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Knoevenagel condensation catalysed by aluminium oxide.
Tetrahedron Letters,Vol 23,No PrInted In Great Brltaln
KNOEVENAGEL
47,pp
CONDENSATION
CATALYSED
de Rennes,
- The Knoevenagel
smaq
carmed
The Knoevenagel ammonia
aldehydes
resins', potassium catalysts Having
and secondary
reactlon
The catalysts
catalyst
are
In condensations
amlnes and their salts'
the commonest
esters,
sites, they could promote
easily performed
malonltrlle,
If the mixture The reactlon
the lsolatlon
base-catalysed
1s the plperldlne
In al-
Weakly basic ion exchange 1s also avaslable3 and ceslum fluoride 425 or TlC14 and base6 has also been used as 7-12 oxide 1s known to effect many organic reactlons under mild condltrons
compound
of aldehyde
was generally
of product
the Knoevenagel
the condensation
cyanoacetic
of active methylene
alumina ted It
alumina 4
compounds
The Cope modlflcatlon
acldlc and basic
compounds
methylene
fluoride
Alumlnlum
commercial
mixture
salts , primary
w?,th actzve
OXL& as catalyst.
1s a typically
and cyanoacetlc
cohollc solution "*
de BeaulIeu,
of carbony 2 conpounds
abrnnawn
condensation
and ammonium
lnvolvlng
Campus
condensatzon
out wzth
OXIDE
Equpe assocl6e au C N R.S , 35042 Rennes, France
Groupe de Chime Structurale,
was readzZy
BY ALUMINIUM
TEXIER-BOULLET and Andr6 FOUCAUD'
FranColse
Unlverslt$
0040-4039/82/474927-02$03.00/o 01982 Perqamon Press Ltd.
4927-4928,1982
esters,
cyanoacetsmlde
and aldehyde,
reactlon
of aldehydes
wlthout
and 2 was not llqud very fast (3-5 mln
We found that
with active methylene
and cyanophosphonates
solvent,
was simply
at room temperature,
) at room temperature
of good purity was very easy, the yields
The
adsorbed
on
we have melor at 50-1OO'C
were high
,
, only (E) ISO-
mer was formed R' 'C=O R2'
CH
densatlon
Condensation
but was performed
2
was more dlfflcult
of malonltrile
acetophenone
+ *'Y
1 The reactlon
R' \CZC' R2'
/m +
+ 'Y
H2°
3 to accomplish
was still possible of methyl
CN
than with aldehydes
at room temperature
cyanoacetate
at 100°C with acetone
with ketones
with balkylketones
was not successful
When the reagents
with
Conand with
aromatlc ketones,
are used In solution
(CH2C12 or
C6H6), the rate of the reaction was dlmlnlshed A general procedure
1s as follows
0 01 mol of methylcyanoacetate mlc
necessary
In vacua, (table)
of acetaldehyde Acknowledgements ---_----- -_----
solution
of 0 01 mol of aldehyde 90
, the product was extracted with dlchloromethane
After 3 min
removed
To a stirred
was added 3 g of alumina Merck
gave a product An excess
of a good purity
of alumina
, generally,
gave side reactions
in
The reactlon was exother(2 x 20 ml)
the purlflcatlon
The solvent, was not
In the case of the condensation
with malonltrlle we thank H
BAUDET
and D
LOZACHMEUR
4927
for their efflclent
collaboration
4928
R'
R2
Mass of alumInaa
Y
3 (A)
CN
Reactlon time
Y1eldb of 1(%)
3 min.
96
81-82
3 run
100
89-90
o1^ (B)
mp(=C)or bp/T0lT
Ph
H
Ph
H
C02Me
3 (A)
Ph
H
CONH2
3 (B)
10 nnn c
85
123
Ph-CH=CH-
H
C02Me
3 (B)
3 m_n
100
146
Ph
Me
CN
5 (A)
3 h.
94
92
H
CO2Me
3 (B)
3 nnn
98
95
H
CN
3 (A)
or
(B)
3 nun
98-91
96
Me
H
CN
3 (B)
or
(C)
2 nun
75
Me
H
C02Me
3 (A)
10 nll_n
54
1 Pr
H
CN
3 (B)
3 nnn
88
Me
Me
CN
2 (B)
3 nnn
98
Et
Et
CN
3 (A)
30 nnn
81
3o”/o
Me
Me
C02Me
3 (A)
77h
d
53
9P/3
Ph
H
PO(OEt)2
5 (A)
48h
d
70
Qg--
200/o 03
200/o 03 108O/23 03
1500/o. 03
a - mass of alumina for 10 mm01 of 2 Alurmnlum oxide Merck 60, catalog no 1103. (A) Alurmnlum oxide Merck 90,Actlvlty II-III, catalog no 1097. (C) Alumlnlum oxide (B) Merck 90, Actlvlty I, catalog no 1076. b - Indlcated yields correspond to crude product unless stated otherwlse, having correct mp, IR, 1H NMR spectra and analytical data c - Temperature 50°C d - Temperature 1OO'C References
and Notes
1
G
JONES,
Organic
2
P D
GARDNER
3
A C
COPE, J
and R L Am
BRANDON,
Chem
J
Sot , 2,
L
5
L. RAND, D
HAIDERKEWYCH
and R J
Tetrahedron,
3,
6
W G H
8
A
9
LEHNERT, POSNER, MC KILLOP
G H
POSNER,
10
G H. POSNER
11
A
REITZ, M
12
J
MUZART,
(Received
SWISHER
Angew
S S and M
Chem
(1937) Org
DOLINSKI,
France
YOUNG,
Ed
Engl.11,
Synthesis,
and M
J
Chem
, 2J, 3505 (1962)
Org
Chem
, 2,
1272 (1966)
487 (1978)
481 (1979)
Lett
GOODMAN,
60 (1982) 20
(1967)
301 (1974)
Int
ODA, Tetrahedron
Synthesis,
New York
, 22, 1704 (1957)
Org 2327
OKADA, K A. BABIAK, K. MIURA
VERLANDER
in
204, Wiley,
p
and C J. CRONIN, J
Chem
and D W
15,
vol
4
7
RAND, J V
Reactions,
May
1982)
2,
and P K
ROSE, Synthesis,
5003 (1981).
Tetrahedron
Lett
, 23, 751 (1982)
789
(1981).
KNOEVENAGEL
47,pp
CONDENSATION
CATALYSED
de Rennes,
- The Knoevenagel
smaq
carmed
The Knoevenagel ammonia
aldehydes
resins', potassium catalysts Having
and secondary
reactlon
The catalysts
catalyst
are
In condensations
amlnes and their salts'
the commonest
esters,
sites, they could promote
easily performed
malonltrlle,
If the mixture The reactlon
the lsolatlon
base-catalysed
1s the plperldlne
In al-
Weakly basic ion exchange 1s also avaslable3 and ceslum fluoride 425 or TlC14 and base6 has also been used as 7-12 oxide 1s known to effect many organic reactlons under mild condltrons
compound
of aldehyde
was generally
of product
the Knoevenagel
the condensation
cyanoacetic
of active methylene
alumina ted It
alumina 4
compounds
The Cope modlflcatlon
acldlc and basic
compounds
methylene
fluoride
Alumlnlum
commercial
mixture
salts , primary
w?,th actzve
OXL& as catalyst.
1s a typically
and cyanoacetlc
cohollc solution "*
de BeaulIeu,
of carbony 2 conpounds
abrnnawn
condensation
and ammonium
lnvolvlng
Campus
condensatzon
out wzth
OXIDE
Equpe assocl6e au C N R.S , 35042 Rennes, France
Groupe de Chime Structurale,
was readzZy
BY ALUMINIUM
TEXIER-BOULLET and Andr6 FOUCAUD'
FranColse
Unlverslt$
0040-4039/82/474927-02$03.00/o 01982 Perqamon Press Ltd.
4927-4928,1982
esters,
cyanoacetsmlde
and aldehyde,
reactlon
of aldehydes
wlthout
and 2 was not llqud very fast (3-5 mln
We found that
with active methylene
and cyanophosphonates
solvent,
was simply
at room temperature,
) at room temperature
of good purity was very easy, the yields
The
adsorbed
on
we have melor at 50-1OO'C
were high
,
, only (E) ISO-
mer was formed R' 'C=O R2'
CH
densatlon
Condensation
but was performed
2
was more dlfflcult
of malonltrile
acetophenone
+ *'Y
1 The reactlon
R' \CZC' R2'
/m +
+ 'Y
H2°
3 to accomplish
was still possible of methyl
CN
than with aldehydes
at room temperature
cyanoacetate
at 100°C with acetone
with ketones
with balkylketones
was not successful
When the reagents
with
Conand with
aromatlc ketones,
are used In solution
(CH2C12 or
C6H6), the rate of the reaction was dlmlnlshed A general procedure
1s as follows
0 01 mol of methylcyanoacetate mlc
necessary
In vacua, (table)
of acetaldehyde Acknowledgements ---_----- -_----
solution
of 0 01 mol of aldehyde 90
, the product was extracted with dlchloromethane
After 3 min
removed
To a stirred
was added 3 g of alumina Merck
gave a product An excess
of a good purity
of alumina
, generally,
gave side reactions
in
The reactlon was exother(2 x 20 ml)
the purlflcatlon
The solvent, was not
In the case of the condensation
with malonltrlle we thank H
BAUDET
and D
LOZACHMEUR
4927
for their efflclent
collaboration
4928
R'
R2
Mass of alumInaa
Y
3 (A)
CN
Reactlon time
Y1eldb of 1(%)
3 min.
96
81-82
3 run
100
89-90
o1^ (B)
mp(=C)or bp/T0lT
Ph
H
Ph
H
C02Me
3 (A)
Ph
H
CONH2
3 (B)
10 nnn c
85
123
Ph-CH=CH-
H
C02Me
3 (B)
3 m_n
100
146
Ph
Me
CN
5 (A)
3 h.
94
92
H
CO2Me
3 (B)
3 nnn
98
95
H
CN
3 (A)
or
(B)
3 nun
98-91
96
Me
H
CN
3 (B)
or
(C)
2 nun
75
Me
H
C02Me
3 (A)
10 nll_n
54
1 Pr
H
CN
3 (B)
3 nnn
88
Me
Me
CN
2 (B)
3 nnn
98
Et
Et
CN
3 (A)
30 nnn
81
3o”/o
Me
Me
C02Me
3 (A)
77h
d
53
9P/3
Ph
H
PO(OEt)2
5 (A)
48h
d
70
Qg--
200/o 03
200/o 03 108O/23 03
1500/o. 03
a - mass of alumina for 10 mm01 of 2 Alurmnlum oxide Merck 60, catalog no 1103. (A) Alurmnlum oxide Merck 90,Actlvlty II-III, catalog no 1097. (C) Alumlnlum oxide (B) Merck 90, Actlvlty I, catalog no 1076. b - Indlcated yields correspond to crude product unless stated otherwlse, having correct mp, IR, 1H NMR spectra and analytical data c - Temperature 50°C d - Temperature 1OO'C References
and Notes
1
G
JONES,
Organic
2
P D
GARDNER
3
A C
COPE, J
and R L Am
BRANDON,
Chem
J
Sot , 2,
L
5
L. RAND, D
HAIDERKEWYCH
and R J
Tetrahedron,
3,
6
W G H
8
A
9
LEHNERT, POSNER, MC KILLOP
G H
POSNER,
10
G H. POSNER
11
A
REITZ, M
12
J
MUZART,
(Received
SWISHER
Angew
S S and M
Chem
(1937) Org
DOLINSKI,
France
YOUNG,
Ed
Engl.11,
Synthesis,
and M
J
Chem
, 2J, 3505 (1962)
Org
Chem
, 2,
1272 (1966)
487 (1978)
481 (1979)
Lett
GOODMAN,
60 (1982) 20
(1967)
301 (1974)
Int
ODA, Tetrahedron
Synthesis,
New York
, 22, 1704 (1957)
Org 2327
OKADA, K A. BABIAK, K. MIURA
VERLANDER
in
204, Wiley,
p
and C J. CRONIN, J
Chem
and D W
15,
vol
4
7
RAND, J V
Reactions,
May
1982)
2,
and P K
ROSE, Synthesis,
5003 (1981).
Tetrahedron
Lett
, 23, 751 (1982)
789
(1981).