20.2 芳香族ヘテロ環化合物の反応

20.2

求電子置換反応

S

HNO₃ Ac₂O, AcOH

S NO

10 ˚C to r.t.

V.S. Babasinian,

Org. Synth., Coll. Vol. 2, 466 (1943).

70~85%

2 h

S

SnCl₄ CH₃COCl

S CH

O

benzene

J.R. Johnson, G.E. May,

Org. Synth., Coll. Vol. 2, 8 (1943).

79~83%

0 ˚C to r.t.

S

Ac₂O

H₃PO₄

S CH

O

A.I. Kosak, H.D. Hartough,

Org. Synth., Coll. Vol. 3, 14 (1955).

reflux, 2 h

74~79%

S

AlCl₃ CS₂ PhCOCl

S Ph

O

W. Minnis,

Org. Synth., Coll. Vol. 2, 520 (1943).

20 ˚C, 3.5 h

88~90%

S

I₂, HNO₃

H₂O, reflux

S I H.Y. Lew, C.R. Noller,

Org. Synth., Coll. Vol. 4, 545 (1963).

68~72%

S

I₂, HgO

benzene

S I W. Minnis,

Org. Synth., Coll. Vol. 2, 257(1943).

72~75%

S

POCl₃ PhN(Me)CHO

S CHO A.W. Weston, R.J. Michaels, Jr., Org. Synth., Coll. Vol. 4, 915 (1963).

71~74%

30 ˚C

Vilsmeier !"

S S CH

Cl

H₂C=O HCl

0 ˚C, 4 h

K.B. Wiberg, H.F. McShane,

Org. Synth., Coll. Vol. 3, 197 (1955).

!""#$%&

40~41%

S

CH₃CHO

HCl

S CHCH

Cl

S CH=CH

W.S. Emerson, T.M. Patrick, Jr., Org. Synth., Coll. Vol. 4, 980 (1963).

pyridine 10 ˚C

50~55%

!""#$%$$&'()

CH

O

H₂C=O Me₂NH

CH

O CH

NMe

AcOH, H₂O

E.L. Eliel, M.T. Fisk,

Org. Synth., Coll. Vol. 4, 626 (1963).

Mannich !"

69~76%

O CH

CH

O O

O O O

HCl, LiClO₄ EtOH, 63~78 ˚C

+

M. Chastrette, F. Chastrette, J. Sabadie, Org. Synth., Coll. Vol. 6, 856 (1988).

24~25%

O

Br₂, MeOH Na₂CO₃

O OMe

benzene, –15~0 ˚C

MeO

75~79%

D.M. Burness,

Org. Synth., Coll. Vol. 5, 403 (1973).

N H

Et₂O CCl₃COCl

N H

OEt O N H

CCl

O

NaOEt/EtOH

D.M. Bailey, et al.,

Org. Synth., Coll. Vol. 6, 618 (1988).

reflux, 4 h

77~80%

90%

N H

ClCH₂CH₂Cl

N H

CHO

DMF, POCl₃

Na₂CO₃/H₂O

R.N. Silverstein, et al.,

Org. Synth., Coll. Vol. 4, 831 (1963).

Vilsmeier !"

1)

2)

78~79%

N H N H

CHO

DMF, POCl₃

NaOH/H₂O

P.N. James, H.R. Snyder,

Org. Synth., Coll. Vol. 4, 539 (1963).

Vilsmeier !"

1) 2)

97%

N H

Br₂

pyridine, 0 ˚C

N

H Br

64%

N H S S

Ph N H

S S

Ph SMe

CuCl₂, CuO acetone

!

LiAlH₄ ZnCl₂, CuCl₂

THF

! N

H Ph N H

Ph O

N H S S

Ph +

CHCl₃, 25 ˚C

72~81%

85~88%

72~82%

P. Stütz, P.A. Stadler, Org. Synth., Coll. Vol. 6, 109 (1988).

BF₃·Et₂O

N H

MeI

NaNH₂, Et₂O

N 85~95% Me

!"

$%&'

K.T. Potts, J.E. Saxton,

Org. Synth., Coll. Vol. 5, 769 (1973).

N H

PhCH₂Br, KOH

DMSO, 25 ˚C

N

CH

Ph 85~89%

!"

$%&'

H. Heaney, S.V. Ley,

Org. Synth., Coll. Vol. 6, 104 (1988).

N H

25 ˚C 1) NaH, HMPA

0~25 ˚C

2) PhCH₂Cl

N

CH

Ph 90~91%

G.M. Rubottom, J.C. Chabala, Org. Synth., Coll. Vol. 6, 106 (1988).

!"

$%&'

N NH

Br₂/AcOH

N NH

Br

N NH

Br NO

N NH

Br NH

N NH

NH

B.A. Fox, T.L. Threlfall, Org. Synth., Coll. Vol. 5, 346 (1973).

Fe, HCl

NaOH, H₂O 20 to 50 ˚C

1)

2) NaOH/H₂O

62~67%

1)

0 ˚C to r.t.

2) NaOH/H₂O

78~85%

95% EtOH

!

69~76% 78~86%

N

MeCO₃H

N O

·AcOH

!

HCl

N O

N O

+ +

·HCl

+ 1 mmHg

78~83%

76~83%

H.S.Mosher, L. Turner, A. Carlsmith, Org. Synth., Coll. Vol. 4, 828 (1963).

N O

CH

H₂SO₄

N O

CH

NO

!"HNO₃

100 ˚C, 2.5 h

E.C. Taylor, Jr., A.J. Crovetti, Org. Synth., Coll. Vol. 4, 654 (1963).

+ –

+

–

70~73%

N O

HNO₃, H₂SO₄

N O

NO

PCl₃

N NO

+ +

N O

POCl₃

N Cl

+

N O

Ac₂O

N OAc

+

N

HNO₃ H₂SO₄

N NO

N NO

!"#$

+

35% 43%

15~20 ˚C

N

HNO₃

H₂SO₄

N

NO

N NO

!"#$%&

+

72% 8%

0˚C

N

NBS

N

1) NBS 2) KNO₃

N Br

NO

N Br

conc. H₂SO₄ –22 ~ –10 ˚C

47~49%

conc. H₂SO₄ –22 ~ –18 ˚C

47~51%

D. Brown, A.H. Gouliaev,

Org. Synth., Vol. 81, 98 (2005).

求核置換反応

N Cl

NaNH₂

N Cl NH

N NH

–

N

Cl

N N

NH

N

NH

+

Me

N NH

NaNO₂, H₂SO₄, H₂O

N Me

1) <0 ˚C, 2) 95 ˚C

OH

61%

E. Kuester, L.S. Hegedus, Org. Synth., Coll. Vol. 10, 517 (2004).

N NH

48% HBr 1) NaNO₂, Br₂, H₂O 2) NaOH

N NH

·HBr N Br

HBr ·

C.F.H. Allen, J.R. Thirtie, Org. Synth., Coll. Vol. 3, 136 (1955).

86~92%

N Cl

(NH₄)₂CO₃ phenol

!

N NH

Cl

H₂O NaOH

N NH

A. Albert, B. Ritchie, Org. Synth., Coll. Vol. 3, 53 (1955).

76~85%

N N Cl

Me₂NH, EtOH

!

N N NMe

C.G, Overberger, I.C. Kogon, R. Minin, Org. Synth., Coll. Vol. 4, 336 (1963).

81~86%

N O

Me

Me₂SO₄

N OMe

Me

NaCN

!

MeSO

N Me NC

+ +

H₂O, 5 ˚C

E. Feely, G. Evanega, E.M. Beavers, Org. Synth., Coll. Vol. 5, 269 (1973).

40~46%

N

PhLi

N Li Ph

H N Ph

Et₂O, toluene 110 ˚C

40~49%

J.C.W. Evans, C.F.H. Allen, Org. Synth., Coll. Vol. 2, 517 (1943).

メタル化を経る反応

S

BuLi

S Li

S,

H₂SO₄, H₂O

S SH

THF, pentane

–70 ~ –10 ˚C

–30 ˚C

1) 2)

E. Jones, I.M. Moodie, Org. Synth., Coll. Vol. 6, 979 (1973).

65~70%

S Br

Mg

S MgBr

PhCO₃-t-Bu

Et₂O Et₂O, 0 ˚C

TsOH

S OH

S O-t-Bu

S O

C. Frisell, S.-O. Lawesson, Org. Synth., Coll. Vol. 5, 642 (1973).

89~94%

N CH

CH

KNH₂, NH₃

NH₄Cl

N CH

K CH

N CH

CO

Et CH

NH₃ (EtO)₂CO

N CHK CH

CO

Et

59~75%

W.G. Kofron, L.M. Baclawski,

Org. Synth., Coll. Vol. 6, 611 (1988).

Me N H

H H Me

Et₂O

ClCO₂Et EtMgBr

N H

H Me

Me

MgBr

N H

CO

Et Me H

Me

N H

MgBr Me H

Me

57~58%

H. Fischer,

Org. Synth., Coll. Vol. 2, 198 (1943).

芳香族ヘテロ環の合成

NaO

C CO

Na

P₂S₃

!

S 25~30%

R. Phillips,

Org. Synth., Coll. Vol. 2, 578 (1943).

Me O

Me O

(NH₄)₂CO₃

! N

H Me Me

81~86% D.M. Young, C.F.H. Allen,

Org. Synth., Coll. Vol. 2, 219 (1943).

Ph Ph

CN O

H₂ (50 psi) Raney Ni

!

Se

Ph

N H

Ph Ph

Ph O

NH

N

H

Ph Ph

C.F.H. Allen, C.V. Willson,

Org. Synth., Coll. Vol. 3, 358 (1955).

42~46%

O OMe MeO

NH

CO

Me

AcOH

! N

CO

Me +

A.D. Josey, Org. Synth., Coll. Vol. 5, 716 (1973).

70~80%

Cl

N H O Me O

N H

OH O Me

1) KNH₂, NH₃ 2) HCl

61~67%

J.F. Bunnett, B.F. Hurtfiord, S.M. Williamson, Org. Synth., Coll. Vol. 5, 12 (1973).