Mendeleev Commun., 2017, 27, 283–284
Ph
Ph
N
Ph
N
HO
H
H
HO H
R2 = H
N
H
Ph
Ph
– H2, – HO–
– H2O
R1
N
NH2
R1
N
NH2
R1
N
NH2
R2
R1
R2
R1
(NH2)2C NH
B
2
NH
Ph
N
O
N
NH2
H
R2
R1
1
A
R2 ¹ H
R2
R1
N
+
PhMe
N
NH2
N
NH2
B
3
Scheme 3
closure to dihydropyrimidines B. The latter further aromatize via
the two different routes. When R2 = H, intermediates B expectedly
(due to tendency of dihydroheterocyclic systems to aromatiza-
tion, sometimes spontaneous) lose hydride anion to afford amino-
pyrimidines 2 along with dihydrogen and hydroxide anion. When
R2 ¹ H, the elimination of toluene (detected by GC) from the
dihydropyrimidine ring takes place to deliver benzyl-free amino-
pyrimidines 3 (see Scheme 3).
Control experiment in argon atmosphere showed that air oxy-
gen was not the reason for aromatization of dihydropyrimidine
intermediates B. Also, DMSO (cf. ref. 5) and nitrate ion were not
the oxidants inasmuch as Me2S was not detected (GC-MS) and
replacement of guanidinium nitrate for its chloride brought about
the same results. Most probably, one should take into considera-
tion the dehydrogenation with the hydride ion transfer commonly
occurring in strongly basic media (cf. ref. 6).
to result from the steric hindrance at the 5-position by substituent
R2 (which prevents the hydroxide ion attack) and from a lower
acidity of the C(5)–H bond due to the donor effect of this alkyl
(alkylene) moiety. This promotes elimination of the benzyl sub-
stituent as a stabilized carbanionic species with simultaneous
proton transfer from the 4-position.
In conclusion, a straightforward synthesis of 2-aminopyrimi-
dines, pharmaceutically appealing precursors, has been developed
via reaction between b,g-enones (readily available from the base-
catalyzed addition of ketones to acetylenes) and guanidine. This
approach features the following synthetic advantages: inexpensive
transition metal-free catalyst (KOH), environmentally benign,
nontoxic solvent (DMSO), diverse structural variation in the
products and operationally simple protocol.
Online Supplementary Materials
The common aromatization (dehydrogenation) is probably
initiated by the abstraction of a proton from the 5-position that is
accompanied by hydride-ion loss from the 4-position, facilitated
by electrophilic assistance by the proton of water (see Scheme 3).
The unusual aromatization (with elimination of toluene) is likely
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2017.05.022.
References
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white solid; mp 163–168°C. 1H NMR, d: 4.00 (s, 2H, CH2Ph), 5.12 (br.s,
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Received: 5th October 2016; Com. 16/5065
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