Reductive dimerization of 2- and 6-iodopurines: Side reaction in Pd-catalyzed cross-coupling of iodopurines

Article abstract of DOI:10.1135/cccc20071365

In the presence of a Pd catalyst and a base, 6- and 2-iodopurine derivatives undergo reductive C-C dimerization with the formation of the corresponding 6,6′- or 2,2′-dimers. The best results of the dimerization were obtained in the presence of i-Pr_2<

Full text of DOI:10.1135/cccc20071365

Reductive Dimerization of 2- and 6-Iodopurines
1365
REDUCTIVE DIMERIZATION OF 2- AND 6-IODOPURINES:
SIDE REACTION IN Pd -CATALYZED CROSS-COUPLING
OF IODOPURINES
1
2,
Tomáš TOBRMAN and Dalimil DVOŘÁK *
Department of Organic Chemistry, Institute of Chemical Technology, Prague, Technická 5,
1
2
166 28 Prague 6, Czech Republic; e-mail: tomas.tobrman@vscht.cz, dvorakd@vscht.cz
Received Septem ber 21, 2007
Accepted October 8, 2007
In th e presen ce of a Pd catalyst an d a base, 6- an d 2-iodopurin e derivatives un dergo reduc-
tive C–C dim erization with th e form ation of th e correspon din g 6,6′- or 2,2′-dim ers. Th e best
results of th e dim erization were obtain ed in th e presen ce of i-Pr2NEt as a base in DMF.
Ph osph in e-free catalysts as well as catalysts con tain in g ph osph in es can be used. In th e presen ce
of catalytic system s con tain in g PPh 3 th e dim erization does n ot proceed. Th is dim erization
m ay becom e an im portan t side reaction in th e Stille or th e Suzuki–Miyaura reaction s of
iodopurin es.
Keyw ord s: Reductive dim erization ; Purin es; Pd catalysis; Cross-couplin g reaction s; Biaryls;
Nucleosides.
Various 2- an d/or 6-substituted purin es display in terestin g biological activi-
ties1. Gen erally th e biological activity screen in g an d oth er application s of
n ovel substituted purin es are lim ited by m eth odologies available for th eir
preparation . Palladium -catalyzed cross-couplin g reaction s2, e.g., th e
Suzuki–Miyaura3, Stille4 an d Son ogash ira5 reaction s of h alopurin es (or po-
ten tially aren esulfon ylpurin es6) are frequen tly utilized for th e syn th esis of
n ovel substituted purin es. In th e course of our on goin g efforts to syn th esize
n ew substituted purin es we observed th e form ation of 6,6′-purin e dim ers in
attem pts to accom plish th e Heck reaction with 6-iodopurin es as substrates.
Such purin e C–C dim ers are virtually un kn own , on ly 8,8′-dim ers of n ucleo-
sides h ave been described as products of oxidative dam age of DNA 7a. For-
m ation of sm all am oun t of 8,8′-purin e dim er was also observed in th e
course of Pd-m ediated direct C–H arylation of purin es in th e presen ce of
CuI 7b. Recen tly th e syn th esis of 6,8′-purin e dim ers, 6,8′:6′,8′′-purin e tri-
m ers, 6,8′:6′,8′′:6′′,8′′-purin e tetram ers an d a Pd com plex of th e correspon d-
in g cyclic tetram er based on th e Negish i cross-couplin g reaction h as been
publish ed8. Sin ce th e form ation of th ese previously un kn own sym m etrical
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374
© 2007 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20071365

1366
Tobrman, Dvořák:
C–C bispurin es m ay becom e a problem in Pd-catalyzed syn th esis of purin e
derivatives, we decided to explore th is side reaction m ore th orough ly.
At first we in vestigated th e in fluen ce of th e Pd catalyst an d its ligan d on
th e dim erization of 9-ben zyl-6-iodopurin e (1a), leadin g to th e form ation of
th e correspon din g 6,6′-dim er 2 (Sch em e 1, Table I).
Ph
N
N
N
I
N
N
N
N
N
N
Pd-catalyst
N
i-Pr2NEt, DMF, 120 °C
N
N
Ph
1a
2
Ph
SCHEME 1
In t h e p resen ce o f p h o sp h in e-free cat alyst s alm o st q u an t it at ive
dim erization was observed with 9-ben zyl-6-iodopurin e (1a) (en tries 1, 2),
wh ile with 9-ben zyl-6-ch loropurin e on ly partial decom position , but n ot
dim erization occurred (en try 3). In con trast, usin g catalysts con tain in g
triph en ylph osph in e led on ly to decom position of th e startin g 1a an d th e
dim er 2 was n ot form ed (en tries 4–6). Surprisin gly, th e reaction in th e pres-
en ce of oth er ph osph in e ligan ds resulted in th e form ation of 2, m ostly in
h igh yield, an d with quan titative con version of 1a (en tries 7–15). Th e in flu-
en ce of biden tate ligan ds was also studied. With 1:1 Pd/ligan d ratio, n o
dim erization was observed with DPPF, wh ile DPPP gave low an d (±)-BINAP
alm ost quan titative yield of dim er 2 (en tries 16, 18 an d 20). Wh en th e ratio
Pd/ligan d 1:2 was used, th e dim erization did n ot occur in an y case (en tries
17, 19 an d 21), probably as a result of saturation of coordin ation sites.
Based on th e above experim en ts we ch ose Pd(OAc)2 as a source of palla-
dium to establish th e in fluen ce of a base, solven t an d th e tem perature on
th e course of th e reaction . Th e results are sum m arized in Table II.
Dim erization of 1a proceeds in DMF at 120 °C in th e presen ce of tertiary
am in es, givin g better yield with i-Pr2NEt (en try 1) th an with Et3N (en try 2).
In th e presen ce of K2CO3 or with out a base th e reaction does n ot occur (en -
tries 3 an d 4). Lowerin g th e tem perature to 100 °C led to a decrease in th e
yield of 2, an d at 80 °C th e dim erization did n ot proceed at all (en tries 5
an d 6). As far as th e solven ts are con cern ed, DMA gave sim ilar results as
DMF (en try 7). In oth er tested solven ts th e dim erization does n ot take place
(en tries 8–11), probably due to low polarity (toluen e) an d/or low boilin g
poin t (aceton itrile, 1,2-dich loroeth an e, THF) of th e solven t.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

Reductive Dimerization of 2- and 6-Iodopurines
1367
TABLE I
In fluen ce of th e Pd catalyst an d ligan d on th e yield of dim er 2 (Sch em e 1)a
En try
Catalystb
Yield of 2, %c
Un reacted 1a, %c
1
2
Pd2(dba)3·CHCl3
Pd(OAc)2
97
0
0
94 (46)d
e
3
Pd(OAc)2
0
0
69
0
4
Pd(PPh 3)4
5
Pd(PPh 3)2Cl2
0
0
6
Pd(OAc)2 + 2 PPh 3
Pd(OAc)2 + 2 TFP
Pd(OAc)2 + 4 TFP
Pd(OAc)2 + 2 (o-tolyl)3P
Pd(OAc)2 + 2 AsPh 3
Pd(OAc)2 + 2 BiPh eCy2P
Pd(OAc)2 + 2 Cy3P
Pd(OAc)2 + 2 t-Bu3P
Pd(OAc)2 + 2 (Ph O)3P
Pd(OAc)2 + 2 (MeO)3P
Pd(OAc)2 + DPPF
0
23
0
7
89
77
54
57
87
32
96
66
86
0
8
0
9
0
10
11
12
13
14
15
16
17
18
19
20
21
0
0
0
0
0
0
96
86
30
66
0
Pd(OAc)2 + 2 DPPF
Pd(OAc)2 + DPPP
0
33
0
Pd(OAc)2 + 2 DPPP
Pd(OAc)2 + (±)-BINAP
Pd(OAc)2 + 2 (±)-BINAP
97
0
64
a
Reaction con dition s: 9-ben zyl-6-iodopurin e, Pd catalyst correspon din g to 5 m ole % of
b
Pd/substrate, i-Pr2NEt (2 equiv.), DMF, 120 °C, 16 h . Abbreviation s: dba, 1,5-diph en yl-
1,4-p en tadien -3-on e ligan d; TFP, tri(2-furyl)ph osph in e; BiPh eCy2P, (2-biph en yl)dicyclo-
h exylph osph in e; Cy3P, tricycloh exylph osph in e; DPPF, 1,1′-bis(diph en ylph osph in o)ferro-
cen e; DPPP, 1,3-bis(dip h en ylp h osp h in o)p rop an e; BINAP, 2,2′-bis(dip h en ylp h osp h in o)-
c
d
1,1′-binaphthalene. NMR yield (1,3,5-trin itroben zen e as in tern al stan dard). Isolated yield.
e
9-Ben zyl-6-ch loropurin e (1b).
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

1368
Tobrman, Dvořák:
TABLE II
In fluen ce of th e base, solven t an d tem perature on th e yield of dim er 2a
En try
Solven t
Tem perature, °C
Base
Yield of 2, %b
Un reacted 1a, %b
1
2
DMF
DMF
120
120
120
120
100
80
i-Pr2NEt
Et3N
94
61
0
0
0
3
DMF
K2CO3
0
4
DMF
n on e
0
0
5
DMF
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
75
0
traces
76
0
6
DMF
7
DMA
Toluen e
MeCN
(CH2Cl)2
THF
120
100
80
95
0
8
62
77
89
96
9
0
10
11
80
0
60
0
a
Reaction con dition s: 9-ben zyl-6-iodopurin e (1a), Pd(OAc)2 (5 m ole %), base (2 equiv.), 16 h .
NMR yield (1,3,5-trin itroben zen e as in tern al stan dard).
b
Th e optim ized reaction con dition s (Pd(OAc)2, DMF, i-Pr2NEt, 120 °C)
were used to exam in e th e reductive dim erization of acetylated 6-iodoribo-
n ucleoside 3 an d 6-ch loro-2-iodo-9-isopropylpurin e (4), respectively
(Sch em e 2). Wh ile th e 6,6′-dim eric n ucleoside 5 was obtain ed in 61% yield,
th e yield of th e purin e 2,2′-dim er 6 was on ly 31%.
AcRf
N
N
Cl
N
Cl
N
X
N
AcO
AcRf =
N
N
N
N
N
N
N
N
(i)
N
N
(i)
O
N N
N
Y
OAc OAc
R
N
AcRf
N
6 (31%)
3, R = AcRf, X = I, Y = H
4, R = i-Pr, X = Cl, Y = I
5 (61%)
Reagents and conditions: (i) Pd(OAc)2 (5 mole %), i-PrNEt (2 equiv.), DMF, 120 °C, 16 h
SCHEME 2
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

Reductive Dimerization of 2- and 6-Iodopurines
1369
Reductive dim erization of aryl h alides in th e course of th e palladium -
catalyzed cross-couplin g reaction s h as been docum en ted m an y tim es. From
th e m ech an istic poin t of view, form ation of PdIV in term ediate by repeated
oxidative addition , disproportion ation of th e origin ally form ed PdII in ter-
m ediate to diarylpalladium an d PdII h alide, an d Heck-type reaction of pri-
m arily form ed arylpalladium h alide with aryl h alide followed by
β-elim in ation of h alogen h ave been con sidered9. However, to th e best of
our kn owledge, n o detailed m ech an istic study h as been m ade so far. In th e
course of th e reductive couplin g of th e above h alopurin es, th e palladium
was n ecessarily oxidized to PdII. Sin ce th e reaction is catalytic with respect
to palladium , th e reduction of PdII to Pd0 occurred, th e m ost likely reducin g
agen t bein g th e am in e used as a base. Th is explain s th at th e reaction pro-
ceeds with i-Pr2NEt or Et3N but n ot with K2CO3.
As we h ave already m en tion ed, form ation of th e purin e 6,6′-dim er 2 h as
been observed in Pd-catalyzed reaction s of 9-ben zyl-6-iodopurin e (1a).
Sin ce cross-couplin g reaction s are com m on ly used for th e preparation of
purin e derivatives, th e form ation of purin e 6,6′-dim ers un der th e con di-
tion s of th e Stille an d Suzuki–Miyaura couplin g of 1a was addressed. For
th is purpose, con dition s described in th e literature an d also com bin ation s
of Pd2(dba)3·CHCl3 as a usual source of Pd(0) with several ph osph in es were
used (Sch em e 3, Tables III an d IV).
Ph
N
N
X
N
Ph
N
N
N
N
N
N
N
N
N
PhM
N
N
+
conditions
Ph
Ph
N
1a, X = I
1b, X = Cl
N
7
M = SnBu3 or B(OH)2
Ph
2
SCHEME 3
Th e Stille reaction h as been com m on ly used for th e preparation of
6-substituted purin es4. Un der th e con dition s reported by Gun dersen 4a,4b
,
on ly th e form ation of th e expected cross-couplin g product 7 was observed
in th e reaction of 1a or 1b with tributyl(ph en yl)stan n an e (Table III, en tries
1, 2). In terestin gly, in th e case of iodo derivative 1a on ly low con version of
th e startin g com poun d was observed. Wh en Pd2(dba)3·CHCl3 as ph osph in e-
free catalyst was used for th e couplin g of 1a, a sign ifican t am oun t of dim er
2 was form ed togeth er with th e expected product of th e cross-couplin g re-
action , com poun d 7. Th e yield of 2 is practically in depen den t of th e cata-
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

1370
Tobrman, Dvořák:
lyst loadin g, wh ile th e yield of 7 decreases with decreasin g am oun t of th e
catalyst (Table III, en tries 3–5). Also, wh en tri(2-furyl)ph osph in e (en tries 6
an d 7) was used as ligan d, form ation of ca. 20% of th e dim er 2 was ob-
served regardless of th e Pd/ligan d ratio used. (±)-BINAP in th e 1:1 Pd/ligan d
ratio gave a sim ilar result (en try 8), wh ile excess of (±)-BINAP suppressed
th e reaction (en try 9).
Th e Suzuki–Miyaura reaction , widely used in th e syn th esis of purin e de-
rivatives3 gave sim ilar results to th e Stille couplin g. Un der two previously
described con dition s (toluen e or DME/H2O m ixture)3a, on ly form ation of
th e cross-couplin g product 7 was observed in th e presen ce of Pd(PPh 3)4
with both ch loro an d iodo derivatives (Table IV, en tries 1–4). Sim ilarly to
Stille couplin g, th e ch loro derivative 1b afforded a m uch h igh er yield of 7
com pared with th e iodo derivative 1a. Again , wh en n o triph en ylph osph in e
was used for th e reaction of iodo derivative 1a, form ation of dim er 2 was
observed. Com pared with th e reaction in toluen e, th e am oun t of 2 was sig-
n ifican tly h igh er if th e reaction was run in DMF (Table III, en tries 5–7). Sur-
prisin gly, 9-ben zyl-6-ch loropurin e 1b rem ain ed practically un ch an ged
un der th ese con dition s (en try 8). With th e TFP/Pd ratio 1:1, dim er 2 be-
TABLE III
Reductive dim erization as a side reaction in th e Stille couplin g (Sch em e 3, M = Sn Bu3)a
En try
X
Catalytic system b
Yield of 2, %c Yield of 7, %c
e
1
2
3
4
5
6
7
8
9
Cl (1b)
I (1a)
I (1a)
I (1a)
I (1a)
I (1a)
I (1a)
I (1a)
I (1a)
Pd(PPh 3)2Cl2
0
0
69
19 (65)d
76
f
Pd(PPh 3)2Cl2
Pd2(dba)3·CHCl3
16
14
15
22
19
23
0
Pd2(dba)3·CHCl3
65 (21)d
53 (30)d
48
Pd2(dba)3·CHCl3
Pd2(dba)3·CHCl3 + 2 TFP
f
Pd2(dba)3·CHCl3 + 4 TFP
54
Pd2(dba)3·CHCl3 + 2 (±)-BINAP
Pd2(dba)3·CHCl3 + 4 (±)-BINAP
36
traces (90)d
a
Reaction con dition s: 9-ben zyl-6-iodopurin e (1a) or 9-ben zyl-6-ch loropurin e (1b), Pd cata-
b
lyst (5 m ole %), Ph Sn Bu3 (1.5 equiv.), DMF, 110 °C, 16 h . For abbreviation s see Table I,
n ote
poun d. 2.5 m ole % of the catalyst. 1.25 m ole % of th e catalyst.
b
c
d
.
NMR yield (1,3,5-trin itroben zen e as in tern al stan dard). Un reacted startin g com -
e
f
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

Reductive Dimerization of 2- and 6-Iodopurines
1371
cam e th e m ain product (en try 9). Excess of TFP suppresses form ation of
both th e dim er 2 an d also th e couplin g product 7 (en tries 10 an d 11).
Th e effect of (±)-BINAP as a represen tative of biden tate ligan ds is sim ilar
(en tries 12 an d 13).
In th e above cross-couplin g reaction s tertiary am in es as reducin g agen ts
do n ot participate. In th ese reaction s, DMF, wh ich is kn own to decom pose
at h igh tem peratures form in g CO an d dim eth ylam in e, m ay serve as reduc-
in g agen t. Wh en DMF is n ot presen t, th e dim erization also proceeds, but to
a m uch lower exten t. In th is case stan n an e or boron ic acid used in th e reac-
tion play probably th e role of th e reducin g agen ts.
TABLE IV
Reductive dim erization as a side reaction in th e Suzuki–Miyaura couplin g (Sch em e 3, M =
B(OH)2)a
En try
X
Catalytic system b
Solven t
Yield of 2, %c Yield of 7, %c
1
2
Cl (1b) Pd(PPh 3)4
toluen e
DME/H2O
toluen e
DME/H2O
toluen e
DMF
0
0
95d
95d
Cl (1b) Pd(PPh 3)4
3
I (1a) Pd(PPh 3)4
0
40
4
I (1a) Pd(PPh 3)4
0
32 (64)e
16 (45)e
43
5
I (1a) Pd2(dba)3·CHCl3
I (1a) Pd2(dba)3·CHCl3
I (1a) Pd2(dba)3·CHCl3
Cl (1b) Pd2(dba)3·CHCl3
6
6
55
26
0
f
7
DMF
30 (35)e
(96)e
8
DMF
9
I (1a) Pd2(dba)3·CHCl3 + 2 TFP
DMF
45
8
18
f
10
11
12
13
I (1a) Pd2(dba)3·CHCl3 + 4 TFP
DMF
13 (69)e
7 (50)e
54 (10)e
0 (38)e
g
I (1a) Pd2(dba)3·CHCl3 + 8 TFP
DMF
4
I (1a) Pd2(dba)3·CHCl3 + 2 (±)-BINAP
I (1a) Pd2(dba)3·CHCl3 + 4 (±)-BINAP
DMF
26
0
DMF
a
Reaction con dition s9a: 9-ben zyl-6-iodopurin e (1a) or 9-ben zyl-6-ch loropurin e (1b), Ph B(OH)2
(1.2 equiv.), Pd catalyst (5 m ole %), 2 M aq. K2CO3 (1.25 equiv.), DME, 80 °C, 16 h . With
b
oth er solven ts, dry K2CO3 (1.25 equiv.) at 100 °C was used. For abbreviation s see Table I,
b
c
d
e
n ote
.
NMR yield (1,3,5-trin itroben zen e as in tern al stan dard). Ref.3 a
.
Unreacted startin g
f
g
com poun d. 2.5 m ole % of th e catalyst. 1.25 m ole % of th e catalyst.
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

1372
Tobrman, Dvořák:
It is worth n otin g, th at in both reaction s 9-ben zyl-6-ch loropurin e always
gives h igh er yields of th e cross-couplig product th an 6-iodo derivative re-
gardless of wh eth er th e dim er is form ed or n ot. 9-Ben zyl-6-iodopurin e
ten ds to decom pose un der th e con dition s of Pd-catalyzed reaction s. Th us,
9-ben zyl-6-ch loropurin e is a m uch better substrate for cross-couplin g reac-
tion s.
In con clusion , iodopurin es are pron e to form sym m etrical C–C dim ers in
th e presen ce of Pd catalysts, especially wh en tertiary am in es are used. Th eir
ten den cy to dim erize is sign ifican t in polar solven ts like DMF at tem pera-
tures above 100 °C. Th e n ature of th e used ligan d is also im portan t. Dim ers
are not form ed when the catalyst contains triphenylphosphine (Pd(PPh 3)2Cl2,
Pd(PPh 3)4, Pd(OAc)2 + PPh 3, etc.), wh ile in th e presen ce of oth er ph os-
ph in es or un der ligan d-free con dition s th e dim erization proceeds. Biden tate
ligan ds except of BINAP suppress dim erization , especially when two equiva-
lents to the palladium are used. The form ation of 6,6′-purine dim ers m ay be-
com e an im portan t side reaction in th e Suzuki–Miyaura an d Stille reaction s
of 6-iodopurin es. To avoid dim erization , th e followin g suggestion s can be
sum m arized: ch loro derivatives are m ore suitable for cross-couplin g reac-
tion s th an th e correspon din g iodo derivatives. Th e yield of th e cross-
coupled product is always h igh er com pared with 6-iodo derivative an d th e
dim er is n ot form ed. If possible, th e reaction sh ould be catalyzed with
PPh 3-con tain in g catalysts below 100 °C. Polar solven ts like DMF or DMA
sh ould be avoided.
Th e described sym m etrical 6,6′- an d 2,2′-purin e dim ers are n ew com -
poun ds, wh ich can be obtain ed by th e above Pd-catalyzed dim erization .
Th e reaction proceeds with h igh yields, h owever, th e product isolation is
laborious an d is accom pan ied by h igh losses due to h igh ly polar n ature of
th ese com poun ds. Th erefore, we developed a differen t, m ore con ven ien t
approach to th ese com poun ds (based on Cu(I) m ediated dim erization of
iodopurin es). Th is will be th e subject of separate publication .
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Kofler block an d are un corrected. NMR spectra (δ, ppm ;
J, Hz) were m easured on a Varian Gem in i 300 (1H, 300.07 MHz; 13C, 75.46 MHz) spectro-
1
m eter at 298 K. Un am biguous assign m en t of NMR sign als is based on 13C{ H}, 13C APT,
COSY, 1H-13C HMQC an d 1H-13C HMBC spectra. IR spectra (cm –1) were recorded on
a
Nicolet 750 FT-IR. Mass spectra were m easured on an Autospec Ultim a (Microm ass) spectro-
m eter. Th e solven ts were dried an d degassed by stan dard procedures. Silica gel (ICN SiliTech ,
32-63) was used for colum n ch rom atograph y. 9-Ben zyl-6-iodopurin e4a (1), 6-iodo-
Collect. Czech. Chem. Commun. 2007, Vol. 72, No. 10, pp. 1365–1374

Reductive Dimerization of 2- and 6-Iodopurines
1373
9-(O-triacetyl-β-D-ribofuran osyl)purin e10 an d 6-ch loro-2-iodo-9-isopropylpurin e11 (4) were
prepared by th e reported procedures.
Gen eral Procedure for Palladium -Catalyzed Reductive Dim erization of Iodopurin es
To a m ixture of iodopurin e (0.25 m m ol) an d Pd(OAc)2 (3 m g, 0.0125 m m ol) un der argon , DMF
(3 m l) was added followed by i-Pr2NEt (0.09 m l, 0.5 m m ol). Th e resultin g m ixture was h eated
to 120 °C and stirred for 16 h. DMF was then rem oved in vacuum , the resulting solid was dis-
solved in acetone and supported on silica (2 g). Flash chrom atography in ethyl acetate:m ethanol
9:1 afforded th e correspon din g dim er.
9,9′-Dibenzyl-9H,9H′-6,6′-bipurine (2). Yield 46%. 1H NMR (CDCl3, 300 MHz): 5.54 (s, 4 H,
CH2Ph); 7.36 (br s, 10 H, ArH); 8.23 (s, 2 H, H-8); 9.31 (s, 2 H, H-2). 13C NMR (CDCl3, 75 MHz):
47.5, 127.8, 128.6, 129.1, 132.2, 134.7, 146.2, 151.8, 152.7, 153.1. IR (CHCl3): 2992, 1578,
1568, 1498, 1457, 1438, 1397, 1329, 1254, 1201, 1174. HR-MS (EI): calculated for C24H18N8
418.1654, foun d 418.1643.
9,9′-Bis(O-triacetyl-β-D-ribofuranosyl)-9H,9′H-6,6′-bipurine (5). Yield 61%. 1H NMR (CDCl3,
300 MHz): 2.09 (s, 6 H, COCH3); 2.14 (s, 6 H, COCH3); 2.17 (s, 6 H, COCH3); 4.44 (m , 4 H,
OCH2); 4.51 (m , 2 H, CH2CHO); 5.68 (m , 2 H, CHOAc); 6.01 (t, J = 5.77, 2 H, CHOAc); 6.37
(d, J = 5.77, 2 H, CH); 8.45 (s, 2 H, H-8); 9.30 (s, 2 H, H-2). 13C NMR (CDCl3, 75 MHz): 20.3,
20.5, 20.7, 63.0, 70.7, 73.0, 80.6, 86.1, 133.0, 144.7, 152.0, 152.8, 152.9, 169.2, 169.5, 170.2.
IR (CHCl3): 2869, 1752, 1673, 1581, 1491, 1437, 1388, 1330, 1266, 1226. HR-MS (EI): calcu-
lated for C32H34N8O14 754.2194, foun d 754.2168.
6,6′-Dichloro-9,9′-diisopropyl-9H,9′H-2,2′-bipurine (6). Yield 31%. 1H NMR (CDCl3, 300 MHz):
1.71 (d, J = 6.78, 12 H, CH(CH3)2); 5.24 (m , 2 H, CH(CH3)2); 8.33 (s, 2 H, H-8). 13C NMR
(CDCl3, 75 MHz): 23.0, 47.8, 131.7, 144.2, 151.4, 152.1, 155.9. IR (CHCl3): 2992, 1729, 1591,
1554, 1489, 1462, 1395, 1376, 1363, 1325. HR-MS (EI): calculated for C16H16Cl2N8 390.0875,
foun d 390.0877.
This project was supported by the Research Centre of the Ministry of Education, Youth and Sports of
the Czech Republic, by the MSM6046137301 research project of the same Ministry, and by the Grant
Agency of the Czech Republic (grant No. 203/06/0888).
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