The Baylis-Hillman reaction: Rate acceleration in silica gel solid

ndian Journal of Chemistry
'ol.40B, October2001, pp. 985-988
The Baylis-Hillman reaction: Rate acceleration in silica gel solid phase medium'
Deevi Basavaiah • & Ravi Mallikarjuna Reddy
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India
Received 24 January 2001 ; accepted 23 May 2001
Remarkable rate acceleration in the Baylis-Hillman reaction of aromatic aldehydes with acrylates, particularly rerrbutyl acrylate, in silica gel solid phase medium has been described.
The Baylis-Hillman reaction is an atom economy
1d versatile carbon-carbon bond forming reaction
~tween the a-position of the activated alkenes and
trbon electrophiles under the influence of catalytic
nount of tertiary amine, particularly
1,4azabicyclo[2.2.2]octane (DABCO), producing densely
mctionalized molecules which have been utilized in
uious important organic transformations t-s. The
ost accepted mechanism of this reaction is described
Scheme I, taking the reaction between alkyl
:rylate and aldehyde as a model case. However,
>plication of this reaction is some what crippled by
; slow reaction rate. Thus, the reaction requires
vera) days to several weeks for completion,
~pending upon the reactivity of both activated alkene
td electrophile.' ·3 As it is desirable for any synthetic
ocess, from both practical and economic point of
ew, to be accomplished faster and high yielding,
trious methods have been described to accelerate the
lylis-Hillman reaction. Thus, the application of high
11
essure, 9· 10 microwave irradiation
have been
ported to provide significant rate acceleration. Rafel
.d Leahy have reported that the reaction is faster at
C. 12 Kawamura and Kobayashi reported remarkable
celeration in the rate of Baylis-Hillman reaction
talyzed by DABCO, using lithium perchlorate as a
-catalyst in ether at -25°C-0°C. 13
Recently, Aggarwal and co-workers described that
1thanum triflates accelerate the Baylis-Hillman
upling of acrylates with aldehydes catalyzed by
14
!\BC0. ·15 Later Aggarwal has also reported that
3U is far superior catalyst for the Baylis-Hillman
1ction between activated alkenes and aldehydes
JViding the adducts at much faster rate than using
\BCO or 3-hydroxyquiniclidine. 16
!dicated to Prof. U. R. Ghatak on his 70'h birthday
Scheme I
Literature survey reveals that rate increase also has
been observed due to the presence of hydrogen
17
bonding using methanol as solvent or using 3hydroxyquiniclidine1 8 as a catalyst or terminal
19
hydroxy acrylates as activated alkenes. Increased
rates have also been reported when the reaction is
21
carried out in water20 or fluorinated solvents due to
hydrophobic and fluorophobic effects respectively.
During our investigations on applications of the
Baylis-Hillman adducts in various stereoselective
transformations, we required these adducts derived
from tert-butyl acrylate. Literature survey reveals that
the usual Baylis-Hillman reaction of benzaldehyde
with tert-butyl acrylate under the catalytic influence
of DABCO requires 28 days to provide the desired
adduct
tert-butyl
3-hydroxy-3-phenyl-2-methylenepropanoate in 65 % yield (93 % yield based on
converted aldehyde) .Z2 Literature survey also reveal s
that the presence of very small amounts of acetic acid
(3 mol%) provide better results, thus Baylis-Hillman
reaction of benzaldehyde and 4-bromobenzaldehyde
with tert-butyl acrylate under the catalytic influence
INDIAN J CHEM . SEC B, OCTOBER 2001
986
OH
PhCHO, 28d
~
DABCO(cat.)
~ /COOBu'
Ph . . ..~
65% yield
93% (Based on recovored aldehyde)
0
OH
{as"'
PhCHO, AcOH(cat.)
DABCO(cat.), 21 d
~
/COOBu'
TI
Ph
77% yield
OH
~
ArCHO, AcOH(cat.)
DABCO(cat.) , 21d
Ar·
/COOBu'
TI
81 % yield
Ar = 4-8rC6 H4
Scheme II
of DAB CO (1 5 mol%) in the presence of aceti c acid
(3 mol%) requires 21 days to provide the desired
adducts, tert-but y l 3-hydroxy-3-phenyl-2-methylenepropanoate and tert-but y l 3-hydroxy-3-(4bromophenyl)-2- methyl enepropanoate in 77% and
8 1% yields respecti vely (Scheme 11)? 3 These are very
inconveni entl y slow reactions and hence there is a
necessity of finding simple meth ods for carrying out
these reactions at faster rates.
Accordingly, we envisioned th at appropriate solid
phase medium reacti on using silica gel or alumina
(both neutral and ac idic) might res ult in accelerati on
of the reacti on rate. During our attempts in this
di rection we have can·ied out the reacti on between
benzaldehyde and tert-butyl acrylate in the presence
of I 5 mol% of DABCO under vari ous condi tions and
the best results were obtained when the reacti on was
carri ed out in silica gel (>200 mesh) solid phase
medium thus providing the required product, tenbutyl 3-hydroxy-3-phenyl-2-meth ylenepropanoate in
8 1% isolated yields in 36h time. Encouraged by the
remark able rate accelerati on in thi s reacti on we have
subjected various aro mati c aldehydes to the Bay li s-
AcCHO +
J
~
Hillman reaction with tert-buty l acry late in the silica
gel solid phase medium to provide the desired adducts
in good yields (eq .l , Table 1).
With a view to furth er understanding this reaction
we have also carried out the reaction of benzaldehyde
and p-tolualdehyde with methyl and ethyl acrylates in
silica gel solid phase medium in the presence of I 5
mol% DABCO (Table I). These res ults are indeed
reasonabl y encourag ing. With a view to have a direct
compari son of these solid phase medium reaction
results with that of the usual DABCO catalyzed
reacti ons, we have also carri ed out parallel
ex periments wi th the catalyti c amount of DABCO
only (without silica gel) under simi lar conditions and
a qui ck compari son has been presented in the Table I.
We have also presented the literature results
(y ields and reaction times) fo r know n mo lecul es in
the Table L
In concl usion, we have demonstrated th e
application of silica gel as solid phase medium for
perfo rming the Bay lis-Hillman reacti on parti cul arl y
between tert-butyl acrylate and aromatic aldehydes
under the influence of catalyti c amou nt of DA BCO
(IS mol%) at increased rates.
.OR . DABCO(cat.) , rt •
Silica gel(>200 mesh)
60-81 %
R =methyl , ethyl,
12h-19d
tert-butyl
AcxTI
/CODA
-
1-10
(eq .l )
BASA VAIAH et a/. : THE BAYLI S-HILLMAN REACTION
987
rable 1-Bayli s-Hillman reac ti on between aromatic aldehydes and acrylates in silica gel solid phase medium": A compari so n with
usual DABC O catal yzed reactio nsb
::HO
COOR
R=
T ime in
hrs/d ays
Product"
Me
Me
Bu'
Bu'
Bu'
Bu'
Bu'
Bu'
Bu'
Et
12h
48h
36h
lOd
12d
16d
J8d
6d
19d
14h
124
224
324
enyl
neth ylphenyl
enyl
n ethylphenyl
n ethylphenyl
:thy Iphenyl
sopropy Iph en y I
~ro mo ph e n y l
phth - 1-yl
enyl
4
5
6
7
g24
9
1024
Yi eldsd(%)
Silica ge l+
Only
DAB CO
DAB CO
78
31
79
21
81
18
66
10
T race
78
62
T race
60
Trace
14
65
T race
63
80
5
Literature results
Time in
Yi eld
days
(%)
22
6d
94
25
30d
95
28d
9322.23
7d
83
22
\II reac ti o ns were carri ed o ut o n I 0 mmo le scale o f aldehyde w ith ac rylate ( 15 mmo le), DA BC O ( 1.5 mmo le), and silica ge l (2 .50ig). b) All reactions were carri ed o ut o n 10 mmo le scale o f aldehyde with acrylate ( 15 mmo le) and DABC O ( 1.5 mmole). c) T hese
ec ul es (1-3, 10) were obtained as colo rless liquids, and the mo lec ul es (4-9) were obtained as s~lid s . d) Yi elds o f the pure produ cts
10) (based o n aldehyde) a fte r column chro matography (s ilica ge l 10% eth yl acetate in hexanes) followed by crystalli zatio n (ethyl
tate:hexanes, I :4) at 0°C or di still atio n.
perimental Section
All melting points were recorded on a Superfit
dia) capillary melting po int apparatu s and are
corrected. IR spectra were recorded on JASCO-FTmodel 5300 or Perkin Elmer model 1310
!ctrometer using samples as neat liquids or as KBr
1
13
ttes. H NMR (200 MHz) and C NMR (50 MHz)
!Ctra were recorded in CDCI 3 on Bruker-AC-200
~c trometer usin g TMS as an intern al stand ard .
emental an alyses were recorded on Perkin-Elmer
OC-CHN analyzer.
General Procedure for the Baylis-Hillman
action in silica gel solid phase medium. Aldehyde
0 mmole), acrylate ( 15 mmole), and DABCO ( 1.5
mo le, 0.168g), silica gel {(>200 mesh), (2.5075g) } were th oroughly and uni fo rmly mixed and
is mixture was left at roo m temperature. Reacti o ns
!re monitored by TLC. After appropriate time (see
tbl e I), ethyl acetate (I 0 mL) was added and stirred
oroughl y and filtered . Th e so lid silica ge l was
ashed with ethyl acetate (4x l0 mL). The co mbined
gani c layer was dri ed ove r anhyd. Na 2S04 and
mcentrated. The crude compo und was purified by
,)umn chromatograph y (s ilica gel, 10% ethyl acetate
hexanes) fo ll owed by di still ati on or by
ystalli zati o n (eth yl acetate: hex an es, I :4) at 0°C to
·ov ide the pure Bayli s-Hillman alcoho ls (1-10). The
>mpounds 1-3, 8, and 10 are known in the literature
1d their spectral (IR, 1H and I o r 13C NMR) data are
:ported. Spectral data of these mo lecul es are in
~reement with literature data. 25
tert - Butyl
3-hydroxy-2-methylene-3-( 4-methylhenyl)propanoate 4: Co lo rl ess crystals; yield : 66%;
1 1
m.p. 41-43 °C; IR : 1639, 1714,3414 cm- ; H NMR:
8 1.40 (s, 9H), 2.33 (s, 3H), 2.98 (b, 1H), 5.47 (s, I H),
5.71 (s, 1H), 6.23 (s, lH), 7.14 (d, 2 H, I= 7.6 Hz),
7.24 (d, 2H, I= 7.6 Hz) ; 13 C NMR: 8 2 1.05, 27 .93,
73 .15, 81.40, 124.71 , 126.54, 128.95 , 137.18 , 138 .79,
143.74, 165 .67. An al. Calcd for Ct 5H2o0 3: C, 72.55;
H, 8. 12. Found : C, 72.65 ; H, 8.10 %.
tert-Butyl 3-hydroxy-2-methylene-3-(2-methylphcnyl)propanoate 5: Co lorl ess crystals; yield: 78%;
1 1
m.p. 54-55 °C ; IR: 1640, 1716, 3350 cm- ; H NMR :
8 1.43 (s, 9H), 2. 33 (s, 3H), 2.90 (b, I H), 5.50 (s, 1H),
5.74 (s, 1H), 6.23 (s, 1H ), 7.13-7 .27 (m, 3H), 7.357.43 (m, 1H) ; 13 C NMR: 8 19. 11 , 27 .97 , 69.52, 8 1.50,
125.05 , 126.14, 126. 26, 127.72, 130.3 8, 135 .70,
139.20, 143.37, 166.07 . An al. Calcd fo r C1 5H2oOf C,
72.55; H, 8.12 . Found : C, 72.31 ; H, 8.16 %.
tert-Butyl 3-hydroxy-2-methylene-3-(4-ethylphenyl)propanoate 6 : Colorl ess crys tals; yield : 62%;
m.p. 46-48 °C ; IR : 1635,- 1714,3337 cm-1; 1H NMR:
8 1.22 (t, 3 H, I= 7 .2 Hz), 1.40 (s, 9 H), 2.64 (q, 2 H, I
= 7.2 Hz), 3.05 (d, lH , I= 5.0 Hz), 5.48 (d, I H, I =
5.0 Hz), 5.72 (s, lH ), 6.24 (s, 1H), 7.1 6 (d, 2 H, I= 7.8
Hz), 7.27 (d, 2 H, I= 7. 8 Hz); 13 C NMR : 8 15.5 1,
28 .00, 28.56, 73.36, 81.51 , 124.77 , 126.65, 127. 83 ,
139.09, 143.74, 165 .78. An al. Calcd fo r C1 6H220 3: C,
73.25; H, 8.45 . Found : C, 72 .97 ; H, 8.42 %.
tert-Butyl 3-hydroxy-2-methylene-3-(4-isopropylphenyl)propanoate 7: Co lorless crystals; yield:
1 1
60%; m.p. 43-45 °C ; lR: 1635, 171 4, 3325 cm- ; H
NMR : 8 1.24 (d, 6H , I= 7.0 Hz), 1.40 (s, 9H ), 2.90
(sept, I H, I= 7.0 Hz), 3.02 (d, I H, I= 5.6 Hz), 5.49
988
INDIAN 1 CHEM. SEC B, OCTOBER 2001
(d, 1H, 1=5.6 Hz), 5.72 (s, 1H), 6.24 (s, 1H), 7.19 (d, 2H,
I= 8.0 Hz), 7.28 (d, 2H, 1 = 8.0 Hz); 13C NMR: 8 23.97,
28.00, 33.85, 73.38, 81.51, 124.77, 126.39, 126.64,
139.22, 143.91, 148.41, 165.80. Anal. Calcd for
C 17 H24 0 3: C, 73.88; H, 8.75. Found: C, 74.09; H, 8.73 %.
tert-Butyl 3-hydroxy-2-methylene-3-(naphth-1yl)propanoate 9: Colorless crystals; yield: 63 %; m.p.
95-98 °C; IR: 1639, 1714, 3412 em·'; 1H NMR: 8
1.42 (s, 9H), 1.91 (b, 1H), 5.51 (s, I H), 6.27 (s, 1H),
6.34 (s, 1H), 7.44-8.09 (m, 7H); 13 C NMR: 8 27.97,
69.38, 81.54, 123.84, 124.41, 125.34, 125 .58, 125.71,
126.15, 128.49, 128.71 , 131.02, 133.85, 137.01 ,
143.62, 166.10. Anal. Calcd for C, 8 H2o0 3 : C, 76.03;
H, 7.09. Found: C, 75 .85; H, 7.12 %.
Acknowledgement
We thank DST, New Delhi for funding this project
and the UGC, New Delhi for the Special Assistance
Program in Organic Chemistry in the School of
Chemistry, University of Hyderabad. RMR. thanks
CSIR, New Delhi for his research fellowship.
References
I Drewes S E & Roos G H P, Tetrahedron , 44, 1988, 4653.
2 Basavaiah D, Dharma Rao P & Suguna Hyma R,
Tetrahedron , 52, 1996, 8001.
3 Ciganek E, Organic reactions, Vol. 51, Edited by Paquette, L.
A. (John Wiley, New York), 1997, p 201-350.
4 lwabuchi Y, Nakatani M, Yokoyama N & Hatakeyama S, 1
Am Chem Soc, 121, 1999, 10219.
5 Sugahara T & Ogasawara K, Synle/1, 1999, 419.
6 Basavaiah D, Krishnamac haryulu M, Suguna Hyma R, Sarma
P K S & Kumaragurubaran N, 1 Org Clwn, 64, 1999, 1197.
7 Basavaiah D, Bakthadoss M &
Pandiaraju S, Chem
Commun, 1998, 1639.
8 Yang K S & Chen K, Organic Lei/, 2, 2000, 729.
9 Hill 1 S & Isaacs N S, Tetrahedron Lell, 27, 1986, 5007.
10 Hill 1 S & Isaacs N S, 1 Chem Res, 1988,330.
II Kundu M K, Mukherjee S B, Balu N, Padmakumar R & Bhat
S V, Syn/e/1, 1994,444.
12 Rafel S & Leahy 1 W, 1 Org Chem, 62. 1997, 1521.
13 Kawamura M & Kobayas hi S, Tetrahedron Lell, 40, 1999,
1539.
14 Aggarwal V K, Tarver G 1 & McCague R, Chem Commun ,
1996,27 13.
15 Aggarwal V K, Mereu A, Tarver G 1 & McCague R, 1 Org
Chem, 63, 1998, 7183.
16 Aggarwal V K & Mereu A, Chem Commun, 1999. 23 11.
17 Ameer F, Drewes S E, Freese S & Kaye P T, Synth Commun,
18, 1988, 495 .
18 Drewes S E, Freese S D, Emslie N D & Roos G H P, Synth
Commun. 18, 1988, 1565.
19 Basavaiah D & Sarma P K S, Synth Commun, 20, 1990, 1611.
20 Auge J, Lubin N & Lubineau A, Tetrah edron Lei/, 35, 1994.
7947.
21 Vojkovsky T, Abstr Pap Am Chem Soc, 211, 1996, 288.
22 Fort Y, Berthe M C & Caubere P, Tetrahedron, 48, 1992,
6371.
23 Hoffman H M R, Gassner A & Eggert U, Chem Ber, 124,
1991 , 2475.
24 These mo lec ules were earlier prepa red and wel l
characterized. Fo r molec ul es I, 3 and 10 see ref. 22. For
molecules 3 and 8, see ref. 23 . For molecu le 2, see ref. 25.
25 Foucaud A & Roui lle E, Synth esis, 1990, 787.