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J. M. Robertson et al. / Tetrahedron Letters 52 (2011) 6080–6081
6081
O
stirred at 25 °C for 16 h, poured into ice-water (50 mL) and imme-
diately extracted with ether (3 Â 50 mL). The ether was evaporated
and the residual oil was chromatographed on silica gel, eluting
with 20% EtOAc/hexanes. 1H NMR spectra at 500 MHz and 13C
spectra at 125 MHz were recorded in CDCl3 on a Bruker DRX 500
spectrometer. Electron impact (EI+) mass spectra were run on an
Agilent Technologies 6890 N Network GC/MS System.
OR
H
H
O
O
H
NMe2
SOCl2
H
RO
RO
NMe2
RO
NMe2
H
H
H
R
R
R
1a
1b
Me
Et
3a
3b
Me
Et
2a
2b
Me
Et
Methyl (E)-(3-dimethylamino)acrylate 2a: 28% yield. 1H NMR: d
2.84 (br s, NCH3), 3.63 (s, OCH3), 4.49 (d, J = 13.0 Hz, CH@CHN),
7.41 (d, J = 13.0 Hz, CH@CHN). 13C NMR: d 50.48 (OCH3), 84.00
(CH@CHN), 152.98 (CH@CHN), 169.45 (C@O). EI+ MS: m/z
129.0794 (calcd for C6H11O2N: 129.0790).
1c -(CH2)4-
3c -(CH2)4Cl
2c -(CH2)4Cl
Scheme 1. Synthesis of alkyl (E)-3-(dimethylamino)acrylates 2a–c; alternative
structures 3a–c.
Ethyl (E)-(3-dimethylamino)acrylate 2b: 29% yield. 1H NMR: d
1.22 (t, J = 7.2 Hz, CCH3), 2.84 (br s, NCH3), 4.09 (q, J = 7.2 Hz,
CH2), 4.48 (d, J = 12.5 Hz, CH@CHN), 7.40 (d, J = 12.5 Hz, CH@CHN).
13C NMR: d 14.60 (CCH3), 58.80 (CH2), 84.28 (CH@CHN), 152.86
(CH@CHN), 169.64 (C@O). EI+ MS: m/z 143.0961 (calcd for
C7H13O2N: 143.0946).
O
R
a
b
Me
Et
H
H
NMe2
c (CH2)4
SOCl2
Cl
Cl-
4-Chlorobutyl (E)-(3-dimethylamino)acrylate 2c: 49% yield. 1H
NMR: d 1.76 (p, J = 5.6 Hz, CH2CH2Cl), 1.84 (p, J = 5.6 Hz, OCH2CH2),
2.85 (br s, NCH3), 3.55 (t, J = 6.5 Hz, CH2Cl), 4.08 (t, J = 6.5 Hz,
OCH2), 4.47 (d, J = 13.0 Hz, CH@CHN), 7.40 (d, J = 13.0 Hz,
CH@CHN). 13C NMR: d 26.49 (CH2CH2Cl), 29.37 (OCH2CH2), 44.69
(CH2Cl), 61.96 (OCH2), 83.94 (CH@CHN), 152.90 (CH@CHN),
169.45 (C@O). EI+ MS: m/z 205.0634 (calcd for C9H14O3Cl:
205.0631).
NMe2
5
OR
H
RO
H
1a-c
Ester 2b from Vilsmeier reagent 5: A mixture of anhydrous K2CO3
(2 mg), triethylamine (1 mL), ketene diethyl acetal, (1b, 0.5 mL)
and Vilsmeier reagent 5 (179 mg; large chunks were broken up)
was heated and stirred at 60 °C. After 1 h, more 1b (0.5 mL) was
added. After 2 h more , the mixture was cooled and extracted with
hexanes (3 Â 10 mL). Evaporation of the hexanes gave ester 2b
(55 mg, 27%).
Methyl 3-(dimethylamino)propionate 4: Acrylate 2a (10 mg) in
methanol (5 mL) was stirred with 10% Pd/C (10 mg) under a
hydrogen atmosphere for 3 h. Filtering and evaporating gave methyl
3-(dimethylamino)propionate (4, 10 mg, 100%, 1H NMR as
reported4).
OR Cl
O
Cl
R-O
Cl-
NMe2
O
NMe2
Cl-
Cl-
6a,6b
6c
Cl-
- RCl
O
Cl
O
Cl
Cl
Cl
O
NMe2
RO
RO
NMe2
NMe2
7c
7a,7b
- HCl
O
- HCl
O
H
H
Acknowledgments
O
NMe2
H
2a,2b
2c
H
We thank Prof. Tarek Sammakia, University of Colorado, for sug-
gesting structures 2a–c, and Solvay Advanced Polymers, Alpharetta,
GA, for financial support.
Scheme 2. Possible mechanisms for syntheses of acrylates 2a–c.
References and notes
Experimental
1. Neuenschwander, M.; Hafner, K. Angew. Chem., Int. Ed. Engl. 1968, 7, 460.
2. Truce, W. E.; Brady, D. G. J. Org. Chem. 1966, 31, 3543–3555.
3. Landau, M. Izvestia Akad. Nauk SSSR 1969, 9, 2053–2055.
General procedure for 2a–c: A mixture of thionyl chloride
(3 mL, 41 mmol), 4-hydroxybenzoic acid (500 mg, 3.6 mmol), and
DMF (7.2 mmol) was stirred until all the acid dissolved (ca
15 min). Excess thionyl chloride was blown off with N2, leaving a
white precipitate. Toluene (3 mL) was added and the mixture
was stirred to make a suspension, which was added dropwise to
a base-washed flask containing triethylamine (5 mL, 36 mmol)
and the ketene acetal 1a–c6,7 (72 mmol) at 0 °C. The reaction was
4. Pouchert, C.; Behnke, J. Aldrich Library of 13C and 1H FT NMR Spectra; Aldrich
Chemical Co.: Milwaukee, 1993. Vol. 1, p. 1070 B..
5. Vilsmeier reagent 5 was purchased from Aldrich Chemical Co. For a review of
the Vilsmeier reaction, see Jones, G.; Stanforth, S. P. Organic Reactions; Hoboken,
NJ, 2000; Vol. 56.
6. Ketene dimethyl acetal (1a) was prepared by the method of Corey, E. J.; Bass, J.
D.; LeMahieu, R.; Mitra, R. B. J. Am. Chem. Soc. 1964, 86, 5570–5583.
7. Ketene acetals 1b and 1c were purchased from Wacker Organics, Adrian, MI.