Naked Fluoride Ion Sources
J. Am. Chem. Soc., Vol. 119, No. 1, 1997 113
spectrophotometer using the 488-nm exciting line of an Ar ion laser
or the 647.1-nm exciting line of a Kr ion laser, respectively.
Water contents were measured by the Karl Fischer method13 in
methanol which was dried over molecular sieves.
vacuum. After 4 days only 0.011 g of a yellow/white solid sublimate
was obtained, which in the 13C-NMR showed only traces of II.
Analytical Data for II. Mp: 80 °C; soluble in DMSO-d6, acetone-
d6, and benzene-d6. 13C{1H} NMR in benzene-d6 δ: 39.55 (s, CH3N,
two carbon atoms), 72.20 and 76.28 (s, NCH2N, four carbon atoms
each), 71.07 (s, NCH2N, two carbon atoms), 75.34 (s, NCH2N, one
bridging carbon atom).
Synthesis of 1-Methylhexamethylenetetramine Fluoride (I). Orig-
inally, this compound was prepared in a manner similar to that reported
by Clark and Nightingale,10 except for the following modifications. In
the metathesis reaction of 1-methylhexamethylenetetramine iodide and
AgF in aqueous solution, the AgF was used in a slight deficiency, the
AgI was filtered off, and the clear solution was titrated with a diluted
aqueous AgF solution until no further AgI precipitation was obtained.
While the water was being distilled off, there was no precipitation of
brown silver salts. The conversion to the 1-methylhexamethylenetet-
ramine fluoride dihydrate was quantitative. 1-Methylhexamethylene-
tetramine fluoride (1.79 g) was suspended in 5 mL of 2-propanol (H2O
< 0.03%) and stirred for 30 min. The solvent was removed at ambient
temperature under vacuum, and the residue was dried for 5 more h.
This process was repeated twice, and the white solid was pumped on
overnight. Azeotroping off the water was continued by using 10 mL
of 2-propanol with a water content of <0.005% (twice) and additional
evacuation overnight. The amount of water in the resulting product
was determined by Karl Fischer titration in methanol and resulted in
0.006 wt % () 60 ppm) of H2O.
1H NMR in benzene-d6: 1.71 (s), 3.24 (s), 3.42 (d), 3.83 (m), 4.06
(m).
Raman (cm-1, peaks with a rel intens <5% are not listed): 200
(m), 250 (s), 325 (w), 351 (m), 385 (w), 418 (s), 445 (s), 455 (s), 488
(m), 530 (w), 553 (vw), 610 (w), 640 (s), 730 (vs), 846 (w), 851 (s),
863 (w), 965 (vs), 991 (vw), 1025 (s), 1028 (m), 1039 (w), 1078 (w),
1098 (w), 1115 (w), 1140 (w), 1222 (m), 1310 (m), 1327 (m), 1380
(m) 1449 (s), 1464 (m), 1478 (m), 2785 (s), 2858 (s), 2869 (s), 2877
(s).
X-ray Structure Determination of II. Data were collected at room
temperature on a Siemens P4/RA diffractometer with Cu KR X-rays.
The structure was solved by direct methods and refined to final
agreement factor of R ) 3.6% and Rw ) 3.9% for 1339 reflections
with F > 4σ(F). Calculated hydrogen positions were included in the
structure analysis.
NMR: 1H NMR (D2O) δ 2.4 (s, NCH3), 4.3 (d.d, 3 × NCH2N), 4.6
(3 × NCH2N); 13C{1H} NMR (D2O) δ 43.2 (NCH3), 70.1 (3 ×
NCH2N), 80.1 (3 × NCH2N). In DMSO solution, anhydrous 1-meth-
ylhexamethylenetetramine fluoride was not detectable by 13C NMR
spectroscopy due to its limited solubility.
Results and Discussion
Synthesis of Anhydrous 1-Methylhexamethylenetetramine
Fluoride. In accord with the procedure of Clark et al.,10
1-methylhexamethylenetetramine iodide was converted into the
corresponding fluoride using AgF in an aqueous solution. To
achieve a complete conversion without having any impurities
of silver salts in our product, a titration with a diluted AgF
solution was used. The water removal by azeotroping off H2O
from an isopropyl alcohol solution under vacuum is based on
the method of Christe et al.3 and lowers the water content to 50
ppm, as shown by a Karl Fischer titration in methanol. In
contrast to the corresponding dihydrate,10 the anhydrous fluoride
is nearly insoluble in all common solvents. Only in DMSO
solution is the fluoride ion detectable by 19F NMR spectroscopy
as a very weak and broad signal at δ -101 ppm. In solvents
IR (cm-1, intens): 446.6 (w), 481.5 (w), 503.4 (vs), 588.4 (m), 651.0
(vs), 714.8 (m), 785.8 (s), 823.8 (vs), 849.6 (m), 959.3 (s), 994.4 (s),
1014.9 (s), 1044.7 (s), 1150.3 (m), 1244.3 (s), 3003.8 (vw).
Raman (cm-1, intens): 445 (s), 480 (s), 500 (m), 589 (m), 649 (m),
716 (vs), 790 (m), 827 (m), 961 (s), 998 (w), 1024 (w), 1151 (w),
1350 (w), 2980 (m).
One-Step Synthesis of 1-Methylhexamethylenetetramine Fluo-
ride. CH3NH2 was bubbled slowly into a tared 100 mL Teflon bottle,
containing 18 mL of CH3OH and a Teflon-coated stirring bar, while
the solution was cooled intermittently in an ice bath. To the resulting
methanolic solution of 3.647 g of CH3NH2 (117.4 mmol) were added
4.911 g of 48% HF (117.9 mmol), 57.192 g of 37.2% HCHO (707.5
mmol), and 24.916 g of 28% NH3 (409.6 mmol) sequentially (the NH4-
OH dropwise) as aqueous solutions. The resulting clear solution was
transferred to a 300 mL round-bottom flask, and volatiles were removed
on a rotary vacuum evaporator while keeping the temperature below
60 °C to obtain approximately 25 g of a slurry of crystals. Rapid
treatment with 13 25 mL portions of 2-propanol (0.04% H2O) on the
rotary evaporater produced 19.3 g of a solid product. Final azeotropic
water removal was accomplished using two 25 mL portions of
2-propanol (H2O < 0.005%), which was added to the solid in a drybox
and removed on a vacuum line. The resulting 15.135 g of dry product
contained 0.005 wt % H2O (Karl Fischer titration). Vibrational spectra
-
such as CH3CN, CH2Cl2, C2H5CN, DMF, and CH3Cl, the HF2
anion14 is the only product detectable by 19F NMR spectroscopy.
The IR spectrum of the anhydrous 1-methylhexamethylene-
tetramine fluoride agrees well with those given for correspond-
ing heavier halides.15 The spectra of the dry fluoride show
neither absorptions in the HOH stretching regions at about 3300
cm-1 nor absorptions in the HOH bending region at ca. 1700
cm-1
.
Direct Synthesis. The cocondensation of aqueous methyl-
amine, HF, ammonia, and formaldehyde resulted in the first
direct synthesis of a quarternized hexamethylenetetramine
fluoride (eq 2):
1
(IR and Raman) of the solid and H NMR in D2O solvent matched
those of 1-methylhexamethylenetetramine fluoride prepared by the
metathesis of 1-methylhexamethylenetetramine iodide and AgF but
indicated the presence of urotropine as an impurity. Extraction with
dry, ethanol-free chloroform was used to remove the urotropine,
resulting in an analytically pure product, identical to that obtained by
the multistep synthesis described above.
CH3NH2 + HF + 6CH2O + 3NH3 f
[CH3N4C6H12]+F- + 6H2O (2)
(I)
Synthesis of Bis(7-N-methyl[3.3.1]-1,3,5,7-tetraazanon-3-N-yl)-
methane (II). 1-Methylhexamethylenetetramine iodide (2.003 g) was
converted to the corresponding fluoride as described above. After most
of the water was distilled off in the rotatry evaporator at 70 °C, the
remaining thick oil was transferred to a sublimation apparatus. After
the formation of 0.12 g of clear and colorless crystals on the cooling
finger (yield ∼6%), no further sublimation was observed after 2 days
at 70 °C in a dynamic vacuum. The remaining residue was pure
This type of self-assembling reaction was previously re-
ported16 by Morgan and Curtis for the synthesis of 1-alkylhexa-
methylenetetramine perchlorates, fluoroborates, bromides, and
chlorides.
Using inexpensive starting materials, the synthesis can be
carried out in a one-pot reaction in aqueous solution. Further-
more, the process is readily scalable and was carried out on a
15 g scale without any problems. Urotropine is the only
detectable side product, but can be easily extracted with
1
1-methylhexamethylenetetramine fluoride, as shown by IR, H NMR,
and 19F NMR.
A sublimation experiment was repeated with 0.947 g of anhydrous
1-methylhexamethylenetetramine fluoride at 70 °C under a dynamic
(14) Christe, K. O.; Wilson,W. W. J. Fluorine Chem. 1990, 46, 339.
(15) Harmon K. M.; Keefer P. K. J. Mol. Struct. 1992, 270, 19.
(16) Morgan K. R.; Curtis N. F. Aust. J. Chem. 1980, 33, 1157.
(13) Scholz, E. Karl Fischer Titration, Methoden zur Wasserbestimmung;
Springer Verlag: Berlin, 1984.