reaction occurs. 9 The product conjugate acid in an acid-base reaction must be weaker and less reactive than the starting base. which resembles the degree to which an acid is ionised in solution.7 Acids and Bases: The BrØnsted-Lowry Definition 9 Acidity and bacidity are related to a molecules electronegativity and polarity. exactly what takes place at each stage of a chemical transformation. and bases accept protons 9 Water can act either as an acid or a base 2.8 Acid and Base Strength 9 Acids differ in their ability to donate protons. Additionally one of the resonance forms stabilises the negative charge by placing it on an electronegative oxygen atom. and are of two main kinds: (1) Contain a hydrogen tom bonded to an electronegative oxygen atom (i.e. and the conjugate base of a weaker acid will remove the proton from a stronger acid. some reacting almost completely and others only slightly. 2. followed by oxygen containing . acetone) 9 In both cases acidity is due to the fact that the conjugate base resulting from loss of proton is stabilized by having its negative charge on a strongly electronegative oxygen atom. methanol and acetic acid) (2) Contain a hydrogen atom bonded to a carbon atom next to a C=O bond (i.10 Organic Acids and Organic Bases 9 Organic acids are characterized by the presence of a positively polarized hydrogen atom.9 Predicting Acid-Base Reactions from pKa Values 9 An acid will donate a proton to the conjugate base of a weaker acid.

has a negatively . they have no net charge. 9 Polar reactions involve unsymmetrical bond-breaking and bond-making and are the most common reaction. 9 Radical (neutral chemical species that contains an odd number of electrons and has single unpaired electron) reactions involve symmetrical bond-breaking and bond-making. 5. 5. 9 Bond polarity is a consequence of an unsymmetrical electron distribution in a bond and is due to the difference in electronegativity of the bonded atoms. This is called heterolytic. electron-rich atom and can form a bond by donating a pair of electrons to a positively charged. 9 Most organic compounds are electrically neutral. leaving the other with a vacant orbital. 9 As the electric field around a given atom changes because of changing interactions with solvent or other polar molecules nearby. the electron distribution around that atom also changes. 9 Large atoms with more. The measure of this response to an external electrical influence is called the Polarizability of the atom. electron poor atom and can form a bond by accepting a pair of electrons from a nucleophile. lOMoARcPSD|2416048 9 A bond can also break in an electronically unsymmetrical way so that both bonding electrons remain with one product fragment. 9 Metals are less electronegative than carbons. loosely held electrons are more polarisable. ammonia. 9 An electrophile has a positively polarized. 9 A bond can form in an electronically symmetrical way if one electron is donated to the new bond by each reactant or in an unsymmetrical way if both bonding electrons are donated by one reactant.6 Using Curved Arrows in Polar Reaction Mechanisms 9 An electron pair moves from the atom at the tail of the arrow to the atom at the head of the arrow. 9 Rules of arrows: (1) Electrons move from a nucleophilic (Nu: or Nu:-) source to an electrophilic sink (E or E+) (2) The nucleophile can be either negatively charged or neutral (3) The electrophile can be either positively charged or neutral (4) The octet rule must be followed. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. water.4 Polar Reactions 9 Polar reactions occur because of the electrical attraction between positive and negative centres on functional groups in molecules. 9 A nucleophile is a substance that is “nucleus-loving”. hydroxide ion. and smaller atoms less so. 9 The fundamental characteristic of all polar organic reactions is that electron rich sites react with electron poor sites.

when only one of the two possible orientations occur. then yields a stable organo-mercury product. 9 Results in a carbon intermediate which reacts with water to yield a protonated alcohol product. 9 Hyperconjugation is the stabilising interaction between a vacant p orbital and properly oriented C-H bonds on neighbouring carbons. 9 The more stable intermediate is forms faster than the less stable one. the more electron density shifts toward the charge and the more inductive stabilisation of the cation occurs. 9 A more highly substituted carbocation is more stable than a less highly substituted one. thus the more alkyl groups there are attached to the positively charged carbon. 9 The stability of carbocations increases with increasing substitution so that the stability order is tertiary > secondary > primary > methyl. and transition states for exergonic steps structurally resemble reactants. 9 Transition states are high-energy activated complexes that occur transiently during the course of a reaction and represent an energy maximum.4 Addition of Water to Alkenes: Oxymercuration 9 Water adds to alkenes to yield alcohols. 9 Alkenes are often hydrated by Oxymercuration 9 Nucleophilic addition of water as in halohydrin formation. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 9 To determine carbocation stabilities one may measure the energy required to form the carbocation by dissociated of the corresponding alkyl halide. the H attaches to the carbon with fewer alkyl substituents and the X attaches to the carbon with more alkyl substituents. in the presence of a strong acid catalyst (HA). lOMoARcPSD|2416048 6. 6. followed by loss of a proton. 9 Hammond Postulate: The structure of a transition state resembles the structure of the nearest stable species. 9 In the addition of HX to an alkene.10 The Hammond Postulate 9 Electrophilic addition to an unsymmetrically substituted alkene gives the more highly substituted carbocation intermediate. 6. with the pi orbital being unoccupied. Transition states for endergonic steps structurally resemble products. 9 Biological hydration requires that the double bond be adjacent to a carbonyl group for reaction to proceed.9 Carbocation Structure and Stability 9 Carbocations are planar.8 Orientation of Electrophilic Additions: Markovnikov’s Rule 9 Reactions in which an unsymmetrical substituted alkene has given a single addition product are regiospecific. 9 The transition state for alkene protonation structurally resembles the carbocation intermediate 9 The transition state is stabilised by hyperconjugation and inductive effects in the same way as the product carbocation. . 9 Inductive effects result from the shifting of electrons in a sigma bond in response to the electronegativity of nearby atoms.

giving the alkane product and regenerating the catalyst. ketones. nucleophilic and bimolecular.e. 11. 9 In organic chemistry a reduction is a reaction that results in a gain of electron density by carbon. 9 Aldehydes. 9 The transition state for reaction of a sterically hindered (i. caused either by bond formation between carbon and a less electronegative atom or by bond-breaking between carbon and a more electronegative atom. 9 Catalytic hydrogenation is a heterogenic process rather than a homogenous one.the hydrogen bond has been hydrogenated or reduced. 3 methyl groups) alkyl halide. Measuring this is an indication of the kinetics of the reaction.takes place on the surface of insoluble catalyst particles.3 Characteristics of the SN2 Reaction 9 The rate of a chemical reaction is determined by the energy difference between reactant ground state and transition state.7 Reduction of Alkenes: Hydrogenation 9 In the presence of a metal catalyst alkenes react with H2. substitution. R-X + Nu:. although reaction with these groups does occur under more vigorous conditions. lOMoARcPSD|2416048 7. A second hydrogen is transferred from the metal to the second carbon. .Æ R-Nu + X:- 9 The inversion of stereo chemical configuration must therefore take place in the second step. the nucleophilic substitution of tosylate ion by acetate ion.2 The SN2 Reaction 9 There is a direct relationship between the rate at which the reaction occurs and the concentrations of the reactants. 9 Stereo chemical configuration is reversed compared the original molecule. 9 Molecular hydrogen and the alkene adsorb to catalyst surface and dissociate. 9 The nucleophilic substitution reaction of a primary or secondary alkyl halide or tosylate always proceeds with inversion of configuration. 11. a hydrogen ion is transferred between them forming an artificially reduced intermediate with a C-H bond. 9 Takes place in a single step without intermediates when the incoming nucleophile reacts with the alkyl halide or tosylate (the substrate) from a direction opposite the group that is displaced (the leaving group) 9 Nucleophile must approach from the opposite end of the molecule to the leaving group. concentrations and pH. esters and nitriles survive normal alkene hydrogenation conditions unchanged. whose carbon atom is shielded from approach of the incoming nucleophile is higher in Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 9 Substitutions occurs at different rates depending upon temperature.1 The Discovery of Nucleophilic Substitution Reactions 9 Nucleophilic substitution reactions involve the substitution of one nucleophile or hydroxide ion with another. 9 Reaction rate = rate of disappearance of reactant = k X [RX] X [OH-] 9 SN2 short for. 9 Second order reaction: reaction rate is linearly dependent on the concentrations of two species.

11. lOMoARcPSD|2416048 energy and forms more slowly than the corresponding transition state for a less hindered alkyl halide. 9 Solvent effects in SN1 reaction are due largely to stabilization or destabilization of the transition state.e.4 The SN1 Reaction 9 Tertiary halide substrates are most effective in SN1 reactions.e. 9 Polar aprotic solvents which surround the accompanying cation.5 Characteristics of the SN1 Reaction 9 Reaction is favoured whenever a stable carbocation is formed. 9 The exact nucleophilicity of a species in a given reaction depends on the substrate. 9 Unimolecular rate limiting step. and even the reaction conditions. with products showing a 1:1 ratio of stereo chemical isomers of original asymmetric molecule. 9 Most stable leaving groups are more reactive. Takes place more rapidly in strongly polar solvents. negatively charged with a higher ground state energy. 9 SN1 reactions are favoured in protic solvents because the transition-state energy leading to carbocation intermediate is lowered by salvation. the solvent. 9 Substrate characteristics: methyl and primary substrates. 9 Nucleophilicity usually increases going down a column of the periodic table as larger atoms hold their valence electrons less tightly are and consequentially more likely to react. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. Cl-. 9 Nucleophiles do not affect the rate of SN1 reactions. 9 Nucleophile attacks carbon from the back 9 SN2 reactions occur only at relatively unhindered sites. 9 Negatively charged nucleophiles are usually more reactive than neutral ones (reactions generally carried out under basic conditions) 9 As the leaving group is expelled with a negative charge the best leaving groups are those that best stabilize the negative charge in the transition state. 9 Nucleophile: basic. As a result of resonance stabilization. usually only primary and a few secondary halides. 11. such as water and methanol. and is the only factor upon which the reaction rate is dependent. 9 Reaction occurs through a carbocation intermediate. 9 An alcohol can be treated with para-toluenesulfonyl chloride to form a tosylate to improve its reactivity towards nucleophilic substitution. i. Reaction takes place by loss of the leaving group before the nucleophile approaches. tertiary alcohols. tertiary carbocations are the most stable and thereby the most likely to react. 9 Leaving group: more stable anions. . 9 Nucleophilicity roughly parallels basicity: strong bases often make strong nucleophiles. 9 Protic solvents (containing an –OH or –NH group) are generally the worst for SN2 as they undergo salvation of the reactant nucleophile and polar aprotic solvents (polar but neither of above groups) are the best as they raise the ground state energy of the nucleophile.

the electrophilic hydrogen is attracted to the p orbitals of the double bond and forms a bond to one carbon. 9 There is no geometric requirement on the E1 reaction because the halide and the hydrogen are lost in separate steps. which expels a leaving group on the adjacent carbon. such as hydroxide ion or alkoxide ion (RO-) 9 Takes place in one step including high energy transition state 9 Both base and alkyl halide determine the reaction rate.7 Elimination Reactions of Alkyl Halides: Zaitsev’s Rule 9 Elimination reactions are more complex due to the issues of regiochemistry and what products are expected to . Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 9 Syn periplanar (requires the substituents be eclipsed) and anti periplaner (preferred because it allows the substituents on the two carbons to adopt a staggered relationship) geometry are possible 11. 9 E1cB reaction. rate-limiting step gives an anion. but Sn1 substitution and E1 elimination occur together under neutral conditions. 9 Zaitsev’s rule: in the elimination of HX from an alkyl halide. E1cB elimination takes place if the leaving group is two carbons away from a carbonyl group. base-induced abstraction of a proton in a slow. E2 elimination occurs when a base is used. 9 Deuterium isotope effect: C-H breaks more quickly than C-D. 9 Tertiary alkyl halides. E2 elimination predominates if a strong base is used. such as in pure ethanol or water. the more highly substituted alkene product predominates. SN2. takes place through a carbanion intermediate. 9 Secondary alkyl halides: Sn2 substitution occurs if a weakly basic nucleophile is used in a polar aprotic solvent. E1 or E2. leaving a positive charge at the other carbon.12 A Summary of Reactivity: SN1. and E1cB elimination takes place if the leaving group is two carbons away from a carbonyl group. E1. E1cB and E2 9 Primary alkyl halides: Sn2 substitutions occurs if a good nucleophile is used. 16. and E1cB elimination occurs if the leaving group is two carbons away from a carbonyl group. lOMoARcPSD|2416048 11. This intermediate then reacts with the nucleophile to yield the addition product. E2 limination occurs if a strong base is used. 9 Occur in a Protic solvent with a non-basic nucleophile. Secondary allylic and benzylic alkyl halides can also undergo Sn1 and E1 reactions if a weakly basic nucleophile is used in a Protic solvent. 11. 9 Can be carried out through different mechanisms.8 The E2 Reaction and the Deuterium Isotope Effect 9 Occurs when an alkyl halide is treated with a strong base. 11.10 The E1 and E1cB Reactions 9 The dissociation of the alkyl halide with the carbocation is the slow rate-limiting step.1 Electrophilic Aromatic Substitution Reactions: Bromination 9 When a reagent approaches an alkene.

3 Alkylation and Acylation of Aromatic Rings: The Friedel-Crafts Reaction 9 Alkylation is the introduction of an alkyl group onto the benzene . Only alkyl halides can be used 2. Not on aromatic rings that are substituted by a strongly electron-withdrawing group such s carbonyl or an amino group. halogens.2 Other Aromatic Substitutions 9 Chlorine and iodine can be introduced into aromatic rings by electrophilic substitution reactions. i. and is rather slow. 9 Hydroxylation of an aromatic ring to yield a hydroxybenzene occurs more frequently in biological processes and is difficult to synthesize in a laboratory. a mixture of H2SO4 and SO3. 9 The reaction of an electrophile with a benzene ring is endergonic. 9 An aromatic ring can be acylated by reaction with a carboxylic acid chloride RCOCl in the presence of AlCl3 (same limitations apply as above) 16. ortho and para directing activators. but fluorine is too reactive and has a poor yield. carbonyl groups.e. e. 3. 16. 16. 9 Alkyl groups inductively donate electrons. 9 An inductive effect is the withdrawal or donation of electrons through sigma bond due to electronegativity. lOMoARcPSD|2416048 9 Aromatic rings are less reactive towards electrophiles than alkenes are. Difficult to stop the reaction after a single substitution. 9 The carbocation intermediate loses H+ from the halide bearing carbon to give a substitution product. 9 A resonance effect is the withdrawal or donation of electrons through a pi bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic group Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 9 Aromatic rings can be nitrated by reaction with a mixture of concentrated nitric and sulphuric acids with the electrophile being NO2+ which is generated from HNO3 by protonation and loss of water. hydroxyl groups. in nitration –OH activates and –NO2 deactivates. Skeletal rearrangement of the alkyl carbocation electrophile sometimes occurs. has a substantial activation energy. some activating or deactivating it.4 Substituent Effects in Substituted Aromatic Rings 9 Substituents affect the reactivity of the aromatic ring. Favoured in strong acid. 4. 1. but desulfonation in hot dilute aqueous acid. ortha and para directing deactivators and meta directing deactivators. 9 Aromatic rings can be sulfonated by reaction with fuming sulphuric acid. by treating the aromatic compound with an alkyl chloride RCl in the presence of AlCl3 to generated a carbon electrophile R+. although they are more stable due to resonance. 9 Substituents affect the orientation of the reaction . 9 Iodine is only reactive towards aromatic rings in the presence of a copper salt or hydrogen peroxide. The electrophile is either HSO3+ or neutral SO3.g. 9 Aromatic rings react with Cl2 in the presence of FeCl3. Forms nitrobenzene. cyano groups and nitro groups.

CrO3 and Na2Cr2O7 may be used depending on availability and cost.4 Nucleophilic Addition Reactions of Aldehydes and Ketones 9 The most general reaction of aldehydes and ketones is the nucleophilic addition reaction. 9 Hydroxyl. E. 9 Inductive and resonance effects account for the directing effects of substituents as well as for their activating or deactivating effects. Have a stronger electron withdrawing inductive effect but a weaker electron-donating resonance effect and are thus deactivators. This is then reacted with an acid to form an alcohol. but for a different reason than for alkyl groups. Lone pair electrons flow through. alkoxyl and amino groups are also ortha-para activators. 9 Reagent s including KMnO4. 9 Aldehydes are generally more reactive than ketones in nucleophilic addition reactions because of the greater polarization of aldehydes carbonyl groups. carbonyl. 9 Halogens are deactivating because their stronger electron withdrawing inductive effect outweighs their weaker electron donating resonance effect. Instantaneously rehybridisation of the carbonyl carbon from sp2 to sp3 occurs and an electron pair moves to the oxygen. Primary alcohols Æ aldehydes or carboxylic acids. 16.g.9 Oxidation of Aromatic Compounds 9 The benzene ring is inert to strong oxidising agents such as KMnO4 and Na2Cr2O7. raising the activation energy for its formation. placing a negative charge in the ring. alkoxyl and amino substituents donate electrons to the aromatic ring by resonance. Bromination occurs exclusively in the benzylic position and does not give a mixture of products. 9 Deactivating groups withdraw electrons from the ring making it more electron poor and thereby destabilizing the carbocation intermediate. . however alkyl side chains react rapidly with oxidising agents and are converted into carbonyl groups. 16. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. converting alkylbenzene into a benzoic acid. cyano and nitro groups. Only ortha and para have resonance forms in which the positive charge is stabilized by donation of an electron pair form oxygen. tertiary alcohols Æ do not normally react. hydroxyl. lOMoARcPSD|2416048 9 Halogen.5 An Explanation of Substituent Effects 9 Activating groups donate electrons to the ring and stabilize the carbocation intermediate and lowering the activation energy for its formation. 9 Side chain bromination at the benzylic position occurs when an alkylbenzene is treated with N-bromosuccinimide. 9 Ortho and para intermediates are more stabilized than the meta intermediate. giving it a negative charge.g. hydroxyl and amino groups. E. secondary alcohols Æ ketones. 19. 9 A primary carbocation is higher in energy and more reactive than a secondary carbocation. A nucleophile approaches along the C=O bond and adds to the electrophilic C=O carbon atom.7 Naming Alcohols and Phenols 9 Alcohols oxidise to yield carbonyl compounds.

Mineral acid protonates the carbonyl-group oxygenation. E. which is further reduced to a primary alcohol by nucleophilic addition. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. 19. 9 Grignard additions are effectively irreversible as the carbanion is too poor a leaving group. reactivity enhanced by HCl or H2SO4. treated with DCC to activate it. 9 Nucleophilic addition of the primary amine to the carbonyl group. 19.7 Nucleophilic Addition of Grignard and Hydride Reagents: Alcohol Formation 9 Aldehyde or ketone + Grignard reagent RMgX Æ alcohol 9 Grignard reaction.g.then adds through nucleophilic addition then produces a tetrahedral magnesium alkoxide intermediate. Leads to a C=N bond. 9 Reduction is a nucleophilic acyl substitution in which –H replaces –OH to give an aldehyde. followed by loss of water. Reversible. 9 Addition of water or aqueous acid after the hydride addition step protonates the tetrahedral alkoxide intermediate and gives the alcohol product.can be reduced be hydrolysed by hot aqueous acid to yield a carboxylic acid.3Nuclephilic Acyl Substitution Reactions of Carboxylic Acids 9 Under circumstances acid chlorides. esters and amides can all be prepared from carboxylic acids. nonacidic leaving group. anhydrides. followed by addition of the amine. 19. and protonation by addition of water or dilute aqueous acid in separate steps.6 Nucleophilic Addition of HCN: Cyanohydrin Formation 9 Aldehydes and unhindered ketones react with HCN to yield cyanohydrins. instead a proton is lost from the neighbouring carbon yielding enamine. Mg2+ adds to the carbonyl oxygen atom of the aldehyde or ketone making the carbonyl group a better electrophile. 21. No proton on nitrogen that can be lost to form a neutral imine product. acid-catalysed process. Occurs slowly when pure HCN is used but rapidly when a small amount of base is added to generate the nucleophilic cyanide ion CN-. 9 Cyanohydrin formation is useful as further chemistry can be carried out on the product. 9 Secondary amines R2NH Æ enamine R2N-CR=CR2. followed by transfer of a proton from nitrogen to oxygen to yield a neutral amino alcohol. R:. thereby giving the carboxylic acid a positive charge and rendering it much more reactive. acetic acid at temperature of 800 degrees 9 Carboxlic acid + CH3X Æ eter 9 Fischer esterification reaction. 9 Maximum rates at weakly acidic pH or 4-5. 9 Carboxylic acids Æ acid chlorides by treatment with SOCl2 forming HCl and SO2 9 Acid anhydrides.8 Nucleophilic Addition of Amines: Imine and Enamine Formation 9 Primary amines RNH2 + aldehyde or ketone Æ imine R2C=NR. Leads to a C=C . 9 In amide formation the OH must be replaced by a better. These are common in biological pathways. lOMoARcPSD|2416048 9 Aromatic aldehydes are less reactive in nucleophilic addition reactions than aliphatic aldehydes because the electron donating resonance effect of the aromatic ring makes the carbonyl group less electrophilic.

Carried out under NaOH catalyst. .4 Chemistry of Acid Halides 9 Acid chlorides are prepared from carboxylic acids by reaction with thionyl chloride SOCl2 9 Carboxylic acid + PBr3 + ether Æ acid bromide 9 Halogens in aid halides can be replaced by –OH or –OCOR or –OR or –NH2. Carried out under NaOH catalyst to remove HCl 9 Acid chloride + carboxylate anion Æ acid anhydride. 2 equivalents of amine must be used. 9 Acid chloride + alcohol Æ ester. lOMoARcPSD|2416048 9 The hydride ion is a base as well as a nucleophile allowing the nucleophilic acyl substitution to take place on the carboxylate ion rather than on the free carboxylic aid and gives a high- energy dianion intermediate. Distributing prohibited | Downloaded by mina anis (minasamy557@hotmail. HCl is a by- product. 9 Acid chloride + LiAlH4 Æ aldehyde Æ primary alcohols 9 Grignard reagents react with acid chlorides to yield tertiary alcohols in which two of the substituents are the same. often achieved by reaction with ATP in living organisms. 9 Acid chlorides react with water to yield carboxylic acids in a hydrolysis reaction. 9 Acid chloride + ammonia Æ amines and amides. 9 Borane reacts with carboxylic aids faster than with any other functional group 9 In the laboratory the acid must first be activated. A KETON INTERMEDIATE IS AMDE. Reaction is affected by Steric hindrance primary > secondary > tertiary alcohols produced.