Synthesis, NMR characterization and ab initio 6-31G* study of 1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium salts

Article abstract of DOI:10.1002/jhet.5570420410

We describe the synthesis of a series of 1-aryl-2,3-dialkyl-1,4,5,6- tetrahydropyrimdinium salts 1, by alkylation of the corresponding 1,4,5,6-tetrahydropyrimidines 2. We analyze the changes in the ¹H and ¹³C NMR spectra of compounds 2 induced by protonation and quaternization. The results of an ab initio theoretical study on amidine 2a, and the cations resulting from its protonation (2aH⁺) and quaternization (1a⁺) are presented. A qualitative correlation was found between ¹³C NMR and theoretical data in the case of protonation. The influence of the substitution oatterns in the ¹H and ¹³C NMR spectra of compounds 1 is also discussed.

Full text of DOI:10.1002/jhet.5570420410

May-Jun 2005
535
Synthesis, NMR Characterization and ab initio 6-31G* Study of
1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium Salts
Fernando Niemevz, Natalia P. Link, Isabel A. Perillo and Liliana R. Orelli
*
Departamento de Química Orgánica. Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín
956 (1113), Buenos Aires, Argentina.
Received September 20, 2004
We describe the synthesis of a series of 1-aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium salts 1, by
1
13
alkylation of the corresponding 1,4,5,6-tetrahydropyrimidines 2. We analyze the changes in the H and
C
NMR spectra of compounds 2 induced by protonation and quaternization. The results of an ab initio theoret-
+
+
ical study on amidine 2a, and the cations resulting from its protonation (2aH ) and quaternization (1a ) are
13
presented. A qualitative correlation was found between C NMR and theoretical data in the case of proto-
nation. The influence of the substitution patterns in the H and C NMR spectra of compounds 1 is also
1
13
discussed.
J. Heterocyclic Chem., 42, 535 (2005).
Introduction.
features of nitrogen containing heterocyclic compounds
have been studied in detail, employing theoretical calcula-
tions in some cases. The reported data are devoted to aro-
matic heterocycles such as pyridine and diazines [12], and
also to saturated azaheterocyles like piperidine and its
derivatives and pyrrolidine [13]. To our knowledge, how-
ever, partially saturated heterocycles like cyclic amidines
have not been investigated yet. A clear understanding of
steric and electronic features operating in such systems,
and the perturbations induced by protonation and quater-
nization of the amidine functionality seemed therefore
interesting. In this sense, NMR spectroscopy represents a
valuable probe for the study of conformational and elec-
tronic features of organic compounds. Theoretical studies
are also a helpful tool to investigate such characteristics.
Here we present the synthesis of a series of 1-aryl-2,3-
dialkyl-1,4,5,6-tetrahydropyrimidinium salts 1a-i and their
NMR spectroscopic characterization. We analyze the
effects of protonation and quaternization of the hetero-
cyclic nucleus in the light of theoretical calculations per-
formed with an ab initio method. We also discuss the influ-
Cyclic amidinium salts have been studied as models of
5
10
the natural cofactor N ,N -methenyltetrahydrofolic acid,
involved in biochemical transfer of one carbon units at the
oxidation level of formic acid [1]. Such reaction takes
10
place via N -formyltetrahydrofolic acid, which plays a
key role in the synthesis of purine nucleotides [2]. In an
attempt to mimic the biological processes, transference of
C2 unit to several nucleophiles was investigated in cyclic
amidinium salts in which C2 is linked to two nitrogen
atoms of different basicities, as occurs in the natural cofac-
tor [3,4]. Such compounds were also employed as syn-
thetic intermediates for the preparation of selectively sub-
stituted alkylenediamine derivatives [3,5-7]. The major
part of the research in this area is devoted to 1H-4,5-dihy-
droimidazolium salts [3,5], while six membered homo-
logues have been less studied [6,7]. Both acyclic and six-
membered cyclic amidines and also their quaternary salts
have found application as suitable probes to evaluate the
importance of stereoelectronic effects in the hydrolysis of
tetrahedral intermediates [8]. 1,3-Dimethyl-5-phenyl-
1,4,5,6-tetrahydropyrimidinium ion was studied in order to
assess the operativity of stereoelectronic control in the for-
mation of tetrahedral intermediates derived from additions
of carbon nucleophiles to nitrogen heterocycles [9].
1
13
ence of the substitution patterns in the H and C NMR
spectra of compounds 1.
Results and Discussion.
1-Aryl-2,3-dialkyltetrahydropyrimidinium salts 1 were
synthesized by alkylation of the corresponding tetrahy-
dropyrimidines 2, themselves obtained by cyclization of
aminoamides 3 (Scheme I). Physical constants and MS
In previous work we reported the alkaline hydrolysis of
1-aryl-3-alkyl-2-unsubstituted-1,4,5,6-tetrahydropyrimi-
dinium salts [10]. The regioselective opening of the hete-
rocyclic ring was analyzed in the light of the stereoelec-
tronic control theory, with the aid of theoretical calcula-
tions. In connection to our investigation about nucleophilic
additions and related stereoelectronic effects in amidinium
systems, we recently needed to prepare some 2-alkylte-
trahydropyrimidines and their quaternary salts. Due to our
previous work on the spectral and stereochemical features
of six-membered 1,3-diazaheterocycles [11], we were also
interested in evaluating the perturbations derived from
protonation and alkylation of the parent amidines. The
effects of protonation and quaternization on the spectral
1
data of salts 1a-i are given in the experimental section. H
13
and C spectra will be discussed separately.
We examined first the changes induced by protonation
1
13
and quaternization on the H and C NMR spectra of
tetrahydropyrimidine 2a, taken as model compound. For
this purpose, resonances of compounds 2a and 1a were
unequivocally assigned by means of the corresponding
HMQC and HMBC spectra, with the exception of 2'- and
4'- signals of the phenyl ring in 1a, which appear as a
broad singlet in the proton spectrum. Those resonances

536
F. Niemevz, N. P. Link, I. A. Perillo and L. R. Orelli
Vol. 42
Scheme 1
For a better understanding of the spectral features of ami-
+
+
dine 2a and amidinium cations 2aH and 1a , the electron
delocalization in such systems must be considered. In the
tetrahydropyrimidine, the presence of a phenyl substituent
on N1 results in a cross-conjugated system where competi-
tive amidine and arylamine-type electron delocalization are
possible (Scheme II, structures I and II, respectively). A
comparison between the aromatic chemical shifts of com-
pound 2a and N-phenyltrimethylenediamine (H2: 6.44,
H3,5: 7.17, H4: 6.69 ppm) [14] shows that shielding of the
ortho and para hydrogen atoms is less significative in the
amidine. This would be the consequence of competitive
amidine-like resonance, enhanced by steric hindrance of the
vicinal 2-tert-butyl group, which forces the phenyl group
out of the plane of the amidine system. To further study res-
onance and steric effects in this heterocycle, we performed
the complete optimization of compound 2a using the HF 6-
31G* method [15], and examined some relevant geometric
parameters. The calculated N1-C2 bond length in 2a (1.416
Å) is longer than the one measured by X-ray diffraction for
1
2
Compound 1,2
Ar
C H
R
R
a
b
c
d
e
f
g
h
i
tert-C H
CH
CH
CH
CH
CH
CH
CH
6
5
4
9
9
9
9
3
3
3
3
3
3
3
4-CH OC H
tert-C H
3
6
4
4
4-NO C H
tert-C H
4
2
6
4
4-ClC H
tert-C H
6
4
4
4
4
4
4
4
4-ClC H
iso-C H
6
3
7
4-ClC H
C H
6
2
5
4-ClC H
CH
6
3
4-ClC H
C H
C H
C H
6
2
5
5
2 5
4-ClC H
iso-C H
3 7
6
2
2
[a] PPSE/Cl CH , reflux, 6 hs; [b] R I/Cl CH , Reflux, 1-6 hs.
2
2
2
2
were assigned by comparison with the aromatic signals of
compounds 1b,c,d (see below). H NMR spectra of
1
the C-NH bond of acetamidine (1.344 Å) [16], while C2-
N3 distance (1.256 Å) is shorter than the corresponding
tetrahydropyrimidine 2a, its trifluoroacetate 2aH and qua-
ternary salt 1a are listed in Table I.
2
Table I
H NMR Spectra of compounds 2a, 2aH, 1a
1
Compound
H4
H6
H5
Aromatics
C(CH )
N-CH
-
3 3
3
2a
3.56 (t)
3.38 (t)
1.73 (p)
2´:7.03 (dd)
3´:7.30 (dt)
1.03 (s)
4´:7.14 (dt)
2aH
1a
3.65-3.68 (m)
2.14 (p)
2.21 (p)
7.25-7.51 (m)
7.34-7.40 (m)
1.15 (s)
1.25 (s)
-
4.09 (t)
3.84 (t)
3.72 (s)
Scheme II

May-Jun 2005
Study of 1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium Salts
537
13
C=N bond in the acyclic amidine (1.298 Å). Besides, dihe-
dral angle C2'-C1'-N1-C6 has a calculated value of –102.9°
in 2a. These results suggest that, due to the steric effect of
the tert-butyl, aniline-type resonance is partially inhibited,
but this does not result in an enhanced participation of the
N1 lone pair in amidine-type resonance.
the effect on C chemical shifts is different for protonation
than for quaternization. Protonation of compound 2a
induced deshielding of C2, C4, C6 and shielding of the tert-
butyl carbons, C5 and C1'. In saturated five and six-mem-
bered azaheterocycles [13] and also in acyclic aliphatic
amines [17], protonation induces a diamagnetic shift of pri-
mary and secondary carbons α to the nitrogen atom, while
tertiary and quaternary α carbons are deshielded. This was
explained considering that N-protonation is accompanied
by electronic redistribution with polarization of C-H bonds,
producing C(δ-)-H(δ+) structures, and thus electron density
on the hydrogen atoms is transmitted through the hydrocar-
bon chain towards the positively charged nitrogen atom.
Therefore, electron density on the carbon atoms remains
constant or may actually increase. Other interesting fea-
tures described by Morishima were the alternation of
shielding and deshielding effects along the hydrocarbon
chain and the conformational dependence of the protona-
Data reported in Table I indicate that both protonation
and quaternization induce a paramagnetic shift of all the
1
H resonances, the effect of N-alkylation being more pro-
nounced. An analogous effect upon protonation was previ-
ously reported by Pugmire for pyridine and diazines [12]
and by Morishima for piperidine and pyrrolidine [13]. The
observed deshielding was attributed to a predominance of
polarization effects due to the presence of a positively
charged nitrogen atom in the cations [13]. In our case,
however, changes in electron delocalization induced by N-
substitution may additionally be involved in the observed
shifts. In order to understand resonance effects in the ami-
dinium salts, we performed a geometry optimization of
13
tion induced C shifts. Both effects were reproduced by
+
+
the author by calculation of the electron densities on C and
H atoms using the semiempirical method CNDO/2. At vari-
ance with the reported data, in our case protonation induces
an unexpected deshielding of the α carbon atoms. In order
to understand the effects of protonation and quaternization
on the C resonances of tetrahydropyrimidine 2a, we cal-
culated the atom charges of the neutral molecule and the
corresponding cations derived from its protonation and
quaternization (2aH and 1a , respectively), using the HF
6-31G* method (Table III). An analysis of the results
shows a correlation between changes in atomic charges and
shielding/ deshielding effects on the C resonances of 2a
and 2aH . The correlation is only qualitative for protona-
cations 2aH and 1a , employing the same method as for
the amidine. The resulting optimized structures showed
very close values for N1-C2 and C2-N3 bond distances
+
+
(2aH : 1.324 and 1.317 Å, 1a : 1.337 and 1.326 Å,
respectively). On the other hand, N1-C1' bond was com-
paratively longer in the cations than in the parent amidine
13
+
+
(2a: 1.427 Å, 2aH : 1.448 Å, 1a : 1.447 Å, respectively).
Both changes suggest that electron delocalization involv-
ing the amidinium system (Scheme II, structures IV, V)
will predominate in the cations. In fact, the small shielding
effect shown by the 2- and 4-phenyl hydrogen atoms in the
amidine disappears upon N-substitution, indicating the
loss of aniline-type resonance. The amidinium moiety
becomes thus an electron withdrawing group acting on the
phenyl ring mainly by inductive effect.
+
+
13
+
tion, and does not hold for quaternization. In the latter case,
the effect of changes in the electron densities of the carbon
atoms are probably overcome by standard β and γ-shifts to
higher frequencies due to the presence of a methyl group on
N3 [18].
13
The C spectra of compounds 2a, 2aH and 1a are pre-
sented in Table II. At variance with H resonances, which
1
were all shifted to higher frequencies by N3 substitution,
Table II
C NMR Spectra of Compounds 2a, 2aH, 1a
13
Compd.
C4
C6
C5
C2
C(CH ) C(CH ) N-CH
3
Aromatics
2'
3 3
3 3
1'
3'
4'
2a
2aH
1a
46.3
55.1
54.5
53.3
55.1
55.1
21. 9
19.2
21.0
167.9
170.3
175.7
40.4
39.8
41.4
31.2
29.3
30.7
-
-
149.8
142.5
127.0
129.4
125.4
129.1
127.9 and 130.1
127.61 130.4
45.9 145.2

538
F. Niemevz, N. P. Link, I. A. Perillo and L. R. Orelli
Vol. 42
Table III
+
+
Selected HF 6-31G* Calculated Atom Charges for Compound 2a and Cations 2aH , 1a
Compd.
C4
C6
C5
C2
C(CH )
C(CH ) [a]
Aromatics
3 3
3 3
1'
2'[a]
3'[a]
4'
2a
-0.122
-0.114
-0.130
-0.137
-0.118
-0.113
-0.360
-0.383
-0.386
0.554
0.839
0.822
-0.057
-0.137
-0.139
-0.470
-0.510
-0.492
0.250
0.202
0.202
-0.220
-0.201
-0.198
-0.196
-0.200
-0.200
-0.208
-0.186
-0.189
+
2aH
+
1a
[a]: averaged.
Table IV
1
H NMR Spectra of 1-Aryl-2,3-Dialkyl-1,4,5,6-tetrahydropyrimidinium Iodides 1b-k
1
2
1
2
Compd.
G
R
R
H4
H6
H5
Ar
R
R
1b
CH O
C(CH )
CH
3.99
(t)
3.81
(t)
2.21
(p)
2': 7.36 (dd)
3': 6.89 (dd)
1.27 (s)
3.70 (s) [a]
3
3 3
3
CH O: 3.78 (s) [a]
3
1c
1d
1e
1f
NO
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
C(CH )
CH
CH
CH
CH
CH
4.12
(t)
4.05
(t)
3.97
(t)
3.90
(t)
3.83
(t)
3.90
(t)
3.78
(t)
3.94
(t) [a]
4.06
(t)
3.94
(t)
3.86
(t)
3.93
(t)
3.85
(t)
3.78
(t)
3.86
(t)
3.81
(t)
3.58
(t) [a]
4.19
(t)
2.28
(p)
2.25
(p)
2.33
(p)
2.40
(p)
2.40
(p)
2.37
(p)
2.34
(p)
2.36
(p)
2': 7.92 (dd)
3': 8.29 (dd)
2': 7.51 (dd)
3': 7.42 (dd)
2': 7.61 (dd)
3': 7.46 (dd)
2': 7.69 (dd)
3': 7.46 (dd)
2': 7.62 (dd)
3': 7.40 (dd)
2': 7.69 (dd)
3': 7.44 (dd)
2': 7.78 (dd)
3': 7.44 (dd)
2': 7.57 (dd)
3': 7.38 (dd)
2': 7.39 (dd)
3': 7.12 (dd)
1.35 (s)
1.33 (s)
3.80 (s)
3.74 (s)
3.42 (s)
3.41 (s)
3.34 (s)
2
3 3
3
3
3
3
3
C(CH )
3 3
CH(CH )
c: 3.00 (m)
d: 1.38 (d)
c: 2.55 (q)
d: 1.17 (t)
2.21 (s)
3 2
(c) (d)
CH CH
2
3
(c) (d)
CH
1g
1h
1i
3
CH CH
CH CH
c: 2.48 (q)
d: 1.17 (t)
c: 2.51 (q)
d: 1.18 (t)
8.80 (s)
e: 3.65 (q)
f: 1.45 (t)
e: 4.29 (m)
f: 1.46 (d)
3.47 (s)
2
3
3
2
3
(c) (d)
(e) (f)
CH(CH )
(e) (f)
CH CH
2
3 2
(c) (d)
H
1j
CH
3
3
1k
C H
CH
2.57
(p)
2": 7.69-7.72 (m)
3",4": 7.30-7.32 (m)
3.08 (s)
6
5
[a]: exchangeable assignment.
1
H NMR spectra of tetrahydropyrimidinium salts 1b-i
are presented in Table IV, together with compounds 1j [19]
and 1k [6] included for comparison. Signals corresponding
to the aromatic substituent and to the heterocyclic ring
were attributed by analogy with the unequivocal assign-
ment of compound 1a (Table I). Some resonances, how-
ever, were assigned only tentatively, due to their very close
values. Analysis of data reported in Table IV indicates that
the more significant effects both on the trimethylene por-
tion, the N–alkyl substituent and the aromatic moiety are
1
associated to the substituent in position 2 (R ).
A comparison between 2-alkyl derivatives 1d-g and 2-
phenyl derivative 1k shows that the presence of a 2-aryl
group shifts the signals of the trimethylene portion to

May-Jun 2005
Study of 1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium Salts
539
higher frequencies, while a shielding effect on N-methyl
and 1-aryl resonances is observed. This may be explained
by considering that the steric tension due to the presence of
vicinal aryl substituents leads to twisting of such groups
with respect to the ring, causing the 1-aryl and the
N-methyl hydrogen atoms to be within the shielding region
of the 2-phenyl group.
gen atom by a methyl group induces a deshielding of ca.
10 ppm in C2 as a consequence of the α−effect. C4 and C6
signals are also shifted ca. 5 ppm to higher frequencies,
while the N-methyl resonance is shielded. This can be
explained taking into account the dihedral angle depen-
dence of the γ−effect, which derives in a shielding effect
when the mentioned angle between the methyl group and
the considered carbon atom is 0º, and in the opposite effect
when the angle is near 180º. Replacement of 2-methyl by a
phenyl group (compounds 1g,k) shifts C2 resonance to
higher frequencies, due to delocalization of the positive
charge density on C2 by the 2-aryl substituent.
Comparing 2-tert-butyl derivatives with different para
substituents 1a-d, a progressive deshielding of the signals
is observed on going from an electron donor such as CH O
3
to a strong electron withdrawing substituent.
13
C NMR spectra of tetrahydropyrimidinium salts 1b-i
1
are presented in Table V together with compounds 1j,k,
included for comparison. Resonances corresponding to
C2, C4, C5 and C6 were assigned by analogy with com-
pound 1a. For all the compounds, resonances correspond-
ing to C4 and C6 show very close values and the proposed
assignment is therefore tentative. For salts 1a-d, signals
corresponding to the 1-aryl carbons were attributed taking
into account standard chemical shift contributions of the
para substituents in benzene rings [20]. A comparison
between salts 1g,j shows that replacement of the 2-hydro-
For compounds 1d-g, the increasing branching of R
induces the expected deshielding of C2 (β−effect). C4
and C6 are also shifted to higher frequencies, while the
effect on the N-methyl is variable. For compounds 1h-i
increasing substitution on the N3-methyl induces a dia-
magnetic shift in C2 signal (γ−effect). The nature of the
para substituent in the 1-aryl modifies the position of C2
signal, which is shielded in the case of the methoxy
derivative 1b and deshielded for G=NO . This effect can
2
be related to an increase in the positive charge density of
Table V
C NMR Spectra of 1-Aryl-2,3-Dialkyl-1,4,5,6-tetrahydropyrimidinium iodides 1a-h
13
1
2
1
2
Compd.
G
R
R
C2
C4
C6
C5
Ar
R
R
1'
2'
3'
4'
1b
CH O C(CH )
CH
174.8
53.8
[a]
54.7
[a]
19.4
CH O: 55.5 [a]
d: 40.8
e: 31.5
45.3
3
3 3
3
3
(d)(e)
137.3
150.1
[a]
128.3
128.5
115.0
125.4
159.5
146.9
[a]
1c
1d
1e
1f
NO
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
C(CH )
CH
CH
CH
CH
CH
176.3
175.3
167.8
165.9
162.5
165.2
164.2
152.5
161.9
54.4
[a]
54.1
[a]
50.7
[a]
49.3
[a]
49.5
[a]
48.7
[a]
51.5
[a]
45.9
[a]
54.5
[a]
54.7
[a]
51.3
[a]
50.7
[a]
50.6
[a]
51.3
[a]
52.7
[a]
45.7
[a]
20.3
20.5
19.8
19.7
d: 41.4
e: 31.5
d:41.1
e:31.5
d:31.9
e:19.00
d:24.5
e:10.5
19.7 [a]
45.7
45.6
41.8
41.4
42.2
2
3 3
3
3
3
3
3
(d)(e)
C(CH )
143.1
128.7
128.4
128.6
128.6
128.8
128.9
124.0
130.3
130.8
130.4
130.4
130.7
130.5
130.0
134.8
3 3
(d)(e)
CH(CH )
140.9
140.2
140.6
140.2
140.4
139.7
140.2
135.7
135.5
135.4
135.9
135.6
134.0
133.3
3 2
(d) (e)
CH CH
2
3
(d) (e)
CH
1g
1h
1i
19.6
[a]
19.6
3
CH CH
CH CH
3
d: 24.0
e: 11.6
d: 24.1
e: 11.5
-
f: 45.9
g:13.2
f: 39.5
g:19.7
43.3
2
3
3
2
(d) (e)
(f) (g)
CH(CH )
(f) (g)
CH CH
19.7
18.8
19.0
2
3 2
(d) (e)
H
1j
CH
3
3
1k
C H
CH
48.0
49.8
1": 127.3
4": 130.4
42.2
6
5
128.6, 128.4, 128.1
[a]: exchangeable assignment.

540
F. Niemevz, N. P. Link, I. A. Perillo and L. R. Orelli
Vol. 42
Anal. Calcd. for C
Found: C, 44.80; H, 5.48; N, 10.38.
H
N O I: C, 44.68; H, 5.50; N, 10.42.
C2 due to the progressively higher inductive electron
withdrawing effect of the 1-aryl substituent. This influ-
ence is stronger for quaternary carbons, where no com-
pensatory release of electron density by attached hydro-
gen atoms can operate [13].
15 22
3 2
1-(4-Chlorophenyl)-2-tert-butyl-3-methyl-1,4,5,6-tetrahydropyrim-
idinium Iodide (1d).
This compound was obtained with 79 % yield; mp 102-104ºC
(anhydrous isopropanol); MS: m/z 265 (M-127 ).
+
Anal. Calcd. for C
H N ClI: C, 45.88; H, 5.65; N, 7.13.
EXPERIMENTAL
15 22 2
Found: C, 45.82; H, 5.66; N, 7.11.
Melting points were taken on a Büchi capillary apparatus and
1-(4-Chlorophenyl)-2-iso-propyl-3-methyl-1,4,5,6-tetrahydropy-
rimidinium Iodide (1e).
1
13
are uncorrected. H and C nmr spectra were recorded on a
Bruker MSL 300 MHz spectrometer. Deuteriochloroform was
used as the solvent, and the standard concentration of the samples
was 10 mg/ml. HMQC and HMBC spectra were recorded in an
AVANCE DRX300 spectrometer. Spectral data for compound
2aH were obtained by addition of a twofold molar excess of tri-
fluoroactic acid to a sample of compound 2a. Chemical shifts are
reported in ppm (δ) relative to TMS as an internal standard.
Splitting multiplicities are reported as singlet (s), broad signal
(bs), doublet (d), double doublet (dd), triplet (t), double triplet
(dt), quartet (q), pentet (p) and multiplet (m). Electron impact
mass spectra were recorded with a GC-MS Shimadzu QP-1000
spectrometer operating at 20 eV. Tlc analyses were carried out on
This compound was obtained as an oil (73%); MS: m/z 251
+
(M-127 ).
Anal. Calcd. for C
H N ClI: C, 44.40; H, 5.32; N, 7.40.
14 20 2
Found: C, 44.29; H, 5.34; N, 7.39.
1-(4-Chlorophenyl)-2-ethyl-3-methyl-1,4,5,6-tetrahydropyrimi-
dinium Iodide (1f).
This compound was obtained in 81 % yield; mp 187-188ºC
+
(anhydrous isopropanol); MS: m/z 237 (M-127 ).
Anal. Calcd. for C
H N ClI: C, 42.82; H, 4.98; N, 7.68.
13 18 2
Found: C, 42.71; H, 5.00; N, 7.69.
aluminium sheets Alumina 60 F
using chloroform as the sol-
254
1-(4-Chlorophenyl)-2,3-dimethyl-1,4,5,6-tetrahydropyrimi-
vent. Reagents, solvents and starting materials were purchased
from standard sources and purified according to literature proce-
dures. 1-Aryl-2-alkyl-1,4,5,6-tetrahydropyrimidines 2a-i were
described in the literature [21].
dinium Iodide (1g).
This compound was obtained in 83 % yield; mp 258-260ºC
(anhydrous isopropanol); MS: m/z 223 (M-127 ).
Anal. Calcd. for C
Found: C, 41.20; H, 4.59; N, 8.00.
+
H N ClI: C, 41.11; H, 4.60; N, 7.99.
12 16 2
1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium Iodides 1.
General Procedure.
1-(4-Chlorophenyl)-2,3-diethyl-1,4,5,6-tetrahydropyrimidinium
Iodide (1h).
A mixture of 1,4,5,6-tetrahydropyrimidine (2) (5 mmol) and
alkyl iodide (6 mmol) in anhydrous methylene chloride (50 ml)
was refluxed protected from moisture. The reaction was moni-
tored by TLC (chloroform:methanol 9:1) until disappearance of
the starting material. The solution was evaporated in vacuo and
the residue purified by recrystalization or by flash column chro-
matography (silica gel, chloroform:methanol 9:1) to yield com-
This compound was obtained in 82 % yield; mp 144-145ºC
(anhydrous isopropanol); MS: m/z 251 (M-127 ).
Anal. Calcd. for C
Found: C, 44.45; H, 5.30; N, 7.42.
+
H N ClI: C, 44.40; H, 5.32; N, 7.40.
14 20 2
1-(4-Chlorophenyl)-2-ethyl-3-iso-propyl-1,4,5,6-tetrahydropy-
rimidinium Iodide (1i).
1
pounds (1a-i). H nmr data of compounds 1a,b-k are given in
13
Tables I and IV, respectively. C nmr data of compounds 1a,b-k
This compound was obtained in 54 % yield; mp 174-176ºC
(anhydrous isopropanol); MS: m/z 265 (M-127 ).
Anal. Calcd. for C
are given in Tables II and V, respectively. Yields, physical data
and elemental analyses are as follows:
+
H N ClI: C, 45.88; H, 5.65; N, 7.13.
15 22 2
Found: C, 45.75; H, 5.65; N, 7.15.
1-Phenyl-2-tert-butyl-3-methyl-1,4,5,6-tetrahydropyrimidinium
Iodide (1a).
Acknowledgement.
This compound was obtained with 77 % yield; mp 96-98 ºC
(anhydrous isopropanol); MS: m/z 231 (M-127 ).
This work was financially supported by the Universidad de
Buenos Aires. The colaboration of Dr. María B. García is also
gratefully acknowledged.
+
Anal. Calcd. for C
H N I: C, 50.29; H, 6.47; N, 7.82.
15 23 2
Found: C, 50.12; H, 6.45; N, 7.84.
1-(4-Methoxyphenyl)-2-tert-butyl-3-methyl-1,4,5,6-tetrahydro-
pyrimidinium iodide (1b).
REFERENCES AND NOTES
This compound was obtained as an oil (74%); MS: m/z 261
(M-127 ).
[*] Author to whom correspondence should be addressed. E-mail:
lorelli@ffyb.uba.ar.
+
Anal. Calcd. for C
H N OI: C, 49.49; H, 6.49; N, 7.21.
16 25 2
[1a] R. L. Blakey and S. J. Benkovic, eds., Folates and Pteridines,
Vol. 1, Wiley, New York (1984), Vol. 2, John Wiley and Sons, New York
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1-(4-Nitrophenyl)-2-tert-butyl-3-methyl-1,4,5,6-tetrahydropy-
rimidinium Iodide (1c).
This compound was obtained with 69 % yield; mp 213-215 ºC
[2] H. Kalasz, Mini-Rev. Med. Chem., 3, 175 (2003)
[3] Among others: U. K. Pandit and H. Bieraugel, J. Chem. Soc.,
+
(anhydrous tetrahydrofurane); MS: m/z 276 (M-127 ).

May-Jun 2005
Study of 1-Aryl-2,3-dialkyl-1,4,5,6-tetrahydropyrimidinium Salts
541
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