平成27年度有機化学IV 前半第三回目講義

平成27年度有機化学IV
前半第三回目講義
宮地弘幸
カルボン酸誘導体の相対的反応性と構造
カルボン酸誘導体は，付加-脱離機構で求核剤と置換反応する。
カルボン酸誘導体の相対的反応性と構造
反応性の序列は，脱離基（L)が如何に優れた脱離基であるか，また，隣接するカル
ボニル基に対してどんな効果を示すか，によって決まる。
L=
X
OCOR
OR’
NR2’
電気陰性度小さい
脱離能小さい
A
B
C
共役酸（HL)の酸性度低い
共鳴構造（C)の寄与大きい
The resonance form on the right is most important in amides and
somewhat less important in esters.
Amides and esters are strongly stabilized by resonance.
Anhydrides are more reactive than esters because the lone pairs
on the central oxygen are shared over two carbonyl groups.
Alkanoyl halides are least stable because of their electronegatives
and the poor overlap between their p-orbitals and those of carbon.
COClのCはよ
り正に強く荷
電しており，
CO酸素はア
ミドの方が負
電荷の広がり
が大きい。
カルボン酸誘導体の相対的反応性と構造
The greater the resonance, the shorter the C-L bond.
The structures of carboxylic acid derivatives are directly related to the
extent of resonance.
In progressing from alkanoyl halides to exters and amides, the C-L bond
becomes progressively shorter (increased double-bond character).
24
ハロゲン化アシルの命名法
英語命名法：
対応するアルカンカルボン酸を
基に，アルカンカルボニルハ
ライドと表記
日本語命名法：
対応するアシル基の名称にハロ
ゲンを接頭語として付加
臭化 3-メチルブタノイル
フッ化ペンタノイル
フッ化シクロヘキサン
カルボニル
Alkanoyl halides undergo addition-elimination reactions:
ハロゲン化アシルの化学
g-Valerolactone
(Systematic: 5-methyloxa-2cyclopentanone)
水によりハロゲン化アシルはカルボン酸に加水分解
Alkanoyl chlorides react with water to give the corresponding carboxylic
acids and hydrogen chloride.
アルコールによりハロゲン化アシルはエステルに変換
Esters can be effectively produced by the reaction of alkanoyl chlorides with
alcohols.
An alkali metal hydroxide, pyridine or a tertiary amine is usually added to
neutralize the HCl produced by the reaction.
The basic or neutral conditions employed in this method avoid the
equilibrium problem of acid-catalyzed ester formation.
アミンによりハロゲン化アシルはアミドに変換
Ammonia, primary amines and secondary amines convert alkanoyl
chlorides into amides.
Aqueous ammonia can be used for the synthesis of simple amines since it
is a much stronger nucleophile than water.
The HCl formed is neutralized by a base, which can be excess amine.
ハロゲン化アシルからアミド変換のメカニズム
The mechanism of amide formation from alkanoyl chlorides is additionelimination:
Tertiary amines cannot form amides since they do not possess a proton to
lose during the last step of the reaction.
有機金属反応剤によりハロゲン化アシルはケトンへ変換
Ketone formation is best achieved by using diorganocuprates rather than
RLi or RMgX. The latter are unselective and tend to attack more than once
leading to alcohol formation.
ハロゲン化アシルの還元によりアルデヒドへ変換
Alkanoyl chlorides are reduced to alcohols when sodium borohydride or
lithium aluminum hydride are used directly.
The reaction stops at the aldehyde if LiAlH4 is first reacted with three
molecules of 2-methyl-2-propanol (tert-butyl alcohol), which reduces the
nucleophilicity of the remaining hydride ion.
酸無水物の命名法
Carboxylic anhydrides are named by adding the term “anhydride” to the
acid name (or names, if a mixed anhydride). This method also applies to
cyclic derivatives.
酸無水物の反応
The reactions of anhydrides with nucleophiles are the same as for alkanoyl
halide, only less vigorous.
The leaving group is a carboxylate instead of a halide.
酸無水物の反応
Cyclic anhydrides undergo similar reactions which lead to ring opening.
Alkanoyl halides are difficult to store for extended periods without
undergoing hydrolysis from atmospheric moisture.
Anhydrides, although less reactive towards nucleophiles, are more stable
and many are commercially available.
For these reasons, anhydrides are often preferred for the preparation of
many carboxylic acid derivatives.
エステルの命名法
Esters are alkyl alkanoates.
Esters are named alkyl alkanoates, and the ester grouping as a substituent is called
“alkoxycarbonyl.”
Cyclical esters are named oxa-2-cycloalkanone (common name, lactone). The
common name is preceded by ,,,etc., depending upon ring size.
g-Valerolactone
(Systematic: 5-methyloxa-2cyclopentanone)
Esters are prevalent in plants and play biological roles in the animal
kingdom, often as pheromones.
(Z)-7-dodecenyl acetate is a component in the pheromone mixture of
several species of moths, as well as the mating pheromone of the
elephant.
In industry, lower esters such as ethyl acetate and butyl acetate are used
as solvents.
Butyl butanoate has replaced trichloroethane as a cleaning solvent in the
electronics industry.
Higher nonvolatile esters are used as softeners (plasticizers) for brittle
polymers.
エステルの化学
Strong bases catalyze the hydrolysis of esters through an additionelimination mechanism. The strong base converts the poor nucleophile H2O
into the higher nucleophilic ion OH-.
Unlike acid-catalyzed hydrolysis, base-catalyzed hydrolysis is driven to
completion by the last step, which converts the carboxylic acid into a
carboxylate ion.
Ester hydrolysis is often carried out using the hydroxide ion
itself, in at least stoichiometric amounts.
アルコールとのエステル交換が起こる
The direct conversion of one ester into another without proceeding through
the free carboxylic acid can be carried out by reacting a second alcohol
with an ester in the presence of strong acid.
This process is called transesterification and is reversible. To shift the
equilibrium, a large excess of the second alcohol is used.
アルコールとのエステル交換が起こる
Lactones may be ring opened by transesterification.
Acid-catalyzed transesterifications proceed by protonation of the carbonyl
oxygen and subsequent attack by the alcohol.
Base-catalyzed transesterifications proceed by deprotonation of the alcohol
and subsequent attack at the carbonyl carbon.
アミンとの反応でエステルはアミドに変換
Amines convert esters into amides.
Amines are more nucleophilic than alcohols.
Esters readily transform into amides by treatment with an amine and
subsequent heating. (A catalyst is not required.)
Grignard反応剤との反応でエステルはアルコールに変換
Two equivalents of a Grignard reagent will react with a normal ester to form a
tertiary alcohol. In the case of a formate ester, a secondary alcohol is formed.
エステルはヒドリド還元剤により還元される
Esters are reduced by hydride reagents to give alcohols or
aldehydes.
LiAlH4 will reduce an ester to an alcohol. Only half the equivalent of LiAlH4
is required per ester function.
The use of the milder reducing agent bis(2-methylpropyl)aluminum hydride at
low temperatures in toluene, allows the reaction to be stopped at the aldehyde
oxidation state.
エステルはアルキル化が可能なエノラートを精製する
Esters form enolates that can be alkylated.
Treatment of esters with a strong base at low temperatures produces ester
enolates (acidic -hydrogens). These enolates react like ketone enolates,
undergoing alkylations.
The pKa of esters is about 25, thus the ester enolates behave as strong
bases. Side reactions include E2 processes and deprotonations.

Download Report