反応例 10.

2 Grignard 反応と関連反応

アルデヒド，ケトンとの反応

Cl MgCl
Mg 1) H2C O OH

Et2O 2) H 2SO4/H2 O
64~69%
H. Gilman, W.E. Catlin, Org. Synth., Coll. Vol. 1, 188 (1941).

Mg 1) CH3CHO
(CH3)2CHBr (CH3)2CHMgBr OH
Et2O 2) H2 SO4/H2O
53~54%
N.L. Drake, G.B. Cooke, Org. Synth., Coll. Vol. 2, 408 (1943).

Cl Br Cl MgBr 1) CH3CHO Cl
Mg OH
Et2O 2) H2SO4/H2 O

82.5~88%
C.G. Overberger, J.H. Saunders, R.E. Allen, R. Gander, Org. Synth., Coll. Vol. 3, 200 (1955).

O 1) Et2O ! OH
PhCH2MgCl + Ph
Ph Ph 2) H2 O Ph Ph
H. Adkins, W. Zartman,
Org. Synth., Coll. Vol. 2, 606 (1943).
H2 SO4/H2O Ph Ph

!
（脱水） H Ph
54~59%

O Ph OH
1) PhMgBr/Et2 O !

2) HCl/H2O
R. Weiss
Org. Synth., Coll. Vol. 3, 729 (1955).
Ph Ph

Ac2O S

! 250~270 ˚C
（脱水素）
30 min
42~48% 91~94%
有機リチウム化合物
O
OH
PhLi/ Et2O 1)
SnPh3 Li
! 2) H2O
70~75%
D. Seyferth, M.A. Weiner, Org. Synth., Coll. Vol. 5, 452 (1973).

PhLi/ Et2O 1) CH3 CHO OH

Li 2) HCl/H2O
N CH3 N N
44~50%
L.A. Walter, Org. Synth., Coll. Vol. 5, 452 (1973).

NMe 2 NMe2 NMe2 OH

BuLi Li 1) Ph 2C=O
Me2 NCH2CH2NMe 2 Et2O, 25 ˚C Ph
Ph
hexane, 25 ˚C 2) AcOH
49~57%
CH3 CH3 CH3
J.V. Hay, T.M. Harris, Org. Synth., Coll. Vol. 6, 478 (1988).

α,β-不飽和カルボニル化合物への 1,2-付加

O OH
1) CH3MgCl/Et2O !
CH3CH CHCH CH3CH CHCHCH3
2) NH4 Cl/H2O 81~86%
E.R. Coburn, Org. Synth., Coll. Vol. 3, 696 (1955).

O
1) OH
Br Mg MgBr Et2O !
Et2O 2) H2SO4/H2O
57~59%
J.C.H. Hwa, H. Sims, Org. Synth., Coll. Vol. 5, 608(1973).
 THF
HC CH + EtMgBr HC C–MgBr

H O H OH
H 1) THF
+ HC C–MgBr
2) NH4Cl/H 2O
58~69%
L. Skattebøl, E.R.H. Jones, M.C. Whiting, Org. Synth., Coll. Vol. 4, 792(1963).

エステルとの反応

O
1) Et2O
2 CH3CH2CH2CH2MgBr + (CH3CH2CH2CH2) 2CHOH
H OEt 2) H SO /H O
2 4 2
83~85%

G.H.Coleman, D. Craig, Org. Synth., Coll. Vol. 2, 179 (1943).

MgBr O 1) Et2O CH3 OH

2 +
CH3 OEt 2) NH 4Cl/H2O Ph Ph

Ph
20% H2SO4 C.F.H. Allen, S. Converse,
Org. Synth., Coll. Vol. 1, 226 (1941).
! Ph
（脱水） 67~70%

1) Et2O
MgBr O
benzene, !
2 + Ph3C–OH
CH3 OEt 2) H2SO4/H2O
89~93%
W.E. Bachmann, H.P. Hetzner, Org. Synth., Coll. Vol. 3, 869 (1955).

O 1) Et2O
3 C2H5MgBr + (C2H5) 3C–OH
EtO OEt 2) NH4Cl/H2O
82~88%
W.W. Moyer, C.S. Marvel, Org. Synth., Coll. Vol. 2, 602 (1943).
 CH3 CH3
1) CH3 MgBr/ Et2O, !
CH3(CH2) 4
CH3(CH2)4 O OH
O 2) HCl/H2O, benzene
OH
57%
J. Colonge, R. Marey, Org. Synth., Coll. Vol. 4, 601 (1963).

有機アルカリ金属化合物

THF
BuBr + 2Li BuLi + LiBr
–20 ˚C
Bu
Bu
CO 2Me 1) THF, –20 ˚C C OH
2 BuLi + CH2 CH2
CH3 2) HCl / H2O CH3
80~86%
P.J. Pearce, D.H. Richards, N.F. Scilly, Org. Synth., Coll. Vol. 6, 478 (1988).

O OH
Br Li
Li CH 3 OEt
CH3CH C CH3CH C
CH3 Et2O Et2 O
CH3

TsOH
S. Threlkel, J.E. Bercaw, P.F. Seidler, J.M. Stryker,
Et2O
R.G. Bergman, Org. Synth., Coll. Vol. 8, 505 (1993).
73~75%

1) Na, benzene
O reflux, 2 h
3 + COH
EtO OEt 2) EtOH, H2O 3
Cl
35~40%
A.A. Morton, J.R. Myles, W.S. Emerson, Org. Synth., Coll. Vol. 3, 831 (1955).
二酸化炭素との反応

Mg 1) CO2 <0 ˚C
R–X R–MgX R–CO 2H
Et2O 2) H2SO4/H2O
Cl
R–X = Cl !"#72~73% !"#85%

Br
!"#76~78% !"#80~85%
Cl

H. Gilman, R.H. Kirby, Org. Synth., Coll. Vol. 1, 361 (1941).

R–X = (CH3) 3C–Cl !"#69~70%

S.V. Puntambeker, E.A. Zoellner, Org. Synth., Coll. Vol. 1, 524 (1941).
Br

R–X = !"#68~70%

H. Gilman, N.B.St. John, F. Schlze, Org. Synth., Coll. Vol. 2, 425 (1943).

CH3 CH3 CH3

Br MgBr 1) CO2 (dry ice) CO 2H
Mg, C2H 5Br

Et2 O, ! 2) HCl/H2O
H3C CH3 H3 C CH3 H3C CH3
84~86%
!"#$%&'()*)+,-./01//23*456
D.M. Bowen, Org. Synth., Coll. Vol. 3, 553 (1955).

Cl Cl Cl
Cl Cl Mg, Et2O Cl MgCl 1) CO2
Cl CO 2H

BrCH 2CH2Br 2) HCl/H2O

Cl Cl benzene Cl Cl Cl Cl
Cl Cl Cl
!"#$%&'()*+,-./012345678 65~77%

D.E. pearson, D. Cowan, Org. Synth., Coll. Vol. 5, 890 (1973).

有機アルカリ金属化合物

1) CO2
PhLi
Et2O 2) HCl/EtOH
N CH3 N CH2Li N CH2CO 2Et
3) K 2CO3/H2O
35~40%
R.B. Woodward, E.C. Komfeld, Org. Synth., Coll. Vol. 3, 413 (1955).

Na, NH3 1) CO2, THF, Et2O

CH3 C C H CH3 C C Na CH3 C C CO2H
2) HCl/H2O
50~59%
J.C. Kauer, M. Brown, Org. Synth., Coll. Vol. 5, 1043 (1973).

アミドとの反応

O
1) H N
Mg
PhCH2CH2Cl PhCH2CH2MgCl PhCH2CH2CHO
THF 2) HCl/H2O
66~76%
G.A. Olah, M. Arvanaghi, Org. Synth., Coll. Vol. 7, 451 (1990).

ニトリルとの反応

NMgBr O
Et2O H2SO4/H2O
PhMgBr + MeOCH2C N OMe OMe
! Ph Ph
71~78%
R.B. Moffett, R.L. Shriner, Org. Synth., Coll. Vol. 3, 567 (1955).

N CH3 CH3
C NMgI O

CH3MgI HCl/H2O
Et2O, ! !

52~59%
J.E. Callen, C.A. Donfeld, G.H. Coleman, Org. Synth., Coll. Vol. 3, 26 (1955).
 Ph Ph
Et2O MeOH
PhMgBr + PhCN NMgBr NH
! Ph Ph
61~81%
P.L. Pickard, T.L. Tolbert, Org. Synth., Coll. Vol. 5, 520 (1973).

イミンとの反応
CH3 MgCl
N
CH3
O CH 3NH2 N PhCH2MgCl

benzene Et2O
87~97%

CH3
NH
H2O

R.B. Moffett,
91~96% Org. Synth., Coll. Vol. 4, 605 (1963).

エポキシドとの反応

O 1) Et2O
CH3(CH2)3MgBr + CH3(CH2)5OH
2) H2SO4/H2O
60~62%
E.E. Dreger, Org. Synth., Coll. Vol. 1, 306 (1941).

1) O OH
Mg
Br MgBr
Et2 O 2) NH4Cl/H 2O
78~90%
L.S. Hegedus, M.S. Holden, J.M. McKearin, Org. Synth., Coll. Vol. 7, 501 (1990).

OH
1) CuCl/THF, –30 ˚C
PhMgBr + O
2) (NH4)2 SO4/H2O Ph
80%
A. Schwartz, P. Madan, J.K. Whitesell, R.M. Lawrence, Org. Synth., Coll. Vol. 8, 516 (1993).
オルトエステルとの反応：アセタールとアルデヒドの合成

Et2O
CH3(CH2)4MgBr + HC(OEt) 3 CH3(CH2) 4CH(OEt)2
!
!"#$%
H2SO4/H2O
CH3(CH2)4CHO G.B. Bachman,
45~50% Org. Synth., Coll. Vol. 2, 323 (1943).

Br MgBr CH(OEt)2

Mg/Et2O HC(OEt)3

! !

CHO

H 2SO4/H2O C.A. Dornfeld, G.H. Coleman,

! Org. Synth., Coll. Vol. 3, 701 (1955).

40~42%

Reformatsky 反応

O 1) Zn, Et2O, benzene, ! OH

+ BrCH2CO2Et CO2Et
Ph H 2) H 2SO4/H2 O Ph
61~64%
C.R. Hauser, D.S. Breslow, Org. Synth., Coll. Vol. 3, 408 (1955).

O OH
Br 1) Zn, benzene, ! CO 2Et
H + CH3CHCO2Et
2) H2SO4 /H 2O

K.L. Rinehart, E.G. Perkins, Org. Synth., Coll. Vol. 4, 444 (1963).

O O
Br
1) Zn, benzene, !
CH3(CH2)4CN + CH3CHCO2- s- Bu CH3(CH2)4 O- s -Bu
2) H2SO4/H2O
50~58% CH3

K.L. Rinehart, Org. Synth., Coll. Vol. 4, 120 (1963).