反応例 ９.1 カルボン酸誘導体の反応

エステルの加水分解： RCOOR → RCOOH

E. L. Eliel, M. T. Fisk, T. Prosser, Org. Synth., Coll. Vol. 4, 169 (1963).

OEt

Cl

O

PhOH

Cl

O

Ph

HCl

reflux, 1.5 h

CH3COOH

reflux, 3 h

R. C. Cambie, D. S. Rutledge, Org. Synth., Coll. Vol. 6, 348 (1988).

95-100%

O

O

Me

Me

O

O

NaOH

EtOH

H2O

OH

OH

reflux, 2 h

EtOH

92-97%

O. Ort, Org. Synth., Coll. Vol. 8, 522 (1993).

O

Ph

Cl

OKOH

OH

Ph

エステルの生成

カルボン酸から： RCOOH → RCOOR

OH

OH

O

PhOEt

OH

O

Ph

HCl

reflux, 5 h

EtOH

E. L. Eliel, M. T. Fisk, T. Prosser, Org. Synth., Coll. Vol. 4, 169 (1963).

reflux, 4 h 93%

P. Kalaritis, R. W. Regenye, Org. Synth., Coll. Vol. 8, 258 (1993).

H2SO4

OH

O

FEtOH

OEt

O

F

OH

OH

O

+

HO

Cl

POCl3

80 °C, 4 h

OH

O

OCl

N. G. Gaylord, P. M. Kamath, Org. Synth., Coll. Vol. 4, 178 (1963).

55-62%

酸ハロゲン化物から： RCOCl → RCOOR

Ph

O

HOCl

Cl

+

55 – 215 °C

A. H. Ford-Moore, Org. Synth., Coll. Vol. 4, 84 (1963).

Ph

O

OCl

89-91%

CH2Cl2

M. Braun, S. Graf, S. Herzog, Org. Synth., Coll. Vol. 9, 507 (1998).

HOOH

Ph

H Ph

Ph

O

ClMe+

N

OOH

Ph

H Ph

Ph

Me

O

0 °C – rt, 4 h 92%

OH NaH

Et2O

S. H. Montgomery, M. C. Pirrung, C. H. Heathcock, Org. Synth., Coll. Vol. 7, 190 (1990).

Et2O

0 °C

Et

O

Cl

0 °C, 1.5 h

O

O

Et

96-97%

G. P. Crowther, E. M. Kaiser, R. A. Woodruff, C. R. Hauser, Org. Synth., Coll. Vol. 6, 259 (1988).

rt, 15 hMe

Cl

O

t-BuOLi

Et2O

+

Me

OBu-t

O

79-82%

reflux, 7.5 h

Et2O

63-67%

R. E. Ireland, M. Chaykovsky, Org. Synth., Coll. Vol. 5, 171 (1973).

PCl5+C

O

OH

N

reflux, 2 h

rt, 15 h

PhNMe2

t-BuOH

C

O

OBu-t

N

酸無水物から： (RCO)2O → RCOOR

25 °C, 6 h

94-98%

R. P. Hanzlik, Org. Synth., Coll. Vol. 6, 560 (1988).

OH

O

O

O

MeMe

N

O Me

O

+0 °C – rt

D. R. Deardorff, C. Q. Windham, C. L. Craney, Org. Synth., Coll. Vol. 9, 487 (1998).

HO O O

O

O

MeMe

Me

O

N

HN

O O Me

O

Me

O

96-98%

toluene

reflux, 24 h

K. Furuta, K. Iwanaga, H. Yamamoto, Org. Synth., Coll. Vol. 8, 141 (1993).

84%

O

O

O

OH

+O

O

O

OTsOH

酸ハロゲン化物の合成

+reflux, 18 h

90%

C. Hubschwerlen, J.-L. Specklin, Org. Synth., Coll. Vol. 9, 13 (1998).

N

O

O

OH

O

SOCl2 N

O

O

Cl

O

H. C. J. Ottenheijm, M. W. Tijhuis, Org. Synth., Coll. Vol. 7, 467 (1990).

+Me

O

OH

H OMe

Cl ClO

25 – 50 °CMe

O

Cl

O

44-50%

reflux, 7.5 h

C6H6

82-94%

E. C. Taylor, A. Mckillop, G. H. Hawks, Org. Synth., Coll. Vol. 6, 549 (1988).

Ph

PhOH

O

SOCl2+

Ph

PhCl

O

75-80%

G. A. Olah, S. J. Kuhn, Org. Synth., Coll. Vol. 5, 66 (1973).

Cl

O

HF

rt, 1 h 30–40 °C, 1 h

F

O

70 °C, 1.5 h

B. Vassel, W. G. Skelly, Org. Synth., Coll. Vol. 4, 154 (1963).

98-100%

SOCl2Me2N

O

OH

+

Cl–

Me2N

O

Cl

+

Cl–

酸無水物の合成

Cl

O

H ONa

OEt2O

MeMe O

O

H

O

L. I. Krimen, Org. Synth., Coll. Vol. 6, 8 (1988).

rt, 5.5 h+

HO

HO

OH

OH

O

O

+

H2SO4

reflux

10 min

EtOH

O

O

O

MeMeO

AcO

AcO

O

O71-77%

R. L. Shriner, C. L. Furrow, Jr., Org. Synth., Coll. Vol. 4, 242 (1963).

アミドの生成

カルボン酸から： RCOOH → RCONR2

CH3 OH

O

CH3 ONH4

O

CH3 NH2

O+ (NH4)2CO3

!"

210~216 ˚C

87~90%

G.H. Coleman, A.M. Alvarado, Org. Synth., Coll. Vol. 1, 3 (1941).

HN

CH3

!

NCH3

CHO

+ HCO2Htoluene

93~97%

L.F. Fieser, J.E. Jones, Org. Synth., Coll. Vol. 3, 590 (1955).

NH2 C NHCO2H +

O

C. N. Webb, Org. Synth., Coll. Vol. 1, 82 (1941).

R. J. Johnson, L. T. Sandborn, Org. Synth., Coll. Vol. 1, 111 (1941).

NH2

AcOH

reflux, 2 h

HN

O

Me

エステルから： RCOOR → RCONR2

ClCH2 C OCH2CH3

O

ClCH2 C NH2

ONH

4OH

0–5 °C

+ CH3CH2OH

W. A. Jacobs, M. Heidelberger, Org. Synth., Coll. Vol. 1, 153 (1941).

NCCH2 C OCH2CH3

O

NCCH2 C NH2

O

+ CH3CH2OHNH3

B. B. Corson, R. W. Scott, C. E. Vose, Org. Synth., Coll. Vol. 1, 179 (1941).

CH3 CH C OCH2CH3

O

OH

CH3 CH C NH2

O

OH

liq. NH3

J. Kleinberg, L. F. Audrieth, Org. Synth., Coll. Vol. 3, 516 (1955).

C CH2 C OCH2CH3

O O

C CH2 C NH

O OPhNH2

135 °C

C. F. H. Allen, W. J. Humphlett, Org. Synth., Coll. Vol. 4, 80 (1963).

CH3CH2O

O

O

OCH2CH3

H2N

O

O

NH2

NH4OH

NH4Cl

D. T. Mowry, J. M. Butler, Org. Synth., Coll. Vol. 4, 486 (1963).

酸無水物から： (RCO)2O → RCONR2

+

40 °C – reflux

EtOH

O

O

O

MeMe

92-97%

K. E. Krakowiak, J. S. Bradshaw, Org. Synth., Coll. Vol. 9, 34 (1998).

HO O NH2 HO O NH

Me

O

H2NCH2 C OH

O

NHCH2 C OH

O(CH3CO)2O, H2O

CH3C

O

R. M. Herbst, D. Shemin, Org. Synth., Coll. Vol. 2, 11 (1943).

酸塩化物から： RCOCl → RCONR2

0 °C

NaOH

77-81%

C. S. Marvel, W. A. Lazier, Org. Synth., Coll. Vol. 1, 99 (1941).

NH

Ph

O

Cl

+Ph

O

N

H2O

PhCH2O CCl

O

PhCH2O C

OH2NCH2CO2H

NaOH

NHCH2CO2H

H. E. Carter, R. L. Frank, H. W. Johnston, Org. Synth., Coll. Vol. 3, 167 (1955).

OMeO

OH + SOCl2

DMF

cat.Et2NH

THF

OMeO

NEt2

X. Wang, S. O. de Silva, J. N. Reed, R. Billadeau, E. J. Griffen, A. Chan, V. Snieckus, Org. Synth., Coll.

Vol. 9, 559 (1998).

(CH3)2CH CCl

O

(CH3)2CH C

O

NH2NH4OH

R. E. Kent, S. M. McElvain, Org. Synth., Coll. Vol. 3, 490 (1955).

C(CH2)8C Cl

OO

CH3O C(CH2)8C NH2

OO

CH3ONH4OH

8 °C W. S. Bishop, Org. Synth., Coll. Vol. 3, 613 (1955).

CH3CH2 CCl

O

CH3CH2 C

O

N O

CH2Cl2

ON

R. B. Lettan, II, B. C. Milgram, K. A. Scheidt, Org. Synth., Annual Vol. 84, 22 (2007).

ラクトンの生成

Br (CH2)10–CO2HK2CO3

(CH2)10

O

C O DMSO100 ˚C, 1 h

C. Galli, L. Mandolini, Org. Synth., Coll. Vol. 6, 698 (1988).

79~83%

CHO

O

OPh3P=CHCO2Me O

O

CO2Me

OO

HO

MeOH, 0 ˚C

H2SO4/MeOH

room temp., 2 h

78%

(trans 10%)

~100%

J. Mann, A.C. Weymouth-Wilson, Org. Synth., Coll. Vol. 10, 152 (2004).

!"#$$#%&'()**+,

HO2C

H2N

H

CO2HOO

H

CO2H

L-glutamic acid

NaNO2/H2SO4

(S)-(+)

70%

O.H. Gringore, F.P. Rouessac, Org. Synth., Coll. Vol. 6, 698 (1988).

ラクタムの生成

CO2–

NH

CH3

O

CO2H CH3NH2

H2O

CO2–

N

CH3

+NH3CH3

N

CH3

CH3O

+NH3CH3

H2 / Ni

74~77%

R.L. Frank, W.R. Schmitz, B. Zeidman, Org. Synth., Coll. Vol. 3, 328 (1955).

CO2H

H2N !

HN

O

cis and trans

Dowtherm

!"#$%

81~84%

W.M. Peariman, Org. Synth., Coll. Vol. 5, 670 (1973).

ラクタムの加水分解

C. Y. Meyers, L. E. Miller, Org. Synth., Coll. Vol. 4, 39 (1963).

reflux, 1 h

90%

NH

O

HCl

H2O Amberlite

resin

HO

O

NH2

（還元的アミノ化：11章）

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