Pintaka KusumaningtyasORGANOHALOGENS

General useful of organohalogens are as solvent, insecticide, and basic material for making synthetic organic compound.The most of organohalogens compounds is synthetic.Anesthethics (halothane and methoxy flurene) are the examples of safe organohalogen Many organohalogen compounds are toxic, and must be handled carefully, for examples : CCl4 and CHCl3 can cause liver damage if over inhaled.Insecticides in agriculture can pollute our environment

Types of Organohalogen compoundsAlkyl halide (R-X) : (Iodomethane) (Chloroethane)

Aryl halide (Ar-X) : (Bromobenzene)

(Poly-chlorinated biphenyl)Halide Vinylic : (Chloroethene)(2-bromo-2-butene)

Pintaka KusumaningtyasAlkyl Halides

*What is an Alkyl Halide ?Alkyl halide is an alkane derivative-compound containing at least one carbon-halogen bond (C-X). The symbol is R-X.X (F, Cl, Br, I) replaces HCan contain many C-X bondsProperties and some uses:Fire-resistant solventsRefrigerantsPharmaceuticals and precursors

*Halogens (X) are more electronegative than Carbon (C), so carbon has partial positive charge.Carbon can be attacked by a nucleophile, and Halogen can leave with the electron pair.Alkyl halides are weak polar molecules. C-X bond is polar, so it exhibits dipole-dipole interactions.Halogenated hydrocarbon doesnt form hydrogen bonding and insoluble in water.

Physical Properties

*The electronegative halogen atom in alkyl halides creates a polar CX bond, making the carbon atom electron deficient. Electrostatic potential maps of four simple alkyl halides illustrate this point.The Polar Carbon-Halogen BondFigure. Electrostatic potential maps of four halomethanes (CH3X)

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Nomenclature

Naming Alkyl Halides *

Naming if Two Halides or Alkyl are Equally Distant from Ends of Chain*Begin at the end nearer the substituent whose name comes first in the alphabetIf there are more than one different halogens, so the priorities of naming is based on reactivity of halogen, the sequence is F Cl Br I. However, the name writing is still based on the alphabet. For example : 3-chloro-2-fluorobutaneWrite name for this following chemical structure :

Exercises : give the names for following chemical structures

Common Name*Common names are often used for simple alkyl halides. To assign a common name:Name all the carbon atoms of the molecule as a single alkyl group.Name the halogen bonded to the alkyl group.Combine the names of the alkyl group and halide, separating the words with a space.

Many Alkyl Halides That Are Widely Used Have Common Names

*Trivial NamesCH2X2 is called methylene halide.CHX3 is a haloform.CX4 is carbon tetrahalide.

Examples: CH2Cl2 is methylene chlorideCHCl3 is chloroform CCl4 is carbon tetrachloride.

*Classes of Alkyl HalidesMethyl halides: only one C, CH3XPrimary: C to which X is bonded has only one C-C bond.Secondary: C to which X is bonded has two C-C bonds.Tertiary: C to which X is bonded has three C-C bonds.

*Figure. Examples of 1, 2, and 3 alkyl halidesFigure. Four types of organic halides (RX) having X near a bond

*Exersice : classify these alkyl halides and write 2 types of name for them :

a). 1,1-dibromobutaneb). 3-chloro-1-butenec). 2-fluoro-1-ethanolExersice : write the structural formula for these compounds

*DihalidesGeminal dihalide: 2 halogen atoms are bonded to the same carbon Vicinal dihalide: 2 halogen atoms are bonded to adjacent carbons.

Uses of Alkyl Halides*Solvents - degreasers and dry cleaning fluidReagents for synthesis of other compoundsAnesthetic: Halothane is CF3CHClBrCHCl3 used originally (toxic and carcinogenic)Freons, chlorofluorocarbons (CFC)Freon 12 (CF2Cl2) now replaced with Freon 22 (CF2CHCl), not as harmful to ozone layer.Pesticides - DDT banned in U.S.

REACTIONS OF ALKYL HALIDES Substitutions and Eliminations

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Alkyl Halides React with Nucleophiles and BasesAlkyl halides are polarized at the carbon-halide bond, making the carbon electrophilicNucleophiles will replace the halide in C-X bonds of many alkyl halides (reaction as Lewis base)Nucleophiles that are also Brnsted bases can produce elimination

*Nucleophiles and bases are structurally similar: both have a lone pair or a bond. They differ in what they attack.Nucleophiles Vs Bases

*Nucleophilicity Vs BasicityAlthough nucleophilicity and basicity are interrelated, they are fundamentally different.Basicity is a measure of how readily an atom donates its electron pair to a proton. Nucleophilicity is a measure of how readily an atom donates its electron pair to other atoms.

*Nucleophilicity parallels basicity in three instances:For two nucleophiles with the same nucleophilic atom, the stronger base is the stronger nucleophile.The relative nucleophilicity of OH and CH3COO, two oxygen nucleophiles, is determined by comparing the pKa values of their conjugate acids (H2O = 15.7, and CH3COOH = 4.8). OH is a stronger base and stronger nucleophile than CH3COO.2.A negatively charged nucleophile is always a stronger nucleophile than its conjugate acid. OH is a stronger base and stronger nucleophile than H2O.3.Right-to-left-across a row of the periodic table, nucleophilicity increases as basicity increases:

*Nucleophilicity does not parallel basicity when steric hindrance becomes important. Steric hindrance is a decrease in reactivity resulting from the presence of bulky groups at the site of a reaction.Steric hindrance decreases nucleophilicity but not basicity.Sterically hindered bases that are poor nucleophiles are called nonnucleophilic bases.

Nucleophilic Substitution (SN) ReactionSubstitution Nucleophilic Unimolecular (SN1)Substituion Nucleophilic Bimolecular (SN2)

*Three components are necessary in any substitution reaction.General Features of Nucleophilic Substitution

*In a nucleophilic substitution reaction of RX, the CX bond is heterolytically cleaved, and the leaving group departs with the electron pair in that bond, forming X:. The more stable the leaving group X:, the better able it is to accept an electron pair.The Leaving GroupFor example, H2O is a better leaving group than OH because H2O is a weaker base.

Chapter 6*Leaving Group AbilityElectron-withdrawingStable once it has left (not a strong base)Polarizable to stabilize the transition state.

*There are periodic trends in leaving group ability:

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*Negatively charged nucleophiles like OH and HS are used as salts with Li+, Na+, or K+ counterions to balance the charge. Since the identity of the counterion is usually inconsequential, it is often omitted from the chemical equation.When a neutral nucleophile is used, the substitution product bears a positive charge.

*In a nucleophilic substitution:Mechanisms of Nucleophilic SubstitutionBut what is the order of bond making and bond breaking? In theory, there are three possibilities.In this scenario, the mechanism is comprised of one step. In such a bimolecular reaction, the rate depends upon the concentration of both reactants, that is, the rate equation is second order.[1] Bond making and bond breaking occur at the same time.

*In this scenario, the mechanism has two steps and a carbocation is formed as an intermediate. Because the first step is rate-determining, the rate depends on the concentration of RX only; that is, the rate equation is first order.[2] Bond breaking occurs before bond making.

*This mechanism has an inherent problem. The intermediate generated in the first step has 10 electrons around carbon, violating the octet rule. Because two other mechanistic possibilities do not violate a fundamental rule, this last possibility can be disregarded.[3] Bond making occurs before bond breaking.

*Consider reaction [1] below:Kinetic data show that the rate of reaction [1] depends on the concentration of both reactants, which suggests a bimolecular reaction with a one-step mechanism. This is an example of an SN2 (substitution nucleophilic bimolecular) mechanism.

*Kinetic data show that the rate of reaction [2] depends on the concentration of only the alkyl halide. This suggests a two-step mechanism in which the rate-determining step involves the alkyl halide only. This is an example of an SN1 (substitution nucleophilic unimolecular) mechanism.Consider reaction [2] below:

*Furthermore, when the substitution product bears a positive charge and also contains a proton bonded to O or N, the initially formed substitution product readily loses a proton in a Brnsted-Lowry acid-base reaction, forming a neutral product.To draw any nucleophilic substitution product:Find the sp3 hybridized carbon with the leaving group.Identify the nucleophile, the species with a lone pair or bond.Substitute the nucleophile for the leaving group and assign charges (if necessary) to any atom that is involved in bond breaking or bond formation.

Kinetics of Nucleophilic SubstitutionRate is change in concentration with timeDepends on concentration(s), temperature, inherent nature of reaction (activation energy)A rate law describes relationship between the concentration of reactants and rate of conversion to products determined by experiment.A rate constant (k) is the proportionality factor between concentration and rate

Example: for S P an experiment might findRate = k [S] (first order)

Reaction KineticsThe study of rates of reactions is called kineticsRates decrease as concentrations decrease but the rate constant does notThe rate law depends on the mechanismThe order of a reaction is sum of the exponents of the concentrations in the rate law the example below is second orderExperiments show that for the reaction :OH- + CH3Br CH3OH + Br-Rate = k[OH-][CH3Br]

The Reaction of (SN2)SN2 = Substitution, Nucleophilic, Bimolecular

*The mechanism of an SN2 reaction would be drawn as follows. Note the curved arrow notation that is used to show the flow of electrons.

*All SN2 reactions proceed with backside attack of the nucleophile, resulting in inversion of configuration (Walden Inversion) at a stereogenic center.StereochemistryFigure. Stereochemistry of the SN2 reaction

Chapter 6*Stereochemistry of SN2Walden Inversion (Configuration Inversion)

*Figure. Two examples of inversionof configuration in the SN2 reaction

SN2 Transition StateThe transition state of an SN2 reaction has a planar arrangement of the carbon atom and the remaining three groups.

Exersice : Write the equation of reaction (that show stereochemistry using dimensional formula) for SN2 reaction from (S)-2-bromobutane with CN- and give a sign the configuration of product using (R) and (S) system.

*An energy diagram for the SN2 reaction:

The Kinetics of SN2 ReactionOne type of SN2 reaction has the following characteristics:Reaction occurs with inversion at reacting centerFollows second order reaction kinetics rate = k [Nu:-][RX]

The rate of reaction is affected by the reactivity of substrates (alkyl halides) and nucleophiles.

*The rate of reaction is affected by reactivity of substrate, and reactivity is affected by the structure of substrate.

For examples :Bromomethane reacts 30 times faster than bromoethane (If bromoethane reaction needs an hour to finish a half of reaction, so bromomethane only needs 1/30 times of those (or 2 minutes) to finish a half of reaction)

Effects of Structure to Reactivity

*The higher the Ea, the slower the reaction rate. Thus, any factor that increases Ea decreases the reaction rate.Effect of Ea to Kinetics and Product of Reactions

Order of Reactivity in SN2The more alkyl groups connected to the reacting carbon, the slower the reaction

*Methyl and 1 alkyl halides undergo SN2 reactions with ease.2 Alkyl halides react more slowly.3 Alkyl halides do not undergo SN2 reactions. This order of reactivity can be explained by steric effects. Steric hindrance caused by bulky R groups makes nucleophilic attack from the backside more difficult, slowing the reaction rate.Steric Hindrance in SN2 Reaction

*Steric Effect in SN2 Reaction

*Increasing the number of R groups on the carbon with the leaving group increases crowding in the transition state, thereby decreasing the reaction rate.The SN2 reaction is fastest with unhindered halides.

Relative Reactivity of NucleophilesDepends on reaction and conditions More basic, nucleophiles react faster (for similar structures).Better nucleophiles are lower in a column of the periodic tableAnions are usually more reactive than neutrals

Exercise :How does the SN2 reaction rates effects between CH3I and CH3O-, If the concentration of second reactant becomes twice faster, whereas all of other variables keep still constant?

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*Alkyl Halides and Nucleophilic Substitution

The Reaction of SN1SN1 = Substitution, Nucleophilic, Unimolecular

*The mechanism of an SN1 reaction would be drawn as follows: Note the curved arrow formalism that is used to show the flow of electrons.Key features of the SN1 mechanism are that it has two steps, and carbocations are formed as reactive intermediates.

Chapter 6*SN1 Mechanism (1)Step 1 : Formation of carbocation (slow)

*SN1 Mechanism (2)Step 2 : Nucleophilic attacks carbocation Step 3 : Loss of H+ (if needed) from protonated alcohol

Since SN1 reactions involve ionization, so these reactions are helped by polar solvent, such as H2O, that can stabilize the ion by solvation.

Stereochemistry of SN1 ReactionThe planar intermediate should lead to loss of chiralityA free carbocation is achiralProduct should be racemic

*Stereochemistry of SN1Racemization: inversion and retention=>

SN1 in RealityCarbocation is biased to react on side opposite leaving groupSuggests reaction occurs with carbocation loosely associated with leaving group during nucleophilic additionAlternative that SN2 is also occuring is unlikely

Effects of Ion Pair FormationIf leaving group remains associated, then product has more inversion than retentionProduct is only partially racemic with more inversion than retentionAssociated carbocation and leaving group is an ion pair

The specific rate of SN1 reaction does not depend on nucleophile reaction, but only depend on alkyl halide concentration.Its due to the reaction between R+ and Nu- occurs very quickly => this combination only occurs if the carbocations is formed.The overall rate of reaction is determined by the rate of RX ionization, and then form carbocation (R+)This ionization step is called rate-determining step or rate-limiting step.The Rate of SN1 Reactions

Rate-Limiting StepThe overall rate of a reaction is controlled by the rate of the slowest step

SN1 reaction is the first order in rate :

Rate SN1 = k [RX]

Nucleophiles in SN1Since nucleophilic addition occurs after formation of carbocation, reaction rate is not affected normally by nature or concentration of nucleophile

SN1 Energy DiagramStep through highest energy point is rate-limiting rate = k[RX]

*Figure.An energy diagramfor the SN1 reaction:

Effect of Leaving Group on SN1Critically dependent on leaving groupReactivity: the larger halides ions are better leaving groupsIn acid, OH of an alcohol is protonated and leaving group is H2O, which is still less reactive than halidep-Toluensulfonate (TosO-) is excellent leaving group

Characteristics of the SN1 ReactionTertiary alkyl halide is most reactive by this mechanismThe effect of the type of alkyl halide on SN1 reaction rates can be explained by considering carbocation stability.

*Inductive effectHyperconjugationFactors Increasing Carbocation Stability

*Inductive effect is the pull of electron density to a positive charge carbon through bonds, so it bears partial positive charge for adjacent atoms and polarizes the next bonds, then stabilize the carbocation.Alkyl groups are electron donating groups that stabilize a positive charge. So, the greater the number of alkyl groups attached to a carbon with a positive charge, the more stable will be the cation.Inductive Effect For Increasing Carbocation Stability

*The Number of R groups Effect to Carbocation StabilityCarbocations are classified as primary (1), secondary (2), or tertiary (3), based on the number of R groups bonded to the charged carbon atom. As the number of R groups increases, carbocation stability increases.

*Figure.Electrostatic potential maps for differerent carbocations

*The Hammond Postulate

*The Hammond postulate relates reaction rate to stability. It provides a quantitative estimate of the energy of a transition state.The Hammond postulate states that the transition state of a reaction resembles the structure of the species (reactant or product) to which it is closer in energy.

*Hyperconjugation is the spreading out of charge by the overlap of an empty p orbital with an adjacent bond. This overlap (hyperconjugation) delocalizes the positive charge on the carbocation, spreading it over a larger volume, and this stabilizes the carbocation.Example: CH3+ cannot be stabilized by hyperconjugation, but (CH3)2CH+ can.Hyperconjugation Effect For Increasing Carbocation Stability

*Carbocation RearrangementsCarbocations can rearrange to form a more stable carbocation :Hydride shift: H- on adjacent carbon bonds with C+.Methyl shift: CH3- moves from adjacent carbon if no Hs are available.

*Hydride Shift

*Methyl Shift

The Substitution Reaction of Allylic and Benzylic Halides

Allylic and Benzylic HalidesAllylic and benzylic intermediates are stabilized by delocalization of charge.Primary allylic and benzylic are also more reactive in the SN2 mechanism

Delocalized CarbocationsDelocalization of cationic charge enhances stabilityPrimary allyl is more stable than primary alkylPrimary benzyl is more stable than allyl

The Substitution Reaction of Vinyl Halides & Aryl Halide

*Vinyl Halides and Aryl Halides.Vinyl and aryl halides do not undergo SN1 or SN2 reactions, because heterolysis of the CX bond would form a highly unstable vinyl or aryl cation.Figure. Vinyl halides and nucleophilic substitution mechanisms

The Nucleophile Substitution and Organic Synthetis

*Nucleophilic Substitution and Organic Synthesis.To carry out the synthesis of a particular compound, we must think backwards, and ask ourselves the question: What starting material and reagents are needed to make it?If we are using nucleophilic substitution, we must determine what alkyl halide and what nucleophile can be used to form a specific product.

*To determine the two components needed for synthesis, remember that the carbon atoms come from the organic starting material, in this case, a 1 alkyl halide. The functional group comes from the nucleophile, HO in this case. With these two components, we can fill in the boxes to complete the synthesis.

The Factors That Determine The SN1 or SN2 MechanismThe structure of alkyl halideThe nature of nucleophile and baseThe nature of solventConcentration of nucleophile and baseTemperature

*The Effect of Alkyl Halides Structures

*Strong nucleophiles (which usually bear a negative charge) present in high concentrations favor SN2 reactions.Weak nucleophiles, such as H2O and ROH favor SN1 reactions by decreasing the rate of any competing SN2 reaction.Let us compare the substitution products formed when the 2 alkyl halide A is treated with either the strong nucleophile HO or the weak nucleophile H2O. Because a 2 alkyl halide can react by either mechanism, the strength of the nucleophile determines which mechanism takes place.The Nature of The Nucleophile

*The strong nucleophile favors an SN2 mechanism.The weak nucleophile favors an SN1 mechanism.

*A better leaving group increases the rate of both SN1 and SN2 reactions.

*Polar protic solvents like H2O and ROH favor SN1 reactions because the ionic intermediates (both cations and anions) are stabilized by solvation.

Polar aprotic solvents favor SN2 reactions because nucleophiles are not well solvated, and therefore, are more nucleophilic.The Nature of The Solvent

*Polar Protic Solvent EffectsPolar protic solvents (O-H or N-H) reduce the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon.

*In polar protic solvents, nucleophilicity increases down a column of the periodic table as the size of the anion increases. This is the opposite of basicity.Figure . Example of polar protic solvents

Chapter 6*Polar Aprotic Solvent EffectsPolar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile

Examples:

*Polar aprotic solvents also exhibit dipoledipole interactions, but they have no OH or NH bonds. Thus, they are incapable of hydrogen bonding.Figure. Examples of polar aprotic solvents

*In polar aprotic solvents, nucleophilicity parallels basicity, and the stronger base is the stronger nucleophile. Because basicity decreases as size increases down a column, nucleophilicity decreases as well.

Effects of Solvent on EnergiesPolar solvent stabilizes transition state and intermediate more than reactant and product

Solvent Is Critical in SN1Stabilizing carbocation also stabilizes associated transition state and controls rateSolvation of a carbocation by water

Polar Solvents Promote IonizationPolar, protic and unreactive Lewis base solvents facilitate formation of R+ Solvent polarity is measured as dielectric polarization (P)Nonpolar solvents have low PPolar SOLVENT have high P values

*Temperature Effects

*In an endothermic reaction, the transition state resembles the products more than the reactants, so anything that stabilizes the product stabilizes the transition state also. Thus, lowering the energy of the transition state decreases Ea, which increases the reaction rate.

If there are two possible products in an endothermic reaction, but one is more stable than the other, the transition state that leads to the formation of the more stable product is lower in energy, so this reaction should occur faster.

*Figure. An endothermic reactionHow the energy of the transition state and products are related

*In the case of an exothermic reaction, the transition state resembles the reactants more than the products. Thus, lowering the energy of the products has little or no effect on the energy of the transition state. Since Ea is unaffected, the reaction rate is unaffected.The conclusion is that in an exothermic reaction, the more stable product may or may not form faster, since Ea is similar for both products.

*Figure. An exothermic reactionHow the energy of the transition state and products are related

*The Hammond postulate estimates the relative energy of transition states, and thus it can be used to predict the relative rates of two reactions.According to the Hammond postulate, the stability of the carbocation determines the rate of its formation.Figure. Energy diagram for carbocation formation in two different SN1 reactions

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SN2 or SN1?Primary, secondary or methylStrong nucleophile

Polar aprotic solvent

Rate = k[halide][Nuc]Inversion at chiral carbonNo rearrangements TertiaryWeak nucleophile (may also be solvent)Polar protic solvent, silver saltsRate = k[halide]Racemization of optically active compoundRearranged products Chapter 6*

Chapter 6

Elimination Reaction

Alkyl Halides: EliminationElimination is an alternative pathway to substitutionOpposite of additionGenerates an alkeneCan compete with substitution and decrease yield, especially for SN1 processes

Zaitsevs Rule for Elimination Reactions (1875)In the elimination of HX from an alkyl halide, the more highly substituted alkene product predominates

Mechanisms of Elimination ReactionsIngold nomenclature: E eliminationE1: X- leaves first to generate a carbocation a base abstracts a proton from the carbocationE2: Concerted (one step) transfer of a proton to a base and departure of leaving group

The E1 ReactionCompetes with SN1 and E2 at 3 centersV = k [RX]

Stereochemistry of E1 ReactionsE1 is not stereospecific and there is no requirement for alignmentProduct has Zaitsev orientation because step that controls product is loss of proton after formation of carbocation

The E2 Reaction MechanismA proton is transferred to base as leaving group begins to departTransition state combines leaving of X and transfer of HProduct alkene forms stereospecifically

E2 Reaction KineticsOne step rate law has base and alkyl halideTransition state bears no resemblance to reactant or productRate = k[R-X][B]Reaction goes faster with stronger base, better leaving group

Geometry of Elimination E2Antiperiplanar allows orbital overlap and minimizes steric interactions

E2 Stereochemistry Overlap of the developing orbital in the transition state requires periplanar geometry, anti arrangementAllows orbital overlap

Chapter 6*E2 Stereochemistry

Predicting ProductE2 is stereospecificMeso-1,2-dibromo-1,2-diphenylethane with base gives cis 1,2-diphenylRR or SS 1,2-dibromo-1,2-diphenylethane gives trans 1,2-diphenyl

Elimination From CyclohexanesAbstracted proton and leaving group should align trans-diaxial to be anti periplanar (app) in approaching transition state.Equatorial groups are not in proper alignment

Kinetic Isotope EffectSubstitute deuterium for hydrogen at positionEffect on rate is kinetic isotope effect (kH/kD = deuterium isotope effect)Rate is reduced in E2 reactionHeavier isotope bond is slower to breakShows C-H bond is broken in or before rate-limiting step

Chapter 6*A Closer Look

*E1 or E2?Tertiary > SecondaryWeak base Good ionizing solvent

Rate = k[halide]Saytzeff productNo required geometry

Rearranged productsTertiary > SecondaryStrong base requiredSolvent polarity not importantRate = k[halide][base]Saytzeff productCoplanar leaving groups (usually anti)No rearrangements

Comparing E1 and E2Strong base is needed for E2 but not for E1E2 is stereospecifc, E1 is notE1 gives Zaitsev orientation

Chapter 6*Substitution or Elimination?Strength of the nucleophile determines order: Strong nuc. will go SN2 or E2.Primary halide usually SN2.Tertiary halide mixture of SN1, E1 or E2High temperature favors elimination.Bulky bases favor elimination.Good nucleophiles, but weak bases, favor substitution.

Summary of Reactivity: SN1, SN2, E1, E2Alkyl halides undergo different reactions in competition, depending on the reacting molecule and the conditionsBased on patterns, we can predict likely outcomes.

*Secondary Halides?Mixtures of products are common.=>

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