Kilic and Taralp
509
herein using alkaline bicarbonate implied a rather flexible
working pH range of reaction.
Product 5a (Entry 5) was directly isolated by evaporating
the ethylacetate layer. To ascertain the in situ yield of imi-
dazole, an aliquot of the domino reaction (48.0 mL) was dis-
solved in deuterium oxide (600 mL) spiked with sodium
acetate (24.0 mg). The sample was immediately analyzed us-
As a final point, the elusive cis-1,2-di(formamido)ethene
was targeted in view of its potential to serve as an easily
polymerizable monomer.1 Just as with prior attempts, how-
ever, no product was isolated when formic acetic anhydride
was added to the in situ-generated imidazole or to commer-
cially produced imidazole as per the established method.1
The fact that imidazole was recovered unchanged was attrib-
uted to the high accessibility and electropositive nature of
the formyl carbonyl center, which presumably served to
speed the hydrolytic deactivation of reagent and formylated
imidazole species.
To summarize, several cis-1,2-diamidoethene monomers
were prepared by manipulating glyoxal, formaldehyde, am-
monia, and an acylating agent in one pot. The process pre-
cluded the purification of intermediates, the deployment of
relatively expensive or volatile compounds like imidazole
and chloroformate, and any laborious workup. The fact that
an industrially applicable end product was prepared and
readily isolable, following a four-component transformation
in the presence of many potentially interfering by-products,7
further attested to the facility and robustness of this strategy.
Finally, whereas cis-1,2-diamidoethene can serve as a mono-
mer, this class of compound may also be converted to the
corresponding N,N’-disubstituted 4-imidazolin-2-one hetero-
cycle,4 which is known to have a much greater propensity
to polymerize.3 All in all, it would appear that the cost effi-
ciency and conveniences imparted by this one-pot approach
could promote the routine preparation and use of oligo- and
polyvicinalamines.
1
ing H NMR (RT, D2O/DHO presaturation, 10 s interpulse
delay, and 256 scans). The signal corresponding to the three
C–H protons of imidazole was compared with the three pro-
tons of acetate, permitting a yield calculation of the former
compound.
Parameters used for characterization
NMR: Inova 500; ATR-FTIR: Bruker Equinox 55; GC–
MS: gas chromatography, Agilent 6890N; GC column:
J&W, DB5, 30 m, i.d. = 0.25 mm; film thickness: 0.25 mm;
carrier gas: He; injection: 50 ng / 1 mL MeOH; injection
temp.: 270 8C; aux. temp.: 240 8C; temp. progr.: 100/5–5–
260; mass spectrometry: Sensi-TOF, Five Technologies,
Munich; mass range: 40–500 amu; ionization energy:
70 eV; DSC: Netzsch 204 Phoenix; temp. ramp rate: 5 K/min;
atmosphere: N2. A chemical shift of 2.5 ppm (1H NMR) and
39.4 ppm (13C NMR) was applied to reference DMSO-d6.15
The melting onset temperature (Tonset) was estimated from
the DSC profile as per ASTM standard test procedure
E794.16 The peak melting temperature (Tm) was obtained by
direct inspection. Both values have been expressed for
clarity. In 1a–5a, the TLC runs showed one spot under UV
light. All GC–MS profiles yielded one peak.
Entry 1
Rf: 0.06 (EtOAc); mp (recrys. EtOH): Tonset = 134.8 8C,
Tm = 136.3 8C, lit. value1 not reported. IR (neat) n: 3301
(w), 3211 (w), 3051 (w), 1708 (w), 1676 (m), 1637 (m),
1560 (m), 1356 (m), 1274 (m), 1164 (s), 1039 (m), 997
Experimental
Technical grade starting materials were obtained from lo-
cal suppliers and were used without further purification.
1
(m), 744 (m), 668 (s). H NMR (500 MHz, DMSO-d6) d:
1.95 (s, 3H), 5.99 (m, 1H), 9.27 (d, 1H). 13C NMR
(125.725 MHz, DMSO-d6) d: 22.61, 105.04, 166.13. GC–
MS m/e: 142 M+. MS (C6H10N2O2) calcd: 142.16; found:
142.09. Anal. calcd: C 50.69, H 7.09, N 19.71; found: C
48.61, H 7.25, N 18.60.
Typical experimental procedure
To a stirred solution of ammonium hydroxide (6.0 g, 22–
25 wt%), a mixture of glyoxal (4.35 g, 30.0 mmol, 40 wt%)
and formaldehyde (2.25 mL, 30.2 mmol, 37 wt%) was cau-
tiously added. The mixture was allowed to stir (60 8C, 1 h),
generating imidazole. Subsequently, distilled water
(150.0 mL), ethylacetate (30.0 mL), and sodium bicarbonate
(25.0 g) were added to the reaction. Acetic anhydride
(12.0 mL, 127.0 mmol, 4.23 equiv with respect to glyoxal)
was slowly added (30 min) under vigorous stirring during
which time effervescence was noted. The reaction vessel
was lightly capped after 1 was fully added and stirring was
continued (13 h, room temperature (RT)) to promote full de-
formylation. The precipitated solid was recovered by filtra-
tion, washed with distilled water (3 Â 5.0 mL), optionally
triturated in distilled water (20.0 mL, 80 8C, 15–30 min),
and lyophilized to yield 1a (1.50 g, 35% with respect to
glyoxal) as a white solid. Di-tert-butyl dicarbonate (3) was
gently warmed prior to use and administered dropwise as in
the case of acetic anhydride. Unlike 1–3 and 5, benzoic an-
hydride (4) was finely pulverized and added in one shot. For
3a and 4a, 1,4-dioxane (75.0 mL) was used in place of eth-
ylacetate (Entries 3–4). Precipitation of 4a (Entry 4) was fa-
cilitated by adding water (250 mL) during the workup.
Entry 2
Rf: 0.58 (EtOAc); mp (recrys. EtOH): Tonset = 141.3 8C,
Tm = 143.7 8C (lit.11 mp 139–141 8C). IR (neat) n: 3338
(w), 3316 (w), 3229 (w), 2976 (w), 1724 (m), 1668 (m),
1525 (s), 1455 (m), 1367 (m), 1308 (m), 1241 (s), 1149 (s),
1081 (s), 870 (m), 765 (m), 718 (s), 675 (m). 1H NMR
(500 MHz, DMSO-d6) d: 1.19 (t, 3H), 4.06 (q, 2H), 5.69
(m, 1H), 8.78 (d, 1H). 13C NMR (125.725 MHz, DMSO-d6)
d: 14.31, 60.38, 105.24, 153.18. GC–MS m/e: 202 M+. MS
(C8H14N2O4) calcd: 202.21; found: 202.12. Anal. calcd: C
47.52, H 6.98, N 13.85; found: C 47.23, H 6.76;, N 13.62.
Entry 3
Rf: 0.66 (EtOAc); mp (recrys. EtOH): Tonset = 221.9 8C,
Tm = 223.7 8C. IR (neat) n: 3340 (w), 3255 (w), 3226 (w),
2975 (w), 1723 (m), 1692 (s), 1525 (s), 1454 (w), 1367 (m),
1307 (m), 1239 (s), 1146 (s), 1080 (s), 869 (m), 772 (m),
1
717 (s), 676 (m). H NMR (500 MHz, DMSO-d6) d: 1.41
(s, 9H), 5.61 (m, 1H), 8.59 (d, 1H). 13C NMR
(125.725 MHz, DMSO-d6) d: 27.92, 78.94, 104.75, 152.29.
Published by NRC Research Press