2
11
Synthesis
H. D. Correia et al.
PSP
O
O
H+
O
H+
Me
H
Me
Me
Me
Me
Me
N
N+
N
N
O
N
H
N
N
2
H O
H2O
H
H+
H O
+
+
2
+ H
HN
HN
N
H
H
H
NH
O
2
H N
O
O
H+
H+
urea
O
O
O
Me
Me
N
N
Me
N+
Me
Me
Me
H+
H+
N
O
N
N
+
H
H
O
H
H
O
H
H
Scheme 2 A possible mechanism of 2,4-dimethylglycoluril decomposition in acidic medium
thesis 1: first portion: 12.136 g, second portion: 2.096 g, (total yield:
4%), purity 97.6%; synthesis 2: first portion: 12.554 g, second por-
tion: 1.354 g (total yield: 33%), purity 96.9%; synthesis 3: first por-
tion: 11.214 g, second portion: 2.71 g (total yield: 33%), purity 98.9%.
White solid; mp 140 °C.
Urea, 1,3-dimethylurea and aqueous glyoxal solution 40% were pur-
chased from Sigma-Aldrich. Concd HCl (37%), EtOH, and NaOH were
procured from Synth (Diadema, S.P. Brazil). NMR spectra were record-
3
ed on a DRX400-Ultra Shield® ( H: 400.13 MHz, C: 100.61 MHz)
1
13
Bruker spectrometer. FTIR spectra were recorded on an ABB Bomem,
MB 100 spectrophotometer, of samples prepared as KBr pellets. Theo-
IR (KBr): 1676 (ν C=O), 1483 (δ CNH in-plane), 1246 (ν C–N), 1058 (ν
®
–1
retical IR spectra were calculated using Wavefun Spartan 14 soft-
C–O), 644–580–544 cm (ω N–H out-of-plane CNC).
ware using Density Function Theory and the B3LYP method [6-31G**
basis set, an equivalent to 6-31G(d,p)]. Purity calculations were car-
1
H NMR (400 MHz DMSO-d , 23 °C): δ = 7.1 (s, 2 H, NH), 5.85 (d, J = 8
6
Hz, 2 H, OH), 4.60 (d, J = 8 Hz, 2 H, CH).
13C NMR (400 MHz, DMSO-d
1
ried out using H NMR, following the procedure described in litera-
12
, 23 °C): δ = 160.4 (s, C=O), 83.9 (s, CH).
6
ture, using hydroquinone as the standard (Tables S1–S4 and S5–S8
and Figures S1–S3 and S9–S11 in the Supporting Information).
2
,4-Dimethylglycoluril
trans-4,5-Dihydroxy-2-imidazolidinone
Prior to the synthesis, a level line at 11 mL was marked with a pen on
a clean 100 mL beaker using this volume of H O. The H O was poured
out and the beaker was dried. In this beaker, trans-4,5-dihydroxy-2-
Aqueous glyoxal (40%, 41 mL, 0.16 mol) was mixed with urea (42.2 g,
2
2
0.7 mol) using a magnetic stirrer in a 100 mL beaker. The reaction
imidazolidinone (11 g, 0.09 mol), 1,3-dimethylurea (8.22 g, 0.09
mixture was stirred and heated until exactly 80 °C. The mixture was
immediately cooled in an ice bath to 25 °C precisely. Once at 25 °C, aq
mmol), distilled H O (46 mL), and concd HCl (37%, 1.39 mL) were
2
mixed under stirring with a watch glass covered over the top of the
beaker. The reaction mixture was stirred and boiled at 97 °C for 2 h.
After this period, the watch glass was removed and the solvent was
evaporated, until the level reached the marked level line or until solid
precipitated. At this point, heating was interrupted and the beaker
was cooled to r.t. While cooling, crude 2,4-dimethylglycoluril precipi-
tated as a light yellow solid. The solid was dried still in the beaker, un-
der reduced pressure for 2 h approximately. Purification: To the solid
in the beaker was added EtOH (25 mL) and the solid 2,4-dimethylgly-
coluril was crushed with a pestle to smaller pieces. Once it was finely
divided, the beaker was placed in an ultrasonic bath for 5 min. During
this procedure, depending on the yield of the synthesis, the mixture
formed a paste or a suspension. The resulting paste, or suspension
was cooled to 5 °C for 20 h in the beaker covered with parafilm. When
treating pastes, they were resuspended in cold EtOH (25 mL) and the
suspension was filtered. All suspensions were filtered without addi-
tion of EtOH. The filtered solids were washed with 95% (v/v) aq EtOH
9
N NaOH (400 μL) was added to the beaker, always under stirring. At
this point, the solution became yellow. Three more additions of the
same aq NaOH (100 ꢀL) were made at 45 min intervals, and the color
of the solution turned to orange. These additions were sufficient to
keep the pH around 8 to 9. After the last addition of NaOH, the beaker
was sealed with parafilm and the mixture was kept under stirring at
r.t. for 28 hours. In such conditions, a colorless solid started precipi-
tating in no more than 7 h and stopped after approximately 21 h. Af-
ter this, the mixture was cooled in a refrigerator for 1 h at 5 °C to
achieve the complete precipitation of the solid. The mixture was fil-
tered immediately after cooling to acquire a first portion of trans-4,5-
dihydroxy-2-imidazolidinone and the filtrate was kept to obtain a
second one. Both portions were purified the same way (described be-
low). Second portion: The filtrate was placed in a beaker and the pH
was adjusted to 8–9 by the addition of aq 9 N NaOH (200 μL). Then,
the beaker was sealed again with parafilm and cooled in a refrigerator
at 5 °C for 15 days affording more trans-4,5-dihydroxy-2-imidazolidi-
none. Purification: After filtration, each portion of the solid was
washed with EtOH (30 mL) and then with cold aq NaOH (15 mL, pH
(20 mL) and absolute EtOH (20 mL). They were dried under reduced
pressure for 48 h. The synthesis was realized in triplicate. Typical
yields and purities: synthesis 1: 6.59 g (42%), purity 96.3%; synthesis
12). Finally, the product was washed with EtOH (2 × 30 mL) and dried
2: 5.128 g (32%), purity 99.8%; synthesis 3: 6.75 g (43%), purity 93.5%.
under vacuum for 48 h. The synthesis of trans-4,5-dihydroxy-2-imid-
azolidinone was realized in triplicate. Typical yields and purities: syn-
White solid; mp 260 °C.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 210–212
Correia, Henrique D.
