An efficient synthesis of alkyl α-(hydroxymethyl)acrylates induced by DABCO in an aqueous medium

Article abstract of DOI:10.1016/j.tetlet.2005.03.005

Alkyl α-(hydroxymethyl)acrylates are prepared in high yields on a synthetic scale by hydroxymethylation of the corresponding acrylates using 30% aqueous formaldehyde in THF or DME as solvent and DABCO as the catalyst.

Full text of DOI:10.1016/j.tetlet.2005.03.005

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3071–3072
An efficient synthesis of alkyl a-(hydroxymethyl)acrylates
induced by DABCO in an aqueous medium
a
Taoufik Turki, Jean Villieras and Hassen Amri
b
a,
*
´
a
´
´
Laboratoire de Chimie Organique & Organometallique, Faculte des Sciences, Campus Universitaire, 2092 Tunis, Tunisia
b
` ´
Laboratoire de Synthese Organique, UMR-CNRS 6513, Faculte des Sciences et des Techniques, BP 92208-2,
`
rue de la Houssiniere 44322 Nantes Cedex 3, France
Received 25 January 2005; revised 23 February 2005; accepted 1 March 2005
Available online 14 March 2005
Abstract—Alkyl a-(hydroxymethyl)acrylates are prepared in high yields on a synthetic scale by hydroxymethylation of the corre-
sponding acrylates using 30% aqueous formaldehyde in THF or DME as solvent and DABCO as the catalyst.
Ó 2005 Elsevier Ltd. All rights reserved.
Since its first preparation on a large scale via the Wittig–
Horner reaction, alkyl a-(hydroxymethyl)acrylate 1a1a–c
has proved to be a key intermediate for the preparation
of alkyl a-(bromomethyl)acrylate 1b1d (Scheme 1),
95 °C for 4 h. However, this reaction gives rise to a mix-
ture of 1a and the difunctional methacrylate ether 27
(60%) (Scheme 2).
a
precursor of a-methylene-c-butyrolactones2 and
Our interest in 1a and also in the Baylis–Hillman reac-
tion8 led us to undertake the synthesis using formalde-
hyde as a 30% aqueous solution. Triethylamine and
DABCO were examined as catalysts (25 mmol %), but
only the latter was consistent with mild reaction condi-
tions. The report that water as solvent accelerated the
DABCO-catalyzed coupling of aromatic aldehydes with
activated alkenes9,10 prompted us to look at the effect of
water on the Baylis–Hillman coupling of formaldehyde
and some alkyl acrylates. Surprisingly, we found that
lactams3 via organozinc chemistry.
The Baylis–Hillman reaction using DABCO as a cata-
lyst for the a-hydroxyalkylation of acrylates,4 acrylo-
nitrile5 and vinyl ketones6 would have been a shorter
route to 1a from formaldehyde but it seems that it has
to be performed in an aprotic medium. Compound 1a
can also be made in 30% yield from paraformadehyde,
methyl acrylate and DABCO in a sealed system at
O
CO2R
Br
CO2R
HCHO aq.
PBr3
(EtO)2P CH2-CO2R
K2CO3
OH
1b
1a
Scheme 1.
CO2Me
CO2Me
(HCHO)n, DABCO
+
CO2Me
sealed system, 95 ˚C, 4 h
O
2
OH
2
1a
Scheme 2.
Keywords: Wittig–Horner reaction; Baylis–Hillman; Triethyl phosphonoacetate; Acrylates; Hydroxymethylation.
*
Corresponding author. Tel.: +216 71 872 600; fax: +216 71 885 008; e-mail: hassen.amri@fst.rnu.tn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.03.005

3072
T. Turki et al. / Tetrahedron Letters 46 (2005) 3071–3072
Table 1. DABCO-catalyzed coupling of acrylates with (30%) aqueous formaldehyde
Entry
R
Solvent
Time (h)
Yield (%)a
1
2
C2H5
CH3
1,4-Dioxane
1,4-Dioxane
DME
12
10
16
16
16
16
12
16
20
12
74
81
60
57
71
50
70
62
72
50
3
C2H5
CH3
4
DME
5
C2H5
tC4H9
C2H5
CH3
tC4H9
C2H5
MeOH
DME
THF
6
7
8
THF
THF
PEG 400
9
10
a Isolated yields. Products were characterized by 1H NMR and mass spectrometry.
OR
N
In conclusion, this communication reports an efficient
and practical methodology for the synthesis of alkyl a-
(hydroxymethyl)acrylates of type 1a using DABCO as
the catalyst in an aqueous medium.
N
O
O
H
O
O
N
H
H
OR
1,2-addition
N
R
O
O
References and notes
H
OH
O
´
elimination
N
1. (a) Villieras, J.; Rambaud, M. Org. Synth. 1988, 66, 220–
H
+
224; (b) Fikentscher, R.; Hahn, E.; Kud, A.; Oftring, A.
German Patent, DE 3,444,098, 1986; Chem. Abstr. 1986,
107, 7781s; U.S. Patent 4,654,432, 1987; (c) Strauss, C. R.;
Galbraith, M. N.; Faux, A. F. PCT Int. Appl. 9118861;
OR
N
N
1a
N
´
Chem. Abstr. 1992, 116, 115538v; (d) Villieras, J.; Ram-
baud, M. Synthesis 1982, 924–926.
Scheme 3.
2. (a) Masuyama, Y.; Nimura, Y.; Kurusu, Y. Tetrahedron
Lett. 1991, 32, 225–228; (b) Knochel, P.; Normant, J. F.
Tetrahedron Lett. 1984, 25, 1475–1478; (c) Hosomi, A.;
Hashimoto, H.; Sakurai, H. Tetrahedron Lett. 1980, 21,
951–954.
the best yields of 1a were obtained when the reaction
takes place in a two-phase liquid–liquid system in the
presence of an ethereal solvent (DME, THF, 1,4-diox-
ane) or in methanol.1b Generally the reaction was
achieved overnight at the reflux temperature of the or-
ganic solvent and gave rise to a-(hydroxymethyl)acryl-
´
3. (a) El Alami, N.; Belaud, C.; Villieras, J. Tetrahedron Lett.
1987, 28, 59–60; (b) El Alami, N.; Belaud, C.; Villieras, J.
´
Synth. Commun. 1988, 18, 2073–2081.
t
4. (a) Baylis, A. B.; Hillman, M. E. D. German Patent
2,155,113, 1972; Chem. Abstr. 1972, 77, 34174q; (b)
Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
4653–4670; (c) Basavaiah, D.; Rao, A. J.; Satyanarayana,
T. Chem. Rev. 2003, 103, 811–892.
ates (R = Me, Et, Bu) as pure, distilled products. It
could be performed on a preparative scale (2 mol). As
listed in Table 1, the best yield (81%, R = Me) we ob-
tained was in a binary medium consisting of 1,4-dioxane
and water. However, the toxicity of this solvent made us
prefer DME and especially THF (70% on 2-M run for
R = Et). Polyethylene glycol PEG 40011 can also be used
as the solvent in place of 1,4-dioxane (Scheme 3).
5. Basavaiah, D.; Gowriswari, V. V. L. Tetrahedron Lett.
1986, 27, 2031–2032.
´
6. (a) Amri, H.; Villieras, J. Tetrahedron Lett. 1986, 27,
4307–4308; (b) Basavaiah, D.; Bharathi, T. K.; Gowris-
wari, V. V. L. Synth. Commun. 1987, 17, 1893–1896.
7. Drewes, S. E.; Loizou, G.; Roos, G. H. P. Synth. Commun.
1987, 17, 291–298.
8. Yu, C.; Liu, B.; Hu, L. J. Org. Chem. 2001, 66, 5413–5418,
and references cited therein.
We must mention that side reactions occurring via trans-
esterification by the methanol or arising from methacryl-
ate ethers and acetals resulting from the reaction of two
molecules of 1a with monomeric and oligomeric formal-
dehyde,12 were avoided when 30% aqueous formalde-
hyde solution was prepared by acidic depolymerization
of paraformaldehyde (10 mol), in water at reflux in the
presence of 25 mL 1 N H3PO4 for 2 h. These side reac-
tions were always observed when 1a was prepared using
commercially available formaldehyde solutions, which
contain up to 10% methanol as stabilizer.
´
9. Auge, J.; Lubin, N.; Lubineau, A. Tetrahedron Lett. 1994,
58, 7947–7948.
10. Cai, J.; Zhou, Z.; Zhao, G.; Tang, Ch. Org. Lett. 2002, 4,
4723–4725.
11. Chandrasekhar, S.; Narsihmulu, Ch.; Saritha, B.; Sha-
meem Sultana, S. Tetrahedron Lett. 2004, 45, 5865–5867.
12. Mathias, L. J.; Kusefoglu, S. H. Macromolecules 1987, 20,
2041–2044.