Synthesis of 1-[(nitroxyalkoxy)methoxy]-1-triazene 2-oxides, new hybrid nitrogen monoxide donors

Article abstract of DOI:10.1007/s11172-014-0457-2

1-[(Nitroxyalkoxy)methoxy]-3,3-dialkyl-1-triazene 2-oxides were obtained by the reaction of 3,3-dialkyl-1-hydroxy-1-triazene 2-oxide sodium salts with β- or γ-nitroxyalcohol chloromethyl ethers or by the reaction of 3,3-dialkyl-1-(bromoalkoxymethoxy)-1-triazene 2-oxides with silver nitrate. These compounds can be of interest as new hybrid NO donors in living organisms.

Full text of DOI:10.1007/s11172-014-0457-2

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Russian Chemical Bulletin, International Edition, Vol. 63, No. 2, pp. 487—490, February, 2014
487
Synthesis of 1ꢀ[(nitroxyalkoxy)methoxy]ꢀ1ꢀtriazene 2ꢀoxides,
new hybrid nitrogen monoxide donors*
G. A. Smirnov, P. B. Gordeev, S. V. Nikitin, and O. A. Luk´yanov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: smir@ioc.ac.ru
1ꢀ[(Nitroxyalkoxy)methoxy]ꢀ3,3ꢀdialkylꢀ1ꢀtriazene 2ꢀoxides were obtained by the reacꢀ
tion of 3,3ꢀdialkylꢀ1ꢀhydroxyꢀ1ꢀtriazene 2ꢀoxide sodium salts with - or -nitroxyalcohol chloroꢀ
methyl ethers or by the reaction of 3,3ꢀdialkylꢀ1ꢀ(bromoalkoxymethoxy)ꢀ1ꢀtriazene 2ꢀoxides
with silver nitrate. These compounds can be of interest as new hybrid NO donors in living
organisms.
Key words: chloromethyl ethers, nitroxy alcohols, nitrogen monoxide, 1ꢀtriazene 2ꢀoxides,
1ꢀchloromethoxyꢀ3ꢀnitroxypropane, silver nitrate, alkylation, bromination.
Nitrogen monoxide NO is one of the versatile and necꢀ
essary regulators of cell metabolism functions in living
organisms. At present, a wide enough body of chemical
compounds capable of function as NO generators in mamꢀ
mal organisms is known: guanidine and hydroxylamine
derivatives, Nꢀnitro derivatives, Cꢀnitrates and nitrites, as
well as representatives of other classes of compounds1 used
in pharmacology. First of all, these are pharmaceutical
agents from the family of organic nitrates: nitroglycerol,
nitrosorbide, isosorbide mononitrate, erinite, nicorandil,
etc. At the same time, active studies are conducted on the
search for new compounds capable of generation of NO in
living organisms. From this point of view, properties of
1ꢀalkoxyꢀ1ꢀtriazene 2ꢀoxide derivatives, which were disꢀ
covered relatively recently, are of undoubted interest.2 In
the last decade, a fast growth of publications devoted to
these compounds is observed, in particular, to the inꢀdepth
biological studies or beforeꢀclinical testing of their pharꢀ
maceutical effects in the treatment of cardioꢀvascular sysꢀ
tem and kidney diseases, lung insufficiency, oncological
diseases, diabetes.3—5
The purpose of our studies consists in the development
of methods for the synthesis of potential hybridꢀtype NO
donors containing both a nitrate group and an alkoxytriꢀ
azene oxide fragment. No such compounds are known.
Their molecules contain structural fragments of two known
classes of compounds, whose many representatives are
nitric oxide donors in living organisms, that suggests that
similar useful properties would be possessed by the comꢀ
pounds to be synthesized. It should be noted that organic
nitrates and functional oxytriazene oxides significantly difꢀ
fer in the rate of the NO generation, that gives us a possiꢀ
bility to design compounds with the favorable dynamics of
the formation of nitric oxide, which can be regulated within
a certain range. In this connection, we performed alkylaꢀ
tion of a number of sodium salts of 3,3ꢀdisubstituted
1ꢀhydroxyꢀ1ꢀtriazene 2ꢀoxides (1—4). These salts were
obtained by the reaction of the corresponding amines with
NO in the presence of sodium methoxide (Scheme 1).
Scheme 1
1: R1 = R2 = Me; 2: R1 = Me, R2 = Et; 3: R1 = R2 = Et; 4: R1 + R2 = (CH2)4
Chloromethyl ethers 5—7 used as alkylating agents
were obtained by the reaction of the corresponding alcoꢀ
hols with aqueous formaldehyde in the presence of hydroꢀ
chloric acid and calcium chloride (Scheme 2).
Scheme 2
X = CH2 (5), (CH2)2 (6), CH(Me) (7)
The reactions between salts 1—4 and chlorides 5—7
gave earlier unknown adducts 8—16 in 23—53% yields
(Scheme 3).
* On the occasion of the 80th anniversary of the N. D. Zelinsky
Institute of Organic Chemistry of the Russian Academy of Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0487—0490, February, 2014.
1066ꢀ5285/14/6302ꢀ0487 © 2014 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
Smirnov et al.
Scheme 3
dangerous alcohol nitrates in the intermediate steps. First,
we used 2ꢀbromopropanꢀ1ꢀol to synthesize chloromethyl
ether 19. Alkylation of salt 1 with the latter gave the broꢀ
mineꢀcontaining adduct 20 (Scheme 5), whose reaction
with silver nitrate in acetonitrile furnished nitrate 15.
Scheme 5
Comꢀ
pound
8
9
10
R1
R1 + R2
R2
X
Me
Me
Et
—
—
—
Me
Et
Et
CH2
CH2
CH2
11
12
13
14
15
16
—
(CH2)4
—
—
(CH2)4
—
(CH2)4
—
Me
Et
—
Me
CH2
Me
Me
—
Me
—
(CH2)2
(CH2)2
(CH2)2
CH(Me)
CH(Me)
The reaction of compound 1 with allyl chloromethyl
ether 21 gave unsaturated compound 22. Its bromination
led to dibromide 23. Dinitrate 24 was synthesized by treatꢀ
ment of the latter with an excess of silver nitrate (Scheme 6).
—
Dinitrate 18 was obtained in 18% yield by alkylation of
bisꢀtriazene disodium salt 17 with chloromethyl ether 5 in
dimethylformamide (Scheme 4).
Scheme 6
Scheme 4
The structures of compounds obtained were confirmed
by spectroscopic data and elemental analysis. The 1ꢀtriꢀ
azene 2ꢀoxides synthesized are promising compounds as
hybrid nitrogen monoxide donors.
It should be noted that anions of salts 1—4 and 17 to
be alkylated are ambident, and the reaction can proceed
either at the distal or the proximal oxygen atoms with the
formation of triazene Nꢀoxides or Nꢀnitroso derivatives,
respectively. However in all the cases, only triazene
Nꢀoxides were isolated. It is probable, that Nꢀnitroso derivaꢀ
tives are also formed under these conditions, but, being
unstable compounds, they would decompose in the course
of the reactions or during isolation. This suggestion is also
supported by the low yields of the alkylation products.
We also studied an alternative possibility of the syntheꢀ
sis of target triazene oxide nitrates depriving potentially
Experimental
Attention! Special attention should be paid to the work with
nitrates, which are highꢀenergy materials requiring careful handling.
IR spectra were obtained on a URꢀ20 spectrometer. NMR
spectra were recorded on a BrukerꢀAMꢀ300 spectrometer, high
resolution spectra were obtained on a Bruker micrOTOF II inꢀ
strument. Compounds 5 and 21 were obtained according to the
described procedures.6,7

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(Nitroxyalkoxy)methoxyꢀ1ꢀtriazene 2ꢀoxides
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 2, February, 2014
489
3,3ꢀDialkylꢀ1ꢀhydroxyꢀ1ꢀtriazene 2ꢀoxide sodium salts (1—4)
(general procedure). Secondary amine (0.34 mmol), sodium
methoxide (0.35 mmol), diethyl ether (600 mL), and methanol
(90 mL) were placed into a 1ꢀL threeꢀneck flask equipped with
a stirrer and reflux condenser with a liquid seal and a gas inlet.
A flow of NO was passed through the mixture with vigorous
stirring at room temperature over 10—12 h at such a rate that the
gas excessive pressure was 13—20 Torr. A dense precipitate
formed was filtered off, washed with diethyl ether, dried first on
the filter, then in vacuo of an oil pump to obtain the correspondꢀ
ing sodium salts 1—4.
3ꢀEthylꢀ3ꢀmethylꢀ1ꢀ[(2ꢀnitroxyethoxy)methoxy]ꢀ1ꢀtriazene
2ꢀoxide (9), the yield was 36.2%. 1H NMR (CDCl3), : 1.15 (t, 3 H,
CH3CH2, J = 7 Hz); 3.0 (s, 3 H, CH3); 3.40 (q, 2 H, CH3CH2,
J = 7 Hz); 4.0 (t, 2 H, OCH2CH2ON, J = 4.5 Hz); 4.65 (t, 2 H,
OCH2CH2ON); 5.30 (s, 2 H, OCH2O). 14N NMR, : –44.83.
IR, /cm–1: 2978, 2942, 2897, 1633, 1500, 1282, 1026, 963.
HRMS, found: m/z 239.0995 [M + H]+; 256.1256 [M + NH4]+;
261.0810 [M + Na]+; 277.0547 [M + K]+. C6H14N4O6. Calcuꢀ
lated: 239.0992 [M + H]+; 256.1257 [M + NH4]+; 261.0811
[M + Na]+; 277.0550 [M + K]+.
3,3ꢀDiethylꢀ1ꢀ[(2ꢀnitroxyethoxy)methoxy]ꢀ1ꢀtriazene 2ꢀoxꢀ
ide (10), the yield was 23%. 1H NMR (CDCl3), : 1.2 (t, 6 H,
2 CH3CH2, J = 7 Hz); 3.4 (q, 4 H, 2 CH3CH2, J = 7 Hz); 4.0
(t, 2 H, OCH2CH2ON, J = 4.5 Hz); 4.7 (t, 2 H, OCH2CH2ON,
J = 4.5 Hz); 5.2 (s, 2 H, OCH2O). 14N NMR, : –44.27. IR,
/cm–1: 2981, 2941, 2897, 2881, 1634, 1512, 1282, 963. HRMS,
found: m/z 253.1154 [M + H]+; 275.0970 [M + Na]+; 291.0705
[M + K]+. C7H16N4O6. Calculated: 253.1148 [M + H]+;
275.0967 [M + Na]+; 291.0707 [M + K]+.
Salt 1 (see Ref. 8). The yield was 85%. 1H NMR (DMSOꢀd6),
: 2.71 (s, 6 H, 2 CH3). IR, /cm–1: 3439, 2975, 1608, 1462,
1448, 1385, 1370, 1231, 1198, 956, 945.
Salt 2. The yield was 78%. 1H NMR (DMSOꢀd6), : 0.86
(t, 3 H, CH3); 2.57 (s, 3 H, CH3); 2.76 (q, 2 H, CH2). IR, /cm–1
:
3439, 2975, 1608, 1462, 1448, 1385, 1370, 1246, 1231, 1198,
1179, 956, 945.
Salt 3 (see Ref. 9). The yield was 80%. 1H NMR (DMSOꢀd6),
: 0.88 (t, 6 H, 2 CH3); 2.76 (q, 4 H, 2 CH2). IR, /cm–1: 3442, 2983,
1606, 1465, 1448, 1385, 1370, 1249, 1233, 1198, 1183, 956, 945.
Salt 4 (see Ref. 10). The yield was 72%. 1H NMR (DMSOꢀd6),
1ꢀ[(2ꢀNitroxyethoxy)methoxy]ꢀ3,3ꢀtetramethyleneꢀ1ꢀtriꢀ
1
azene 2ꢀoxide (11), the yield was 51.3%. H NMR (CDCl3), :
2.0 (m, 4 H, 2 CH2); 3.60 (m, 4 H, 2 CH2N); 4.0 (t, 2 H,
OCH2CH2ON, J = 4.5 Hz); 4.65 (t, 2 H, OCH2CH2ON,
J = 4.5 Hz); 5.25 (s, 2 H, OCH2O). 14N NMR, : –44.49. IR,
/cm–1: 2963, 2886, 1633, 1486, 1281, 958. HRMS, found: m/z
251.0998 [M + H]+; 268.1259 [M + NH4]+; 273.0810 [M + Na]+;
289.0543 [M + K]+. C7H14N4O6. Calculated: 251.0992 [M + H]+;
268.1257 [M + NH4]+; 273.0811 [M + Na]+; 289.055 [M + K]+.
3,3ꢀDimethylꢀ1ꢀ[(3ꢀnitroxypropoxy)methoxy]ꢀ1ꢀtriazene
2ꢀoxide (12), the yield was 53%. 1H NMR (CDCl3), : 2.0 (t, 2 H,
CH2CH2CH2, J = 6.5 Hz); 3.1 (s, 6 H, CH3N); 3.8 (t, 2 H,
CH2OCH2O, J = 6 Hz); 4.55 (t, 2 H, CH2ON, J = 6 Hz); 5.25
(s, 2 H, OCH2O). 14N NMR, : –43; –55. HRMS, found: m/z
239.0095 [M + H]+; 261.0809 [M + Na]+. C6H14N4O6. Calcuꢀ
lated: 239.0992 [M + H]+; 261.0811 [M + Na]+.
3ꢀEthylꢀ3ꢀmethylꢀ1ꢀ[(3ꢀnitroxypropoxy)methoxy]ꢀ1ꢀtriazꢀ
ene 2ꢀoxide (13), the yield was 32%. 1H NMR (CDCl3), : 1.1
(t, 3 H, CH3CH2, J = 7 Hz); 2.0 (t, 2 H, CH2CH2CH2, J = 6 Hz);
2.9 (s, 6 H, CH3N); 3.3 (dd, 2 H, CH2N, J = 6 Hz); 3.85 (t, 2 H,
CH2CH2O, J = 6 Hz); 4.5 (t, 2 H, CH2ON, J = 6 Hz); 5.2 (s, 2 H,
OCH2O). IR, /cm–1: 2941, 1631, 1500, 1281. HRMS, found:
m/z 253.1173 [M + H]+; 275.0965 [M + Na]+. C7H16N4O6.
Calculated: 253.1148 [M + H]+; 275.0967 [M + Na]+.
: 3.06 (br.s, 4 H, 2 CH2); 1.78 (br.s, 4 H, 2 CH2). IR, /cm–1
:
2971, 2873, 1464, 1423, 1393, 1224, 1183, 985, 903.
Chloromethyl ethers 6, 7, and 19 (general procedure). A mixꢀ
ture of the corresponding alcohol (31 mmol), 36% aqueous formꢀ
aldehyde (16 mL), 35% aq. HCl (24 mL), and CH2Cl2 (24 mL)
was cooled to (–10)—(–5) C, followed by the in portions addition
of CaCl2 (30 g) over 1 h with stirring. The reaction mixture was
allowed to stand at –10 C for 3 h, the organic phase was separatꢀ
ed, remaining CaCl2 was washed with CH2Cl2, which then was
concentrated, the residue was distilled to obtain the products.
1ꢀChloromethoxyꢀ3ꢀnitroxypropane (6), the yield was 68%.
B.p. 80—85 C (10 Torr.). 1H NMR (CDCl3), : 2.1 (m, 2 H,
CH2CH2CH2, J = 6 Hz); 3.8 (t, 2 H, OCH2CH2, J = 6 Hz); 4.6
(t, 2 H, CH2ON, J = 6 Hz); 5.5 (s, 2 H, ClCH2O).
1ꢀChloromethoxyꢀ2ꢀnitroxypropane (7), the yield was 50%.
1H NMR (CDCl3), : 1.35 (d, 3 H, CH3); 3.60 (d, 2 H, OCH2C);
3.65 (m, 1 H, CH, 1J = 5 Hz, 2J = 6 Hz); 5.25 (s, 2 H, ClCH2O).
2ꢀBromoꢀ1ꢀ(chloromethoxy)propane (19), the yield was 70%.
1H NMR (CDCl3), : 1.75 (d, 3 H, CH3); 3.80 (d, 2 H, OCH2);
4.25 (m, 1 H, CH); 5.20 (s, 2 H, ClCH2O).
Alkylation of sodium salts 1—4 with chloromethyl ethers 5—7
(general procedure). Chloromethyl ether 5—7 (2 mmol) was addꢀ
ed in small portions to a suspension of sodium salt 1—4 (2 mmol)
in DMF (2 mL) at ~0 C over 30 min. After addition of the ether,
the reaction mixture was warmed up to room temperature and
allowed to stand for another 2.5 h. Then, it was poured into
water (30 mL) and extracted with dichloromethane (5×5 mL).
The combined extracts were washed with water (2×10 mL), dried
with sodium sulfate, the drying agent was filtered off, the filtrate
was concentrated in vacuo. The residue was subjected to chroꢀ
matography on silica gel to isolate the products.
1ꢀ[3ꢀ(Nitroxypropoxy)methoxy]ꢀ3,3ꢀtetramethyleneꢀ1ꢀtriꢀ
azene 2ꢀoxide (14), the yield was 42%. 1H NMR (CDCl3), : 1.8
(m, 6 H, CH2 + CH2CH2CH2, 1J = 6.5 Hz, 2J = 6 Hz); 3.5 (t, 4 H,
CH2N, J = 6 Hz); 3.75 (t, 2 H, CH2CH2O, J = 6.5 Hz); 4.5
(t, 2 H, CH2ON, J = 6.5 Hz); 5.3 (s, 2 H, OCH2O). 14N NMR,
: –42.57; –53.25. HRMS, found: m/z 265.1146 [M + H]+,
287.0966 [M + Na]+. C8H16N4O6. Calculated: 265.1148 [M + H]+;
287.0968 [M + Na]+.
3,3ꢀDimethylꢀ1ꢀ[(2ꢀnitroxypropoxy)methoxy]ꢀ1ꢀtriazene
1
2ꢀoxide (15). A. The yield was 40%. H NMR (CDCl3), : 1.35
3,3ꢀDimethylꢀ1ꢀ[(2ꢀnitroxyethoxy)methoxy]ꢀ1ꢀtriazene
2ꢀoxide (8), the yield was 46%. 1H NMR (CDCl3), : 3.05 (s, 6 H,
CH3); 4.0 (t, 2 H, OCH2CH2ON, J = 4.5 Hz); 4.6 (t, 2 H,
OCH2CH2ON); 5.3 (s, 2 H, OCH2O). 14N NMR, : –44.7. IR,
/cm–1: 2915, 2898, 1633, 1501, 1282, 1024, 970. HRMS, found:
m/z 225.0830 [M + H]+; 242.1091 [M + NH4]+; 247.0640
[M + Na]+; 263.0380 [M + K]+. C5H12N4O6. Calculated:
225.0835 [M + H]+; 242.1100 [M + NH4]+; 247.0654 [M + Na]+;
263.0393 [M + K]+.
(d, 3 H, CHCH3, J = 5 Hz); 3.0 (s, 6 H, CH3N); 3.75 (m, 2 H,
CH2CH2O, J = 6 Hz); 5.2 (s, 2 H, OCH2O); 5.25 (m, 1 H,
CH2CHCH3, J = 6 Hz). HRMS, found: m/z 239.0991 [M + H]+;
261.0808 [M + Na]+. C6H14N4O6. Calculated: 239.0992 [M + H]+;
261.0811 [M + Na]+. Found (%): C, 30.29; H, 5.97; N, 23.48.
C6H14N4O6. Calculated (%): C, 30.25; H, 5.92; N, 23.52.
B. A mixture of compound 20 (0.2 g, 0.7 mmol) and AgNO3
(0.15 g, 0.8 mmol) was refluxed in anhydrous MeCN (5 mL) for
3 h. The solvent was evaporated, the residue was diluted with

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CHCl3, a precipitate was filtered off, the filtrate was concentratꢀ
ed. The residue was subjected to chromatography on silica gel to
isolate product 15 in 71% yield, which was identical to the subꢀ
stance obtained above.
1ꢀ[(2ꢀNitroxypropoxy)methoxy]ꢀ3,3ꢀtetramethyleneꢀ1ꢀtriaꢀ
zene 2ꢀoxide (16), the yield was 35%. 1H NMR (CDCl3), : 1.35
(d, 3 H, CH3CH, J = 5 Hz); 1.90 (s, 4 H, CH2CH2); 3.50 (s, 4 H,
CH2N); 3.75 (m, 2 H, CHCH2O); 5.20 (m, 3 H, OCH2O); 5.25
(m, 3 H, CH2CHCH2, J = 6 Hz). HRMS, found: m/z 265.1146
[M + H]+; 287.0966 [M + Na]+. C8H16N4O6. Calculated:
265.1148 [M + H]+; 287.0968 [M + Na]+.
Disodium 3,7ꢀdimethylꢀ1,2,3,7,8,9ꢀhexaazanonaꢀ1,8ꢀdieneꢀ
1,9ꢀdiolate 2,8ꢀdioxide (17) (see Ref. 11). N1,N3ꢀDimethylꢀ1,3ꢀ
diaminopropane (4.09 g, 0.04 mol), sodium methoxide (4.32 g,
0.04 mol), diethyl ether (150 mL), and methanol (20 mL) were
placed into a threeꢀneck flask equipped with a stirrer, a reflux
condenser with a liquid seal and a gas inlet. A flow of NO was
passed with vigorous stirring at room temperature for 10—12 h at
such a rate that the gas excessive pressure was 13—20 Torr.
A dense precipitate formed was filtered off, washed with diethyl
ether, dried first on the filter, then in vacuo of an oil pump to
obtain the product 17 (8.8 g, 82%). 1H NMR (DMSOꢀd6),
: 1.21 (m, 2 H, CH2CH2CH2); 2.55 (s, 6 H, 2 CH3); 2.76 (m, 4 H,
CH2CH2CH2). IR, /cm–1: 3441, 2965, 1609, 1463, 1380, 1369,
1246, 1229, 957, 933.
tracts were washed with water (2×10 mL) and dried with sodium
sulfate. The drying agent was filtered off, the liquid was concentratꢀ
ed in vacuo, the residue was subjected to chromatography on silica
gel to isolate product 22 as an oil, the yield was 0.1 g (29%). 1H NMR
(CDCl3), : 3.1 (s, 6 H, CH3); 4.2 (d, 2 H, CH2, J = 5.6 Hz);
5.25 (m, 2 H, CH2); 5.3 (s, 2 H, OCH2O); 5.9 (m, 1 H, CH).
1ꢀ[(2,3ꢀDibromopropoxy)methoxy]ꢀ3,3ꢀdimethylꢀ1ꢀtriazene
2ꢀoxide (23). Bromine (0.7 g, 4.5 mmol, 0.22 mL) was added in
small portions to a solution of compound 22 (0.5 g, 2.8 mmol) in
dichloromethane (10 mL) with stirring at temperature below
0 C, and the mixture was allowed to stand at 10 C for 24 h, then
washed with saturated aqueous sodium thiosulfate, dried with
sodium sulfate, the drying agent was filtered off, the solvent was
evaporated. The residue was subjected to chromatography on
silica gel to isolate product 23 as an oil, the yield was 0.7 g (73%).
1H NMR (CDCl3), : 3.05 (s, 6 H, CH3); 3.8 (d, 2 H, OCH2CH,
J = 6.9 Hz); 4.1 (m, 2 H, BrCH2, 1J = 6.6 Hz, 2J = 4.6 Hz); 4.3
(m, 1 H, CH); 5.3 (dd, 2 H, OCH2O, 1J = 7.6 Hz, 2J = 4.0 Hz).
3,3ꢀDimethylꢀ1ꢀ[(2,3ꢀdinitroxypropoxy)methoxy]ꢀ1ꢀtriazene
2ꢀoxide (24). A mixture of compound 23 (0.7 g, 2.1 mmol), silver
nitrate (2.14 g, 12.6 mmol), and dry acetonitrile (10 mL) was
stirred at 60 C for 40 h without exposure to light. A precipitate
was filtered off, the solvent was evaporated in vacuo. The residue
was subjected to chromatography on silica gel to isolated prodꢀ
1
uct 24 as an oil, the yield was 0.3 g (48%). H NMR (CDCl3),
8,12ꢀDimethylꢀ1,19ꢀdinitroxyꢀ3,5,15,17ꢀtetraoxaꢀ6,7,
8,12,13,14ꢀhexaazanonadecaꢀ6,13ꢀdiene 7,13ꢀdioxide (18).
Chloromethyl ether 5 (4 mmol) was added in small portions to
a suspension of sodium salt 17 (2 mmol) in DMF (4 mL) at ~0 C
over 30 min. After the addition, the reaction mixture was warmed
up to room temperature and allowed to stand for another 2.5 h,
then poured into water (30 mL) and extracted with dichloroꢀ
methane (5×5 mL). The combined extracts were washed with
water (2×10 mL), dried with sodium sulfate, the drying agent
was filtered off, the filtrate was concentrated in vacuo. The resiꢀ
due was subjected to chromatography on silica gel to isolate
product 18 in 18% yield as an oil. 1H NMR (CDCl3), : 2.0 (m, 2 H,
CH2CH2CH2); 2.95 (s, 3 H, CH3); 3.05 (s, 3 H, CH3); 3.9 (t, 4 H,
2 CH2CH2CH2, J = 4.5 Hz); 4.2 (m, 4 H, 2 OCH2CH2ON); 4.6
(t, 4 H, 2 OCH2CH2ON, J = 3.6 Hz); 5.2 (s, 4 H, 2 OCH2O).
14N NMR, : –43.86. HRMS, found: m/z 461.1580 [M + H]+;
478.1844 [M + NH4]+; 483.1392 [M + Na]+; 499.1140 [M + K]+.
C11H24N8O12. Calculated: 461.1591 [M + H]+; 478.1857
[M + NH4]+; 483.1411 [M + Na]+; 499.1151 [M + K]+.
1ꢀ[(2ꢀBromopropoxy)methoxy]ꢀ3,3ꢀdimethylꢀ1ꢀtriazene
2ꢀoxide (20). Chloromethyl ether 19 (0.3 g, 1.6 mmol) was added
to a mixture of compound 1 (0.2 g, 1.6 mmol) in DMF (5 mL)
with stirring at room temperature. After 4 h, the mixture was
diluted with water (10 mL), extracted with dichloromethane
(3×5 mL), the extract was concentrated in vacuo. The residue
was subjected to chromatography on silica gel to isolate product
20 as an oil, the yield was 34%. 1H NMR (CDCl3), : 1.7 (d, 3 H,
CH3CH, J = 5 Hz); 3.15 (s, 6 H, 2 CH3); 3.85 (m, 2 H, CH2CH,
J = 5.5 Hz); 4.4 (m, 1 H, CH, 1J = 5 Hz, 2J = 5.5 Hz); 5.3
(s, 2 H, OCH2O).
: 3.2 (s, 6 H, CH3); 4.0 (d, 2 H, CH2); 4.75 (m, 2 H, CH2); 5.25
(s, 2 H, OCH2O); 5.45 (m, 1 H, CH). 14N NMR, : –47.9. 13
C
NMR, : 42.35 (CH3), 65.90 (OCH2), 68.97 (CH2ONO2), 77.29
(CH), 96.18 (OCH2O). IR, /cm–1: 2917, 1645, 1500, 1272,
972. HRMS, found: m/z 322.0610 [M + Na]+; 338.0341 [M + K]+.
C6H13N5O9. Calculated: 322.0611 [M + Na]+; 338.035 [M + K]+.
Found (%): C, 24.06; H, 4.33; N, 23.51. C6H13N5O9. Calculatꢀ
ed (%): C, 24.09; H, 4.38; N, 23.41.
References
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1ꢀAllyloxymethoxyꢀ3,3ꢀdimethylꢀ1ꢀtriazene 2ꢀoxide (22).
Chloromethyl ether 21 (0.21 g, 2 mmol) (see Ref. 7) was added
in small portions to a suspension of sodium salt 1 (0.25 g,
2 mmol) in DMF (2 mL) at ~0 C over 30 min. Then the reaction
mixture was warmedꢀup to room temperature and allowed to
stand for another 1.5 h, then poured into water (30 mL) and
extracted with dichloromethane (5×5 mL). The combined exꢀ
Received April 11, 2013;
in revised form September 25, 2013