Chapter 8 Nucleophilic Substitution 8.1 Functional Group Transformation By Nucleophilic Substitution Nucleophilic Substitution
– – Y : + R X Y R + : X nucleophile is a Lewis base (electron-pair donor) often negatively charged and used as Na+ or K+ salt substrate is usually an alkyl halide Nucleophilic Substitution
Substrate cannot be an a vinylic halide or an aryl halide, except under certain conditions to be discussed in Chapter 23.
X C C X Table 8.1 Examples of Nucleophilic Substitution
Alkoxide ion as the nucleophile
..– R' O.. : + R X
gives an ether .. + – R' O.. R : X Example
(CH3)2CHCH2ONa + CH3CH2Br
Isobutyl alcohol
(CH3)2CHCH2OCH2CH3 + NaBr
Ethyl isobutyl ether (66%) Table 8.1 Examples of Nucleophilic Substitution
Carboxylate ion as the nucleophile O ..– R'C O.. : + R X
gives an ester O .. + – R'C O.. R : X Example O
CH3(CH2)16C OK + CH3CH2I
O + CH3(CH2)16C O CH2CH3 + KI
Ethyl octadecanoate (95%) Table 8.1 Examples of Nucleophilic Substitution
Hydrogen sulfide ion as the nucleophile
..– H S..: + R X
gives a thiol .. + – H S.. R : X Example
KSH + CH3CH(CH2)6CH3 Br
ethanol, water
CH3CH(CH2)6CH3 + KBr SH
2-Nonanethiol (74%) Table 8.1 Examples of Nucleophilic Substitution
Cyanide ion as the nucleophile
– : N C: + R X
gives a nitrile – : N C R + : X Example
NaCN + Br
DMSO
CN + NaCN
Cyclopentyl cyanide (70%) Table 8.1 Examples of Nucleophilic Substitution
Azide ion as the nucleophile
– + – : : N.. N N.. + R X
gives an alkyl azide – + : + – N.. N N.. R : X Example
NaN3 + CH3CH2CH2CH2CH2I
2-Propanol-water
CH3CH2CH2CH2CH2N3 + NaI Pentyl azide (52%) Table 8.1 Examples of Nucleophilic Substitution
Iodide ion as the nucleophile
..– : ..I: + R X
gives an alkyl iodide .. + – :..I R : X Example
CH3CHCH3 + NaI
Br
acetone
CH3CHCH3 + NaBr NaI is soluble in acetone; NaCl and NaBr are not I soluble in acetone. 63% 8.2 Relative Reactivity of Halide Leaving Groups Generalization
Reactivity of halide leaving groups in nucleophilic substitution is the same as for elimination. RI most reactive
RBr
RCl
RF least reactive Problem 8.2
A single organic product was obtained when 1-bromo-3-chloropropane was allowed to react with one molar equivalent of sodium cyanide in aqueous ethanol. What was this product?
BrCH2CH2CH2Cl + NaCN
Br is a better leaving group than Cl Problem 8.2
A single organic product was obtained when 1-bromo-3-chloropropane was allowed to react with one molar equivalent of sodium cyanide in aqueous ethanol. What was this product?
BrCH2CH2CH2Cl + NaCN
:N C CH2CH2CH2Cl + NaBr