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Carlos Montanari

montana@iqsc.usp.br

http://www.nequimed.iqsc.usp.br/

UNIVERSIDADE DE SÃO PAULO - USP

Instituto de Química de São Carlos - IQSC

Grupo de Estudos em Química Medicinal NEQUIMED

Conteúdo

• Ligações químicas localizadas

• Ligações químicas deslocalizadas

• Ligações químicas mais fracas que a covalente

• Estereoquímica

• Carbocátions, carbânions, radicais livre

• Mecanismos e métodos de determinação de mecanismos de reações

• Ácidos e bases Efeitos da estrutura sobre a reatividade

– Evans, Kwan, March, Carey

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Acids and Bases Effects of Structure

and Medium on Reactivity

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A hydrogen-bond basicity scale. pKHB Values for Many Types of Bases

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THE MECHANISM OF PROTON-TRANSFER REACTIONS

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Not all such proton transfers are diffusion controlled

The Hammett Acidity Functions

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Remember that

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Numbers to Know

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Here are twenty numbers to know in DMSO:

Hammett acidity function

where pKBH+ is −log(K) for the dissociation of BH+,

which is the conjugate acid of a very weak base B, with a very negative pKBH

+

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where aH+ is the activity of the proton and fI and fHI+ are the activity coefficients of the indicator and

conjugate acid of the indicator, respectively.

Anitha et al. Acta Crystallogr Sect E Struct Rep Online. 2011

Typical indicators are weak bases (B)

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Pure H2SO4 (18.4 M) H0 = -12 ≠ pH = -12:

impossible high [ H3O+] of 10+12 mol L-1

in ideal solution.

In dilute aqueous solution (pH 0-14): H3O+ [H(H2O)n]

+ and aH = 1 and H0 ~ pH.

Acidity Concepts

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Acidity and Hybridization. Other examples

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pKa = 10.63 (H2O)

Why is cyclopropyl amine much less basic than cyclohexyl amine?

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From NBO

Cyclopropyl Amine:

(nN to *C-H: 9.0 kcal mol-1) Cyclohexyl Amine:

(nN to *C-H: 7.6 kcal mol-1)

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Carbanion Stabilization by 2nd-Row Atoms: SR, SO2R, PR3, etc

The accepted explanation for carbanion stabilization in 2nd

row elements is delocalization into vicinal antibonding orbitals

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Effects of Structure and Medium on Reactivity

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B strain

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I strain

Conformational effects

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Conformational Analysis and Reactivity: The Curtin-Hammett Principle

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For example,

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QUANTITATIVE TREATMENTS OF THE EFFECT

OF STRUCTURE ON REACTIVITY

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The Hammett equation is a linear free-energy relationship (LFER).

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Taft hydrolysis of carboxylic esters

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The Swain and Lupton values

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Taft steric effects

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