Mendeleev
Communications
Mendeleev Commun., 2013, 23, 106–107
Synthesis of 2-hydroxymalonamides
from carbamoylsilane and a-keto carboxamides
Xiao Juan Chen and Jian Xin Chen*
College of Chemistry and Materials Science, Shanxi Normal University, Linfen 041004, P. R. China.
E-mail: jjxxcc2002@yahoo.com
DOI: 10.1016/j.mencom.2013.03.019
Reaction between N,N-dimethylcarbamoylsilane and N,N-dimethyl-a-keto carboxamides affords 2-hydroxy-N,N,N',N'-tetramethyl-2-
R-malonamides in good yields.
Carbamoylsilanes have proved to be useful synthetic reagents
in the past few years.1–3 Aldehydes may be directly converted
to O-silyl-2-hydroxyalkanamides by reaction with (N-methoxy-
methyl-N-methylcarbamoyl)(trimethyl)silane.4 The thus accessed
2-hydroxyalkanamides find wide applications in biomedical
fields.5,6 In an attempt to extend this chemistry, we found that
(N-methoxymethyl-N-methylcarbamoyl)(trimethyl)silane reacted
poorly with ketones and did not react with a-keto carboxamides.
However, in some instances, we observed formation of 2-silyl-
oxymalonamide derivatives in the reaction of acid chlorides with
N,N-dimethylcarbamoylsilane 1.7 So we started testing activity
within the variety of carbonyl compounds towards N,N-dimethyl-
carbamoylsilane. Herein, we report our results on the reaction
between N,N-dimethyl-a-keto carboxamides 2 as the C=O sub-
strate with the reagent 1 (Scheme 1) leading to 2-hydroxy-
N,N,N',N'-tetramethyl-2-R-malonamides 4.†
O
O
toluene
NMe2
+
NMe2
R
TMS
O
O
1
2a–k
O
O
O
Me2N
NMe2
OTMS
3a–k
Me2N
NMe2
R
R OH
4a–f,j,k
69–86%
e R = Ph
R = 2-ClC6H4
g R = 4-O2NC6H4
h R = 3-MeOC6H4
i R = 4-MeC6H4
j R = PhCH=CH
k R = 2-furyl
a R = Pr
b R = Pri
c R = But
f
d R = cyclohexyl
Initial experiments were carried out with equimolar amounts
of the reactants. However, when the starting a-keto carboxamides
contained enolizable b-hydrogen atoms (2a,b,d), higher yields
were achieved on using excess of carbamoylsilane. This may
reflect competitive protonolysis of the carbamoylsilane. Similar
phenomenon was previously8 observed when iminium salts with
enolizable a-hydrogens were used as substrates and when car-
bamoylsilane was completely destroyed. A comparison of the
results obtained from 2a–d indicates that the steric envoronment
is an important factor since longer reaction time was needed both
Scheme 1
in case of 2b (144 h) and 2d (95 h) than in case of 2a (76 h),
whereas no product was obtained from substrate 2c. The reaction
of 2g–i affords the O-silylated adducts 3g–i while others directly
give hydroxy derivatives 4a–f,j,k. Olefinic substrate 2j was
investigated to determine whether 1,2- or 1,4-addition would
occur in a conjugated system. Although the yield of the product
4j was somewhat lower, it was good, while the structure of 4j
corresponded to 1,2-addition product. a-Keto amide 2k containing
an electron-rich heterocyclic ring reacted with carbamoylsilane 1
giving a good yield of 4k, although it needed longer time for its
completion. Further investigations of this carbamoylation are in
progress.
†
General procedure for the synthesis of malonamides 3 or 4. A Schlenk
tube fitted with a Teflon vacuum stopcock and a micro stirbar was flame-
heated in vacuo and refilled with argon. a-Keto carboxamide (1.0 mmol),
1.6 ml of anhydrous toluene and 1.2 equiv. of (N,N-dimethylcarbamoyl)-
trimethylsilane 1 were then added. The sealed reaction mixture was
stirred at 105°C until no carbamoylsilane could be detected by TLC.
Volatiles were removed in vacuo, and the residue was chromatographed
using 30–50% acetone–hexane as eluent to yield products 3 or 4.
A plausible mechanism of the process is presented in Scheme 2.
Carbamoylsilane 1 can rearrange to its nucleophilic carbene form
O
1
For 3g: yield 85%, mp 139–140°C. H NMR (600 MHz, CDCl3) d:
O
R
8.23–7.57 (q, 4H, C6H4), 3.06 (s, 6H, 2NMe), 2.98 (s, 6H, 2NMe), 0.05
(s, 9H, Me3Si). 13C NMR (151 MHz, CDCl3) d: 169.1, 147.5, 146.6,
129.6, 122.7, 85.3, 37.9, 37.4, 2.0. IR (KBr, n/cm–1): 1630, 1503, 1150,
623. Found (%): C, 52.33; H, 6.82; N, 11.29. Calc. for C16H25N3O5Si (%):
C, 52.30; H, 6.86; N, 11.43.
O
NMe2
OTMS
2
O
NMe2
TMS
TMS
NMe2
Me2N
A
B
For 4a: yield 76%, mp 82–84°C. 1H NMR (600 MHz, CDCl3) d: 5.02
(s, 1H, OH), 3.03 (s, 6H, 2NMe), 2.97 (s, 6H, 2NMe), 1.99 (t, 2H, CH2,
J 8.4 Hz), 1.25 (m, 2H, CH2, J 8.4 Hz, J 7.2 Hz), 0.94 (t, 3H, CMe, J 7.2 Hz).
13C NMR (151 MHz, CDCl3) d: 170.9, 77.6, 38.4, 37.4, 37.1, 16.2, 14.3.
IR (KBr, n/cm–1): 3480, 1720, 850. Found (%): C, 55.69; H, 9.48; N, 12.73.
Calc. for C10H20N2O3 (%): C, 55.53; H, 9.32; N, 12.95.
O
O
O
O
R
R
H2O
Me2N
NMe2
Me2N
NMe2
OTMS
OH
4
3
For characteristics of compounds 3h,i and 4b,d–f,j,k, see Online Supple-
mentary Materials.
Scheme 2
© 2013 Mendeleev Communications. All rights reserved.
– 106 –
Chen, Xiao Juan
