8-Purinyl versus 2-Benzimidazolyl Carbanions: Charge Demands of the Heterocycles and Ligand Properties of the Bis(heteroaryl)methanes

Article abstract of DOI:10.1021/jo970958l

Two new purinyl derivatives, 8-benzyl-7-methylpurine (8) and bis(7-methylpurin-8-yl)methane (9), have been synthesized and their corresponding carbanions investigated in DMSO. The application of our previously proposed π-charge/shift relationships to the ¹³C and ¹⁵N shifts of the carbanions has made it possible to map π-charges and obtain the values of the charge demand of the heterocyclic rings, a resonance index of the π-electron-withdrawing power of the substituent. The charge demand of the 7-methylpurin-8-yl substituent is found to be the highest among the previously investigated azinyl and azolyl substituents and is comparable with that of the strongest classical electron-withdrawing functions. The replacement of the fused benzene ring in the benzimidazolyl substituent by a pyrimidine ring containing the nitrogen atoms in appropriate positions causes a considerable increase in the electron-withdrawing capacity of the heterocycle. Spectroscopic and reactivity data confirm the strong electron-withdrawing nature of the purinyl ring. The ¹³C NMR spectrum shows the existence of the carbanions of both purinyl derivatives as a mixture of geometric isomers, a consequence of the high double-bond character along the bond linking the carbanionic carbon to C(8) of the purinyl ring. Bis(7-methylpurin-8-yl)methane can be easily converted to its stable NH tautomer by means of basic catalysis. It behaves as an "active methylene" compound giving high-yield condensations with electrophiles. Finally, unlike the corresponding benzimidazol-2-yl derivative, bis(7-methylpurin-8-yl)methane reacts with metal acetates to give neutral methanates [ML₂] (M = Zn, Cu, Co; LH = bis(7-methylpurin-8-yl)methane), where the ligand is present as an anionic system. On the basis of this and previous data, it is concluded that charge demand plays a strategic role in obtaining stable chelates of this sort.

Full text of DOI:10.1021/jo970958l

436
J . Org. Chem. 1998, 63, 436-444
Articles
8-P u r in yl ver su s 2-Ben zim id a zolyl Ca r ba n ion s: Ch a r ge Dem a n d s
of th e Heter ocycles a n d Liga n d P r op er ties of th e
Bis(h eter oa r yl)m eth a n es1
Alessandro Abbotto, Antonio Facchetti, Silvia Bradamante,* and Giorgio A. Pagani*
Dipartimento di Scienza dei Materiali, Universita` di Milano, via Emanueli 15, I-20126 Milano, Italy, and
Centro CNR Speciali Sistemi Organici, via Golgi 19, I-20133 Milano, Italy
Received May 30, 1997
Two new purinyl derivatives, 8-benzyl-7-methylpurine (8) and bis(7-methylpurin-8-yl)methane (9),
have been synthesized and their corresponding carbanions investigated in DMSO. The application
of our previously proposed π-charge/shift relationships to the 13C and 15N shifts of the carbanions
has made it possible to map π-charges and obtain the values of the charge demand of the heterocyclic
rings, a resonance index of the π-electron-withdrawing power of the substituent. The charge demand
of the 7-methylpurin-8-yl substituent is found to be the highest among the previously investigated
azinyl and azolyl substituents and is comparable with that of the strongest classical electron-
withdrawing functions. The replacement of the fused benzene ring in the benzimidazolyl substituent
by a pyrimidine ring containing the nitrogen atoms in appropriate positions causes a considerable
increase in the electron-withdrawing capacity of the heterocycle. Spectroscopic and reactivity data
confirm the strong electron-withdrawing nature of the purinyl ring. The 13C NMR spectrum shows
the existence of the carbanions of both purinyl derivatives as a mixture of geometric isomers, a
consequence of the high double-bond character along the bond linking the carbanionic carbon to
C(8) of the purinyl ring. Bis(7-methylpurin-8-yl)methane can be easily converted to its stable NH
tautomer by means of basic catalysis. It behaves as an “active methylene” compound giving high-
yield condensations with electrophiles. Finally, unlike the corresponding benzimidazol-2-yl
derivative, bis(7-methylpurin-8-yl)methane reacts with metal acetates to give neutral methanates
[ML2] (M ) Zn, Cu, Co; LH ) bis(7-methylpurin-8-yl)methane), where the ligand is present as an
anionic system. On the basis of this and previous data, it is concluded that charge demand plays
a strategic role in obtaining stable chelates of this sort.
In a series of papers,2,3 we have shown that 13C NMR
carbanionic carbon to its π-electron density qC by means
of an intercept correction constituted by the 13C shift of
ethene (122.8 ppm) and the shielding contribution Ai of
the various substituents directly bonded to the anionic
site. In this relationship, the carbon atom of ethylene
plays the role of a neutral model of the trigonal carbon
atom, and the shielding Ai accounts for all of the
interactions (except for resonance effects) exerted by the
substituent on the adjacent carbon atom. The Ai values
can be obtained as the difference between the 13C shift
of the â-carbons of the â-heteroarylstyrene and styrene
itself, by following a previously used procedure (we have
already shown that styrene derivatives, in addition to the
vinyl systems CH2dCHX, are good models for obtaining
the shielding contribution for the substituent X).2,4
shifts of trigonal delocalized carbanions give access to the
π-electron density qC residing on the carbanionic carbon
and to the charge demands cX of groups X attached to it
by means of relationships 1-3.
δ13C ) 122.8 + A - 160(qπ - 1)
(1)
(2)
(3)
∑
i
C
cXX ) (2 - qπC)/2
cPXh ) 2 - cPh - qπC
Relationship 1 relates the experimental 13C shift of a
(1) Part 7 in bis(heteroaryl)methanes. For part 6, see: Abbotto, A.;
Bradamante, S.; Capri, N.; Rzepa, H.; Williams, D. J .; White, A. J .
Org. Chem. 1996, 61, 1770-1778. For part 5, see ref 3.
(2) (a) Bradamante, S.; Pagani, G. A. J . Org. Chem. 1984, 49, 2863-
2870. (b) Bradamante, S.; Pagani, G. A. J . Chem. Soc., Perkin Trans.
2 1986, 1035-1046. (c) Bradamante, S.; Pagani, G. A. Pure Appl. Chem.
1989, 61, 709-716. (d) Barchiesi, E.; Bradamante, S.; Ferraccioli, R.;
Pagani, G. A. J . Chem. Soc., Perkin Trans. 2 1990, 375-383. (e) Berlin,
A.; Bradamante, S.; Pagani, G. A. J . Chem. Soc., Perkin Trans. 2 1988,
1525-1530. (f) Abbotto, A.; Alanzo, V.; Bradamante, S.; Pagani, G. A.
J . Chem. Soc., Perkin Trans. 2 1991, 481-488. (g) Abbotto, A.;
Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993, 58, 444-448. (h)
Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1993, 58,
449-455.
Relationships 2 and 3 allow an empirical evaluation
of the charge demands c, defined as the fraction of
π-charge withdrawn by a group X from the carbanionic
carbon bonded to it; these are available once the π-elec-
(4) For a detailed description of the origin of relationship 1, its
parameters, and assumed 13C shift sensitivity (160 ppm/electron), see
refs 2a,c and Bradamante, S.; Pagani, G. A. Benzyl and Heteroaryl-
methyl Carbanions: Structure and Substituent Effects In Advances
in Carbanion Chemistry; Snieckus, V., Ed.; J ai Press: London, 1996;
Vol. 2, pp 189-263.
(3) Abbotto, A.; Bradamante, S.; Pagani, G. A. J . Org. Chem. 1996,
61, 1761-1769.
S0022-3263(97)00958-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/22/1998

8-Purinyl vs 2-Benzimidazolyl Carbanions
J . Org. Chem., Vol. 63, No. 3, 1998 437
Ta ble 1. Ch a r ge Dem a n d of Heter oa r yl Su bstitu en ts in
bility to the carbanionic frame. In terms of the equilib-
rium (eq 4), the chelates based on strongly electron-
P h CH-X (cPXh) a n d X2CH- (cXX)
X
cPXh
cXX
2-thiazolyla
2-oxazolyla
0.413-0.380
0.346
0.283
0.457-0.471
0.424-0.436
0.382
0.318
2LH + M(AcO)2 a [ML]2 + 2AcOH
(4)
N-methylimidazol-2-yla
2-benzothiazolyla
2-benzoxazolyla
N-methylbenzimidazol-2-yla
2-pyridylc
0.254
0.316
0.288
0.276b
0.302d
0.299d
0.313
withdrawing systems (e.g., 1 and 2) are not basic enough
to be protonated by the acetic acid formed in the reaction.
Further evidence that stabilization of the carbanionic
structure of the ligand is a decisive factor in allowing the
formation of neutral chelates is provided by two ad-
ditional examples: bis(pyrid-2-yl)acetonitrile gives the
neutral methanate 6,6 whereas bis(pyrid-2-yl)methane
does not.
0.411
0.408
4-pyridylc
2-quinolyld
3-pyridazinyle
2-pyrimidyle
0.417
0.430
0.501
0.446
4-pyrimidyle
pyrazinyle
a
b
Reference 3. This work. c Reference 2b. dReference 6. e Ref-
erence 2f.
tron density qC residing on the carbanionic carbon (and
therefore its 13C chemical shift) is known. We used
charge demands as a quantitative resonance index of the
electron-withdrawing power of the X substituents: in
particular, the PhCH-X systems originated the cPXh val-
ues5 and the -CHX2 carbanions originated the cXX val-
ues5 (both scales are shown in Table 1). Relationships
1-3 have been validated by means of their successful
application to a large number of benzyl and methylene
anions stabilized by primary electron-withdrawing groups
(NO2, COR, CO2R, SOR, SO2R, etc.),2b-d,h pyridines,2e,6
azines,2f,6 and azoles.3
We have communicated3 that the charge demands
cPXh and cXX of the heterocycles in the carbanions of
2-benzylimidazole, 2-benzylbenzimidazole, and bis(imid-
azol-2-yl)methane are particularly small. The insolubil-
ity of the carbanion of bis(N-methylbenzimidazol-2-
yl)methane (3) prevents the cXX of the benzimidazol-2-yl
group in this system from being obtained.3 Charge
demands cXX are thought to affect7 the capacity of the
bis(heteroaryl)methane systems LH to act as bidentate
carbanionic ligands L- and give neutral methanates
[ML2]. Bis(benzothiazol-2-yl)methane (1) and bis(benz-
oxazol-2-yl)methane (2) give the neutral methanates 48,9
and 59 (M ) Zn, Cu, Co, Ni, Pd) with metal acetates,
whereas bis(N-methylbenzimidazol-2-yl)methane (3) does
not.9 We ascribe this behavior to the fact that the
heterocycle in compounds 1 and 2, but not in compound
3, is strongly electron-withdrawing, as is demonstrated
by the charge demand cPXh and cXX values of the ben-
zothiazol-2-yl, benzoxazol-2-yl, and benzimidazol-2-yl
groups (Table 1). In fact, since the ligands in chelates
4-6 are present as carbanionic entities, strongly electron-
withdrawing heterocycles with large cXX values give sta-
In order to obtain definitive evidence concerning the
role of the charge demand of the heterocyclic ligand in
allowing the formation of neutral chelates from bis(het-
eroaryl)methanes, we identified our target with a het-
erocycle that would present a much higher charge
demand with a minimum of structural and steric modi-
fication in comparison with the benzimidazolyl ring. We
chose the 8-purinyl system in which the benzene ring
fused to the imidazole is replaced by a pyrimidine, a
heterocycle that we have shown2f possesses a high charge
demand. We here report the synthesis of 8-benzyl-7-
methylpurine (7) and the 13C NMR study of the corre-
sponding anion to obtain the cPXh value. As before,2,3 we
obtained the shielding contribution Ai of the substituent
as the difference in the shifts of â-carbons in styrene and
7-methyl-8-styrylpurine (8). Finally, we synthesized
bis(7-methylpurin-8-yl)methane (9) (BPUMH) in order to
obtain the cXX value from the 13C shifts of the corre-
sponding carbanion and to ascertain whether this system
can provide neutral methanates upon contact with diva-
lent transition metal acetates. The investigation into the
obtaining of neutral methanates [ML2] was completed by
checking the reaction of bis(N-methylbenzimidazol-2-
yl)methane (3) with transition divalent metal ions under
basic conditions. In addition to its possible bioorganic
significance, the interest and relevance of compound 9
is that it is a bis-aza analogue of (3); the differences
between heterocycles 3 and 9 are therefore amenable to
(5) In charge demand notation, the subscript identifies the group X
for which the charge demand is evaluated, and the superscript
identifies the system (benzylic or symmetrically disubstituted) from
which cX is calculated and to which it refers. A detailed description of
the significance of charge demands c can be found in refs 2b,d, 3, and
4.
(6) Abbotto, A.; Bradamante, S.; Pagani, G. A.; Rzepa, H.; Stoppa,
F. Heterocycles 1995, 40, 757-776.
(7) Another factor exerted by the heterocycle that possibly affects
the stability of chelates is the ring size of the heterocycles (five- or
six-membered). An account describing the results of
a detailed
investigation into this subject will be submitted elsewhere; Abbotto,
A.; Bradamante, S.; Pagani, G. A. Manuscript in preparation.
(8) Abbotto, A.; Alanzo, V.; Bradamante, S.; Pagani, G. A.; Rizzoli,
C.; Calestani, G. Gazz. Chim. Ital. 1991, 121, 365-368.
(9) Abbotto, A. Ph.D. Thesis, University of Milano, Milano, Italy,
1993.

438 J . Org. Chem., Vol. 63, No. 3, 1998
Abbotto et al.
Sch em e 1
Sch em e 2
Sch em e 3
carboxamides appears to be unprecedented and should
be preferred to the reaction with ammidines, which has
been reported in the literature as a pathway for the
production of purine derivatives.11
electronic effects only, which makes the comparison of
their behavior toward metal ions particularly instructive.
A stable enamine tautomer of BPUMH can be obtained
by heating a methanolic solution of 9 at reflux in the
presence of MeONa under an inert atmosphere. The NH-
enamine 12 is formed almost quantitatively (Scheme 3).
The two purinyl rings and the two methyl groups are
isochronous at room temperature in DMSO-d6, showing
a fast intermolecular proton exchange. The 4.60 ppm
peak due to the enamine proton disappears upon deu-
teration. Further evidence of the formation of the
enamine is provided by the 13C NMR (Table 2) and the
MS spectrum, which shows the expected molecular peak
as the parent peak.
From 8-benzyl-7-methylpurine (7) and bis(7-methylpu-
rin-8-yl)methane (9), the corresponding conjugate car-
banions 7- and 9- were prepared in DMSO using
dimsylsodium as a base. The reasons for our choice of
DMSO as a solvent have been documented elsewhere.2
Under these conditions, the interaction with the gegenions
and the effect of this on the π-electronic distribution in
the anionssis minimized and much smaller than in other
common organic solvents, as is suggested by the fact that
DMSO is known to be a highly dissociating medium and
a good coordinating system for the sodium cation.12
NMR Sh ift Assign m en ts. The 13C and 15N NMR
shifts of compounds 7 and 9, as well as of their conjugate
carbanions 7- and 9-, are shown in Table 2. We here
provide a detailed interpretation of the NMR data when
the assignments are not straightforward.
Resu lts
Syn th esis. All of the synthetic strategies we have
envisaged for the preparation of purine derivatives
7-9 involve 4-amino-5-(N-methylamino)pyrimidine (10)
(AMAP) as a starting material. This compound was
prepared according to Bredereck’s procedure10 by alkaline
ring opening of 7-methylpurine. The treatment of AMAP
(10) with phenylacetyl chloride gave a mixture of acyla-
tion products that underwent ring closure upon heating
at 210 °C and removing of the formed water (Scheme 1).
Neither phenylacetic acid at 200 °C nor phenylacetamide
in ethylene glycol at 200 °C reacted with AMAP. The
styryl derivative 8 was prepared by base-catalyzed
condensation of benzaldehyde with 7,8-dimethylpurine
(11), which was in turn prepared by the action of acetic
anhydride on AMAP (Scheme 1).
The general entry we followed for the preparation of
bis(7-methylpurin-8-yl)methane (BPUMH) (9) was the
condensation of AMAP (10) with malonic acid derivatives.
The reaction of 10 with malonammidine bis-hydrochlo-
ride at 200 °C without solvent afforded 9 in 25% yields;
when malonamide was used under the same conditions,
the yields could be increased to 48% (Scheme 2).
(a ) 13C Sh ifts. The 13C shift assignments of com-
pounds 7, 7-, 9, 9-, 12, and 15 were based on splitting
patterns and the known chemical shifts of purine.13
Ambiguities sometimes occurred, and when possible,
discrimination was based on the multiplicity of patterns
and the values of the long-range coupling constants. In
BPUMH is almost insoluble in all nonhydroxylic
organic solvents but is appreciably soluble in water.
Consequently, the second synthetic approach provides a
crude reaction mixture from which BPUMH can be
purified more easily (because no inorganic salts (NH4Cl)
are formed unlike in the reaction with malonammidine
hydrochloride), and no tediously long extractions are
needed to obtain the product. The reaction of AMAP with
compound 9, the assignments of C(4) and C(8) were as
3
follows: 158.78 ppm, C(4), double doublet, J C(4)-H(2)
)
(11) For the synthesis of 8-alkylpurines, see: Bredereck, H.; Effen-
berger, F.; O¨ sterlin, H. G. Chem. Ber. 1967, 100, 2280-2291.
(12) (a) Hogen-Esch, T. E.; Smid, J . J . Am. Chem. Soc. 1966, 88,
307-324. (b) Arnett, E. M.; McKelvey, D. R. J . Am. Chem. Soc. 1966,
88, 2598-2599. (c) Gutman, V. The Donor-Acceptor Approach to
Molecular Interactions; Plenum Press: New York, 1978; Chapters 7
and 10.
(10) Bredereck, H.; Effenberger, F.; Rainer, G. J . Lieb. Ann. Chem.
1964, 673, 82.
(13) Breitmaier, E.; Voelter, W. Carbon-13 NMR Spectroscopy;
VCH: Weinheim, 1987; p 284.

8-Purinyl vs 2-Benzimidazolyl Carbanions
J . Org. Chem., Vol. 63, No. 3, 1998 439
Ta ble 2. 13Ca a n d 15Nb NMR Sh ifts (p p m ) of 8-Ben zyl-7-m eth ylp u r in e (7), Its Con ju ga te Ca r ba n ion 7-,
Bis(7-m eth ylp u r in -8-yl)Meth a n e (9), Its Con ju ga te Ca r ba n ion 9-, Its En a m in ic F or m 12, a n d Its Neu tr a l Com p lex w ith
Zn (II) 15, in DMSOc
purine ring positions
phenyl ring positions
ortho meta para
ipso CH2/CH- 1J , Hzd CH3
compd
1
2
3
4
5
6
7
8
9
7e
276.6 152.05 269.3 159.83f 127.20 139.72 139.4 159.07f 244.0 128.89 128.63 126.82 135.67
244.8 150.63 237.2 165.61 130.78 121.55 98.6 158.67 200.6 123.82 128.30 117.33 144.02
32.90
73.52
71.14
26.88
60.12
60.76j
60.84j
130.5 30.47
149.1 29.24
150.5 27.60
131.8 30.75
153.4 29.12
7- g 95%
5%h
143.86
156.42
157.96
129.20
144.55
9
279.7 152.15 271.5 158.78 127.26 140.09 146.2 155.90 246.0
9- i 50%
150.58
149.14
155.72
155.60
162.58 127.25 129.46
164.84 130.24 121.35
160.49
156.27
145.13
145.04
25%
148
148
28.46
29.62
29.44
147.28 101.58
147.14 101.14
l
l
25%k
{
m
262.0 151.01 255.4 163.02 128.16 129.86 110.7 160.96 202.5
60.46
60.07
60.02
153.3 29.53
153.7 29.09
168.5 29.60
12
15
150.48
151.33
162.54 127.71 129.96
160.46
158.26n 126.34 132.80
157.44n
a
b
Relative to Me4Si (0.0 ppm). Relative to liquid NH3 (0.0 ppm), 380.23 ppm from neat nitromethane. c 0.50 M solutions at 27 °C,
unless otherwise noted. Relative to the methylene or methine bridge. e 0.10 M. f Values can be exchanged. 0.25 M. Only a limited
number of signals of the minor isomer were detected and assigned. 0.15 M. Broad. Two series of signals, each corresponding to one
purine ring, were detected for this isomer. Assignment for this position was not unequivocally performed. 45 °C. Values can be
exchanged.
d
g
h
i
j
k
l
m
n
3
9.7 Hz, in line with J C(4)-H(2) ) 10.9 Hz in purine,14 and
(or PM3), EF, PRECISE, and CHARGE)-1. The coun-
terion was not included in the calculation in order to
properly mimic the nature of anionic species in DMSO,
where they exist as solvent-separated or free ions. The
geometries were fully optimized without any constraint,
in the gas phase.
3J C(4)-H(6) ) 3.4 Hz, in line with J C(4)-H(6) ) 4.8 Hz in
3
purine;14 155.90, C(8), triplet, 2J ) 9 Hz, in line for
instance with C(2) of 1, 2, and corresponding benzyl
2
derivatives (triplet, J ) 8.5-9 Hz).3 In compound 9-,
the assignments of C(4) and C(8) at 45 °C were as
3
follows: 163.02 ppm, C(4), double doublet, J C(4)-H(2)
)
3
9.6 Hz and J C(4)-H(6) ) 3.4 Hz; 160.96, C(8), singlet, in
line for instance with C(2) of 1, 2, and corresponding
benzyl derivatives (singlet or doublet with 2J < 2 Hz).3
(b) 15N Sh ifts. The shift assignments of the four
nitrogen atoms of the purine ring in the neutral com-
pounds 7 and 9 were based on the reported nitrogen
shieldings for 7-methylpurine.15 In anions 7- and 9-, all
of the nitrogen atoms experience a high-field displace-
ment with respect to the neutrals. This is related to an
increase in π-electron density and is consistent with the
observed behavior of the pyridine-like and pyrrole-like
nitrogen atoms of previously investigated anions.2e,f,3,6 On
the basis of this, it is assumed that the chemical shift
order of the four nitrogen atoms of the neutrals is
maintained in the anions.
Geom etr ic Isom er ism in th e An ion s. The 13C NMR
spectrum of the benzyl anion 7- shows that two distinct
isomers (E and Z) are present in DMSO solution at 27
°C, one of which is largely predominant. The presence
of geometric isomers is due to the partial double-bond
character of the bond linking the carbanionic carbon and
the heterocycle and is in line with the isomer equilibrium
observed for the anions of benzylazoles3 and benzyl-
azines.2e,f,6 NOE experiments on the anions of benzyla-
zines (e.g., 2-benzylpyridine, benzylpyrazine, etc.) allowed
it to be determined that the phenyl ring in the most
stable isomer prefers to stay syn to the pyridic nitrogen
atom of the heterocyclic ring (the atom bearing the
delocalized negative charge). Because of the lack of
protons in proper positions, we could not perform the
same measurement for anion 7-. Semiempirical calcula-
tions using the AM1 and the PM3 SCF-MO Hamiltonian
included in the MOPAC package16 were performed on the
geometric isomers of anion 7-, with the keywords AM1
Both the AM1 and PM3 computations predict that
isomer E is the most stable by 0.9 and 4.1 kcal/mol,
respectively; however, the small difference in relative
energy and the known limited accuracy of semiempiri-
cally computed energy values does not allow any defini-
tive conclusion to be drawn concerning the relative
stability of the two isomers. Since the semiempirical
approach is usually considered to be sufficiently accurate
in geometry optimization, the computed planar structure
of the E isomer (against the nonplanar geometry of the
second species) suggests that its predicted higher stability
is justified by a more efficient delocalization along the
entire system.
Three sets of 13C NMR resonances were detected for
the solution of the anion (9-) of BPUMH at 27 °C in
DMSO, with two of them having the two purine rings as
isochronous and the third having two series of signals,
each corresponding to a heterocyclic ring. At 45 °C all
of the multiple peaks of the decoupled 13C NMR spectrum
collapse into a single set of resonances, thus showing that
the three species undergo a fast interconversion (in the
NMR time scale) under these conditions. The three
anionic species slowly interconverting at room temper-
ature were identified as the three geometric isomers
(E,E)-9-, (E,Z)-9-, and (Z,Z)-9-.
As in the case of benzyl anion 7-, we cannot assign
each set of NMR signals to a specific isomer, with the
exception of the species (E,Z)-9-, in which the corre-
sponding carbon sites of the two rings are chemically
nonequivalent. In agreement with the simultaneous
presence of the three isomers at the equilibrium, AM1
computations in the gas phase do not predict any of these
species as being much more stable than the others (the
(14) See ref 13, p 290.
(15) Witanowski, M.; Stefaniak, L.; Webb, G. A. In Annual Reports
on NMR Spectroscopy; Webb, G. A., Ed.; Academic Press: London,
1986; Vol. 18, p 483.
(16) MOPAC 6.0: Stewart, J . J . P. QCPE 1990, 455.

440 J . Org. Chem., Vol. 63, No. 3, 1998
Abbotto et al.
Ta ble 3. Va r ia tion s of th e Loca l π-Electr on Den sities ∆qπ (m e) for Ea ch ith P osition on Goin g fr om th e Neu tr a l
8-Ben zyl-7-m eth ylp u r in e (7) a n d Bis(7-m eth ylp u r in -8-yl)Meth a n e (9) to Th eir Con ju ga te An ion s 7- a n d 9-,
Resp ectivelya ,b
purine ring positions
phenyl ring positions
compd
1
2
3
4
5
6
7
8
9
ortho
32
meta
2
para
59
ipso
7-
9-
c
d
87
48
9
7
88
44
-36
-27
-22
-6
114
64
111
97
3
118
119
-52
-32
a
b
Positive values correspond to an increment of π-electron density. Obtained from ∆qπ ) -(∆δ13C/160) and ∆qπ ) -(∆δ15N/366.34) for
carbon and nitrogen atoms, respectively. c 95% isomer. Chemical shift values of 9- obtained at 45 °C were used.
d
Ta ble 4. Exp er im en ta l π-Electr on Den sities q (e) for
Con ju ga te An ion s 7- a n d 9- of 8-Ben zyl-7-m eth ylp u r in e
(7) a n d Bis(7-m eth ylp u r in -8-yl)Meth a n e (9)
a
b
c
d
compd
qHet
qPh
6.075
qC
qtot
7-
9-
10.471
10.315
1.389
1.390
17.935c
22.020f
a
π-Electron density resident on the purine ring: qHet ) 10 +
∑(∆qπ)purine ring; data are taken from Table 3. π-Electron density
b
resident on the phenyl ring: qPh ) 6 + ∑(∆qπ)phenyl ring; data are
taken from Table 3. c π-Electron density resident on the carban-
ionic carbon, calculated applying relationship 1, using APh ) 13.00
(ref 2b), Apurine ) 0.0 (see Table 5), and chemical shift values
d
reported in Table 2. Total π-electron density of the anionic
system, to be compared with the theoretical value of 18 and 22
π-electrons for 7- and 9-, respectively. qtot ) qHet + qPh + qC.
e
f qtot ) 2qHet + qC.
relative energies of the three optimized geometries fall
in a range of 2.5 kcal/mol). It is worth noting that the
calculated nonplanarity of the Z,Z isomer, which is
probably due to the steric interaction of the methyl
groups (the dihedral angle between the planes of the two
rings is ca. 45°), does not seem to affect the energy
dramatically. This, together with the similar result
found in the case of benzyl anion 8, suggests that the
deviation from planarity of the anionic system has little
effect on its stabilization.
π-Ch a r ge Ma p p in g of th e An ion s a n d Ch a r ge
Dem a n d s of th e 8-P u r in yl Su bstitu en t. The varia-
tions in the local π-electron densities of each carbon atom
of the phenyl and heterocyclic rings going from the
neutral to the conjugate anion can be calculated from
relationship 5, which is derived from relationship 1.
Similarly, the 15N-shift/π-electron density relationship (eq
6)2f-h,3 makes it possible to calculate the variations in the
local π-electron density of nitrogen atoms.
Ta ble 5. Sh ield in g Con tr ibu tion AX a n d Ch a r ge Dem a n d
of th e 7-Meth ylp u r in -8-yl Su bstitu en t (X) in P h CH-X 7-
(cPXh) a n d X2CH- 9- (cXX)
a
b
c
AX
0.0
cPXh
cXX
0.536
0.305
a
Calculated from the difference between the shifts of â-carbons
in 4-methyl-8-styrylpurine (8) (113.17 ppm) and styrene (113.2
b
ppm; ref 18, p 161); see text. Calculated applying relationship
3, with cPh ) qPh - 6; data are taken from Table 4. c Calculated
applying relationship 2; data are taken from Table 4.
R ea ct ion of BP UMH w it h E lect r op h iles a n d
P r ep a r a tion of Neu tr a l Ch ela tes w ith Diva len t
Tr a n sition Meta ls. The high charge demand cXX of the
7-methylpurin-8-yl substituent (0.305), which is compa-
rable with that of the COR (0.32-0.34) and COOR (0.27)
groups,2g suggests that BPUMH might behave as an
“active methylene” compound and react with electrophiles
at the central methylene. We have already shown that
∆δ13C ) -160∆qπC
(5)
(6)
2-benzothiazolyl (cXX ) 0.316),3 2-benzoxazolyl (cXX
)
0.288),3 and 2-thiazolyl (cXX ) 0.318)3 methylene deriva-
tives undergo azo coupling with benzendiazonium chlo-
ride, nitrosation, condensation with aliphatic and aro-
matic aldehydes,17 and condensation with dimethyl-
formamide dimethyl acetal and triethyl orthoformate to
give enamine and enol ether derivatives, respectively.1
∆δ15N ) -366.34∆qπN
The calculated values for the systems 7-7- and 9-9-
are shown in Table 3. The data for 7- refer to the
predominant (95%) species in solution, whereas the
chemical shifts in anion 9- at coalescence temperature
were considered when applying the π-charge/shift rela-
tionships. Table 4 summarizes the π-electron density of
the central carbanionic carbon, qC (as obtained from
relationship 1), and of the aromatic rings, qHet and qPh
(the latter values account for how many electrons have
been withdrawn by these groups from the deprotonated
carbanionic carbon). Table 4 also shows the total π-elec-
tron densities qtot of anions 7- and 9- as the sum of their
calculated partial π-electron densities. Finally the charge
demands cPXh and cXX of the 7-methylpurin-8-yl ring have
been calculated by applying relationships 2 and 3 and
from the data of Table 4 (Table 5). Details of the
procedure we followed in order to obtain the above values
have been previously reported.3
Scheme 4 summarizes the selected reactions with
electrophiles investigated in this study. BPUMH (9)
undergoes high-yield nitrosation with HNO2 (formed in
situ from sodium nitrite and acetic acid) to give the oxime
13. Condensation of 9 with dimethylformamide dimethyl
acetal furnished the enamine 14. The reaction conditions
were consistently milder than those required by the
2-benzothiazolyl and 2-benzoxazolyl derivatives 1 and 2.
The practically pure enamine 14 could be directly isolated
from the reaction mixture: the absence of the need for
chromatographic purification required in the previous
cases led to a 2-fold increase in final yields.
Like the 2-benzothiazolyl and 2-benzoxazolyl methyl-
ene derivatives 1 and 2, BPUMH reacts with metal

8-Purinyl vs 2-Benzimidazolyl Carbanions
J . Org. Chem., Vol. 63, No. 3, 1998 441
Sch em e 4
Sch em e 6
the neutral chelate of 3 with Zn(II). The application of
relationships 1 and 2, together with the use of the already
determined shielding contribution Ai,3 gives a value of
0.276 for the cXX of the N-methylbenzimidazol-2-yl sub-
stituent. This procedure is legitimate because the chemi-
cal shifts of the carbanionic carbon in the sodium salts
and neutral chelates with Zn(II) are practically identical
for both the benzothiazol-2-yl (81.43 vs 80.68 ppm) and
purinyl (60.5 vs 60.0 ppm (Table 2)) derivatives.
Sch em e 5
Discu ssion
The use of new or improved synthetic schemes has
made it possible to obtain some attractive new purinyl
derivatives. Our multinuclear NMR and charge demand
approaches have provided interesting insights into the
electronic nature of this heteroaromatic substituent.
First of all, the existence of anions 7- and 9- as mixtures
of geometric isomers is a consequence of the high double-
bond character of the bond linking the carbanionic carbon
and C(8) of the purine ring, thus demonstrating the
considerable delocalizing capacity of the heterocycle. In
particular, the cPXh value (0.536) for the 7-methylpurin-
8-yl substituent is not only higher than that of the azinyl
and azolyl substituents investigated in our previous
studies (Table 1) but also very close to that of COPh
(0.56), one of the stronger classical electron-withdrawing
groups.2g It is worth noting that both the imidazolyl and
benzimidazolyl rings rank low among the electron-
withdrawing heterocyclic groups shown in Table 1. Thus,
the main reason of the high charge demand of the purinyl
substituent is the fusion of the imidazolyl fragment to a
pyrimidine ring. The properly designed position of the
nitrogen atoms in the six-membered ring fused to the
imidazolyl ring in this isomer of the purinyl substituent
(7-methylpurin-8-yl rather than 9-methylpurin-8-yl) al-
lows highly effective resonance delocalization of the
negative charge resident on an adjacent carbanionic site,
as can be seen from resonance structures A-C.
acetates in H2O to furnish the corresponding neutral
methanates [ML2] 15-17 (M ) Zn, Cu, Co), in which the
purinyl derivative acts as a carbanionic ligand (Scheme
5). Zn(II) and Cu(II) chelates form immediately upon the
mixing of the reagents at room temperature, whereas the
Co(II) chelate requires several hours of reaction under
an inert atmosphere. All of the obtained chelates are
stable in air and do not need any particular storage
precautions. They are moderately soluble in hydroxylic
solvents. The 13C NMR data concerning the Zn(II)
chelate 15 (Table 2) provide unequivocal evidence of the
carbanionic nature of the ligand in the complex. In
particular, the chemical shift of the carbanionic carbon
(60.02 ppm) is almost identical with that of the corre-
sponding site of the anion (9-) of BPUMH (60.46 ppm).
All of the chelates have almost superimposable IR
spectra. Given that the 2-benzothiazolyl derivative 1
affords a tetrahedral Zn(II) neutral chelate,8 it is likely
that all of the complexes prepared in this study have a
similar arrangement around the metal.
The reaction of bis(N-methylbenzimidazol-2-yl)methane
(3) with metal acetates does not lead to the formation of
chelates, although chelates can be obtained provided that
the weak base AcO- is replaced by the stronger base
MeO- (Scheme 6). In this manner the Zn(II), Cu(II), and
Co(II) neutral methanates can be isolated. The stability
of these complexes is much less than that of the analo-
gous derivatives of the purinyl-based ligand. However,
the Zn(II) chelate is strategic for the evaluation of the
charge demand of the heterocycle. In fact, the cXX value
for the N-methylbenzimidazol-2-yl substituent is not
available because of the solubility problems of the anion
of 3,3 and no direct comparison can be made between the
benzimidazolyl and purinyl groups. A reliable estimate
of this value can be obtained by exploiting the chemical
shift of 53.53 ppm for the central carbanionic carbon of
In the benzyl anion 7-, almost 50% of the negative
charge resides on the heterocyclic ring and only 7% is
delocalized into the phenyl ring. The four nitrogen atoms
host 85% of the total negative charge of the purinyl ring,
a value which becomes almost 100% in the case of the

442 J . Org. Chem., Vol. 63, No. 3, 1998
Abbotto et al.
Ta ble 6. Ca lcu la ted Sem iem p ir ica l (AM1) π-Ch a r ges
(m e) for Ea ch ith P osition of th e P u r in e Rin g of
8-Ben zyl-7-m eth ylp u r in e (7) a n d Its Con ju ga te An ion 7-
condensation with electrophiles behaving as an “active
methylene” compound. With the exception of our own
previous studies, electrophilic reactions of the methylene
of bis(heteroaryl)methanes have rarely been reported in
the literature.19
A further manifestation of the overall electron defi-
ciency of the purine system provided by the fused
pyrimidine ring can be identified in the hydroxyl ion
attack at position 8 of 7-methylpurine (as correctly
reported by Bredereck),10 which leads to the opening of
the imidazole ring and affords 4-amino-5-(N-methylami-
no)pyrimidine. No similar reaction in benzimidazole
derivatives appears to be known insofar as their ring
opening requires N-quaternarization.
Finally, the high charge demand of the purine ring and
the consequent relative stability of the carbanion of
BPUMH clearly provide the basis for the easy formation
of the neutral chelates [ML2], in which the heterocyclic
derivative is present as an anionic ligand. The estimated
cXX value of the N-benzimidazol-2-yl groups is smaller
than that of any of the benzofused heterocycles so far
investigated by our group (see Table 1). This result
rationalizes the unique behavior of the benzimidazolyl
derivative toward coordination with divalent metals in
comparison with the other bis(heteroaryl)methanes. To
obtain the corresponding neutral chelate, a stronger base
than AcO- must be used. In other words, the acetic acid
in eq 4 must be replaced by a weaker acid (such as
methanol), which is no longer capable of reacting with
the carbanionic site of the ligand in the complex in order
to shift the equilibrium toward the uncomplexed neutral
heterocycle.
compd
1
2
3
4
5
6
7
8
9
7
-147 +76 -135 +28 -103 +64 +338 +52 -224
7- a -237 +61 -239 +106 -101 -14 +287 +118 -406
Calculated qπC ) 1.384.
a
symmetrically disubstituted carbanion 9-. The low
π-charge resident on the aromatic carbon atoms of anions
7
- and 9- is actually the average result of increases and
decreases in π-electron density in comparison with the
neutral precursors. The quaternary carbons at positions
4, 5, and 8 experience a decrease in π-electron density
when going from the neutral to the anion, whereas a
considerable increase in the negative π-charge is mea-
sured for position 6. Although the former result can be
rationalized in terms of the usual π-electron density
decrease in Ci of the phenyl ring (polarization effects or
an increase in the σ-charge),2d,18 the latter is clearly
unexpected since no resonance structures of the type
A-C can be written with the negative charge delocalized
into this position. In an attempt to rationalize this
unexpected NMR result, we calculated the π-charges for
the benzyl derivative 7 and its conjugate anion 7- at the
AM1 semiempirical level. Table 6 shows that the carbon
atoms 2 and 6 are positively charged in the neutral
system as a result of the electron-withdrawing mesomeric
effect of the aza groups in the ortho and para positions.
After deprotonation, the nitrogen atoms receive a con-
siderable amount of negative charge, which leads to a
decrease (or saturation) in their mesomeric effects toward
the adjacent carbon atoms: as a consequence, there is a
decrease in the positive charge on these carbon atoms
that leads to an increase in π-electron density when going
from the neutral to the anion.
The already established validity of the applied shift/
charge relationships 1, 5, and 6 and the charge demand
approach is further confirmed by the reactivity of BPUMH
(9). Particularly important experimental evidence is
provided by the stability of the BPUMH NH-tautomer.
We have previously shown that, although enamine forms
of bis(benzothiazol-2-yl)methane (1) and bis(benzoxazol-
2-yl)methane (2) have never been isolated, substitution
with a third strong electron-withdrawing group at the
central carbon atom stabilizes the corresponding enamine
tautomers.1 Similarly, bis(pyrid-2-yl)acetonitrile exists
as the corresponding NH tautomer, but bis(pyrid-2-
yl)methane does not.6 Given that the charge demand of
2-benzothiazolyl, 2-benzoxazolyl, and 2-pyridyl is already
highly ranked among the π-deficient heterocycles, the
stability of the BPUMH NH-enamine tautomer alone
(that is, without any need for further substitution by
activating groups) provides unequivocal evidence of the
exceptionally high electron-withdrawing capacity of the
purinyl ring. It is interesting to note that the 13C NMR
of the enamine 12 is almost identical with that of the
carbanion 9-, which suggests that both species have a
similar π-electronic distribution despite the fact that the
former is neutral and the latter is anionic.
We therefore conclude that the charge demand of the
heterocycles plays a primary and strategic role in the
formation of this type of chelates and provides clear and
definitive insights into this novel and interesting class
of coordination compounds.
Exp er im en ta l Section
13C and 15N NMR spectra were recorded using a Bruker
AMX-500 spectrometer operating at 125.78 and 50.75 MHz,
respectively. The spectral parameters and calibrations have
been previously reported.2f Anhydrous N,N-dimethylform-
amide (DMF) was supplied by Fluka and stored over molecular
sieves. Extracts were dried over Na2SO4. Melting points are
uncorrected. Anions were prepared following the procedure
already described.2a
4-Am in o-5-(m eth yla m in o)p yr im id in e (10). A mixture
20
of 7-methylpurine10
,
(1.82 g, 13.6 mmol) and 1 M NaOH (10
mL) was refluxed for 2 h. The yellow solution was acidified
with diluted HCl, and Na2CO3 was added in order to adjust
the pH to about 9. The solution was then evaporated to
dryness. The solid residue was continuously extracted (5 h)
in a Kumagawa apparatus with THF (100 mL). The yellow
solution was evaporated to dryness to leave the compound
(1.23 g, 9.90 mmol, 73%): mp 190-195 °C (lit.10 mp 191-192
°C); 1H NMR (CDCl3) δ 8.25 (s, 1 H), 7.77 (s, 1 H), 4.8 (broad,
3 H), 2.88 (s, 3 H); 1H NMR (DMSO-d6) δ 7.84 (s, 1 H), 7.40 (s,
1 H), 6.33 (s, 2 H), 4.90 (bq, 1 H), 2.73 (d, 3 H).
Bis(7-m eth ylp u r in -8-yl)m eth a n e (9). Meth od A. An
intimate mixture of 4-amino-5-(methylamino)pyrimidine (10)
(1.00 g, 8.05 mmol) and malonamide (0.822 g, 8.05 mmol) was
heated under nitrogen at 180 °C for 1 h. The reaction took
In line with these considerations, it has been shown
that BPUMH undergoes easy, clean, and high-yield
(19) (a) Scheibe, G.; Friedrich, H. J . Chem. Ber. 1961, 94, 1336. (b)
Shivanyuk, A. F.; Dashkovskaya, E. V.; Lozinskii, M. O. Zh. Org. Khim.
1986, 22, 200.
(20) Pugmuire, R. J .; Grant, D. M.; Townsend, L. B.; Robins, R. K.
J . Am. Chem. Soc. 1973, 95, 2791.
(17) Abbotto, A.; Bradamante, S.; Pagani, G. A. Gazz. Chim. Ital.
1994, 124, 301-308.
(18) Kalinowski, H. O.; Berger, S.; Braun, S. Carbon-13 NMR
Spectroscopy; J ohn Wiley & Sons: Chichester, 1988; p 297.

8-Purinyl vs 2-Benzimidazolyl Carbanions
J . Org. Chem., Vol. 63, No. 3, 1998 443
place in the melt. After all 10 had reacted, another aliquot of
10 (1.00 g, 8.05 mmol) was added and the mixture was heated
for another 3 h at 180 °C. The solid, red mass was treated at
reflux with acetonitrile (12 mL) for 15 min. The cool mixture
was then filtered, and the solid was thoroughly washed with
acetonitrile (6 mL) to give the compound as a red solid (1.08
g, 3.85 mmol, 48%): mp >300 °C; 1H NMR (DMSO-d6) δ 9.17
(s, 2 H), 8.91 (s, 2 H), 4.93 (s, 2 H), 3.96 (s, 6 H). Anal. Calcd
for C13H12N8: C, 55.70; H, 4.32; N, 39.98. Found: C, 55.22;
H, 4.31; N, 39.62.
Meth od B. An intimate mixture of 4-amino-5-(methyl-
amino)pyrimidine (10) (2.83 g, 22.8 mmol) and malonoammi-
dine dihydrochloride21 (1.97 g, 11.4 mmol) was heated under
nitrogen at 200 °C for 8 h. The reaction took place in the melt.
The solid mass was then submitted to continuous extraction
with THF (250 mL) in a Kumagawa apparatus. The solvent
was removed from the obtained yellow solution to leave a
residue which was taken up with MeOH (3 mL). The solid
was separated by filtration and dried under reduced pressure
to give the compound as a red solid (0.750 g, 2.67 mmol,
23%): mp >300 °C.
7,8-Dim eth ylp u r in e (11). A solution of 4-amino-5-(meth-
ylamino)pyrimidine (10) (0.400 g, 3.22 mmol) in acetic anhy-
dride (20 mL) was refluxed for 10 h. The yellow solution
turned to brown during the reaction. The mixture was allowed
to cool, and the excess acetic anhydride was removed by
distillation under reduced pressure. The brown residue was
taken up with EtOH (2 mL), and the mixture refluxed for 30
min. Upon cooling a precipitate was formed which was
separated by filtration to afford the compound (0.123 g, 0.830
mmol, 26%): mp 193-194 °C (lit.11 mp 196-197 °C); 1H NMR
(DMSO-d6) δ 9.04 (s, 1 H), 8.85 (s, 1 H), 3.85 (s, 3 H), 2.62 (s,
3 H).
En am in e Tau tom er of Bis(7-m eth ylpu r in -8-yl)m eth an e
(12). Bis(7-methylpurin-8-yl)methane (9) (0.200 g, 0.713
mmol) was added portionwise to a 1 M solution of MeONa in
MeOH (20 mL) under nitrogen. The reaction mixture was
refluxed for 1 h. The formation of a precipitate was observed.
After cooling, the solid was separated by filtration to give the
raw product 12 as a brownish solid (0.188 g, 0.671 mmol,
94.1%): mp >250 °C. An analytical sample was recrystallized
from water and washed with MeOH to give yellow needles:
1H NMR (DMSO-d6) δ 8.38 (s, 2 H), 8.15 (s, 2 H), 4.60 (s, 1 H),
3.97 (s, 1 H), 3.55 (s, 6 H) (peak at 4.60 ppm disappears upon
deuteration); MS (EI) m/z 280 (M•+, 100), 265 (10), 248 (45),
134 (25). Anal. Calcd for C13H12N8: C, 55.70; H, 4.32; N,
39.98. Found: C, 55.21; H, 4.12; N, 40.32.
Nitr osa tion of Bis(7-m eth ylp u r in -8-yl)m eth a n e. Finely
divided NaNO2 (0.110 g, 1.59 mmol) was added portionwise
to a stirred solution of bis(7-methylpurin-8-yl)methane (9)
(0.230 g, 0.821 mmol) in AcOH (10 mL) and water (2 mL),
maintaining the temperature between 0 and 5 °C. After
stirring for 20 min the solution was evaporated to dryness to
leave a yellow residue which was taken up with water (3 mL).
The pH of the suspension was adjusted to neutral with
NaHCO3, and the solid was separated by filtration and washed
with water (2 mL) to give the product 13 as a light-brown solid
(0.204 g, 0.659 mmol, 80.3%): mp >250 °C. An analytical
sample was purified to give a whitish solid (water): 1H NMR
(DMSO-d6) δ 9.29 (s, 1 H), 9.24 (s, 1 H), 9.02 (s, 1 H), 8.93 (s,
1 H), 4.23 (s, 3 H), 3.83 (s, 3 H). Anal. Calcd for C13H11N9O:
C, 50.48; H, 3.59; N, 40.76. Found: C, 50.33; H, 3.62; N, 40.61.
Con den sation of Bis(7-m eth ylpu r in -8-yl)m eth an e with
N,N-Dim eth ylfor m a m id e Dim eth yl Aceta l: r,r-Bis(7-
m eth ylp u r in -8-yl)-â-(d im eth yla m in o)eth en e (14). Bis(7-
methylpurin-8-yl)methane (9) (0.040 g, 0.14 mmol) was added
portionwise under nitrogen to a stirred solution of N,N-
dimethylformamide dimethyl acetal (0.050 g, 0.42 mmol) in
anhydrous DMF (4 mL). After stirring for 5 h at 50 °C, the
resulting red solution was evaporated to dryness to leave an
orange oil. This residue was taken up with Et2O to give the
product as a dark-orange solid (0.040 g, 0.12 mmol, 86%): mp
>240 °C; 1H NMR (DMSO-d6) δ 9.09 (s, 1 H), 8.94 (s, 1 H),
8.79 (s, 1 H), 8.77 (s, 1 H), 7.87 (s, 1 H), 3.58 (s, 3 H), 3.24 (s,
3 H), 2.9 (broad, 6 H); HRMS m/z calcd for C16H17N9 335.1607,
found 335.1612.
Met a l Ch ela t es of Bis(7-m et h ylp u r in -8-yl)m et h a n e
(15-17). A solution of Zn(OAc)2‚2H2O (0.059 g, 0.27 mmol)
in water (2 mL) was added to a solution of bis(7-methylpurin-
8-yl)methane (9) (0.150 g, 0.54 mmol) in water (15 mL). After
the mixture stirred for 15 min at room temperature, the green
crystalline precipitate was filtered, washed with water, and
dried under reduced pressure to afford 15 as a green solid
(0.098 g, 0.16 mmol, 59%): mp >250 °C; 1H NMR (DMSO-d6)
δ 8.49 (s, 4 H), 8.32 (s, 4 H), 5.28 (s, 2 H), 3.77 (s, 12 H). Anal.
Calcd for C26H22N16Zn: C, 50.04; H, 3.56; N, 35.92. Found:
C, 49.97; H, 3.79; N, 36.06.
In the same manner from Cu(OAc)2‚H2O (0.054 g, 0.27
mmol) and bis(7-methylpurin-8-yl)methane (9) (0.150 g, 0.54
mmol) was obtained chelate 16 as a green solid (0.064 g, 0.10
mmol, 38%): mp >250 °C. Anal. Calcd for C26H22N16Cu: C,
50.19; H, 3.57; N, 36.03. Found: C, 50.40; H, 3.68; N, 36.49.
Similarly, from Co(OAc)2‚4H2O (0.067 g, 0.27 mmol) and
bis(7-methylpurin-8-yl)methane (9) (0.150 g, 0.54 mmol) was
obtained chelate 17, after stirring for 30 h at room temperature
under nitrogen, as an orange solid (0.105 g, 0.17 mmol, 63%):
mp >250 °C. Anal. Calcd for C26H22N16Co: C, 50.56; H, 3.60;
N, 36.30. Found: C, 50.36; H, 3.58; N, 36.47.
7-Met h yl-8-(â-st yr yl)p u r in e (8). A 1
M solution of
MeONa in MeOH (6 mL) was added to a mixture of 7,8-
dimethylpurine (0.100 g, 0.675 mmol) and freshly distilled
benzaldehyde (0.079 g, 0.74 mmol). After stirring for 3 days
at room temperature, the red solution was concentrated to 2
mL and the solid was filtered to give the compound (0.089 g,
0.38 mmol, 56%): mp 244-246 °C. A white sample was
obtained by recrystallization from EtOH: mp 245-247 °C; 1H
NMR (DMSO-d6) δ 9.07 (s, 1 H), 8.90 (s, 1 H), 8.05 (d, 1 H, J
) 16 Hz), 7.95-7.40 (m, 6 H), 4.03 (s, 3 H); 13C NMR (DMSO-
d6) δ 159.17, 156.00, 152.62, 140.78, 139.74, 135.26, 129.89,
128.92, 128.10, 127.50, 113.17 (Câ with respect to phenyl ring),
29.09. Anal. Calcd for C14H12N4: C, 71.16; H, 5.13; N, 23.72.
Found: C, 71.29; H, 4.76; N, 23.96.
8-Ben zyl-7-m eth ylp u r in e (7). A solution of phenylacetyl
chloride (2.23 g, 14.4 mmol) in anhydrous DMF (20 mL) was
added dropwise to a mixture of 4-amino-5-(methylamino)py-
rimidine (1.79 g, 14.4 mmol) and Et3N (1.46 g, 14.4 mmol) in
anhydrous DMF (30 mL) at room temperature. A white
precipitate was formed. After stirring for 2 h, the solid was
filtered off and the obtained solution was evaporated to dryness
at reduced pressure. The resulting reddish oil was heated in
a Kugelrohr apparatus at 220 °C under reduced pressure, and
water was distilled off to leave a reddish glassy mass which
was treated with a solution of HgCl2 (3.00 g, 11.0 mmol) in
EtOH (20 mL). The resulting yellow precipitate (the adduct
of 7-methyl-8-benzylpurine with HgCl2) (1.21 g) was treated
for 1 h with a 0.1 M aqueous solution of Na2S‚9H2O (25 mL).
The black precipitate (HgS) was filtered off, and the obtained
yellow solution was evaporated to dryness. The residue was
then taken up with water and extracted with ethyl acetate (3
× 25 mL). The solvent was removed from the dried combined
organic extracts to leave the product as a yellow solid (0.358
g, 1.60 mmol, 11.1%): mp 118-120 °C. An analytical sample
was purified to give a pale-yellow solid: mp 122-123 °C
(MeOH); 1H NMR (DMSO-d6) δ 9.08 (s, 1 H), 8.91 (s, 1 H),
7.33 (s, 5 H), 4.41 (s, 2 H), 3.85 (s, 3 H). Anal. Calcd for
Met a l Ch ela t es of Bis(N-b en zim id a zol-2-yl)m et h a n e
(18-20). A 1 M methanolic solution of MeONa (1 mL) was
added to a solution of bis(N-benzimidazol-2-yl)methane (3)
(0.276 g, 1.00 mmol) in MeOH (8 mL) under nitrogen. After
a few minutes a solution of Zn(OAc)2‚2H2O (0.109 g, 0.50
mmol) in MeOH (2 mL) was added to the reaction mixture.
After the mixture was stirred for 30 min at room temperature,
the yellow crystalline precipitate was filtered, washed with
MeOH, and dried under reduced pressure to afford 18 as a
light-yellow solid (0.287 g, 0.47 mmol, 93%): mp >250 °C; 1H
C
13H12N4: C, 69.62; H, 5.39; N, 24.98. Found: C, 69.90; H,
5.42; N, 24.76.
(21) Kenner, G. W.; Lythgoe, B.; Todd, A. R.; Topham, A. J . Chem.
Soc. 1943, 574-575.

444 J . Org. Chem., Vol. 63, No. 3, 1998
Abbotto et al.
NMR (DMSO-d6) δ 6.95 (d, 4 H), 6.86 (t, 4 H), 6.80 (d, 4 H),
6.72 (t, 4 H), 4.60 (s, 2 H), 3.63 (s, 12 H); 13C NMR (CDCl3) δ
157.07, 141.34, 134.76, 120.78, 118.94, 112.57, 106.00, 53.53
(central CH-), 29.14. Anal. Calcd for C34H30N8Zn: C, 66.29;
H, 4.91; N, 18.19. Found: C, 66.51; H, 4.62; N, 18.18.
In the same manner from Cu(OAc)2‚H2O (0.050 g, 0.25
mmol) and 3 (0.138 g, 0.50 mmol), after stirring for 1 h under
nitrogen, was obtained chelate 19 as a green solid (0.105 g,
0.17 mmol, 69%): mp >250 °C. Anal. Calcd for C34H30N8Cu:
C, 66.49; H, 4.92; N, 18.24. Found: C, 66.11; H, 4.18; N, 18.69.
Similarly, from Co(OAc)2‚4H2O (0.062 g, 0.25 mmol) and 3
(0.138 g, 0.50 mmol) was obtained chelate 20, after stirring
for 30 h at room temperature under nitrogen, as an orange
solid (0.116 g, 0.19 mmol, 76%): mp >250 °C. Anal. Calcd
for C34H30N8Co: C, 66.99; H, 4.96; N, 18.38. Found: C, 66.53;
H, 5.07; N, 18.47.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR (DMSO-d6) spectrum (full and aromatic region) of
compound 14 (with DMF) (2 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O970958L