2011 Chem 251 Lecture 11

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CHEM251 Fall 2011 Pg 1 of 14 CHEM 251 LECTURE 11 Chapter 6: Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic Substituion By Dr. Kevin S. Huang Department of Biology & Chemistry Azusa Pacific University Materials from Organic Chemistry by Peter Vollhardt & Neil Schore (Sixth Edition)

Transcript of 2011 Chem 251 Lecture 11

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CHEM 251 LECTURE 11

Chapter 6: Properties and Reactions of Haloalkanes: Bimolecular Nucleophilic

Substituion

By Dr. Kevin S. Huang Department of Biology & Chemistry

Azusa Pacific University

Materials from Organic Chemistry by Peter Vollhardt & Neil Schore

(Sixth Edition)

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The dilemma of bromomethane: Highly useful but also … (Pg 241)

Plant pathologist Frank Westerlund demonstrates the “bromomethane difference” between strawberries grown in a fumigated plot (right) and those not (left). The latter are withered by verticillium wilt, a fungus.

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(I) STRUCTURE AND SN2 REACTIVITY: THE LEAVING GROUP • The rates of SN2 reactions depend upon:

o Nature of the leaving group. o Reactivity of the nucleophile o Structure of the alkyl portion of the substrate

Leaving-group ability is a measure of the ease of displacement.

• The leaving group ability of a leaving group can be correlated to its ability to accommodate a negative charge.

• For halogens, iodide is a good leaving group, while fluoride is a poor leaving group in SN2 reactions. SN2 reactions of fluoroalkanes are rarely observed.

Leaving-Group Ability: Problem: Predict the product of the reactin of 1-chloro-6-iodohexane with one equivalent of sodium methylselendie (NaSeCH3)

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Other good leaving groups that can be displaced by nucleophiles in SN2 reactions are: Weak bases are good leaving groups.

• Leaving group ability is inversely related to base strength. • ____________________ are best able to accommodate negative charge and are

the best leaving groups. (Weak bases are the conjugate bases of strong acids.)

Note the sequence: I- > Br- > Cl- > F-

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(II) STRUCTURE AND SN2 REACTIVITY: THE NUCLEOPHILE • Nucleophilicity of the nucleophile depends upon:

o Charge o Solvent o Polarizability o Nature of substituents

(A) Increasing negative charge increases nucliophilicity.

• Consider these experiments: Conclusion: Comparing nucleophiles having the same reactive atom, the species with the negative charge is the more powerful nucleophile. A base is always more nucleophilic than its conjugate acid.

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(B) Nucleophilicity decreases to the right in the periodic table. • Consider these experiments:

Conclusion: Nucleophilicity correlates with basicity. As we proceed from left to right across the periodic table, nucleophilicity decreases. (best) H2N- > HO- > NH3 > F- > H2O (worst nucleophile)

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(C) Solvation impedes nucleophilicity. • When a solid dissolves in a polar solvent the molecules or ions are surrounded

by solvent molecules and are said to be solvated. • Generally solvation weakens a nucleophile by forming a shell of solvent

molecules around the nucleophile which impedes its ability to attack an electrophile.

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• Protic and aprotic solvents: the effect of hydrogen bonding.

o Protic solvents are those containing a hydrogen atom attached to an electronegative atom and are capable of hydrogen bonding.

o Aprotic solvents lack positively polarized hydrogen atoms and are also often used in SN2 reactions:

• Because aprotic solvents do not form hydrogen bonds, they solvate anionic nucleophiles relatively weakly.

• This results in an increase in the nucleophiles reactivity. • Bromomethane reacts with KI 500 times faster in propanone than in methanol.

Consider the reaction of iodomethane with chloride:

The rate of the reaction is more than 106 times greater in the aprotic solvent DMF than in methanol.

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Increasing polarizability improves nucleophilic power. • The degree of nucleophilicity increases down the periodic table, even for

uncharged nucleophiles, for which the solvent effects would be much weaker. H2Se > H2S > H2O, and PH3 > NH3 Sterically hindered nucleophiles are poorer reagents.

• Nucleophiles having large bulky substituents are not as reactive as unhindered nucleophiles:

Sterically bulky nucleophiles react more slowly.

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Problem. Which of the two nucleophiles in the following pairs will react more rapidly with bromomethane? Problem. Treatment of 4-chloro-1-butanol with NaOH in DMF solvent leads to rapid formation of a compound with the molecular formula C4H8O. Propose a structure for the product and suggest a mechanism for its formation. Draw a potential energy diagram.

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(III) STRUCTURE AND SN2 REACTIVITY: THE SUBSTRATE (A) Branching at the reacting carbon decreases the rate of the SN2 reaction.

• The effects of substituents on the reacting carbon can be seen in the following data:

Relative rates of SN2 reaction of branced bromoalkanes with iodide.

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The transition states of the reaction of OH- with methyl, primary, secondary and tertiary carbon centers explain the decrease in activity:

The steric hindrance caused by adding successive methyl groups to the electrophilic carbon decreases the transition state stability to the point that substitution at a tertiary carbon does not occur at all. Relative SN2 displacement reactivity of haloalkanes:

(fast) Methyl > primary > secondary > tertiary (does not occur) (very slow)

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Lengthening the chain by one or two carbons reduces SN2 reactivity. • Replacement of one hydrogen in chloromethane by a methyl group to form

chloroethane reduces the rate of SN2 displacement of the chlorine atom by about a factor of 100.

• Replacement of the hydrogen by an ethyl group to form chloropropane reduces the rate of SN2 displacement of the chlorine atom by another factor of 2.

Branching next to the reacting carbon also retards substitution.

• Multiple substitution at the position next to the electrophilic carbon causes a dramatic decrease in reactivity in SN2 substitution reactions.

• 1-Bromo-2,2-dimethylpropane is virtually inert. Relative reactivities of branced bromoalkanes with iodide

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Problem. Predict the relative rates of the SN2 reaction of cyanide with these substrates.