Synthesis of isopropylidene 5-alkyl-5-hydroxy-methylmalonates and their application to the preparation of 2-alkylacrylic acids

Article abstract of DOI:10.1081/SCC-100000531

Hydroxymethylated derivatives of isopropylidene 5-alkyl-malonates 3 were synthesized, via which 2-alkylacrylic acids 4 were prepared using isopropylidene 5-alkylmalonates 1 as starting materials.

Full text of DOI:10.1081/SCC-100000531

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SYNTHESIS OF ISOPROPYLIDENE 5-ALKYL-5-HYDROXY-
METHYLMALONATES AND THEIR APPLICATION TO THE
PREPARATION OF 2-ALKYLACRYLIC ACIDS
Zhen-Chu Chen a , Jing-Hua Li b & Wei-Ke Su b
a Department of Chemistry , Zhejiang University at Xixi Campus , Hangzhou, 310028,
People's Republic of China
b College of Chemical Engineering, Zhejiang University of Technology , Hangzhou,
310014, People's Republic of China
Published online: 09 Nov 2006.
To cite this article: Zhen-Chu Chen , Jing-Hua Li & Wei-Ke Su (2001) SYNTHESIS OF ISOPROPYLIDENE 5-ALKYL-5-HYDROXY-
METHYLMALONATES AND THEIR APPLICATION TO THE PREPARATION OF 2-ALKYLACRYLIC ACIDS, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:3, 409-413, DOI: 10.1081/
SCC-100000531
To link to this article: http://dx.doi.org/10.1081/SCC-100000531
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SYNTHETIC COMMUNICATIONS, 31(3), 409–413 (2001)
SYNTHESIS OF ISOPROPYLIDENE
5-ALKYL-5-HYDROXY-
METHYLMALONATES AND THEIR
APPLICATION TO THE PREPARATION
OF 2-ALKYLACRYLIC ACIDS
Zhen-Chu Chen1,∗, Jing-Hua Li2, and Wei-Ke Su2
1Department of Chemistry, Zhejiang University at Xixi
Campus, Hangzhou, 310028, People’s Republic of China
2College of Chemical Engineering, Zhejiang University of
Technology, Hangzhou, 310014, People’s Republic of China
ABSTRACT
Hydroxymethylated derivatives of isopropylidene 5-alkyl-
malonates 3 were synthesized, via which 2-alkylacrylic acids 4
were prepared using isopropylidene 5-alkylmalonates 1 as starting
materials.
As is well-known, acyclic malonic ester is a versatile reagent. Its hydrox-
ymethylated derivative, which is useful in some fields, is prepared from acyclic
malonic ester and formaldehyde or paraformaldehyde (1–3). However, so far the
preparation of hydroxymethylated cyclic malonic esters has been seldom reported.
Only recently, Nemes and Laronze (4) reported that the trimolecular condensation
∗Corresponding author.
409
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

ORDER
REPRINTS
410
CHEN, LI, AND SU
O
O
O
O
O
CH2NMe2
R
CH2OH
R
O
O
O
O
O
O
Ac2O, (Me2N)2CH2
H2O
R
O
1
2
3
yield(%)
92
1a
1b
1c
R=PhCH2
3a
3b
3c
R=PhCH : CHCH2
R=CH3OC6H4CH2
96
90
Scheme 1.
of substituted indoles with paraformaldehyde and Meldrum’s acid gave the adducts
along with their hydroxymethylated derivatives as by-products. Here we report a
convenient method for the preparation of the hydroxymethylated derivatives of
isopropylidene 5-alkylmalonates.
Previously we synthesized Mannich bases of Meldrum’s acid (the cyclic iso-
propylideneesterofmalonicacid)andits5-substitutedderivatives(5). Inthecourse
of studies on their application in organic synthesis, we found that hydroxymethy-
lated derivatives 3 are easily prepared from isopropylidene 5-alkylmalonates 1 via
Mannich bases 2.
After pouring the reaction mixture of isopropylidene 5-alkylmalonates 1,
Ac2O and (Me2N)2CH2 in MeCN into water, we found that the final products were
not Mannich bases 2 (5), but hydroxymethylated derivatives 3 (Sch. 1, Table 1).
The result shows that Mannich bases 2 (tertiary amines), unlike the normal
tertiary amine which does not afford corresponding hydroxylated compound under
general condition (6), can be hydrolyzed readily in the presence of faint acid to
give hydroxymethylated derivatives 3, owing to their high reactivity. In view of
the fact that the substituted isopropylidene malonates are easily hydrolyzed to
give carboxylic acids (8,9), the hydrolysis of 3 with dehydration in the presence
of strong acid can be anticipitated to give 2-alkylacrylic acid. Thus, treatment
of 3 with hydrobromic acid afforded the expected 2-alkylacrylic acids 4 (Sch. 2,
Table 1).
In conclusion, the new compounds 3 were easily prepared from isopropyli-
dene 5-alkylmalonates 1 by aminomethylation and then hydrolysis at room tem-
perature. The hydrolysis of compounds 3 provided a simple and effective way of
synthesis of 2-alkylacrylic acids 4. Further studies on reactivity of new compounds
3 will be reported in due course.

ORDER
REPRINTS
2-ALKYLACRYLIC ACIDS
411
Table 1. Physical Property and Date or IR, 1H NMR, and Microanalysis of 3 and 4
1H NMRa
δ (ppm)
Microanalysis m.p. Uncorrected
Found/Calc.
Product Formula
IR (cm−1
)
(◦C)
3a
C14H16O5 0.93 (3H, s)
1.66 (3H, s)
3440, 1760, C 63.71/63.61
1735, 1720, H 6.09/6.10
1605, 1500,
138–139
3.08 (1H, s)
3.18 (2H, s)
1395, 1385,
4.26 (2H, s)
1060, 750,
7.27 (5H, m)
710
3b
C16H18O5 1.60 (3H, s)
1.78 (3H, s)
3450, 1770, C 66.18/66.20
1725, 1600, H 6.29/6.25
1500, 1400,
130
2.40 (1H, s)
2.77 (2H, d)
1385, 1060,
4.17 (2H, s)
970, 750,
5.74–6.71 (2H, m) 700
7.33 (5H, m)
3c
C15H18O6 1.00 (3H, s)
1.65 (3H, s)
3450, 1770, C 61.14/61.22
1720, 1615, H 6.15/6.16
1395, 1385,
122–123
2.37 (1H, s)
3.13 (2H, s)
1515, 1040,
3.75 (3H, s)
850
4.21 (2H, s)
6.73–7.18 (4H, q)
4a
4b
4c
C10H10O2 3.62 (2H, s)
5.57 (1H, d)
2500–3300, C 74.00/74.06
1685, 1620, H 6.24/6.21
1495, 1230,
965, 925,
835, 740,
70
68–69, lit. (7)
6.38 (1H, d)
7.25 (5H, m)
9.61 (1H, w)
700
C12H12O2 2.54, 3.20 (2H, dd) 2500–3300, C 76.35/76.57
66–68
86–67
5.40 (1H, d)
6.38 (1H, d)
6.02–6.60 (2H, m) 945, 835,
7.21–7.38 (5H, m) 750, 690
10.70 (1H, w)
1690, 1625, H 6.58/6.43
1225, 965,
C11H12O3 3.57 (2H, s)
2500–3300, C 68.78/68.74
3.77 (3H, s)
5.55 (1H, d)
6.36 (1H, d)
1680, 1625, H 6.19/6.08
1610, 1580,
1510, 1250,
6.78–7.07 (4H, q) 960, 940,
10.40 (1H, w)
910, 850,
820
a1H-NMR spectra were determined in CDCl3 solution, using TMS as the internal standard.

ORDER
REPRINTS
412
CHEN, LI, AND SU
O
O
R
COOH
CH2OH
R
O
O
HBr / AcOH, H2O
4
yield(%)
3
3a
3b
3c
R = PhCH2
4a
4b
4c
76
66
78
R = PhCH : CHCH2
R = CH3OC6H4CH2
Scheme 2.
EXPERIMENTAL
Preparation of 3: General Procedure. To a stirred solution of 1 (R =
alkyl; 2.5 mmol) and Ac2O (2.6 mmol) in acetonitrile (2 mL) was slowly added
(Me2N)2CH2 (2.5 mmol) with cooling. The mixture was stirred at room temper-
ature for 30 min to complete the reaction, then poured into water (20 mL). The
whole mixture was stirred at room temperature for 20 min. The precipitated crystal
was collected by filtration and washed with water to give 3.
Preparation of 4: General Procedure. A mixture of 3 (2.5 mmol), acetic
acid (5 mL), 40% hydrobromic acid (2 mL), and water (2.5 mL) was refluxed
for 2 h, then poured into water (30 mL) after cooling. After the resulting mixture
had stood overnight in a refrigerator, it was filtered, and the crystalline precipitate
was washed three times with water and further purified by recrystallization with
ether–petroleum ether to give pure product 4.
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bonyliron. J. Organomet. Chem. 1982, 236 (2), 257.
3. Livermore, D.G.H.; Widdowson, D.A. Cobaloximes. Part 2. A Modified

ORDER
REPRINTS
2-ALKYLACRYLIC ACIDS
413
Schrauzer Synthesis for Base-Sensitive Cobaloximes. J. Chem. Soc., Perkin
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4. Nemes, C.; Laronze, J.Y. Trimolecular Condensation of Substituted Indoles
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Received in Japan December 17, 1999

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