N1-substituted hypoxanthine derivatives from the reaction of 6-halopurines with Michael acceptors under the conditions of Heck reaction

Article abstract of DOI:10.1135/cccc20000797

The reaction of 6-iodo-, 9-benzyl-6-chloropurine and 7-benzyl-6-chloropurine with butyl acrylate, acrylonitrile, methyl vinyl ketone or methyl methacrylate under conditions of the Heck reaction in the presence of TlOAc or AgOAc afforded N¹-alky

Full text of DOI:10.1135/cccc20000797

Hypoxanthine Derivatives
797
N1-SUBSTITUTED HYPOXANTHINE DERIVATIVES FROM THE
REACTION OF 6-HALOPURINES WITH MICHAEL ACCEPTORS
UNDER THE CONDITIONS OF HECK REACTION
1
2,
Martina HAVELKOVÁ , Martin STUDENOVSKÝ and Dalimil DVOŘÁK *
Department of Organic Chemistry, Prague Institute of Chemical Technology, Technická 5,
1
2
166 28 Prague 6;e-mail: martina.havelkova@vscht.cz, dvorakd@vscht.cz
Received Jan uary 26, 2000
Accepted April 6, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday.
Th e reaction of 6-iodo-, 9-ben zyl-6-ch loropurin e an d 7-ben zyl-6-ch loropurin e with butyl
acrylate, acrylon itrile, m eth yl vin yl keton e or m eth yl m eth acrylate un der con dition s of th e
Heck reaction in th e presen ce of TlOAc or AgOAc afforded N1-alkylh ypoxan th in e derivatives.
Form ation of th ese un expected products can be ration alised as a Tl+- or Ag+-assisted substitu-
tion of h alogen with acetate an ion . Th e 6-acetoxypurin e derivative th us form ed th en elim i-
n ates keten e an d gives 7-ben zyl- or 9-ben zylh ypoxan th in e. Con jugate addition of th ese
com poun ds on to Mich ael acceptors furn ish es th e N1-substituted h ypoxan th in e derivatives.
Key w ord s: Purin es; Hypoxan th in es; Heck reaction ; Mich ael addition s; Palladium ; Th allium
acetate.
Th e Heck reaction is a well establish ed m eth od for th e preparation of fun c-
tion alised arom atic an d h eteroarom atic alken yl derivatives1. To th e best of
our kn owledge, th is m eth odology h as n ot been used for syn th esis of
6-alken ylpurin es. Such reaction would be very useful sin ce som e
6-alken ylpurin es exh ibit biological activity2 an d th e C=C double bon d can
be, in prin ciple, furth er m odified (h ydroxylation , h ydration , am in ation ,
etc.), servin g as a source of oth er purin e derivatives.
To elaborate th is m eth odology for th e syn th esis of purin e derivatives, we
ch ose th e reaction of 9-ben zyl-6-iodopurin e (1a) or 9-ben zyl-6-ch loropu-
rin e (1b) with butyl acrylate as a m odel reaction (Sch em e 1). Despite th e
fact th at various catalytic system s, ([Pd(PPh 3)4], [Pd(PPh 3)2Cl2], Herrm an n
catalyst3 (2), [Pd2(dba)3]·CHCl3 in com bin ation with (2-tolyl)3P, (2-furyl)3P,
AsPh 3 an d dppe), bases (Et3N, Et(iPr)2N, Na2CO3, NaOAc) an d solven ts
(aceton itrile, DMF, NMP, toluen e) were used, all attem pts to obtain th e de-
sired butyl 3-(9-ben zylpurin -6-yl)propen oate h ave failed. Th e un reacted
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

798
Havelková, Studenovský, Dvořák:
6-h alopurin e was always recovered accom pan ied by 9-ben zylpurin e (prod-
uct of deh alogen ation ) in several cases. Th is fin din gs are som ewh at surpris-
in g, sin ce Pd catalysed reaction s with alkyl(aryl)zin c or tin reagen ts4 as well
as Suzuki couplin g5 work well with 6-h alopurin es.
Wh en th e reaction of 9-ben zyl-6-iodopurin e (1a) with butyl acrylate was
run in th e presen ce of Herm an n catalyst (2) an d th allium acetate, an oth er
1
product was isolated in a low yield. Its H NMR spectrum revealed th e pres-
en ce of butyl group an d two triplets with ch em ical sh ifts 2.93 an d 4.33
ppm , each correspon din g to two proton s. Th is clearly sh ows th at th e prod-
uct is a derivative of propan oic but n ot propen oic acid. HR MS gave th e ele-
m en tal com position C19H22N4O3. Th e above data correspon d to th e
h ypoxan th in e derivatives 3 or 4a.
CO2Bu
H2C
2'
CH2
H2C1'
1'CH2
Ar
Ar
BuO2C
O
O
O
O
P
6
6
1 N
Pd
O
Pd
5
4
5
4
N
N
N
N
1
N
P
O
2
2
Ar Ar
N
N
3
3
CH2Ph
CH2Ph
2 Ar = 2-tolyl
3
4a
Th e structure of th e product was un am biguously establish ed by HMBC
experim en t wh ich provides th e in form ation on th ree-bon d carbon –proton
in teraction s. Th e proton s at position 1′ in teract with carbon atom s in posi-
tion s 2 an d 6, wh ich is possible on ly for th e structure 4a. An oth er piece of
eviden ce com es from IR, wh ich sh ows two carbon yl stretch in g frequen cies
at 1 725 an d 1 700 cm –1 in accordan ce with th e structure 4a.
Wh en th e reaction was run in th e presen ce of 1.5 equivalen ts of trieth yl-
am in e, th e product 4a was obtain ed in 84% yield (Table I, en try 2). Th e
9-ben zyl-6-ch loropurin e (1b) appeared to be som ewh at less reactive com -
pared with iodo derivative 1a, but still givin g a h igh yield of 4a togeth er
with som e un reacted 1b (Table I, en try 3). Oth er typical Mich ael acceptors
– acrylon itrile, m eth yl vin yl keton e an d m eth yl m eth acrylate – reacted sim -
ilarly to butyl acrylate furn ish in g N1-substituted h ypoxan th in es 4b–4d
(Sch em e 1) (Table I, en tries 4–6).
Alken es-like m eth yl but-2-en oate, m eth yl cin n am ate, 4-m eth ylbut-3-en -
2-on e, styren e an d vin yl acetate were un reactive. Sim ilarly to 1a an d 1b
7-ben zyl-6-ch loropurin e (5) furn ish ed th e correspon din g h ypoxan th in e de-
rivative 6 in th e reaction (Sch em e 2) with butyl acrylate (Table I, en try 7).
Th e structure of com poun d 6 was also con firm ed by HMBC. In terestin gly,
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Hypoxanthine Derivatives
799
Z
R
N
X
O
N
R
TlOAc or AgOAc
N
N
N
N
+
Z
catalyst 2, Et3N, DMF
N
N
CH2Ph
CH2Ph
1a, X = I
1b, X = Cl
4a, R = H, Z = CO2Bu
4b, R = H, Z = CN
4c, R = H, Z = COCH3
4d, R = CH3, Z = CO2CH3
SCHEME 1
wh ereas silver acetate gave th e sam e results as th allium acetate, oth er silver
salts – ben zoate, trifluoroacetate an d trifluorom eth an e sulfon ate were in ef-
fective.
H3CO2C
Cl
N
CH2Ph
O
N
CH2Ph
N
N
TlOAc
N
N
+
CO2Bu
catalyst 2, Et3N, DMF
N
N
5
6
SCHEME 2
Th e form ation of h ypoxan th in e derivatives 4a–4d an d 6 can be ration al-
ised as a Mich ael addition of 9-ben zylh ypoxan th in e (7) to activated
sterically n on h in dered alken es. 9-Ben zylh ypoxan th in e (7) was really iso-
lated from th e reaction wh ich was run with out butyl acrylate un der oth er-
TABLE I
Reaction of 6-h alopurin es with Mich ael acceptors un der th e con dition s of Heck reaction a
Mich ael
acceptor
Product
(Yield, %)
Mich ael
acceptor
Product
(Yield, %)
En try Halopurin e
En try Halopurin e
1
2
1a
1a
Butyl
4a (20)
4a (84)
5
6
1a
1a
Meth yl vin yl
keton e
4c (72)
4d (51)
acrylateb
Butyl
Meth yl
acrylate
m eth acrylate
Butyl
acrylate
3
4
1b
1a
4a (74)c
7
8
5
Butyl acrylate
6 (45)
Acrylon itrile 4b (90)
1a
Butyl acrylated 4a (15)
a
Reaction con dition s: Halopurin e 1 equivalen t, TlOAc 1.35 equivalen t, Et3N 1.5 equivalen t,
b
Mich ael acceptor 6 equivalen ts, catalyst 2 0.06 equivalen t, DMF, 80 °C, 20 h ; with out
Et3N; 20% of 1b recovered; with out Pd catalyst.
c
d
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

800
Havelková, Studenovský, Dvořák:
wise iden tical con dition s. To explain form ation of 7, we assum e Tl+- or
Ag+-assisted displacem en t of th e h alogen in position 6 of purin e with ace-
tate an ion an d form ation of 6-acetoxy-9-ben zylpurin e (8), wh ich un der th e
reaction con dition s elim in ates keten e furn ish in g 9-ben zylh ypoxan th in e (7)
(Sch em e 3). It appeared, th at 7 was also form ed in th e reaction of
9-ben zyl-6-iodoropurin e (1a) with TlOAc itself (23%), with TlOAc in th e
presen ce of Et3N (45%) an d also with TlOAc an d catalyst 2 with out Et3N
(59%). Th ese reaction s were run in DMF at 80 °C for 20 h . Th e results sh ow,
th at 7 can be form ed directly by th e reaction of 1a with TlOAc an d th at th e
reaction is facilitates by Et3N or by Pd catalyst 2 in absen ce of trieth yl-
am in e. Th e role of trieth ylam in e can be explain ed by form ation of reactive
quartery trieth yl am m on ium salt from trieth ylam in e an d 1a in presen ce of
TlOAc an d its subsequen t reaction with acetate an ion . Trieth ylam in e can
also facilitate elim in ation of keten e. Th e palladium catalyst 2 m ay assist in
th e form ation of acetate 8 via oxidative addition of palladium followed by
displacem en t of ch loride ligan d with acetate an ion an d reductive elim in a-
tion . Elim in ation of keten e can proceed in tram olecularly in th e absen ce of
trieth ylam in e or in term olecularly in its presen ce. Th is idea is supported by
th e well-kn own h igh electron deficien cy of th e purin e rin g system 6 an d th e
fact th at of all th e silver salts used, on ly silver acetate, wh ich can elim in ate
keten e, furn ish es products 4a–4d an d 6.
O
O
N
X
H3C
O
N
N
N
N
N
N
N
-
TlOAc or AgOAc
H2C C O
HN
N
N
N
CH2Ph
CH2Ph
CH2Ph
1a, X = I
1b, X = Cl
7
8
SCHEME 3
If th e above m ech an ism really operates, on e of th e h ydrogen atom s in
position 2′ of th e product sh ould com e from acetate. Th erefore th e reaction
of 7-ben zyl-6-ch loropurin e (5) with butyl acrylate was repeated in th e pres-
en ce of deuterated silver acetate. Really, 2′-m on odeuterated 6 was obtain ed
as eviden t from its 1H NMR spectrum (Sch em e 4). An oth er in direct evi-
den ce of keten e form ation com es from th e experim en t, in wh ich th e
volatiles were after reaction distilled un der h igh vacuum directly from th e
reaction m ixture in to a dry ice-cooled solution of an ilin e in toluen e. As ex-
pected, N-acetan ilide was isolated from th is solution in 32% yield. How-
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Hypoxanthine Derivatives
801
ever, attem pts at a direct proof of keten e in th e reaction m ixture by GC MS
h ave failed. Th e last step in th e reaction sequen ce outlin ed in Sch em e 3 –
con jugate addition of 7 – was verified by th e reaction of in depen den tly pre-
pared 9-ben zylh ypoxan th in e (7) with butylacrylate. Expected h ypoxan -
th in e derivative 4a was form ed in quan titative yield in th is reaction n o
m atter wh at reaction con dition s were used (Et3N, Pd catalyst 2, Et3N an d Pd
catalyst 2 an d even with out an y oth er additives). Fin ally, th e above m ech a-
n ism does n ot require th e presen ce of Pd catalyst. It appeared th at th e reac-
tion with out Pd catalyst really occurs, but slower an d with a lower yield
(Table I, en try 8). Th e last fin din g is in agreem en t with th e above observa-
tion th at Pd catalyst 2 accelerates form ation of 7.
Wh atever th e real m ech an ism of th is reaction is, it seem s th at th e Heck
reaction is n ot a useful m eth odology for th e preparation of 6-alken ylpuri-
n es. However, th e reaction of h ypoxan th in e derivatives with Mich ael ac-
ceptors m igh t be an efficien t route to th e com poun ds of th e type 4 an d 6,
wh ich are to th e best of our kn owledge un kn own . From 1,9- an d
1,7-disubstituted h ypoxan th in e derivatives on ly 1,9-dim eth ylh ypo-
xan th in e an d 1,7-dim eth ylh ypoxan th in e prepared by alkylation of
9-m eth ylh ypoxan th in e7 an d 7-m eth ylh ypoxan th in e8, respectively, were
m en tion ed in literature.
O
Cl
N
D3C
O
N
CH2Ph
CH2Ph
N
N
-
D2C C O
N
AgOCOCD3
N
N
N
5
D
H3CO2C
H
N
O
N
O
DN
CH2Ph
CH2Ph
N
N
CO2Bu
N
N
2'-D-6
N
SCHEME 4
EXPERIMENTAL
Meltin g poin ts were determ in ed on
a
Kofler block an d are un corrected. IR spectra
(waven um bers in cm –1) were recorded on Nicolet 750FT-IR spectrom eter. NMR spectra were
m easured on eith er a Varian Gem in i 300 (1H, 300.07 MHz; 13C, 75.46 MHz) or a Bruker DRX
500 Avan ce (1H, 500.13 MHz; 13C, 125.77 MHz) spectrom eters at 298 K. Ch em ical sh ifts are
given in ppm (δ-scale) an d couplin g con stan ts (J) in Hz. Un am biguous assign m en t of th e NMR
1
sign als is based on 13C{ H}, 13C APT, COSY an d 13C HMBC spectra. Mass spectra (FAB) were re-
corded on ZAB-SEQ (VG An alytical). Elem en tal an alyses were perform ed by th e An alytical De-
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

802
Havelková, Studenovský, Dvořák:
partm en t of Prague In stitute of Ch em ical Tech n ology. All reaction s were perform ed un der a
dry argon atm osph ere. 9-Ben zyl-6-ch loropurin e4b (1b ), 7-ben zyl-6-ch loropurin e4b (5),
9-ben zyl-6-iodopurin e4b (1a) an d Herrm an n catalyst3 2 were by th e reported procedures. Th e
ligh t petroleum used refers to th e fraction boilin g at 40–60 °C. DMF was distilled from P2O5
an d stored over m olecular sieves. Oth er ch em icals were obtain ed from Aldrich .
Syn th esis of Hypoxan th in e Derivatives 4a–4d an d 6. Gen eral Meth od
A m ixture of 9-benzyl-6-iodopurine (0.168 g, 0.5 m m ol), thallium acetate (0.178 g, 0.675 m m ol),
trieth ylam in e (0.1 m l, 0.75 m m ol), Mich ael acceptor (3 m m ol) an d Herrm an n catalyst (0.016
g, 0.03 m m ol) was h eated in DMF (3 m l) un der argon atm osph ere to 80 °C for 20 h . Th e reac-
tion m ixture was th en cooled, filtered th rough Celite, wh ich was wash ed with a sm all
am oun t of DMF. Th e filtrate was th en evaporated in vacuum an d th e residue purified by
ch rom atograph y on silica (ligh t petroleum –aceton e 7 : 3).
9-Benzyl-1-[2-(butoxycarbonyl)ethyl]hypoxanthine (4a). Th e ch rom atograph y afforded 0.148 g
(83.6%) of th e product. An alytical sam ple was obtain ed by crystallisation from eth er. M.p.
86–87 °C. 1H NMR (500.13 MHz, CDCl3): 0.91 t, 3 H, J = 7.4 (CH3); 1.33 m , 2 H (CH2CH3);
1.58 m , 2 H (CH2CH2CH3); 2.93 t, 2 H, J = 6.0 (NCH2CH2CO2Bu); 4.08 t, 2 H, J = 6.7
(OCH2CH2CH2CH3); 4.33 t, 2 H, J = 6.0 (NCH2CH2CO2Bu); 5.33 s, 2 H (CH2Ph ); 7.29 m , 2 H
(Ph); 7.31–7.40 m , 3 H (Ph); 7.75 s, 1 H (8-PuH); 8.21 s, 1 H (2-PuH). 13C APT NMR (127.77 MHz,
CDCl3) CH, CH3: 14.3 (CH3), 128.4 (Ph ), 129.2 (Ph ), 129.8 (Ph ), 140.5 (8-Pu), 148.8 (2-Pu);
C, CH2: 19.7 (CH2), 31.2 (CH2), 33.8 (CH2), 43.9 (CH2), 48.2 (CH2), 65.6 (CH2), 125.0 (5-Pu),
135.9 (Ph ), 148.6 (4-Pu), 157.3 (6-PuH), 172.2 (C=O). IR (CHCl3): 3 015 m , 2 964 m , 1 725 s,
1 700 s, 1 577 m , 1 548 m , 1 512 m . For C19H22N4O3 (354.4) calculated: 64.39% C, 6.26% H,
15.81% N; foun d: 64.34% C, 6.03% H, 15.60% N.
Th e sam e reaction startin g from 9-ben zyl-6-ch loropurin e (1b) afforded 4a in 74% yield to-
geth er with 20% of un reacted 1b.
9-Benzyl-1-(2-cyanoethyl)hypoxanthine (4b). Th e ch rom atograph y furn ish ed 0.120 g ( 90%)
of th e product. Crystallisation from toluen e gave 0.081 g of an alytically pure 4b with m .p.
158–160 °C. 1H NMR (300.07 MHz, CDCl3): 2.98 t, 2 H, J = 6.0 (CH2); 4.32 t, 2 H, J = 6.0
(CH2); 5.34 s, 2 H (CH2Ph ); 7.25–7.40 m , 5 H (Ph ); 7.82 s, 1 H (8-PuH); 8.11 s, 1 H (2-PuH).
IR (CHCl3): 3 014 w, 1 709 s, 1 576 m , 1 546 m , 1 523 m , 1 359 m . FAB MS, m/z: 280.5
(M + 1)+. For C15H13N5O (279.3) calculated: 64.51% C, 4.69% H, 25.07% N; foun d: 65.02% C,
5.23% H, 24.99% N.
9-Benzyl-1-(3-oxobutyl)hypoxanthine (4c). Th e product was obtain ed as an oil 0.106 g
(71.6%). 1H NMR (300.07 MHz, CDCl3): 2.13 s, 3 H (CH3); 3.07 t, 2 H, J = 5.8 (CH2); 4.26 t,
2 H, J = 5.8 (CH2); 5.30 s, 2 H (CH2Ph ); 7.24–7.40 m , 5 H (Ph ); 7.74 s, 1 H (8-PuH); 8.25 s,
1 H (2-PuH). IR (CHCl3): 3 012 m , 1 717 s, 1 697 s, 1 578 m , 1 548 m , 1 512 m . FAB HR MS:
calculated for C16H17N4O2 (M + 1) 297.1351; foun d 297.1336.
9-Benzyl-1-[2-(methoxycarbonyl]propyl]hypoxanthine (4d ). Th e ch rom atograph y afforded
0.022 g (24%) of oily product togeth er with 0.086 g (51%) of startin g 9-ben zyl-6-iodopurin e.
1H NMR (300.03 MHz, CDCl3): 1.28 d, 3 H, J = 7.2 (CHCH3); 3.23 m , 1 H (CHCO2CH3); 3.64 s,
3 H (CO2CH3); 4.04 dd, 1 H, J = 9.3, 13.2 (CH2CH); 4.25 dd, 1 H, J = 4.4, 13.2 (CH2CH); 5.30 s,
2 H (CH2Ph ); 7.24–7.40 m , 5 H (Ph ); 7.72 s, 1 H (8-PuH); 8.08 s, 1 H (2-PuH). IR (CHCl3):
3 017 m , 2 928 m , 2 195 m , 1 729 s, 1 703 s, 1 563 m , 1 511 m . FAB HR MS: calculated for
C
17H19N4O3 (M + 1)+ 327.1457; foun d 327.1471.
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Hypoxanthine Derivatives
803
7-Ben zyl-1-[2-(butoxycarbon yl]eth yl]h ypoxan th in e (6). Trappin g of Keten e
Th e reaction of 7-ben zyl-6-ch loropurin e (5) (0.743 g, 3.04 m m ol), butyl acrylate (2.7 m l,
18.8 m m ol), th allium acetate (1.067 g, 4.05 m m ol), trieth ylam in e (0.63 m l, 4.5 m m ol) an d
catalyst 2 (0.121 g, 0.13 m m ol) in DMF (5 m l) was run as above for 31 h . Approxim ately 3 m l
of th e solven t were th en distilled in vacuum directly to a solution of an ilin e (0.3 m l, 3.3
m m ol) in dry toluen e (5 m l) cooled to –78 °C an d left stan din g at room tem perature over-
n igh t. Evaporation of toluen e an d ch rom atograph y on silica afforded 0.133 g of acetan ilide
(32%) iden tical with an auth en tic sam ple. Th e work-up of th e reaction m ixture followin g
th e gen eral procedure afforded 0.487 g (45.2%) of 6 as a wh ite solid with m .p. 83–85 °C.
1H NMR (500.13 MHz, CDCl3): 0.89 t, 3 H, J = 7.2 (CH3); 1.31 m , 2 H (CH2CH3); 1.57 m ,
2 H (CH2CH2CH3); 2.85 t, 2 H,
J = 6.3 (NCH2CH2CO2Bu); 4.07 t, 2 H, J = 6.6
(OCH2CH2CH2CH3); 4.28 t, 2 H, J = 6.3 (NCH2CH2CO2Bu); 5.59 s, 2 H (CH2Ph ); 7.30–7.40
m , 5 H (Ph ); 7.87 s, 1 H (8-PuH); 8.16 s, 1 H, (2-PuH). 13C APT NMR (127.77 MHz, CDCl3)
CH, CH3: 13.6 (CH3), 127.9 (Ph ), 128.5 (Ph ), 129.0 (Ph ), 143.3 (8-Pu), 147.2 (2-Pu); C, CH2:
19.0 (CH2CH3), 30.4 (CH2CH2CH3), 33.3 (NCH2CH2), 42.8 (NCH2), 50.6 (CH2Ph ), 64.9
(OCH2), 115.0 (5-Pu), 135.6 (Ph ), 154.3 (6-Pu), 157.1 (4-PuH), 170.9 (C=O). IR (CHCl3):
2 964 m , 1 730 s, 1 688 vs, 1 577 w, 1 500 m , 1 403 m . For C19H22N4O3 (354.4) calculated:
64.39% C, 6.26% H, 15.81% N; foun d: 64.43% C, 6.24% H, 15.75% N.
Reaction of 9-Ben zyl-6-iodopurin e (1a) with Th allium Acetate
in th e Absen ce of Butyl Acrylate
A m ixture of 1a (0.084 g, 0.25 m m ol), th allium acetate (0.072 g, 0.27 m m ol), trieth ylam in e
(0.05 m l, 0.4 m m ol) an d catalyst 2 (0.008 g, 0.015 m m ol) was h eated in DMF (1.5 m l) un der
argon atm osph ere to 80 °C for 20 h . Th e reaction m ixture was th en cooled, diluted with di-
ch lorom eth an e an d filtered th rough Celite. Th e filtrate was th en evaporated in vacuum an d
th e residue was purified by HPLC ch rom atograph y (Lich rosfer 100 RP-18, m eth an ol–water)
affordin g 0.031 g (55%) of 9-ben zylh ypoxan th in e (7). M.p. 290–300 °C (ref.9 295–298 °C).
1H NMR (300.07 MHz, DMSO-d6): 5.37 s, 2 H (CH2Ph ); 7.28–7.34 m , 5 H (Ph ); 8.04 s, 1 H
(PuH); 8.20 s, 1 H (PuH); iden tical with th at in ref.10. FAB MS, m/z: 227.5 (M + 1)+.
Reaction of 9-Ben zyl-6-iodopurin e (1a) with Butyl Acrylate
in th e Presen ce of Silver Acetate-d3
Th e sam e procedure as above, startin g from 9-ben zyl-6-iodopurin e (0.084 g, 0.25 m m ol), cata-
lyst 2 (0.008 g, 0.015 m m ol), butyl acrylate (0.18 m l, 1.25 m m ol), trieth ylam in e (0.05 m l,
0.3 m m ol) an d silver acetate-d3 (0.046 g, 0.27 m m ol) in DMF (0.6 m l), gave upon ch rom a-
tograph y 0.046g (51.8%) of th e product. 1H NMR (300.07 MHz, CDCl3): 0.88 t, 3 H, J = 7.2
(CH3); 1.20–1.40 m , 2 H (CH2CH3); 1.49–1.61 m , 2 H (CH2CH2CH3); 2.89 m , 1 H
(CHDCO2Bu); 4.05 t, 2 H, J = 6.8 (OCH2CH2CH2CH3); 4.31 m , 2 H (NCH2CHDCO2Bu); 5.30 s,
2 H (CH2Ph ); 7.23–7.29 m , 2 H (Ph ); 7.31–7.39 m , 3 H (Ph ); 7.73 s, 1 H (8-PuH); 8.19 s, 1 H
(2-PuH).
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

804
Havelková, Studenovský, Dvořák:
9-Ben zylh ypoxan th in e (7)
Th is com poun d was prepared as described for th e preparation of 9-ben zylguan in e11, by re-
flux of 9-ben zyl-6-ch loropurin e with 1 equivalen t of DABCO in water an d acidification in
73% yield. M.p. 286–288 °C (ref.9 295–298 °C).
Reaction of 9-Ben zylh ypoxan th in e (7) with Butyl Acrylate
A m ixture of 9-ben zylh ypoxan th in e (7) (0.030 g, 0.133 m m ol) an d butyl acrylate (0.12 m l,
0.829 m m ol) in DMF (2 m l) was h eated un der argon atm osph ere to 80 °C for 20 h . Th e reac-
tion m ixture was th en cooled, DMF was evaporated in vacuum an d th e residue was purified
by ch rom atograph y on silica (eth yl acetate–m eth an ol 8 : 1) givin g 0.047 g (100%) of 4a as
th e on ly product. Sim ilar results were obtain ed wh en th e reaction was run in th e presen ce
of trieth ylam in e, palladim catalyst 2 or th e m ixture of trieth ylam in e an d 2.
This work was supported by the Grant Agency of the Czech Republic (grants No. 203/96/005 and
No. 203/00/0036) and Prague Institute of Chemical Technology (grant No. 110010015).
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