Triazinines
J . Org. Chem., Vol. 62, No. 25, 1997 8665
tions for both chemical analysis and kinetic studies have been
reported.4-7 NMR spectra were obtained on a Varian XL-200
spectrometer. All samples submitted for exact mass determi-
nation were shown to be of >92% purity by 1H NMR analysis.
The major impurity in these samples was found to be the
corresponding azimine. Removal of final traces of this impu-
rity is extremely difficult due to the extreme sensitivity of
1-alkyltriazinines to hydrolytic decomposition.
addition of this cosolvent, however, permits the use of more
highly concentrated, and thus more easily analyzed, reaction
solutions. In a typical experiment, buffer plus acetonitrile-d3
was added to a weighed amount of the compound. The sample
was mixed thoroughly to ensure homogeneity, and 0.5 mL was
placed in a capped NMR tube. The reaction course was
followed7 until all of the starting triazinine had been decom-
posed. The initial triazinine concentration in each reaction
was 0.050 M. It was shown that after the triazinine was
completely decomposed, the pH had changed by no more than
(0.4 pH unit. Assignment of the NMR peaks arising from
the various products was made by comparison with authentic
samples and by coincidence of peaks upon the addition of
authentic materials. Yields were determined by comparative
integration of the product peaks. In the case of 1-benzyltri-
azinine, several products were confirmed by reports in the
literature.20,21
Kin etic Stu d ies. The method employed for the preparation
of the buffers used in these kinetic studies has been reported
previously.4-7 Rates of triazinine decomposition in aqueous
solution were followed spectrophotometrically.4-7 The reaction
solutions were contained in thermostated 1-cm cells, and the
temperature was held constant to within (0.1 °C. The
disappearance of each triazinine was followed by monitoring
the change in absorbance at its highest wavelength λmax (see
Experimental Section). In a typical kinetic run, the reaction
cuvette was charged with 1.341 mL of a 0.1 M lysine buffer
(ionic strength ) 0.25 M maintained with Na2SO4) and the
reaction was initiated by the addition of 9 µL of a 4.5 × 10-3
M solution of the 1-alkyltriazinine in acetonitrile; the initial
triazinine concentration was thus 3.0 × 10-5 M. The reference
cuvette contained 1.341 mL of buffer (the addition of 9 µL of
acetonitrile proved unnecessary). A minimum of 100 absor-
bance vs time readings were obtained over 3.5 half-lives. The
first-order rate constants were calculated from these data by
means of a computer program based on the Guggenheim
approximation least-squares method.22 The rate constants
were an average of at least two separate runs with standard
errors of less than 3%. In several cases, 100 absorbance vs
time readings were unable to be obtained; in those experiments
a minimum of at least three independent runs were used with
standard errors of less than 3%. Temperature studies were
performed in a similar fashion, using 1-cm thermostated cells
connected to a circulating waterbath maintaining constant
temperature to within (0.1 °C. Buffers used in these studies
were pH adjusted at the temperature at which a particular
rate was to be determined.
Because of the above-stated reactivity of 1-alkyltriazinines,
we determined that combustion analysis is not an appropriate
method of establishing purity or identity. An alternative
method, high-resolution mass spectrometric molecular formula
determination, was instead chosen. Exact mass measure-
ments were determined on either a VG 70-250 mass spectrom-
eter using a peak matching technique or on a ZAB-2F, using
fast atom bombardment (FAB) and peak matching. (See
Supporting Information for availability of these spectra.)
1-Eth yltr ia zin in e (1). To a 2.4 g (20 mmol) solution of
chloropropyl azide in 30 mL of dry THF was added, dropwise,
21 mmol of ethylmagnesium chloride under N2 at -30 °C. Over
the next 30-45 min the reaction warmed to -10 °C and was
hydrolyzed with 5 g of DOWEX (RG 501-X8, 20-50 mesh, fully
generated). The magnesium salt was precipitated with 30 mL
of diethyl ether and filtered, and the filtrate was concentrated
in vacuo. The yellowish oil was immediately diluted with 8.5
mL of isopropylamine and refrigerated overnight. The pre-
cipitate was filtered off and the filtrate concentrated. The
resultant oil was purified by column chromatography, using
basic Al2O3 eluted with (90:10) diethyl ether/isopropylamine
[Rf ) 0.7] to yield 735.9 mg (31%): UV (CH3CN) λmax 243 nm
1
(log ꢀ 3.90); H NMR (CDCl3, Me4Si) δ 1.25 (3H, t, J ) 7.21
Hz), 1.79 (2H, dt, J ) 5.84 Hz, J ) 6.60 Hz), 3.22 (2H, dt, J )
6.60 Hz, J ) 1.54 Hz), 3.47 (2H, dt, J ) 5.84 Hz, J ) 1.54 Hz),
3.61 (2H, q, J ) 7.21 Hz); proton-decoupled 13C NMR (CDCl3,
Me4Si) δ 13.0, 15.7, 43.3, 47.0, 50.9; exact mass calcd m/z for
M+, C5H11N3 113.0953, found 113.0977 (by EI).
P r ep a r a tion of Oth er Tr ia zin in es. The above reaction
procedure was used in the synthesis of each of the following
triazinines.
1-Bu tyltr ia zin in e (2) was obtained in 10% yield following
purification by column chromatography, using neutral alumina
eluted with (9:1:0.5) pentane/diethyl ether/isopropylamine [Rf
1
) 0.4]: UV (CH3CN) λmax 243 nm (log ꢀ 3.83); H NMR (500
MHz, CDCl3, Me4Si) δ 0.95 (3H, t, J ) 7.38 Hz), 1.37 (2H, m),
1.63 (2H, m), 1.79 (2H, dq, J ) 6.55 Hz, 5.87 Hz), 3.22 (2H, tt,
J ) 6.55 Hz, 1.51 Hz), 3.37 (2H, dt, J ) 5.87 Hz, 1.51 Hz),
3.56 (2H, t, 7.3 Hz); proton-decoupled 13C NMR (CDCl3, Me4-
Si) δ 13.8, 15.7, 19.8, 30.0, 44.0, 46.9, 56.2; exact mass calcd
m/z for MH+ C7H16N3 142.1344, found 142.1347 (by FAB).
1-Ben zyltr ia zin in e (3) was obtained in 47% yield following
purification by column chromatography, using neutral alumina
eluted with (9:1:0.5) pentane/diethyl ether/isopropylamine [Rf
) 0.3]: UV (CH3CN) λmax 244 nm (log ꢀ 4.02); 1H NMR (CDCl3,
Me4Si) δ 1.73 (2H, m), 3.11 (2H, tt, J ) 6.50 Hz, J ) 1.56 Hz),
3.48 (2H, tt, J ) 7.86 Hz, J ) 1.56 Hz), 4.77 (2H,s), 7.32 (5H,
m); proton-decoupled 13C NMR (CDCl3, Me4Si) δ 15.5, 43.3,
46.9, 60.3, 126.9, 127.9, 128.6, 136.9; mass calcd m/z for M+,
C10H13N3 175.1205, found 175.1109 (by EI).
Ack n ow led gm en t. Research sponsored by the Na-
tional Cancer Institute, DHHS, under contract with
A.B.L. and (R.H.S., in part) by grants from the National
Science Foundation (CHE-8521385 and CHE-8910890).
The contents of this publication do not necessarily
reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names,
commercial products, or organizations imply endorse-
ment by the U.S. Government. We are grateful to Mr.
J ohn Roman for providing mass spectrometry data, Mr.
J ohn Klose and Mrs. Mary McGuire for providing NMR
spectrometry data, and Ms. Lisa Taneyhill for assistance
with NMR data.
(3,3-Dieth oxyp r op yl)tr ia zin in e (4) was obtained in 47%
yield following purification by column chromatography, using
neutral alumina eluted with (7:5:0.5) pentane/diethyl ether/
isopropylamine [Rf ) 0.5]: UV (CH3CN) λmax 243 nm (log ꢀ
3.84); 1H NMR (CDCl3, Me4Si) δ 1.21 (3H, t, J ) 7.05 Hz),
1.79 (2H, dt, J ) 5.95 Hz, J ) 6.60 Hz), 2.0 (2H, dt, J ) 5.67
Hz, J ) 7.33 Hz), 3.23 (2H, tt, J ) 6.60 Hz, J ) 1.56 Hz), 3.47
(2H, tt, J ) 5.95 Hz, J ) 1.56 Hz), 3.58 (2H, q, J ) 7.05 Hz),
3.64 (2H, t, J ) 7.33 Hz), 4.58 (1H, t, J ) 5.59 Hz); proton-
decoupled 13C NMR (CDCl3, Me4Si) δ 15.3, 15.8, 32.4, 44.4,
47.1, 52.4, 61.6, 101.1; mass calcd m/z for MH+, C10H22N3O2
216.1712, found (relative intensity) 216 (by FAB).
P r od u ct Stu d ies. The products of hydrolytic decomposi-
tion were determined for 1-ethyl- and 1-benzyltriazinine by
carrying out reactions in solutions containing 25% (v/v) ac-
etonitrile-d3 dissolved in 0.05 M buffers of sodium phosphate
in D2O adjusted to the appropriate pH with a D2O solution of
NaOD. A previous study7 determined that the formation of
products was unaffected by the presence of acetonitrile. The
Su p p or tin g In for m a tion Ava ila ble: Supporting 1H NMR
and 13C NMR spectra (12 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O970721P
(20) Pouchert, C. J . and Campbell, J . R. Aromatic alcohols, mer-
captans, sulfides, amines, nitro and nitroso compounds In The Aldrich
Library of NMR Spectra, Aldrich Chemical Co., Inc., 1974; Vol. 5, pp
41, and 96.
(21) Saavedra, J . E. J . Org. Chem. 1985, 50, 2271-2273.
(22) Guggenheim, E. A. Philos. Magn. 1926, 2, 538-543.