目次
序文 iii
略語表 xiii

第Ⅰ部

有機合成ラボガイド

1

1 本書の目的 ··························································································································3
2 実験に際して留意すべきこと ·······················································································4
2.1 反応試薬，溶媒の性質の調査と準備 ···············································································4
2.2 反応試薬の選択···················································································································5
2.3 実験条件の設定と実施 ·······································································································7
A.
B.
C.

合成スケールの設定 7
実験装置の組み立てと反応試薬
・溶液のしこみ 7
実験の記録作成 8

D.
E.
F.

後処理と生成物の単離・精製
9
生成物の構造確認 910

実験廃棄物の処理

3 溶媒の精製法 ···················································································································12
3.1
3.2
3.3
3.4

炭化水素類 ·························································································································12アルコール類 ······················································································································13
エーテル類 ··························································································································14ケトン類 ······························································································································15

3.5 エステル ······························································································································16
3.6 カルボン酸 ··························································································································16
3.7 ハロゲン化物 ······················································································································16
3.8 極性溶媒（非プロトン性）··································································································17

第Ⅱ部

実験例

21

A アルカン誘導体 ···············································································································23A-1

炭素 - 炭素二重結合の還元 ··················································································· 23
v

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次

A-2 ベンゼン環の還元 ···································································································· 24
A-3 Wolf-Kischner 還元···································································································· 25
A-4 ボランによる Wolf-Kischner 型還元······································································· 26
A-5 ハロゲン化物の還元 ································································································ 27

B アルケン誘導体 ···············································································································29
B-1
B-2
B-3
B-4
B-5
B-6
B-7
B-8
B-9
B-10
B-11
B-12
B-13
B-14
B-15
B-16

アルコールの脱水によるアルケン合成 ······························································ 29
脱ハロゲン化水素反応によるアルケン合成 ······················································ 30
ジハロアルカンの脱ハロゲン反応によるアルケン合成 ·································· 32
アルキン還元による cis- アルケン ······································································· 33
Birch 還元による非共役ジエン合成····································································· 34
カルボニル化合物とジハロメタンからの 1- アルケン合成 ····························· 36
アミンの酸化による 1- アルケン合成 ································································· 37
Bamford-Stevens 反応（ヒドラゾンからのアルケン合成）································ 38
Wittig 反応（カルボニル化合物とリンイリドからアルケン合成）················· 40
Horner-Emmons 反応（カルボニル化合物とホスホナートカルボアニオンによるアルケン合成）···································································································· 41
McMurry 反応（カルボニル化合物のカップリングによるアルケン合成）···· 44
オレフィンメタセシス ·························································································· 46
Suzuki カップリング反応 ······················································································ 48
Knoevenagel 縮合によるアルケン合成································································· 50
ニトロアルドール反応によるニトロアルケン合成 ·········································· 51
デヒドロアミノ酸合成 ·························································································· 52

C アルキン誘導体 ···············································································································54
C-1

脱ハロゲン化水素によるアルキン合成 ······························································ 54

C-2
C-3
C-4
C-5
C-6
C-7

脱ハロゲン化水素によるシクロアルキン合成 ·················································· 56
1- アルキンのアルキル化 ······················································································ 57
トリメチルシリルジアゾメタンによるアルキン合成 ······································ 59
Fritsch-Wiechell 転位（ハロゲン化ビニルからアルキン）································· 61
1- アルキンの酸化カップリングによるジアセチレン化合物 ·························· 62
Sonogashira カップリングによるアリールアセチレン化合物 ·························· 63
1- アルキンとハロゲン化ビニルから共役エンイン化合物 ······························ 65

C-8
C-9

アルキンのカップリングによる共役エンイン化合物 ······································ 66

D アルコールおよびフェノール誘導体 ········································································68
D-1カルボニル基の還元によるアルコール合成（NaBH4 還元）···························· 68

D-2カルボン酸，エステルの NaBH4-AlCl3 還元 ······················································· 69

vi

目

D-3
D-4
D-5
D-6
D-7
D-8
D-9
D-10
D-11
D-12
D-13
D-14
D-15
D-16
D-17
D-18

次

共役エノンの選択的還元（NaBH4-CeCl3 還元）················································· 71
共役エノンの選択的還元（9-BBN 還元）···························································· 72
アミノ酸の還元によるアミノアルコール（NaBH4-I2 還元）···························· 73
カルボン酸，エステルの LiAlH4 還元 ································································· 74
カルボン酸，エステルの選択的還元（AlH3 還元）··········································· 76
カルボン酸の選択的還元（ボラン還元）···························································· 77
ケトエステルの選択的還元（LiAlH4-SiO2）························································ 79
アルケン類のヒドロホウ素化と酸化 ·································································· 80
エステルと Grignard 試薬から第三級アルコール合成 ······································ 81
RLi によるエポキシドの開環 ··············································································· 82
エポキシアルコールの還元による 1,3- ジオール合成（SMEAH 還元）········· 83
アルケン酸化による cis- ジオール（KMnO4）···················································· 84
アルケン酸化による cis- ジオール（OsO4 酸化）··············································· 86
アルケン酸化による trans- ジオール ··································································· 88
アリールボロン酸からフェノール誘導体 ·························································· 89
Dakin 反応（芳香族アルデヒドからフェノール誘導体）·································· 90

E ハロゲン化アルキルおよびハロゲン化アリール誘導体 ·····································92
E-1

ハロゲン交換反応（Finkelstein 反応）·································································· 92

E-2
E-3
E-4

アルコールのハロゲン置換 ·················································································· 94
アルケンへのハロゲン化水素付加 ······································································ 95
アルケンへの Br2 付加 ··························································································· 97
活性メチル，メチレン基のモノブロム化 ·························································· 98
α- ブロモケトン合成 ······························································································ 99
Hell-Volhard-Zelinsky 反応（α- ハロカルボン酸合成）····································· 101
アルキンからハロゲン化ビニル ········································································ 102
芳香環のブロモメチル化 ···················································································· 103
芳香環のブロム化 ································································································ 104
Sandmeyer 反応（アリールアミンからアリールハライド）···························· 106
フェノール性 OH のハロゲン化 ········································································· 107

E-5
E-6
E-7
E-8
E-9
E-10
E-11
E-12

F エーテル類 ······················································································································109
F-2
F-3
F-4

大環状エーテル合成 ···························································································· 109
アセタールからビニルエーテル合成 ································································ 111
アリールボロン酸とフェノールのカップリング ············································ 112
アルケンのエポキシ化 ························································································ 113

F-5

アリルアルコールの立体選択的エポキシ化 ···················································· 114

F-1

vii

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次

G アルデヒドおよびケトン誘導体 ···············································································116
G-1
G-2
G-3
G-4
G-5
G-6
G-7
G-8
G-9
G-10
G-11
G-12
G-13
G-14
G-15
G-16
G-17
G-18
G-19
G-20
G-21
G-22

アルコールの酸化によるアルデヒド合成（PCC 酸化）·································· 116
アルコールの酸化によるアルデヒド合成（PDC 酸化）·································· 119
アルコールの酸化によるアルデヒド合成（Swern 酸化）······························· 121
アルコールの酸化によるアルデヒド合成（Ru 触媒酸化）····························· 122
アルケン酸化によるアルデヒド合成（KMnO4/Al2O3）···································· 124
二重結合のオゾン酸化 ························································································ 125
vic- ジオールの酸化開裂によるカルボニル基形成·········································· 126
シリルエノールエーテルの酸化による共役エノン合成 ································ 127
エステルの還元によるアルデヒド合成（SMEAH 還元）······························· 128
酸クロリド，混合酸無水物からアルデヒド合成 ············································ 129
ニトリルの還元によるアルデヒド合成（DIBAH 還元）································· 131
Grignard 試薬とホルムアミド誘導体によるアルデヒド合成 ························· 133
Grignard 試薬とオルトエステルからアルデヒド合成 ····································· 135
Grignard 試薬とギ酸からアルデヒド合成 ························································· 136
第二級アルコールからケトン合成（Jones 酸化）············································· 137
ケトンカップリングとピナコール - ピナコロン転位 ····································· 138
Grignard 試薬とアシルイミダゾール（アシルアミド）からケトン合成 ····· 139
Grignard 試薬とニトリルからケトン合成 ························································· 140
アルキンのヒドロホウ素化反応によるケトン，アルデヒド合成 ················ 141
Sommelet 反応（ハロメチル基からホルミル基）············································· 143
Vilsmeier 反応（芳香環のホルミル化）······························································ 144
Duff 反応（芳香環のホルミル化）······································································ 145

H カルボン酸およびカルボン酸誘導体 ······································································147
H-1
H-2
H-3
H-4
H-5
H-6
H-7
H-8
H-9
H-10
H-11
H-12

viii

アルデヒドの酸化によるカルボン酸合成 ························································ 147
メチルケトンの酸化によるカルボン酸合成（ハロホルム反応）·················· 149
立体障害の大きなエステルの加水分解 ···························································· 150
ニトリルの酸化的加水分解 ················································································ 152
Grignard 試薬（有機リチウム化合物）のカルボキシル化 ····························· 153
Koch-Haaf 反応によるカルボン酸合成 ······························································ 154
カルボン酸エステル合成 ···················································································· 156
カルボン酸フェニルエステル合成 ···································································· 157
Baeyer-Villiger 酸化（ケトンの酸化によるエステル合成）····························· 159
ヒドロキシカルボン酸からラクトン形成 ························································ 161
カルボン酸からカルボン酸クロリド合成 ························································ 162
ヘキサメチルジシラザンによるラクタム合成 ················································ 164

目

次ペプチド合成（活性エステル法）······································································ 166
ペプチド合成（混合酸無水物法）······································································ 167
ニトリル加水分解によるアミド合成 ································································ 168
Ritter 反応によるアミド合成 ·············································································· 170
H-17 アミドの脱水によるニトリル合成 ···································································· 172
H-18 オキシムの脱水によるニトリル合成 ································································ 173
H-19 芳香族アミンのシアノエチル化 ········································································ 175
H-13
H-14
H-15
H-16

I

アミン，イミン誘導体 ································································································176
I-1
I-2
I-3
I-4
I-5
I-6
I-7
I-8
I-9
I-10
I-11
I-12
I-13
I-14

Gabriel 合成（第一級アミン合成）······································································ 176
オキシムの水素化による第一級アミン合成 ···················································· 178
ニトリルの還元による第一級アミン合成 ························································ 179
イミンの還元による第二級アミン合成 ···························································· 181
アミドの還元によるアミン合成 ········································································ 182
第三級アミドのシラン還元による第三級アミン合成 ···································· 184
アミノ基のメチル化による第三級アミン合成 ················································ 185
Mannich 反応（カルボニル化合物のアミノメチル化）··································· 187
Grignard 試薬とイミニウム塩による第三級アミン合成 ································· 189
芳香族アミン合成（ニトロ化合物の還元）······················································ 190
Tröger 塩基合成 ····································································································· 192
アミンとカルボニル化合物からイミン合成 ···················································· 193
Grignard 試薬とニトリルからのイミン合成 ····················································· 194
第二級アミンとカルボニル化合物からエナミン合成 ···································· 196

J 硫黄化合物 ······················································································································198
J-1

ハロゲン化アルキルの求核置換によるスルフィド合成 ································ 198

J-2
J-3
J-4

アルキルチオシランとカルボニル化合物からスルフィド合成 ···················· 199
スルホキシドの Pummerer 転位 ·········································································· 201
ジトシラート合成 ································································································ 202

K 等価体，試薬 ·················································································································204
K-1

多官能性 Grignard 試薬 ························································································ 204

K-2
K-3
K-4
K-5

シリルエノールエーテル，ケテンシリルアセタール合成 ···························· 206
アリールボロン酸合成 ························································································ 207
Arbuzov 反応（ホスホン酸エステル合成）························································ 211
Meerwein 試薬によるアルキル化 ······································································· 212

K-6

イミニウム塩合成 ································································································ 213

ix

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L 官能基保護 ······················································································································216
L-1
L-2
L-3
L-4
L-5

テトラヒドロピラニルエーテル（ヒドロキシ基保護）·································· 216
アセタール（カルボニル基保護）······································································ 217
カルボニル基の保護（ジチオアセタール合成）·············································· 220
アミノ酸のカルボキシル基の保護 ···································································· 222
アミノ酸のアミノ基の保護 ················································································ 225

M 炭素̶炭素結合形成 ····································································································227
M-1マロン酸合成 ········································································································ 227

M-2
M-3
M-4
M-5
M-6
M-7
M-8
M-9

β- ケトエステルの γ 位アルキル化 ···································································· 228
イミンの α- アルキル化による α- アミノ酸合成 ············································· 230
ジチオアセタールからのカルボアニオン生成 ················································ 231
エノンへの Michael 付加反応 ············································································· 233
エナミンの求電子試薬との反応 ········································································ 235
エナミンとアルデヒドのアルドール反応 ························································ 236
ケトンとアルデヒドから α,β- 不飽和ケトン（アルドール反応）················· 238
向山アルドール反応 ···························································································· 239

M-10
M-11
M-12
M-13

Reformatsky 反応（有機亜鉛化合物による β- ヒドロキシエステル合成）··· 241
Claisen 縮合（エステルから β- ケトエステル）················································ 243
Dieckmann 縮合（分子内 Claisen 縮合）····························································· 245
Heck 反応（ハロゲン化アリールとビニル化合物からビニルアレーン合成）··································································································································· 246
Grignard 試薬とハロゲン化物のクロスカップリング（Ni 触媒）·················· 248
有機亜鉛化合物とハロゲン化物のクロスカップリング（Pd 触媒）············· 250
ハロゲン化アリールのホモカップリング（Ni 触媒）····································· 251
ハロゲン化アリールの Ullmann カップリング（銅触媒）······························ 252
ナフトールの酸化カップリングによるビナフトール合成 ···························· 254
Friedel-Crafts 反応（アルキル化）······································································· 255
Friedel-Crafts 反応（アシル化）··········································································· 259
α- ジアゾ化合物による環拡大反応（Rh 触媒）················································ 261
Arndt-Eistert 反応（ジアゾメタン誘導体による酸クロリドの増炭反応）···· 262
芳香環オルト位のアルキル化 ············································································ 264

M-14
M-15
M-16
M-17
M-18
M-19
M-20
M-21
M-22
M-23

N 環形成 ······························································································································266
N-1
N-2
N-3

x

Robinson 環化 ········································································································ 266
Diels-Alder 反応（六員環形成）··········································································· 268
ベンザイン中間体による Diels-Alder 反応························································ 271

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N-4
N-5
N-6
N-7
N-8
N-9
N-10
N-11
N-12

次

1,3- 双極子付加環化反応（五員環形成）··························································· 273
Nazarov 環化（ジビニルケトンからシクロペンテノン誘導体）···················· 274
α- ハロケトンの Favorskii 転位（環縮小反応）················································· 275
ジハロケトンの Favorskii 型反応········································································ 276
分子内 McMurry 反応（三員環，四員環形成）················································· 277
Simmons-Smith 反応（シクロプロパン環形成）··············································· 278
ジクロロカルベンによるシクロプロパン環形成 ············································ 280
オキソスルホニウムイリドによるシクロプロパン環合成 ···························· 281
スルホニウムイリドによるオキシラン環，アジリジン環形成 ···················· 282

O 転位，シグマトロピー ································································································284
O-1

Beckmann 転位 ······································································································ 284

塩基による Beckmann 転位 ················································································· 286
アミドの Hofmann 転位によるアミン形成 ······················································· 287
フェニルエステルの Fries 転位 ·········································································· 288
Claisen 転位（O- アリルから C- アリルへ）······················································ 289
Lewis 酸触媒による Claisen 転位 ········································································ 290
Cope 転位 ··············································································································· 291
O-8 oxy-Cope 転位 ········································································································ 292
O-9 [2,3]-Wittig 転位 ···································································································· 294
O-10 [2,3]-Stevens 転位 ·································································································· 295
O-11 エン反応 ················································································································ 297
O-2
O-3
O-4
O-5
O-6
O-7

P 芳香族化合物 ·················································································································299
P-1
P-2
P-3
P-4
P-5
P-6
P-7
P-8
P-9
P-10

Suzuki カップリング反応（アリールボロン酸とハロゲン化アリールからビア
リール合成）·········································································································· 299
Friedel-Crafts によるナフタレン環形成 ····························································· 300
アントラキノンからアントラセン（NaBH4 還元）·········································· 301
酸化的光閉環反応 ································································································ 302
芳香族アミドの求核的光閉環 ············································································ 305
カリックスアレーン合成 ···················································································· 306
カリックスレゾルシノール合成 ········································································ 308
芳香環のニトロ化 ································································································ 309
ジニトロベンゼンのニトロ化 ············································································ 310
芳香族ジアゾニウム塩の還元 ············································································ 311

Q ヘテロ芳香族化合物 ····································································································312
Q-1ピリジン合成（Kröhnke 法）················································································ 312

xi

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Q-2
Q-3
Q-4
Q-5
Q-6
Q-7
Q-8
Q-9
Q-10
Q-11
Q-12
Q-13

キノリン化合物合成 ···························································································· 313
イソキノリン合成（Pomeranz-Fritsch 法）························································· 315
キノリジニウム塩合成（Westphal 縮合）··························································· 317
ベンゾキノリジニウム塩合成 ············································································ 318
ピロール合成（Paal-Knorr 法）············································································ 321
インドール合成 ···································································································· 323
脱水素閉環によるヘテロ環形成 ········································································ 325
イミダゾール合成 ································································································ 326
イミダゾリウム化合物合成 ················································································ 328
ベンズイミダゾール合成 ···················································································· 329
オキサゾール合成 ································································································ 330
ピラゾール合成 ···································································································· 331

R 触媒的不斉合成 ·············································································································333
R-1
R-2
R-3
R-4
R-5
R-6
R-7
R-8
R-9
R-10
R-11
R-12
R-13
R-14
R-15
R-16
R-17
R-18

索

xii

引

デヒドロアミノ酸の不斉水素化（Rh 触媒）····················································· 333
ケトエステルの不斉水素化 ················································································ 335
ケトンの不斉水素移動還元（Ru 触媒）····························································· 336
アリルアルコールの Sharpless 酸化（不斉エポキシ化）（Ti 触媒）··············· 337
cis- アルケンの不斉エポキシ化（Mn 触媒）····················································· 339
スルフィドの不斉酸化（Ti 触媒）······································································ 341
アルケンの不斉ジヒドロキシ化反応（Os 触媒）············································· 342
不斉 Baeyer-Villiger 酸化（Zr 触媒）··································································· 344
不斉アリルアルキル化（Pd 触媒）····································································· 346
不斉向山アルドール反応 ···················································································· 348
不斉ニトロアルドール反応（La 触媒）····························································· 350
不斉 Michael 付加（ボロン酸の付加）······························································· 351
不斉 Michael 付加（アルキル亜鉛 - 銅触媒）···················································· 353
不斉 Michael 付加（アミン系触媒）··································································· 354
不斉 Robinson 環化 ······························································································· 356
ケトエステルの不斉 α- アルキル化（第四級アンモニウム塩触媒）············· 357
不斉 Diels-Alder 反応（Ti 触媒）········································································· 359
不斉 Simmons-Smith 反応（ジオキソボロラン触媒）······································ 360
362