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Synthesis of 5-Hydroxymethyl-2-deoxycytidine.

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group is released from the boron trifluoride and subsequently
reacts according to the Fischer-Hepp "rearrangement"
The complex of diphenylnitrosamine is not isolable; on
mixing the nitrosamine and boron trifluorideetherate solution,
the reaction mixture immediately turns deep blue-black at
-2OOC even with strictest exclusion of moisture, and a small
amount of black precipitate separates.
The boron trifluoride complexes of the nitrosamines all show
a characteristic infrared band at 1500-1560 cm-1 (cf. Table
1); this lies in the region of the band between 1540 and 1575
cm-1 assigned by Hiinig [21 to the mesomeric system
From spectroscopic measurements of
the pK values, the N-nitrosamines are protonated predominantly on the oxygen [3]. The 0-alkylation of the N-nitrosamines [2] and the spectroscopic proof of complex formation
at the oxygen atom in Pd(I1) complexes of N-nitrosamines
[4] lead to the conclusion that the oxygen atom likewise serves
as donor atom in the BF3-nitrosamine complexes.
Table 1 . Nitrosarnine-BF3 complexes RIR*N--NO-.-BF3
120.- I22
ca. 65 (decamp.)
184.5 (decomp.)
170-172 (decamp.)
I500 (sh)
[a] Determined in a sealed tube. uncorrected.
[b] Measured in Nujol.
The crystals are mostly colorless and were prepared in
quantitative yield in a glove box with absolute exclusion of
moisture; they were washed with ether and then freed from
adhering solvent in a vacuum desiccator. The BF3-nitrosamine complexes are strongly hygroscopic.
Received, October 1 lth, 1963
[Z 597/423 E
German version: Angew. Chern. 75, 1104 (1963)
[I]Short original communication; no extended report will be
[2] S. Hiinig, L. Geldern, and E. Lucke, Angew. Chem. 75, 476
(1963); Angew. Chem. internat. Edit. 2, 327 (1963).
[3] W. S. Layne, H . H . Jaffe. and H . Zimmer, J. Amer. chem.
SOC.85,435 (1963).
[4] R. D. Brown and G . E. Confes, J. chem. SOC.(London) 1962,
Preparation of True Sodium Hexametaphosphate
Na6 t p 6 0 1 8 1
By Prof. Dr. E. Thilo and Dip1.-Chem. U. Schiilke
Institut fur Anorganische Chemie der Deutschen Akademie
der Wissenschaften ZLI Berlin, Berlin-Adlershof (Germany)
Of the condensed phosphates with cyclic anions, onl) the
srimeta- and tetrametaphosphates were hitherto known and
ttudied. However, in 1956, Van Woter and Karl-Kroupa [l]
found indications by means of two-dimensional paper chromatography [2] that phosphates with cyclic anions, i.e. metaphosphates, with more than four PO3 groups per anion, are
present in solutions and hydrolysates of Graham's salt. This
was confirmed in 1961 by Rudy and Ruj [31.
From new studies of Graham's salt, we have now found that a
good paper-chromatographic separation of the metaphosphates up to the octametaphosphate is possible by varying
the composition of the eluant. In addition, by rapid heating
of anhydrous sodium trimetaphosphate, we succeeded in
preparing a Graham's glass i n which higher metaphosphates
with cyclic anions are considerably concentrated.
Furthermore, by combined fractionating precipitation of
aqueous solutions of such preparations with acetone, silver
nitrate, and hexamminecobah(1I I) chloride, we succeeded in
isolating the hexameta- and the pentametaphosphates as
such, and the hexametaphosphate in the form of its crystalline hexamminecobdlt(llI), barium, and silver salts and in
preparing pure Na6[P6Ols] and its hydrate Na&"018]-6H20.
The Debye diagrams of these salts are characteristically
different from those of all othcr phosphates.
Proof of the cyclic structure of the hexametaphosphate is
afforded by titration of the free acid with 0.1 N sodium
hydroxide; the titration curvc shows only strongly acidic
P-OH groups.
Weakly acidic P--OH terminal groups, such as those encountered in the chain phosphates, were not found. A dilute
aqueous solution of the free acid may be prepared by treating
sodium hexametaphosphate with the H-form of Wofatit KPS
ion-exchange resin.
Unequivocal proof for the constitution is furnished, just as
with trimetaphosphate [4] and tetrametaphosphate 151, by
alkaline ring cleavage. In this reaction, the hexametaphosphate is converted into hexaphosphate which, however, undergoes degradation to a small ex!cnt by secondary hydrolysis to
lower polyphosphates.
The name 'sodium hexametaphosphate' has persisted in the
chemical literature since 1840 I61 to denote Graham's salt.
This name has now not only lost its significance but is incorrect, misleading, and hencc to be avoided.
Received, October 14th, 1963
[Z 601/429 IE]
German verhion: Angew. Chem. 75, 1175 (1963)
[I]J . R. Van Wuzer and E. Karl-Kroupa, J. Amer. chem. SOC.78,
1772 (1956);J. F. McCulIough. J . R. Van Wuzer, and E. G. Griffiih
ibid. 78,4528 (1956).
121 J. P. Ebel, Bull. SOC.Chim. France 20, 991 (1953).
131 H. Rudy and F. Ruf, personal communication.
141 E.Thilo and R. Rufz, Z. anorg. allg. Chem. 258, 33 (1949).
151 E.Thi/o and R . Rutz, Z. anorg. allg. Chem. 260, 255(1949).
[6]Th. Fleitmann, Poggendorffs Ann. physik Chem. 78,233 (1849).
Synthesis of 5-Hydroxymethyl-2'-deoxycytidine
By I h . R. Brossmer and E. Rbhm
Max-Pkanck-Institit1 fur Medizinische Forschung,
Tnstitut fur ('hemie, Heidelberg (Germany)
5-Hydroxymethyl-2'-deoxycytidine (9) replaces all of the deoxycytidine in the DNA of various bacteriophages and is
therefore of special interest.
Benzylation of 5-hydroxymethylcytosine gave the benzyl
ether ( I ) , m.p. 25OoC (decomp.) in 90 "/, yield; on subsequent acylation, e.g. with benLoyI chloride in pyridine, this
afforded (2), m.p. 174--175'7': in 80 "/, yield.
Compound (2) forms a mercury salt (3) which is soluble in
toluene; condensation of (3) with 3,5-di-p-toluyl-2-deoxy-Dribofuranosyl chloride at room temperature affords a mixture of the anomeric nuclcosidcs in almost quantitative yield.
Their separation is based on dilrerences in their solubilities:
p-anomer (4), m.p. 170-1 7 1 "C', [a]$'= -52 ' in chloroform;
48%; a-anomer (S), m.p. 128 129"C, [al'f?= -114' in
chloroform, 35 %.
Angew. Chrrrr. inierntri. Edit.
I Vol. 2 (1963)
No. I 2
In boiling methanol, (4) yields 80-85 "/, (6), m.p. 163-164 "C,
in chloroform. Catalytic hydrogenation of (4)
yields (7), m.p. 151-152"C, [a]: = -64.5' in chloroform,
i n 86 "/, yield, and both (4) and (6) afford, after the removal
M - -42.7
The extinction coefficient is almost twice that of bicyclo[0,1,2]pentane [2], viz. hmax = 216 my; E = 137. Theinfrared
spectrum shows characteristic bands at 912 cm-1 (strong) and
1070 cm-I (weak). Thermal isomerization at, 390°C of (2)
and (3) to durene ( 5 ) occurs in 40 % yield with the loss of
two methyl groups, and probably proceeds via the as yet
unknown 1,4-cyclohexadiene derivative (4).
H c11,
(4) R' = Benzoyl
R2= B e n z y l
R3= p-Toluyl
R' = Benzoyl
R2= B e n z y l
RS= p-Toluyl
of the acyl residues with sodium methoxide solution, 91 %,
(a), m.p. 198-199 "C, [a]: = +33 O in dimethylformamide.
Catalytic hydrogenation of (8) or treatment of (7) with
sodium methoxide yields the same free (S), m.p. 203 "C (decamp.), [a]'," = + 5 1 " in water; yield: 35 % based on (3).
R F of (9):0.16-0.18 in n-butanol/water (saturated), 0.31 to
0.33 in n-propanol/water ( 5 : 1) ascending. Ultraviolet absorption of (9) at pH 1: hmax = 283 mp; 212 mp; EmaX =
1 2 . 6 ~103, 11.9x 103; Amin = 243 mp; Emin = 1.6x 103;
A 2501260 = 0.43; A 2801260 = 2.68.
R' = H
R2 = Benzyl
R3 = p-Toluyl
R1 = Benzoyl
R3 = p-Toluyl
R3= H
R2 = Benzyl
The structure of (4) was proved by degradation to P-thymidine. The configuration assigned was supported by the
N MR-spectrum. If merely the preparation of the unsubstituted (9) is desired, doubly benzoylated ( 2 4 , m.p. 154-155 "C,
yield: 80 %, is used as starting material; the condensation of
( 2 4 to the protected nucleoside, m.p. 181-182"C, proceeds
equally smoothly. Removal of all the acyl groups jields (9)
in one stage. We shall report soon on the preparation of other
hydroxymethylcytosine nucleosides and of nucleotides.
Received. October 1 5 t h 1963
[Z 602/425 IE]
German version: Angew. Chem. 75, 1105 (1963)
Photochemical and Catalytic Dimerization of
By Dipl.-Chem. H . H. Stechl
lnstitut fur Organische Chemie der Technischen Hochschule
Karlsruhe (Germany)
1,3,3-Trimethylcyclopropene(I) [I 1 dimerizes on irradiation
(Hanau high-pressure mercury lamp) in acetone with benzophenone as sensitizer. The dimer (15 % yield after 48 h)
consists of a difficultly separable 4: 1 mixture of the tricyclic
hydrocarbons (2) and ( 3 ) of b.p. 66"C/17 mm. Unreacted
(I) can be recovered. Evidence for the structure of (2) is
derived from its NMR spectrum, which shows singlets at
8.99 T (bridge protons), 9.127 (bridge methyl groups), and
at 8.80 T and 8.89 T (geminal methyl groups) with area ratios
of 2:6:6:6. The signals of (3) are at slightly higher field
intensities, viz. r = 9.02; 9.12; 8.82; 8.91; its ultraviolet spectrum has hmax= 216 mp; e = 250.
Angew. Chem. internat. Edit. I Vol. 2 (1963)
/ No. 12
The C-H bond on the ring in (I) has 44 s-character [3].
The expected oxidative coupling which is typical of acetylenes
does not occur with (I). Instead, under the catalytic influence
of Cu(1) or Cu(I1) ions, dimerization occurs and both of the
three-membered rings are then opened to give hexamethylhexatriene (7), m.p. 47 'C, yield: 60%,(double-bond bands at
1790 cm-1 and 1630 cm-1, strong band at 95Ocm-1). The
NMR signal of the vinyl protons lies at 3.38 T. The methyl
groups (8.21 T) appear as broad bands, which cannot be
further resolved. The ultraviolet spectrum shows a principal
maximum at ,,A,
= 282 mp; log E = 4.75.
The product of Wittig reaction of trimethylacrolein with I bromo-2,3-dimethyl-2-butene
is identical with (7).
Received, October 17th, 1963
[Z 603/432IEI
German version: Angew. Chem. 75, 1176 (1963)
[I] G. L. Closs and L. E. Closs, J. Amer. chem. SOC. 83, 2015
(1961), and personal communication.
[2] R . Criegee and A. Rimmelin, Chem. Ber. YO, 414 (1957).
[3] G. L. Closs, Proc. chem. SOC. (London) 1962, 152.
The Action of Sodium Hydrazide on h i d e s
By Doz. Dr. T h . Kauffmann and Dipl.-lng. J. Sobel
Institut fur Organische Chemie der Technischen Hochschule
Darmstadt (Germany)
Experiments with N-caproylpiperidine, N-benzoylpiperidine
[l], N-benzyl-2-pyrrolidone, glycyl-L-proline, and glycyl-L4-hydroxyproline have shown that N,N-dialkylamides [group
( I ) ] are split almost quantitatively by
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synthesis, deoxycytidine, hydroxymethyl
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