2007 5 1

2007 5 1

2 1.1 1.1.1 1. 2. 3. 4. 5. 1.1.2 1. 1 2 3 4 5 1 2 3 2. 1 2

3 3 4 3. 1 2 3 1.1.3 1. 2. 3. 3% 5% 2% 4. 5. 30

1.2 1.2.1 1.4 1.4(1) 1.4(2) ( ) 1.4(3) 1.2.2 1.6 ( ) 1.6(1) 1.6(2) 1.6(3) ( ) 1.6(3) Y 1.6(4) 1.2.3 1.4(1) 1.5(2) 130 1.5(3) 4

1.2.4 1.7 1.7(1) 1.7(2) Y [ 1.8(1)(2)] 1.8 (3)(4) 1.8 (3) 1.8 (4) 1.9 T T A 5

500mL 1.2m 1mm 1.10 ( 110 3 4 h) C B ( -78 ) F 1.11 E F E 6

1.2.5 Mayo williamson Mayo ( 4.1) ( 4.1 k l) ( 4.1 a 1 a 3 ) 5mL 3mL 1mL Hickman ( 4.1 e) 50 L ( 4.1 g) 4.2 Mayc williamson ( 4.3 B C G H R) ( 4.3 D) [ 4.4(b)] ( 4 14) 4.4 williams()n 7

4.5 Hickman 4mL 4.6 4.7 Hickman 4.3 ( 4.8) 4.9 8

10mL 4.10 2mL 4.11 4.12 4.13 9

4.10 4.14 1.3 1.3.1 1. 2. 3. 1.3.2 10

1.3.3 : (1) (2) (3) (4) (5) (6) (7) (8) (9) 11

2.1 10 2.1.1 2.1.2 80 100 2.1.3 80 250 1 1 1% 2.1.4 250 350 2.1.5 2.2 12

0 2-1 2-1 100 NH 4 Cl NaNO 3 NaCl CaCl 2 6H 2 O CaCl 2 6H 2 O 25 50 33 100 143-15 -18-21 -29-55 -50-78 -38 2.3 2.3.1 1 2 13

2-2 CaCl 2 Na P 2 O 5 CaCl 2 MgSO 4 Na 2 SO 4 P 2 O 5 K 2 CO 3 MgSO 4 CaO Na 2 SO 4 CaCl 2 Na P 2 O 5 MgSO 4 Na 2 SO 4 K 2 CO 3 CaCl 2 MgSO 4 Na 2 SO 4 MgSO 4 Na 2 SO 4 MgSO 4 K 2 CO 3 Na 2 SO 4 2-2 KOH NaOH K 2 CO 3 CaO CaCl 2 MgSO 4 Na 2 SO 4 2-3 2-3 CaCl 2 nh 2 O 0.97 MgSO 4 nh 2 O 1.05 Na 2 SO 4 nh 2 O 1.25 K 2 CO 3 nh 2 O 0.2 CaSO 4 nh 2 O 0.06 Na+H 2 O CaO+ H 2 O P 2 O 5 +H 2 O 0.25 14

10 0.5 1.0 2.3.2 1 2 3 2.3.3 1 2 2-4 2-4 CaO KOH NaOH CaCl 2 P 2 O 5 H 2 SO 4 CaBr 2 ZnBr 2 NH 3 H 2 HCl CO 2 CO SO 2 N 2 O 2 H 2 CO 2 CO SO 2 N 2 O 2 H 2 N 2 CO 2 HCl Cl 2 HBr 15

3.1 Grignard 2 (2 methyl 2 hexanol) Grignard 2.4g(0.10mol) 14.5g(11 5mL 0 106mol) 6.4g(8 1mL 0.11mol) 10 5 250mL 2.4 g 12mL 11.5mL 12mL 3 5mL ( ) 20mL 15min 8.1mL 12mL 15min 75mL10 40mL 25mL5 25mL 137 141 5.5 6g 2 2 143 n D 20 1.4175 5 6 h [1] 16

[2] [3] [4] [5] [6] [7] 1 2 3 4 5 6 Grignard 2 2 3.2 Friedel-Crafts (p methyl acetophenone) 17

1 20 (20+5)mL 3.7mL( 4.0g 0.039mol) 13.0 g(0.098mol) 5 100mL 13.0g 20mL 3.7mL 5mL 15min 90 95 30min 30mL 30mL 5 15mL 140 220 222 140 112.5 1 46kPa(11mmHg) 93.5 0.93kPa(7 mmhg) 4 4.5g 225 98 12kPa(736mmHg) 28 n D 20 1.5353 102G 3m 101 SE-30 200 250 2µL -l 2 6 8h [1] ( ) 2.5 [2] [3] [4] [5] [6] [7] 1 2 3 18

4 FriedeI Crafts 5 6 1 1 2 2 TBHQ (tert butylhydroquinone) ( ) ( 120 ) RH+O 2 ROOH ROOH RO + OH C O e c TBHQ TBHQ 19

BHA(2 3 4 ) Lewis Freidel-Crafts 4.0g (0.036 mol) 2.67g (3.5mL 0.036mol) 100mL 4.0g 15mL 15mL 90 3.5mL 40min 90 95 15min 45mL ( ) 3.8g 128 TBHQ 129 4 h [1] 25 26 [2] [3] [4] 1 2 3 3.3 Perkin Perkin 20

Perkin ( 133 ) ( 68 ) (cinhamic aeid) Kalnin ( )2.7g (2.5mL 0.025mol) ( )7.5 g (7mL 0.074mol) 3.5g (0.025mol) 10 3.5g 2.5mL 7mL 100mL 170 180 40min 20mL ( ) 20mL10 45mL 10mL 10mL 2 2.5g 21

3 1 130 132 133 4 h [1] [2] [3] [4] [5] 1 2 3 Perkin Kalnin K 2 CO 3 3 (coumarin 3 carboxylic acid) 1 2 ( ) 1820 1868 Perkin ( ) Perkin Perkin Knoevenagel Perkin 22

3 3 2.0g (1.7mL 0.016mol) 3.0g (2.8mL 0.019mol) 95 1 3 50mL 1.7mL 2.8mL 10mL 0.2mL 2 h 12mL 2 3mL 50 2 3 3 2.5 3.0g 91 92 25 3 93 2 3 50mL 2 g -3-1.5 gnaoh 10mL95 5mL 15min 5mL 25mL 1.5g 188.5 3 190 ( ) 7 8 h 23

[1] 50 1 2 3 3.4 α α (aldolcondensation) α α α α Claisen-Schmidt 24

2 2 (2-ethyl-2-hexenal) 2 3 2 2 (2 1 ) ( )13.3mL(10.6 g 0.15mol) 2 12.5mL 100mL 12.5mL 2 13.3mL 20min 85 1h ( ) 10mL 2 ( ) 60 70 1.33 4.0kPa(10 30 mmhg) 6 7g 2 2 177 ( ) 6h [1] ( 75 ) [2] 90 [3] 1 2 3 (benzal acetophenone) ( )2.7 g(2.5ml 0.025mol) 3.0g(3.0mL 0.025 mol) 10 25

95 100mL 12mL10 8mL 95 3.0mL 22 2.5mL 25 30 0.5h 1 1.5 h 15min 2 3mL 95 ( 4 5mL ) 3.0 3.5g 56 57 58 59 5 6 h [1] [2] 25 30 [3] 0.5h 1 1.5h [4] [5] α β γ α ( ) 58 59 β ( ) 56 57 γ 48 α 1 2 3 (benzal acetophenone) ( )2.7g (2.5mL 0.025mol) 3.0g (3.0mL 0.025mol) 10 95 100mL 12mL10 26

8mL 95 3.0mL 22 2.5mL 25 30 0.5h 1 1.5h 15min 2 3mL 95 ( 4 5mL ) 3.0 3.5g 56 57 58 59 5 6 h [1] [2] 25 30 [3] 0.5h 1 1.5 h [4] [5] α γ α ( ) 58 59 ( ) 56 57 γ 48 α 1 2 3 27

1 3 2 1 (1 p methyphenyl 3 phenyl 2 propene 1 one) Claisen-Schmidt 1 3 2 1 E 3.4g(3.4mL 0.025mol) 2.7g(2.6mL 0.025mol) 1.3g 95 7.5mL 100mL 1.3g 12mL 7.5mL 95 3.4mL 2.6mL 25 30 2 5 3h 95 4.8g 95 4.0g 72 73 1 3 2 1 75 6h [1] [2] [3] [4] 95 1 Claisen Schmidt 2 E 3.5 wittig wittig G 1953 (R 2 CHx) ( ) α (THF DMF ) (C 6 H 5 Li n C 4 H 9 Li ) (phosphor yild) 28

(ylene) wittig wittig ylid Wittig wittig wittig 1979 ylid α C α C ylid ylid ylid ylid wittig wittig 29

wittig E wittig (E) 1 2 ylid 1 2 (stilbene) 3g(2.8mL 0.024mol) 6.2g(0.024mol) 1.6g(1.5mL 0.015mol) 50 95 1 ( ) 50mL 3g 6.2g 20mL 2.5 3h 5mL 110 1 h 6 5 7 g 3lO 312 2 1 2 50mL 5.8g 1.6g 10mL 7.5mL 50 10 15min 30min 10mL 20mL 10mL 3 95 ( 10mL) 1 2 1.0 g 122 123 1 2 124 8 h [1] 30

[2] [3] 1 1 2 2 3 1 2 Br 2 CCl 4 4 wittig 3 6 (anthranilic acid) Hofmann Hofmann (rearrangemenl) Hofmann (degradation) 31

(acynitrene) Hofmann 6 g(0.04mol) 7.2g(2.3mL 0.045mol) (7.5+5.5)g 150mL 7.5g 30mL 0 2.3mL 5.5g 20mL 0 6g 0 15 20min 20 25 ( 18!) 10min 25 30 0.5h 70 2min 2 ml 32

( 15mL) 6 6.5mL 3 3.5g 144 145 145 5 6 h [1] [2] [3] pi=3 4 1 2 3 3.7 (enamine) 1954 StoI k G α α α Micheal 33

2 (2 acetylcyclohexanone) 15 g(16ml 0.153mol) g(17.4ml 0.176mol) ( )9.0g(8.2mL 0.115mol) 0.15g 10mL 1 N (1 ) 100mL 16mL 17.4mL 0.15g 50mL 2.5 3 h 2.75mL 118 120 1.33kPa(10mmHg) 94 96 1 07kPa(8mmHg) 15g 2 2 250mL 12.5g(0.076mol) 34

N (1 ) 10mL 90mL 8.2mL 40mL 45min 1h 20mL 20mL 1 h 40mL 25mL 106 112 2.4kPa(18 mmhg) 2 6g 2 111 112 2.4kPa(18 mmhg) n 20 D 1.5090 10 12 h [1] [2] 1 2 3 2 1 H NMR ( 3 27) 6mm(δ=7.7) 92mm(δ=1.5 2.8) 2 35

(Microscale Laboratory of organic Chemistry) 20 90 (GC) (HPLC) (IR) (UV) (NMR) 4R Reject( ) Reduce( ) Recycle( ) Reuse( ) 21 4.1 Grignard ( ) ( ) ( ) ( ) ( ) Lewis α H α 4 (4 bromoacetoaniline) 4 200 mg(1 5 mmol) 85 mg(0 5 mmol) 2 ml 40 300αL(2 6 mmol) 95 36

10mL 200mg 85mg 2mL 0.3mL40 30min 5mL 15min ( 4.10) 95 4 180mg 170 171 1.5 2 h [1] [2] 3 (3 bromocyciohexene) N NBS ( ) α H ( ) α HBr NBS Br 2 α H 37

NBS ( ) NBS NBS CCl 4 α H 3 NBS CCl 4 CCl 4 NBS CCl 4 CCl 4 280 mg(3.4mmol) N 356mg(2.0mmol) 10mg ( )4mL 10mL 280mg 4mL 356mg N 10mg N 5min( 45min ) 5mL ( 4.8) 3 70 72 4.4kPa(33 mmhg) 76 78 4.8kPa(36 mmhg) 210 218 mg 1.5 2h [1] [2]! 1 NBS 2 4.2 Pechmann Pechmann 38

Pechmann a b c 4 7 (4 methyl 7 hydroxycoumarin) ( ) 15( ) Pechmann 4 7-110mg(1.0mmol) 127 L(130mg 1.0mmol) 1.5mL 15100mg 10mL 110mg 127 L 1.5mL 100mg 15 90min 2mL ( 4.10) 4 7 60 95mg 186 188 4 7 190 192 2 2.5 h [1] 15 (C 10 H 10 C 8 H 8 O 3 S) x 39

100mg 15 [2] [3] 1 2 40

80 (0.8) 5 100 =32.8 5 1 Claisen α Claisen 41

92 8 4 2 4 2 (ethyl acetoacetate) 27.5mL(25g 0.38mol) 2.5g(0.11mol) 12.5mL 100mL 28mL 2.5g 42

1.5 2 h 50 ( 15mL) 10mL 5 100mL 25mL 80 83 2 7kPa(20mmHg) 6 6.5g 6 8h 180.4 d 20 4 1.0282 n 20 D 1.4194 /kpa 101.3 10 7 8 0 5 3 4 0 2 7 2 4 1 87 1 6 (mmhg) (76 0) (80) (60) (40) (30) (20) (18) (14) (12) / 181 100 97 92 88 82 78 74 71 [1] [2] 76 77 1 2 [3] 2.5g 15mL 100mL 5 min 0.5min ( ) 27.5mL 1 1.5h [4] 50 ( 2 2.5h) [5] [6] [7] [8] 43

4 2 ( ) (4 phenyl 2 butanone) 0.9g (0.040mol) 5mL(5.1g 0.04mol) 5.5g(5mL 0.043mol) 13mL 3.2g(0.033mol) 95 1. 4 2 100mL 3mL 0.9g 5mL 10min 5mL 10 15min ( ) 10min 1.5h 44

2g 15mL 10min 1.5h ph 8 9 40 5mL (ph 1 2) 10min 1 h 15mL ( ) 5g 70 75 4 2 233 234 111 1.6kPa(12 mmhg) 96 1.07kPa(8 mmhg) 102 1.2kPa(9 mmhg) d 20 4 0.9849 n 20 D 1.5122 8 h [1] [2] [3] 2 100mL 35mL95 60 3.3g 27.5mL 80 15min 4 2 70 3 4g 2 h [1] 1 2 3 45

5.2 B 1 (thiamine) B 1 B 1 ( R R ) (1) (yiid) 46

(2) (3) (4) ( ) α 47

α α (benzil) ( )4.3g(0.02mol) 2g(0.025mol) 12.5mL 2 95 50mL 4.3g ( ) 12.5mL 2g 2.5mL2 1.5 h 50 60 20mL 3 3.5g 75 48

94 96 95 4 h [1] α α [2]2 2 5 g 100 mll0 (Benzilic acid) ( )2.5g(0.012mol) 2.5g(0.037mol) 95 50mL 2.5g 5mL 5mL95 2.5g 15min 1 h 65mL 3mL 20mL 1.5 1.8g 147 148 1.5g 148 149 4 h [1] 49

[2] 6mL 1 5.3 50

(acetanilide) 51

5.5mL(5.6g 0.06mol) 7.3mL(7.5g 0.073mol) (CH 3 CO 2 Na 3H 2 O)9g(0.065mol) 5mL 500mL 120mL 5mL 5 6g(5.5mL) ( 1 g) 5min 400mL 50 7.3mL 9g 20mL 5 6g 113 114 2 3h 6mL(6.1g 0.065mol) 8.8mL(18.6g 0.31mol) 50mL 6mL 8.8mL ( 0.05g) 15min 100 100 110 1.5h 100mL 5 5.5g 113 114 114.3 4 h 52

[1] [2] 100 [3] 2.2mL [4] ( ) 1 ( ) 100 110 2 ( ) 3 ( ) (SN) (suifanilamide) ( )5g(0.037mol) 22.5g(12.5mL 0.19mol) (28 d=0.9)17.5ml 1 100mL 5g 53

12.5mL ( 5.10) ( 1.6(4)) 75mL 10mL 2 17.5mL ( ) 15min 10mL 10min 3 3.5mL 0.5h 10min ( ) ( 3.5 4g) ( 12mL ) 3 4g 161 162 163 164 6 8 h 54

[1] 148 150 [2] [3] [4] [5] 1 2 h [6] 250mL 250mL 149 [7] 55

[8] 219 220 [9] 3.5mL [10] 1 2 5.4 90 155 156 ( ) 56

(ph 6) N N (p aminobenzoic acid) 57

7.5g(0.07mol) 8.7g(8mL 0.085mol) 12g 20.5g(0.13mol) (MgSO 4 7H 2 O) 20g(0.08mol) 1 500mL 7.5g 175mL 7.5mL 12g 20mL 50 8mL 154 7.5g 2 600mL ( 7.5g) 20g 350mL 85 20.5g 70mL 30min 85 15min 2 3mL 20 5 6g 250 252 3 5mLl8 250mL 30min 30mL 10 30mL 1mL 186 187 6 8 h ( ) (ethyl p aminobenzoate) 2g(0.014mol) 95 (25mL) 2mL 10 58

100mL 2g 2mL95 2mL ( ) 1 h 10 ( 12mL) ( ) ph 9 ( ) 40mL 2mL 1g 90 9l 92 4 6 h Sn HCl Fischer Spier-( ) HCl HCl 0.5g(0.0077mol) 2.7mL 1.5g(0.015mol) ( )0.25g(0.0015mol) 0.9g(0.0076mol) 1 1.5g 3mL 1.5mL 0.5g 2.7mL 10mL CrO 3 +H 2 SO 4 0.5 h 7mL 100 110 0.95g 2 5mL 0.25g 0.9g 2.5mL 59

( ) 160mg 184 186 3 5mL [100mL HCl 45.4g(0 ) 42.7g(10 ) 41.0g(20 )] 3mL 150mg 1.5mL l h 25 ml 7 8 h [1] [Cr 2 (SO 4 ) [2] [3] [4] 10mg 1 2 (Procaine) 60

5.5 5 5 1 3 5 5 l 3 ( ) 61

15 4 3 2 Michael Dieckmann 5 5 l 3 (5 5 dimethyl 1 3 cyciohexanedione) 1.2g(0.052 mol) 8mL(8.5g 0.053mol) 4 3 2 6mL(5g 0.051mol) 20mL 100mL 20mL 1.2g 8mL(8.5g) 6mL(5 g) 4 3 2 1 h 6.3g 25mL 2 h 1 3 10min 62

4 5g 147 148 5 5 1 3 148 149 6 h [1] [2] [3] 63