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C-Substitution of Nucleosides with the Aid of the Eschenmoser Sulfide Contraction.

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least a qualitative knowledge of their variation with temperature.
Received: May 12, 1976;
revised: June 30, 1976 [Z 534 IE]
German version: Angew. Chem. 88,723 (1976)
CAS Registry numbers:
( I ) , 19067-45-9; ( 2 ) . 58281-61-1 ; ( 3 ) , 22904-47-8; ( 4 ) . 4566-80-7;
( S I , 3170-58-9; (6), 3268-43-7; (7), 3356-67-0; (81, 2229-07-4
N. B. Chopmun and J . Shorrer: Advances in Linear Free Energy Relationships. Plenum Press, London 1972.
Equilibrium constants can be treated in analogous manner.
The log k values should be defined as reactivities. Selectivities indicate
differences in reactivities.
B. Giese, Angew. Chem. 88, 159 (1976); Angew. Chem. Int. Ed. Engl.
15, 173 ( I 976).
R . W Tujt in M. S. Newman: Steric Effects in Organic Chemistry.
Wiley, New York 1956, Chap. 13; C.K. Huncock, E . A . Meyeus. and
B . J Yugur, J. Am. Chem. SOC.83. 4211 (1961).
T Fajita, C.Tukuyumu, and M . Nakajima, J. Org. Chem. 38%1623 (1973).
X. L'. Ingold and B. P. Roberts: Free-Radical Substitution Reactions.
Wiley, New York 1971.
W C. Dunen in E . S . H u y s e r : Methods in Free-Radical Chemistry,
Vol. 5. Dekker, New York 1974.
R. W Hendermn and R . D. Ward, J. Am. Chem. Soc. 96, 7556 (1974);
W. A . Pryor and W H . D a r k s , h i d . 96, 7557 (1974); A. A . Zacirsas
and C . M . Hannu, J. Org. Chem. 40, 3782 (1975).
K. Hrrwig, P. Lorenz, and C . Riichardt, Chem. Ber. 108, 1421 (1975).
€3. Giese, Angew. Chem. X8. 161 (1976); Angew Chem. Int. Ed. Engl.
15. 174 11976).
Fig. 1. Instantaneous photograph of an oscillating chemical system which
forms a pattern varying in space and time. The solution (see text for details)
is located in a Petri dish standing on light-sensitive paper (Agfa Brovira
BH II I ) . T o increase the contrast a cobalt glass was placed between the
light source (normal 100 W light bulb) and the Petri dish.
the experimental and theoretical study of chemical oscillations
in time and space. At present, however, too little is known
about the reaction course to explain the observed phenomena.
Received: January 22, 1976:
in abridged form: August 10, 1976 [Z 5.36 IE]
German version: Angew. Chem. XN. 728 (1976)
CAS Registry numbers:
KBrO,, 7758-01-2; tris(2,4-pentanedionato)manganese(ni),14284-89-0
-~
-~-
Chemical Waves in the 2,4-Pentanedione/Potassium
Bromate System
By Wolfgung Jessen, Heinrich G . Busse, and Bent Hausteen[*]
A homogeneous solution in which a chemical reaction is
taking place usually remains monodisperse. We now report
an exception['!
Into the lid of a Petri dish (90mm diameter) at 10°C were
successively introduced: 2.0 M HzS04 (7.5ml), 0.3 M K B r 0 3
(3.75m1), H ,O (3.75 ml), and tris(2,4-pentanedionato)manganese(iii) (81.4 mg). After mixing, the bottom of the Petri dish
is placed in the solution. Glass spacers ensure that there
is a 2 mm-thick liquid layer between the two glass surfaces.
After about lOmin, a small yellow spot (pacemaker) suddenly appears in the initially homogeneous solution which
is kept at room temperature. The spot steadily expands while
the remaining solution stays colorless. Once it has reached
a diameter of about IOmm, the solution decolorizes starting
from the center of the circle, while the periphery continues
to grow. After a brief pause a yellow spot is reformed in
the center of the ring, and a second ring migrates through
the solution. Instead of a system of concentric rings, spirals
may appear or ring formation may simultaneously occur at
several places in the solution to give a pattern of the kind
shown in Figure 1. This Figure shows the state of a solution
20min after the admixture of 2,4-pentanedione (as its Mn"'
complex). About 40 min later, the pattern had disappeared
and the solution was again monodisperse. The solution
remained clear all the time; toward the end of the reaction
only a slight cloudiness appeared but no precipitate was
formed.
Compared with other known systems['], the one described
here has the advantage that it neither forms a precipitate
nor liberates a gas. Consequently, it can also be contained
in a sealed vessel. We believe it to be a suitable model for
[I]
C-Substitution of Nucleosides with the Aid of the
Eschenmoser Sulfide Contraction['
By Helmut Vorbriiggen and Konrad Krolikiewicz"]
Among the numerous chemical modifications of nucleosides
and nucleotides suitable for preparing analogs of biological
interest, very little attention has so far been paid to C-substitution in the a- or y-position to the heterocyclic nitrogen
atoms['].
We have therefore applied the Eschenmoser sulfide contractionL3Jto the readily accessible S-alkyl derivative^'^] of h-thiopurine and of 2- or 4-thiopyrimidine nucleosides.
The S-alkyl derivatives (I ) of 6-thiopurine nucleosides
reacted with strong bases and triphenylphosphane to give
the C-alkylated nucleosides (2), generally in good yield. The
products were hydrolyzed to give the free crystalline compounds (3)C51 (see Table 1 for details).
The 6-phenacylthiopurine afforded, analogously to ( I a ) ,
6-phenacylpurine (m. p. 248°C) in 88 % yield.
S-CH~-R'
CH~-R'
['I and K. Krolikiewicz
Research Laboratories of Schering AG, Berlin/Bergkamen
Postfach 6503 1 I . D-1000 Berlin 65 (Germany)
T o whom correspondence should be addressed
[*] Dr. H. Vorbriiggen
~
[*] W. Jessen, H. G . Busse, and Prof. B. H. Havsteen
Biochemisches lnstitut im Fachbereich Medizin der Universitar
Olshausenstrasse 40-60, D-2300 Kiel (Germany)
A n g e ~ Chem.
.
Int. Ed. Enyl.
CL A . 7: Winfree, Sci. Am., June 1974, p. 82.
/
Vol. 15 ( 1 9 7 6 ) No. 1 I
['I
689
Table I . 6-C-substitutedpurine nucleosides.
[a] 0.1 equiv. (CH&COK/4 equiv. P(C,Hs)a/xylene/A.
[b] 2 equiv. LiN[CH(CH3)2]2/2 equiv. P(CsH5)~/1equiv. HMPT/THF/-70"C
[c] CH30H/NH3/18h/24"C.
On refluxing for 2 h in DMF the S-phenacyl derivatives
of 2-thio- and 2-thio-6-azauridine 2',3',5'-tri-O-ben~oate[~]
furnished the crystalline benzoylated 2-phenacyi derivatives
( 4 a ) [m.p. 120 to 122"C, 76% yield] and ( 4 b ) [m.p. 170
to
173"C, 83 % yield].
On
hydrolysis with
CH30H/NH3/18h/24"C ( 4 a ) is transformed in 90 % yield
into the free phenacyl derivative ( 5 a ) , m.p. 204 to 208"C,
whereas ( 4 6 ) undergoes a retroaldol cleavage to afford the
free 2-methyl derivative (56), m.p. 183 to 185"C, in 90%
yield.
+
+24"C.
c41 Alkylation of the thionucleosides with pheuacyl bromide, tert-butyl bromoacetate, or p-nitrobenzyl chloride can be accomplished in high yield
with K,C03 in D M F or with triethylamine in CH,CI, at 24°C.
[5] Analytical and physical data in accord with the postulated structures.
[6] H. Vorhriiggen and P . Strehike, Chem. Ber. 106,3039 (1973); U . Niedboila
and H . Vorbriiggen, J. Org. Chem. 3 9 , 3654 (1974).
[7] J . J . Fox. D. Van Praag, I . Wempen, I . L . Doerr, L . Cheony, J . E.
Knoll, M . L. Eidinofl, A . Eendich, and G . Bosworth Brown, J. Am. Chem.
SOC.81, 178 (1959).
Allylation of 4-Hydroxyarsenin-Arsenic-Carbon
Hetero-Cope Rearrangement
A
R ~ / L ~ N , X ( 4 a ) , R 2 = C O C ~ H SR
,' = C H ~ C O C B H ,X
. = CH
( 4 b ) . RZ = COCsHS. R' = CHzCOC6H5, X = X
(Sa) R 2 = H , R'
(561, R 2 = H , R'
= CH2COC,HS, X = C H
= CH3, X = K
By Gotlfried Markl and Jany 3.Rarnpal[*l
Dedicated to Pyofessor Leopold Horner on the occasion of
his 65th birthday
We recently reported 4-hydroxyarsenin (I ) (arsaphenol)"],
the first simple heterocyclic phenol, which exists only in the
hydroxy form. On reaction with allyl bromide in boiling acetone (12h in the presence of K2C03) according to the general
synthesisof allyl phenyl ethersl21,(1 ) gives 1,3,5-trialIyl-l-arsacyclohexa-2,5-dien-4-one (2) as the sole product.
CHpCHCHlBr
H
K2COdCH3COCH3
In analogous manner, 2 hours' refluxing of the S-phenacyl
derivative of 4-thiouridine 2',3',5'-tri-O-benzoate['I in DMF
gave the benzoylated 4-phenacyl derivative ( 6 a ) [m.p. 213
to 215"C]rS1in 66 % yield, but 6 hours' refluxing in xylene
with 0.1 equiv. (CH3)3COK/4 equiv. triphenylphosphane
afforded the same product in 90 % yield. Saponification with
CH30H/NH3 gave the free phenacyl derivative ( 6 b ) , m. p.
182 to 184"C, in 90 % yield.
Nucleoside Syntheses, Part 19.-Part 18: Justus Liebigs Ann. Chem.
1976, 745.
[2] E. C . Taylor and S. F . Martin, J. Am. Chem. SOC.9 4 , 2874 (1972);
96, 8095 (1974); R R . Henderson, C . R . Friharl, and N. L. Leonhard,
Phytochemistry 14, 1687 (1975).
[3] M . Roth, P . Dubs, E . GBtschi, and A . Eschenmoser, Helv. Chim. Acta
54,710(1971).--Weareindebted to Prof. Eschenmoser for communication
of the manuscript prior to publication.-H. Singh, K . S . Kumar, and
K . B . Lal, Chem. Ind. (London) 15, 649 (1975).
H
There are three possible pathways for the formation of
(2):
a) Formation of the allyl ether ( 3 ) , subsequent Claisen
ortho-ally1 ether rearrangement, and repetition of this reaction
sequence leads to 3,5-diallyl-4-hydroxyarsenin( 4 ) . Renewed
allyl ether formation followed by para-Claisen rearrangement
or direct allylation at the arsenic can give (2).
-
Received: July 12, 1976;
revised: August 20, 1976 [Z 537 IE]
German version: Angew. Chem. 88, 724 (1976)
CAS Registry numbers:
( 1 a),60363-84-0; ilbl.60363-85-1; ( I c ) . 60363-86-2; ( I d ) , 60363-87-3; ( 3 a A
60363-88-4; ( 3 6 ) . 60363-89-5; ( 3 ~ ) 60363-90-8;
,
/ 3 d ) , 56987-12-2; ( 4 ~ ) .
60363-91-9; ( 4 h ) . 60363-92-0; ( 5 a ) , 60363-93.1; ( 6 a ) , 60363-95-3; ( 6 b ) ,
60363-96-4; 2-thiouridine 2',3',S-tri-O-benzoate S-phenacyl derivate, 6036397-5 ; 2-thio-6-azauridine 2',3',5'-tri-0-benzoate S-phenacyl derivative, 6036398-6; 4-thiouridine 2',3',5'-tri-O-benzoate S-pbenacyl derivative, 60363-99-7
4s
131
121
14)
(b) Direct C-allylation in the 2,5-position and subsequent
allylation at the arsenic.
0
OH
[l]
690
p]
Prof. Dr. G. Markl and Dr. J. B. Rampal
Fachbereich Cbemie und Pharmazie der Universitat
Universitatsstrasse 31, D-8400 Regensburg (Germany)
Angew. Chem. Int. Ed. Engl.
/ Voi. 15 (1976)
No. I 1
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