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Unformatted text preview: Organic Organic Lecture Series CH 310/318 M
Textbook Assignment: LECTURE 31 Chapter 9- Nucleophilic Substitution Today’s Topics: The The Sn1 and Sn2 Reactions Notice & Announcements: Office Moved to WEL 4.242 1 Organic Lecture Series Nucleophilic Substitution and β-Elimination
2 Structure of R-X R- Organic Organic Lecture Series • SN1 reactions: governed by electronic factors
– namely, the relative stabilities of the carbocation intermediates. • SN2 reactions: governed by steric factors
– namely, the relative ease of approach of a nucleophile to the reaction site.
Governed by electronic factors SN 1 Carbocation stability R3 CX (3°) R2 CHX (2°) RCH2 X (1°) CH3 X (methyl) SN 2
3 Access to the site of reaction Governed by steric factors The Leaving Group Organic Lecture Series • The more stable the anion, the better the leaving ability.
– The most stable anions are the conjugate bases bases of strong acids.
rarely function as leaving groups Reactivity as a leaving group
Br > _
Cl > H 2 O > > _
F> O _ _
HO > CH 3 O _ _
> NH2 CH 3 CO > Stability of anion; strength of conjugate acid
4 Solvents Organic Organic Lecture Series • Protic solvent: A solvent that is a hydrogen bond donor.
– The most common protic solvents contain OH groups. • Aprotic solvent: A solvent that cannot serve as a hydrogen bond donor.
– Nowhere in the molecule is there a hydrogen bonded to an atom of high electronegativity. 5 Dielectric Constant Organic Lecture Series • Solvents are classified as polar and nonpolar
– The most common measure of solvent polarity is dielectric constant. • Dielectric constant: A measure of a solvent’s ability to insulate opposite charges from one another. another.
– The greater the value of the dielectric constant of a solvent, the smaller the interaction between ions of opposite charge dissolved in that solvent. – Polar solvent: dielectric constant > 15. – Nonpolar solvent: dielectric constant < 15. 6 Aprotic Solvents
Solven t Polar D imethyl su lfoxide (D MSO) Acetonitrile Acetone N on p o l ar N on polar D ichloromethane
D iethyl eth er Tolu ene Hexane Organic Organic Lecture Series Structure ( CH3 ) 2 S=O CH3 C N ( CH3 ) 2 C=O D ielectric Constan t 48.9 37.5 36.7 20.7 N,N-D imethylformamide (D MF) ( CH3 ) 2 NCHO CH2 Cl2 CH3 CH2 OCH2 CH3 C6 H5 CH3 CH3 ( CH2 ) 4 CH3 9.1 4.3 2.3 1.9
7 Protic Solvents Organic Lecture Series Solvent Water Fo rm i c ac i d Meth anol Ethanol Acetic acid Stru cture H2 O HCOOH CH3 OH CH3 CH2 OH CH3 COOH D ielectric Cons tant (25°C) 79 59 33 24 6 8 The Solvent – SN2 Organic Organic Lecture Series • The most common type of SN2 reaction involves a negative Nu:- and a negative leaving group.
negatively charged nu cleophile negative ch arge disp ers ed in the transition state negatively charged leaving group Nu: - + C Lv δ− Nu C δ− Lv Nu C + Lv Tran si ti o n state – The weaker the solvation of Nu:-, the less the energy required to remove it from its solvation shell and the greater the rate of SN2.
9 The Solvent – SN2
Br + N3
- Organic Lecture Series SN 2 solvent N3 + k(solvent) k(methanol) 5000 2800 1300 7 1 Br - Solvent Type
Weak solvation of N3polar aprotic Solvent CH3 C N ( CH3 ) 2 N CHO ( CH3 ) 2 S= O H2 O CH3 OH polar protic 10 The The Solvent – SN1 Organic Organic Lecture Series • SN1 reactions involve creation and separation of unlike charges in the transition state of the rate-determining step. • Rate depends on the ability of the solvent solvent to keep these charges separated and to solvate both the anion and the cation. • Polar protic solvents (formic acid, water, methanol) are the most effective solvents for SN1 reactions.
11 The Solvent – SN1
CH3 CH3 CCl + ROH CH3
solvolysis Organic Lecture Series CH3 CH3 COR + HCl CH3 k(solvent) Solvent water 80% water: 20% ethanol 40% water: 60% ethanol ethanol k(ethanol) 100,000 14,000 100 1
12 Nucleophilicity Organic Organic Lecture Series • Nucleophilicity: A kinetic property measured by the rate at which a Nu: causes a nucleophilic substitution under a standardized set of experimental conditions. • Basicity: A equilibrium property measured by the position of equilibrium in an acid-base reaction. • Because all nucleophiles are also bases, correlations between nucleophilicity and basicity are studied.
13 Organic Lecture Series Effectiveness
Increasing Nucleophilicity Increasing Nucleophilicity Increasing Nucleophilicity Increasing Nucleophilicity Good Nucleophile Br-, I CH S - RS , HO-, C H O- RO , CN - N ,
3 3 3 Cl , F -- C H3 C OO , R COO Moderate CH3 SH, RSH, R2 S NH 3 , RN H2 , R2 NH, R3 N H2 O Poor CH3 O H, ROH CH3 COO H, RCO OH 14 Nucleophilicity Organic Organic Lecture Series • A guiding principle is the “freer” the nucleophile, the greater greater its nucleophilicity. 15 Nucleophilicity Nucleophilicity Organic Lecture Series • Polar aprotic solvents (e.g., DMSO, acetone, acetonitrile, DMF)
– are very effective in solvating cations, but not nearly so effective in solvating anions. – because anions are only poorly solvated, they participate readily in SN2 reactions, and nucleophilicity parallels basicity: F- > Cl- > Br- > I16 Nucleophilicity Organic Organic Lecture Series • Polar protic solvents (e.g., water, methanol)
– Anions are highly solvated by hydrogen bonding with the solvent. – The more concentrated the negative charge of the anion, the more tightly it is held in a solvent shell. – The nucleophile must be at least partially removed from its solvent shell to participate in SN2 reactions. Because F- is most tightly solvated and I- the least, nucleophilicity is I- > Br- > Cl- > F17 Nucleophilicity • Generalization Organic Lecture Series – In a series of reagents with the same nucleophilic atom, anionic reagents are stronger nucleophiles than neutral reagents; this trend parallels the basicity of the the nucleophile.
Increasing Nucleophilicity H2 O ROH N H3 RSH < < < < OH RO RS
- N H2 18 Nucleophilicity • Generalization Organic Organic Lecture Series – When comparing groups of reagents in which the nucleophilic atom is the same, the stronger the base, the greater the nucleophilicity.
N u cleophile RCOO Carb oxylate ion
- HO Hydroxide ion - RO Alk oxide ion - In creasing N ucleoph ilicity Con jugate acid pK a RCOOH 4-5 HOH 15.7 Increasin g A cidity ROH 16-18 (stronger the conj base, the weaker the acid) 19 ...
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