北京大学：《有机化学》（双语版）第十三章（13-3）有机含氮化合物

yy)Acylation and Sulfonylation Reaction 缚酸剂 除酸剂 R-C-CI or 0 RNh2 R一C-NHR+ hCi or RCOoH R一C O Acylation R一C O SO2Cl RNH R—C-NHR HCI 苯磺酰氯 苯磺酰胺 Sulfonylation

(四) Acylation and Sulfonylation Reaction R C O Cl R C O R C O O or + R'NH2 R C O NHR' + HCl or RCOOH 缚酸剂 除酸剂 + R'NH2 R C O SO2Cl NHR' + HCl 苯磺酰氯 苯磺酰胺 Acylation Sulfonylation

Acylation and sulfonylation Applications 药物合成中的应用 NE NHCOCH NH2 NHCOCH (CH3 COhO (CH3CO)O OH OC oCh OH 扑热息痛 非那西丁 (paraspen) (phenacetin) H2N SO2 NH2 H2N SO2NHR 磺胺药(抗菌剂,利尿药,降糖药)

Acylation and Sulfonylation Applications 药物合成中的应用 NH2 OH (CH3CO) 2O NHCOCH3 OH (CH3CO) 2O NHCOCH3 OC2H5 NH2 OC2H5 扑热息痛 (paraspen) 非那西丁 (phenacetin) H2N SO2NHR 磺胺药 (抗菌剂，利尿药，降糖药) H2N SO2NH2

Acylation and sulfonylation O-N OO N N N H H2N HoN H2N 磺胺异口恶唑 磺胺嘧啶 磺胺地托辛 (Sulfafurazole) (Sulfadiazine) (Sulfadimethoxine) NH2 H2N NH 乙酰唑胺( Acetazolamide) 氢氯噻嗪( Hydrochlorothiazide) O N-C-NHCH CH2 SNH-C. NH Me 格列美脲( Glimepiride)

S N O O O N H2N H S N O O H2N H N N S N O O H2N H N N O O 磺胺异 恶唑 (Sulfafurazole) 口 磺胺嘧啶 (Sulfadiazine) 磺胺地托辛 (Sulfadimethoxine) Acylation and Sulfonylation S NH2 O O N N N S O H S H2N O O S NH N O O H Cl 乙酰唑胺(Acetazolamide) 氢氯噻嗪(Hydrochlorothiazide) N O C O NHCH2CH2 S O O NH C NH O Me 格列美脲 (Glimepiride)

Acylation and sulfonylation 昴氨基的保护 NH2 NHCOCH NHCOCH3 NH2 CH3COC HNO/H2SO4 OH H2O NO2 芳胺的易氧化性 乙酰氨基的定位规律 昴胺的分离、鉴定 Hinsberg reaction RNH, Na溶解 C6HSSO2NR C6HSSO2NR R2NH C6HsSO2CI NaoH(aq C6HSSO2NR2 CAHsSO2NR2不溶 R3N RN不反应

氨基的保护 NH2 NH2 NO2 CH3COCl NHCOCH3 HNO3 /H2 SO4 NHCOCH3 NO2 OH- /H2 O 芳胺的易氧化性 乙酰氨基的定位规律 胺的分离、鉴定 Hinsberg Reaction RNH2 R2NH R3N C6H5 SO2Cl C6H5SO2NR H C6H5SO2NR2 R3N NaOH(aq.) C6H5SO2N - R Na + C6H5SO2NR2 R3N 溶解 不溶 不反应 Acylation and Sulfonylation

()Reaction with Nitrous Acid HNO2,亚硝酸 NaNO2/HCl, NaNO2/H2sO4 芳香伯胺 重氮化反应 NH] Diazotization 2Cl NaNO2/HCi(aq nacl Diazonium salt 氯化重氮苯 重氮盐 Mechanism H HONO+H÷HO-NONO+H2O Ar-NH2 NO Ar-N-NO -Ar-N-N=OTAr-N=N-OH H H +h Ar--N=N-OH hoo Ar-N三N

(五) Reaction with Nitrous Acid HNO2 , 亚硝酸 NaNO2 /HCl, NaNO2 /H2SO4 芳香伯胺 NH2 NaNO2/HCl(aq.) 0-5 C o N2 + Cl - + NaCl 氯化重氮苯 Diazonium Salt 重氮盐 重氮化反应 Diazotization HONO + H + HO NO H + NO + H2O Ar NH2 + NO Ar N NO H H -H + Ar N N H O Ar N N OH + H + Ar N N OH2 -H2O Ar N N Mechanism

Reaction with Nitrous acid 脂肪伯胺 RNH HO-N=O HO R-N三N N2↑+醇烯烃的混合物 OH CH3(CH2)3OH CH3 CH2 CHCH3 13% CH3(CH2)3NH2 NaNO2/HCI(aq 25% CH3 (CH2)3Cl CH3 CH2 CHCH3 25C 5% 3% H CH CH3 CH3 CH,CH=CH, CH3 26% 3% 7% CH3CH2 CH2 CH2N2 CI CH3 CH2CH2CI t rearrangement CH3 CH2CHCH

脂肪伯胺 e.g. CH3 (CH2 )3NH2 NaNO2 /HCl(aq.) 25 C o CH3(CH2)3OH CH3CH2CHCH3 OH CH3(CH2)3Cl CH3CH2CHCH3 Cl CH3CH2CH=CH2 CH3 C C CH3 H H CH3 C C CH3 H H 26% 3% 7% 5% 3% 13% 25% Reaction with Nitrous Acid -N2 Rearrangement RNH2 HO N=O R N N + H2O N2 + 醇, 烯烃的混合物 CH3CH2CH2CH2N2 + Cl - CH3CH2CH2CH2 + CH3CH2CHCH3

Reaction with Nitrous acid 仲胺 R ArNER Ar-N-N=O HNO2 R R2NH R-N-N=O N亚硝基胺 黄色油状物,难溶于水和稀酸

仲胺 ArNHR or R2NH HNO2 Ar N N R O R N N R O N-亚硝基胺 黄色油状物，难溶于水和稀酸 Reaction with Nitrous Acid

Reaction with Nitrous acid 脂肪叔胺 Rrn t hno 成盐 rohn NO2 芳香叔胺 hNO2 (CH3)2N一 (CH3N NO (CH3)2N CH HNO (CH3N NO 苯环上取代

脂肪叔胺 R3N + HNO2 R3HN + NO2 - 芳香叔胺 (CH3)2N HNO2 (CH3)2N CH3 HNO2 (CH3) 2N NO (CH3)2N CH3 NO 成盐 苯环上取代 Reaction with Nitrous Acid

(六) Schiffs base& Enamine( Schiff碱和烯醇) Schiff’ s base OH NH2+ -CHO NH-CH- 水解 Schiff's base Imine enamine Imine C=o hnr N-R C=N-R OH H Imine ho C-C=O + HnR2 C-C—N一R C=C--NR2 H OH R Enamine

(六) Schiff’s base & Enamine (Schiff 碱和烯醇) NH2 + CHO NH CH OH N CH 水解 Schiff’s Base Imine Schiff’s base Imine & Enamine -H2O C O + H2NR 1 o C OH N H R C N R -H2O C C O H H + HNR2 2 o C C OH N R R H C C NR2 Imine Enamine

Enamine(烯胺) Formation NR2 HNR,H + H2O 酸催化 除水环状仲胺 H 吡咯烷 哌啶 吗啉

Enamine (烯胺) Formation 酸催化 除水 环状仲胺 N H 吡咯烷 N H N O H 哌啶 吗啉 HNR2 O + H+ NR2 + H2O