synthesis of phosphorus-containing fused heterocyclic systems based on...
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Synthesis of phosphorus-containing fused
heterocyclic systems based on 2-substituted-1-arylimidazoles
Carried out by: Kirilchyuk Andrey
Supervisor: Zarudnitskii Evgeniy,
Institute of Organic Chemistry
Kyiv – 2010
National Technical Institute of Ukraine“Kyiv Polytechnical Institute”
Introduction
N
N
PR2
Me Me
Me
N
N
NH2
P(OEt)2
O
Rib
N
N
R P
CH(OMe)2
N
PO3H2
N
NH
O
CO2H
N
N
N
NRP
NHRO
R'
N
N
i-Pr P
Et3
R = i-Pr, t-Bu, Ph
R = Cy, Bu-t
RPR 119990
P
3
1
2
3
4 5 6
Harkal S., Beller M. et al. // Adv. Synth. Catal. 2004, 346, 1742.
Kunz P. C., Kläui W. //Collect. Czech. Chem. Commun., 2007, 72, 492
Jimonet P. et al. // Bioorg. Med. Chem. Lett. 2001, 11, 127.
Bartlett P. A., Hunt J. T. et al. // Bioorg. Chem. 1978, 7, 421.
Buchanan J. G., Wightman R. H. // J. Chem. Soc. Perkin. Trans. 1, 1990, 955.
Bell R.A.et al. // Inorg. Chim. Acta, 1998, 274, 137.
2
Introduction
Kunz P. C., Kläui W. // Eur. J.
Inorg. Chem. 2003, 21, 3945.
(EtO)2P
O
NC
NH2
N
NBr
MeS CO2Me
bn
N
N
R P
R'
N
ON
EtO2C
P(OEt)2
H
O
NH
NP(OEt)2
O
EtO2C N
NP(OEt)2
N
O
bz
N
N
PR''2
Ar
N
N
Alk .
PPh2
(EtO)3CH
BzNH2
(EtO)2P(O)H
(Ph3P)4Pd
3 n-BuLi, -78oCPCl3 or R''2PCl
+
+
7
8
9 10 11
12
13
14
15
Толмачев А. А., Юрченко А. А и др. // ЖОХ, 1993, 63, 714.
Lin J., Thompson Ch. M. // J. Heterocycl. Chem., 1994, 31, 1701.
Bartlett P. A., Hunt J. T. et al. // Bioorg. Chem. 1978, 7, 421.
Jimonet P. et al. // Bioorg. Med. Chem. Lett. 2001, 11, 127.
Nishikawa H. et al. // Polyhedron 2001, 20, 627
3
4,5-dihydrobenzo[е]imidazo[2,1-с]
[1,4,2]diazophosphinine
N
N
N
P
Ar
O
X
R
16
Ivanov, V. V. et al. Heteroat. Chem., 2002, 13, 84 – 92. Ivanov, V. V. et al. Chem. Heterocyc. Compd., 2002, 38, 349 – 353.
4
5-Phosphorylation of 1,2-disubstituted imidazoles
N
N
Me
R
N
N
Me
R PHal2
N
N
Me
PCl
PhR
N
N
Me
PPh2R
B
B
B
17a-d
Py,
exc. PHal3
1/2 PhPCl2
Ph2PHal
Py,
Py
Hal= Cl (18a-d), Br (19d)21a,b,d
18a-d 19d
20a,b,d
= Et3N, imidazole 17a-d
Conditions of interaction of imidazoles 17a-d
with PhnPHal3-n
R = NMe2 (a) > SMe (b) > i-Pr (c) > Ph (d)
PCl3
20 ºC2 h
100 ºC3 h
100ºC15 h
100ºC48 h
92 % 90 % 70 % 62 %
PhPCl2
20 ºC4 h
65 ºC48 h -
130 ºC72 h
44 % 45 % 55 %
Ph2PCl20 ºC20 h
N/R-
N/R
84 % 0 0
5
5-phosphorylated imidazole derivatives
N
N
PCl2
Me
RN
N
R
Me
P(NMe2)
N
N
Me
R P(OPr-i)2 N
N
Me
Ph PPh2 N
N
P
Me
Me2NBu-t
Cl
N
N
Me
PCCl3
ClMe2N
18a-d22a-d
23a,b
4 Me2NH
2 i-PrOH/Et3N
R= NMe2 (a), SMe (b), i-Pr (c), Ph (d)
2 PhLi
26
24 25
i: t-BuMgCl/ HNMe2
CCl4 /(Et2N)3P
18d ii:PCl3
6
Tris(imidazolyl)phosphines
N
N
MeP
Me2N
N
N
Me
PR
NN
R
N
N
Me
PR
N
N
Me
R
3
27a
PCl3
Py, Et3N
1/3
1/6 PBr3
Py
17a,b,d
23
+
H2O2
27b,d
29b,d
28b,d
30 b,d
H2O2 30 d
δ31Р~ -85.5 ppm 70%
δ31Р~ -82.0 ppm 30%
δ31Р= -84 ppmR= SMe (b), Ph (d) R =
NMe2 27 a30 h20 ºС
SMe27 b28 b
15days20 ºС
Ph29 d30 d
7 days75 ºС
7
NH2
NO2
O2NN
N
SH N
N
SO2N
NH2
N
N
S
ClO
Cl
NH N
N
S
O
Cl
N
N
N
P
O
Cl
S
1) CSCl2, HCl
2)(EtO2)2CH2CH2NH2, HCl MeI FeSO4, NH3 (aq.)
C5H5NPhPBr2
3132 33
34 35
36
28% 90.1% 77%
51% 91%
Synthesis of cmpd. 36
δ 31P 5.5 ppm in pyridineOverall yield 9 % 8
5-(4-chlorobenzoyl)-1-(methylthio)-4-phenyl-4,5-dihydroimidazo[5,1-c][1,4,2]benzodiazaphosphinine
N
N
N
P
O
Cl
S
36
mp 148-149 ºC
MS (70 eV) m/z (%) : 449 (20.17, M+), 325 (37.07), 312 (45,79), 237 (21.33), 139
(100), 111 (48.25). 9
Synthesis of cmpd. 41
N
N
NH2
S N
N
S
NO
H
N
N
S
NH
PhPBr2, PyN
S
N
NP
N
S
N
NP
O
HCOOH LiAlH4, THF
H2O2
37 38 39
40 41
68% 77%
33%
δ 31P 9.52 ppm in pyridineOverall yield 3.3%
10
1-ethyl-5-methyl-4-phenyl-4,5-dihydroimidazo[5,1-c][1,4,2]benzodiazaphosphinine 4-oxide
N
S
N
NP
O
41
11
M=341
14.0 13.0 12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0PP
M
PHze601
File name: PHze601
Date: 17-Mar-2010
Operator: root
Solvent: DMSO
SF: 500.1300 MHz
SW: 8013 Hz
NSC: 1
TE: 683 K
PW: 0.00 usec, RG: 40
AQ: 2.04 sec, RD: 0.00 sec
SI: 32768
Parameter file, XWIN-NMRVersion 3.5
8.2 8.0 7.8 7.6 7.4 7.2PP
MP
PM
8.1
51
8.1
35
7.7
13
7.6
98
7.6
87
7.6
72
7.5
75
7.5
61
7.5
53
7.5
46
7.5
30
7.4
55
7.3
92
7.3
77
7.3
62
7.2
89
7.2
22
7.2
06
7.1
94
7.1
78
0.98
2.07
2.10
2.05
1.03
2.02
3.10 3.00 2.90 2.80PP
MP
PM
3.1
35
3.1
18
2.8
20
3.08
3.00
Summary
• 1,2-Disubstituted imidazoles react with phosphorus (III) halides in pyridine regioselectively at position 5. The reaction proceeds more readily, the higher the electron-donating ability of the 2-substituent in the starting imidazole.
• Interaction of tri-valent phosphorus halides with 1-(2-(4-R-amino)phenyl)-2-methylthio-imidazole in basic medium proceeds at amino-group and the 5th position of the imidazole ring affording a derivative of previously unknown heterocyclic system – benzo[e]imidazo[1,5-c][1,4,2]diazophosphinine.
12
Published works
• Kyrylchuk A. Enhancement of the Classical Suzuki Coupling in Transactions of Annual Students Conference “Innovations in Science and Technology”, Kyiv, March 25, 2008.: Book of Abstracts
• Кирильчук А. А., Зарудницкий Е. В. Синтез катализаторов нового типа для реакции сочетания Сузуки в Збірці тез доповідей учасників І Міжнародної (ІІІ Всеукраїнської) конференції студентів, аспірантів та молодих вчених з хімії та хімічної технології, Київ, 23 – 25 квітня 2008 р.
N
N+
Me
R'2P
R
X
N
N
Me
R PR'2N
N
Me
R'2P
R
X
N
N
Me
R'2P
R
A
R= H
B C
B:+
-+-BH
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