4-Methylpyrimidinium ylides, 1

Article abstract of DOI:10.1002/(sici)1099-0690(199903)1999:3<703::aid-ejoc703>3.0.co;2-6

For the first time in the pyrimidinium ylides series we present a theoretical and experimental study concerning the structure, stability and reactivity of pyrimidinium ylides and interesting correlations between these properties. 4-Methylpyrimidinium ylid

Full text of DOI:10.1002/(sici)1099-0690(199903)1999:3<703::aid-ejoc703>3.0.co;2-6

FULL PAPER
4-Methylpyrimidinium Ylides, 1
Geanina Mangalagiu,[a] Ionel Mangalagiu,*[a] Ionel Humelnicu,[a] and Magda Petrovanu[a]
Keywords: 4-Methylpyrimidine / Ylides / Quantum chemical calculations
For the first time in the pyrimidinium ylides series we present
theoretical and experimental study concerning the
structure, stability and reactivity of pyrimidinium ylides and
interesting correlations between these properties. 4-
Methylpyrimidinium ylides are relatively stable compounds,
their stability varying with the nature of the ylide carbanion
therefore the higher the stability. The data from experiments
and quantum chemical calculations are in agreement with
each other. The quantum chemical calculations show the
possibility of using pyrimidinium ylides as nucleophilic
reagents as well as 1,3-dipoles in reaction with appropriate
reagents. Eight new pyrimidine compounds (4 salts and 4
ylides) were obtained.
a
substituent.
The
more
electron-withdrawing
these
substituents, the more the anionic charge is delocalized and
Introduction
In previous work,[1Ϫ4] the synthesis, structure and reac-
tivity of 1,2-diazinium ylides derived from pyridazine and
phthalazine (unsubstituted or substituted) have been stud-
ied. The main target in this previous work was the synthesis
of new stable 1,2-diazine ylides, and the correlation between
their structure, stability and reactivity (biological, acid-base,
semiconductor properties, etc.). Continuing in this line of
research, it was decided to study the 1,3-diazine ylides de-
rived from 4-methylpyrimidine, with the intention of in-
creasing both the breadth and depth of knowledge in the
field of diazine ylides.
Results and Discussion.
Scheme 1. Reaction pathway to obtain 4-methylpyrimidinium
ylides
In order to obtain new pyrimidinium ylides derived from
4-methylpyrimidine the salt method of Kröhnke was
used.[5] Thus, N-(p-R-benzoyl)pyrimidinium salts 3aϪd
were prepared by treating 4-methylpyrimidine (1) with p-
R-phenacyl bromides 2, which, in an aqueous solution of
alkaline carbonates, afforded the corresponding pyrimidi-
nium ylides 4aϪd (Scheme 1).
In order to establish the correlation between structure,
stability and reactivity in the 4-methylpyrimidinium ylides
a series of theoretical calculations were carried out using
a. The ylide carbanion center C7, the ylide nitrogen atom
N1 and the α-endocyclic carbon atoms are co-planar
(valence angles to the atoms involved ca. 120°, torsion
angles 0° or 180°).
b. The bond lengths ylide carbanion center (C7)Ϫylide ni-
1
1
2
1
6
˚
trogen atom (N ), N ϪC , and N ϪC are ca. 1.40 A
(intermediate between simple and double bond).
The analysis of the data from Table 1 leads to the follow-
the General Theory of Perturbation Limited to the Frontier ing conclusions:
Molecular Orbitals.[6Ϫ11] The geometry of the 4-methylpyri-
midinium ylides (Figure 1), the atomic charges, the coef-
ficients of the atomic orbitals, and the values of the energy
of the frontier molecular orbitals were calculated using the
AM1 method (Table 1).[12]
c. The ylide carbanion centers C7 have a negative atomic
charge, subunity, but significant (larger than all the other
charges on the molecule).
d. The ylide nitrogen atoms N1 have a positive atomic
charge, subunity, significant but smaller (in absolute
value) than for the ylide carbanion centers.
The data from Figure 1 show the following:
e. The α-endocyclic carbanion centers C2 and C6 have
small negative atomic charges, both being subunity.
[a]
“Al. I. Cuza” University Iasi,
B-dul Copou, No. 11, RO-6600 Iasi, Romania
Fax: (internat.) ϩ 40-32/213330
E-mail: ionelm@uaic.ro
The fact that the total atomic charges are subunity indi-
cates the delocalization of the anionic charge from the ylide
Eur. J. Org. Chem. 1999, 703Ϫ706
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
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G. Mangalagiu, I. Mangalagiu, I. Humelnicu, M. Petrovanu
FULL PAPER
Figure 2. Canonical structures for 4-methylpyrimidinium ylides
Figure 3. Supplementary canonical structures for 4-methylpyrimi-
dinium p-nitobenzoylmethylide (4b)
Figure 1. Geometry of 4-methylpyrimidinium benzoylmethylide:
˚
bond lengths [A], valence angles [°], torsion angles [°]; torsion an-
dipolar one (Figure 4), which make then very good inter-
mediate reagents in 3ϩ2 dipolar cycloadditions.
gles [°]: C6N1C7C8 (0.00), C2N1C7C8 (180.00), N1C7C8O9 (0.00)
carbanion center to the ylide substituents and of the posi-
tive charge from the ylide nitrogen atom to the pyrimidine
heterocycle as shown in Figure 2; implying a good stability
for these ylides.
It can also be seen that the ylide 4b (R ϭ NO2) has a
smaller charge value than the ylide 4a (R ϭ H), which me-
ans that the delocalization is extended (Figure 3), increasing
Figure 4. Dipolar structure of ylides: 1,2-dipole (octet form) and
1,3-dipole (sextet form without double bond)
The experimental data that we obtained confirm the re-
the stability of the ylide 4b. The opposite is true for ylide sults of the theoretical calculations presented above. Indeed,
4d (R ϭ OCH3). the new ylides that we obtained, 4aϪd, have a different sta-
The fact that ylide carbanions have a negative atomic bility according to the nature of the R group. Thus, 4-meth-
charge indicates that 4-methylpyrimidinium ylides could be ylpyrimidinium p-nitrobenzoylmethylide (4b) is a highly
used as nucleophilic reagents in appropriate reactions. Also, stable compound, while 4-methylpyrimidinium p-bromo-
the data from Table 1 and Figures 2, 3 and 4, show that benzoylmethylide (4c) is only moderately stable. The
ylides have two resonance forms, a 1,2-dipolar and a 1,3- pyrimididinium ylides 4a and 4d are unstable, and both un-
Table 1. Coefficients of atomic orbitals (pz), the total atomic charge Q and energies [eV] of 4-methylpyrimidinium ylides 4
Ylides
Orbital and
atomic charge
Energy
Coefficients of atomic orbitals (pz)
C-6 C-7 (ylide) N-3
N-1
C-2
C-8
O-9
4a
4b
4c
4d
HOMO
LUMO
Q
HOMO
LUMO
Q
HOMO
LUMO
Q
HOMO
LUMO
Q
Ϫ7.8661
Ϫ0.9978
Ϫ
Ϫ8.2648
Ϫ1.3214
Ϫ
Ϫ7.9776
Ϫ1.1356
Ϫ
Ϫ7.8330
Ϫ0.9672
Ϫ
Ϫ0.0545
Ϫ0.4565
ϩ0.146
Ϫ0.0705
ϩ0.3622
ϩ0.140
Ϫ0.0632
ϩ0.4623
ϩ0.142
Ϫ0.0529
Ϫ0.4631
ϩ0.147
Ϫ0.3496
ϩ0.3196
Ϫ0.107
Ϫ0.3388
Ϫ0.2673
Ϫ0.090
Ϫ0.3541
Ϫ0.2388
Ϫ0.083
Ϫ0.3543
ϩ0.3237
Ϫ0.110
Ϫ0.3387
ϩ0.2106
Ϫ0.136
Ϫ0.3282
Ϫ0.2085
Ϫ0.119
Ϫ0.3396
Ϫ0.3143
Ϫ0.147
Ϫ0.3427
ϩ0.2096
0.137
ϩ0.6681
ϩ0.2864
Ϫ0.413
ϩ0.6868
Ϫ0.1573
Ϫ0.424
ϩ0.6873
Ϫ0.2710
Ϫ0.417
ϩ0.6728
ϩ0.2956
Ϫ0.413
ϩ0.0639
ϩ0.1124
ϩ0.2689
ϩ0.323
ϩ0.1282
Ϫ0.2693
ϩ0.315
ϩ0.1200
Ϫ0.2860
ϩ0.321
ϩ0.1093
ϩ0.2692
ϩ0.328
Ϫ0.2693
0.2608
ϩ0.0914
Ϫ0.090
Ϫ0.383
Ϫ0.2987
ϩ0.2702
Ϫ0.381
Ϫ0.2826
ϩ0.2786
Ϫ0.380
Ϫ0.2598
Ϫ0.2609
Ϫ0.385
ϩ0.0682
Ϫ0.0728
Ϫ0.093
ϩ0.0512
Ϫ0.1964
Ϫ0.093
ϩ0.0668
ϩ0.0920
Ϫ0.089
704
Eur. J. Org. Chem. 1999, 703Ϫ706

4-Methylpyrimidinium Ylides, 1
FULL PAPER
1
Table 2. H-NMR data (δ values, J [Hz]) and carbonyl valence group vibration data [Ϫ1] of pyrimidinium salts 3
Salts
2-H
5-H
6-H
7-H
10-H
11-H
13-H
14-H
νCϭO
3a
3b
3c
3d
9.70
s
8.50Ϫ8.45
d, J ϭ 5.5
8.50Ϫ8.45
9.45Ϫ9.38
d, J ϭ 5.5
9.22Ϫ9.18
8.30Ϫ8.20
Ϫ
Ϫ
7.90Ϫ7.50
2.90
7.90Ϫ7.50
1695
Ϫ
1710
Ϫ
1698
Ϫ
1710
Ϫ
2 H, d, J ϭ 9.0
2 H, m, J ϭ 9.0 s (CH3)
m
9.64
s
6.50
s
8.32Ϫ8.22
2 H, d, J ϭ 9.0
7.85Ϫ7.70
m, 2 H
8.05Ϫ7.95
2 H, d, J ϭ 9.4
8.38Ϫ8.32
2.85
Ϫ
Ϫ
Ϫ
Ϫ
d, J ϭ 5 .4 d, J ϭ 5.4
2 H, d, J ϭ 9.0
7.85Ϫ7.70
s (CH3)
2.80
9.60
s
9.60
s
8.30Ϫ8.25
d, J ϭ 5.6
8.26Ϫ8.20
d, J ϭ 5.6
9.16Ϫ9.11
d, J ϭ 5.6
9.20Ϫ9.15
d, J ϭ 5.6
6.45
s
m, 2 H
s (CH3)
2.80
6.40
s
7.20Ϫ7.14
3.80
s (OCH3)
2 H, d, J ϭ 9.4
s (CH3)
dergo a rapid dimerisation process immediately after prep- ably, the dimer [two ketone bands: ν˜ ϭ 1675 cmϪ1 (ylide)
aration, to afford an ylide/dimer mixture (Scheme 1). This 1705 (dimer); large range of melting points].
means that, when the substituent R has an electron-with-
drawing effect (as in the case of a nitro group) the delocaliz-
Conclusions
ation of ylide carbanion charge to the benzoyl group is fav-
oured and consequently the stability of the ylides is higher
(Figure 3). When the substituent R has a repulsive effect
(as in the case of a methoxy group) the delocalization of the
ylide carbanion charge to the benzoyl group is unfavoured,
consequently the stability of the ylides decreases and the
dimerisation process occurs easily (Figures 1 and 3). The
structure of the new pyrimidine compounds was confirmed
by elemental and spectral (IR, 1H and 13C NMR) analyses.
Elemental (C, H, N) analyses are compatible with the pro-
posed structures for the salts and ylides. Essential data are
furnished by spectral analysis. In the IR spectra of salts 3
(Table 2) the signals corresponding to the ketone group are
situated between 1710 (R ϭ NO2, 3b) and 1680 cmϪ1 (R ϭ
OCH3, 3d), in accordance with the effect of the substituent
in para position of the phenyl ring.
1. The stability of 4-metylpyrimidinium ylides varies with
the nature of the ylide carbanion substituent. The higher
the electron-withdrawing effect of these substituents, the
more is the anionic charge delocalized and therefore the
higher the stability. The experimental data and quantum
chemical calculations confirm this hypothesis and are in
agreement with each other.
2. The quantum chemical calculations show the possibi-
lity of using pyrimidinium ylides as nucleophilic reagents as
well as 1,3-dipoles in reactions with appropriate reagents.
3. Eight new pyrimidine compounds, 4 salts and 4 ylides,
have been obtained. The dimer structures and properties
remain to be studied.
In the 1H-NMR spectra (Table 2) the most important
signals are those of 2-H, 6-H and 7-H. As can be seen in
Table 2 the 2-H signal appears at δ ഠ 9.60 (s), the 6-H
signal at δ ഠ 9.45Ϫ9.10 (d, J ഠ 5.5 Hz) and the 7-H signal
at δ ഠ 6.60Ϫ6.40 (s), in accordance with the proposed
structure. The 13C-NMR spectrum of 3b also confirms the
structure: C-8: δ ϭ 189.66 (alkyl aryl ketone): C-2: δ ϭ
177.72 [pyrimidine carbon atom (one α-nitrogen, one posi-
tive α-nitrogen atom)]; C-6: δ ϭ 172.28 [pyrimidine carbon
atom (one positive α-nitrogen, one α-carbon atom)]; C-7:
δ ϭ 63.42 [alkyl carbon atom (α-ketone, positive α-nitrogen
from pyrimidine)]. All the remaining signals from IR and
NMR spectra are in accordance with the proposed struc-
ture for the pyrimidine salts. The IR spectra of ylides 4 con-
firm the proposed structure. Thus, the signal for the ketone
group appears at 1660 and 1670 cmϪ1, for ylides 4b and 4c
respectively. The difference ν˜CϭO(salts) Ϫ ν˜CϭO(ylides) ഠ 50
cmϪ1 is in accordance with the delocalization phenomena
of the negative charge from the ylide carbanion to the
phenyl ring (Figures 3 and 4) and confirms our previous
Experimental Section
1H and 13C NMR: Gemini 200 MHz spectrometer, internal stand-
ard, [D6]DMSO, coupling constants are given in Hz. Ϫ IR: SPE-
CORD-71 spectrometer (KBr). Ϫ M.p.: Uncorrected values. Ϫ
Quantum chemical calculations: HYPERCHEM 5.02 program.[13]
General Procedure A to Obtain Pyrimidinium Salts: 4-Methylpyrim-
idine (0.2 mL, 2 mmol) and ω-bromo-p-acetophenone (2 mmol)
were dissolved in acetone (10 mL). The solution was heated to re-
flux with a steam bath for 1 h. Ethyl ether was than added and the
pyrimidinium salt obtained was filtered rapidly and dried in vacuo.
General Procedure B to Obtain Pyrimidinium Ylides: The 4-methyl-
pyrimidinium salt (1 mmol) was dissolved in water (50 mL) and
treated with a 40% aqueous solution of K2CO3. The ylide was fil-
tered, washed with a large amount of water and dried in vacuo.
N-Benzoyl-4-methylpyrimidinium Bromide (3a): Prepared according
to General Procedure A using 0.398 g of ω-bromoacetophenone.
Cream-yellow crystals. Yield 0.562 g (96%), m.p. 163Ϫ165°C. Ϫ
IR (KBr): ν˜ ϭ 3100Ϫ3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH), 1695
(CϭO), 1620, 1550, 1455 (CϭC, CϭN). Ϫ H NMR: Table 2. Ϫ
C13H13BrN2O (293): calcd. C 53.26, H 4.47, N 9.56; found C 53.10,
H 4.45, N 9.30.
1
1
supposition. The H-NMR spectrum of ylide 4b also con-
firms the structure. There are two signals: δ ϭ 8.40Ϫ7.50
[m, 8 H (7 aromatic and 1 ylidic proton)]; δ ϭ 2.65 [s, 3 H
(methyl)]. The IR spectra and melting points of ylides 4a
4-Methyl-N-(p-nitrobenzoyl)pyrimidinium Bromide (3b): Prepared
according to General Procedure A using 0.488 g of ω-bromo-p-
nitroacetophenone. Yellow crystals. Yield 0.622 g (92%), m.p.
and 4d show that we have a mixture of the ylide and, prob- 165Ϫ167°C. Ϫ IR (KBr): ν˜ ϭ 3100Ϫ3050 cmϪ1 (ϭCϪH), 1710
Eur. J. Org. Chem. 1999, 703Ϫ706
705

G. Mangalagiu, I. Mangalagiu, I. Humelnicu, M. Petrovanu
FULL PAPER
(CϭO), 1635, 1600, 1450, 1400 (CϭC, CϭN), 1515, 1355 (NO2).
4-Methylpyrimidinium Benzoylmethylide (4a): CAUTION: Hazard-
1
Ϫ H NMR: Table 2. Ϫ 13C NMR ([D6]DMSO): δ ϭ 189.6 (C-8, ous compound! Prepared according to General Procedure B using
CϭO), 177.7 (C-2), 172.2 (C-6), 153.7 (C-12), 151.9 (C-4), 150.5 compound 3a (0.293 g, 1.0 mmol). Mixed with dimer, orange/
(C-9), 128.2 (C-10), 124.1 (C-11), 122.8 (C-5), 63.4 (C-7, CH2), 25.4 brownish. Yield 0.210 g (99%), m.p. 125Ϫ130°C. Ϫ IR (KBr): ν˜ ϭ
(C-13, CH3). Ϫ C13H12BrN3O3 (338): calcd. C 46.17, H 3.58, N
12.43; found C 46.10, H 3.65, N 12.40.
3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH), 1705 (CϭO from dimer), 1675
(CϭO from ylide), 1605, 1590, 1465, 1400 (CϭC, CϭN).
N-(p-Bromobenzoyl)-4-methylpyrimidinium Bromide (3c): Prepared
according to General Procedure A using 0.556 g of p,ω-dibromoac-
etophenone. Yellow crystals. Yield 0.714 g (96%), m.p. 166Ϫ167°C.
Ϫ IR (KBr): ν˜ ϭ 3100Ϫ3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH), 1698
(CϭO), 1625, 1575, 1460 (CϭC, CϭN). Ϫ H NMR: Table 2. Ϫ
C13H12Br2N2O (372): calcd. C 41.97, H 3.25, N 7.53; found C
41.80, H 3.30, N 7.30.
4-Methylpyrimidinium p-Methoxybenzoylmethylide (4d): CAU-
TION: Hazardous compound! Prepared according to General Pro-
cedure B using compound 3d (0.323 g, 1.0 mmol). Mixed with di-
mer, orange. Yield 0.240 g (99%), m.p. 140Ϫ145°C. Ϫ IR (KBr):
ν˜ ϭ 3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH), 1680 (CϭO from dimer),
1670 (CϭO from ylide), 1600, 1515, 1465, 1420, 1400 (CϭC, Cϭ
N), 1265, 1035 (CϪOϪC).
1
N-(p-Methoxybenzoyl)-4-methylpyrimidinium Bromide (3d): Pre-
pared according to General Procedure A using 0.458 g of ω-bromo-
p-methoxyacetophenone. Cream-colored crystals. Yield 0.581 g
(90%), m.p. 138Ϫ141°C. Ϫ IR (KBr): ν˜ ϭ 3100Ϫ3050 cmϪ1 (ϭ
CϪH), 2980 (ϪCϪH), 1680 (CϭO), 1630, 1605, 1455 (CϭC, Cϭ
N), 1260, 1030 (CϪOϪC). Ϫ 1H NMR: Table 2. Ϫ C14H16BrN2O2
(323): calcd. N 8.67; found N 8.35.
[1]
I. Zugravescu, M. Petrovanu, N-Ylid Chemistry, McGraw-Hill,
London, 1976, pp. 247Ϫ314.
[2]
I. Mangalagiu, PhD Thesis, University of Iasi, Romania, 1996.
[3]
I. Mangalagiu, I. Druta, M. Caprosu, M. Petrovanu, Ann. Sci.
Univ. Iassi 1993, 1(s1c), 51Ϫ59.
[4]
I. Mangalagiu, I. Druta, M. Caprosu, M. Petrovanu, Ann. Sci.
Univ. Iassi 1994, 2(s1c), 49Ϫ56.
[5]
4-Methylpyrimidinium p-Nitrobenzoylmethylide (4b): Prepared ac-
cording to General Procedure B using compound 3b (0.338 g, 1.0
mmol). Cherry-colored compound. Yield 0.254 g (99%), m.p.
153Ϫ156°C. Ϫ IR (KBr): ν˜ ϭ 3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH),
1660 (CϭO), 1570, 1465, 1410 (CϭC, CϭN), 1510, 1355 (NO2). Ϫ
C13H11N3O3 (257): calcd. N 16.33; found N 16.20.
F. Krohnke, Ber. Dtsch. Chem. Ges. 1935, 68, 1177Ϫ1185.
[6]
I. Zugravescu, M. Petrovanu, Cicloaditii 3ϩ2 dipolare, Ed. Aca-
`
demiei, Bucureste, 1987, pp.1Ϫ76.
[7]
F. Texier, M. Mazari, R. Carrie, Tetrahedron 1990, 46,
3515Ϫ3523.
[8]
G. J. Klopman, J. Am. Chem. Soc. 1968, 90, 223Ϫ231.
L. Salem, J. Am. Chem. Soc. 1968, 90, 543Ϫ547.
W. C. Herdon, Chem. Rev. 1972, 72, 157Ϫ165.
R. F. Hudson, Angew. Chem. Int. Ed. Engl. 1972, 12, 36Ϫ44.
M. J. S. Dewar, J. Am. Chem. Soc. 1985, 107, 3902Ϫ3910.
We wish to thank Prof. Mircea Constantinescu for the HYPER-
CHEM program (version 5.02 for Windows 95 Ϫ Molecular
Modeling System, Hypercube, Inc. Gainesville, USA).
Received August 26, 1998
[9]
[10]
[11]
[12]
[13]
4-Methylpyrimidinium p-Bromobenzoylmethylide (4c): Prepared ac-
cording to General Procedure B using compound 3c (0.372 g, 1.0
mmol). Red compound. Yield 0.288 g (99%), m.p. 138Ϫ140°C. Ϫ
IR (KBr): ν˜ ϭ 3050 cmϪ1 (ϭCϪH), 2980 (ϪCϪH), 1670 (CϭO),
1590, 1490, 1455, 1400 (CϭC, CϭN). Ϫ C13H11BrN2O (291):
calcd. N 9.62; found N 9.45.
[O98397]
706
Eur. J. Org. Chem. 1999, 703Ϫ706