Difluoroalkylamines from high temperature vapor phase reactions of nitrogen trifluoride with alkanes, ethers and benzene

Article abstract of DOI:10.1016/j.jfluchem.2011.07.024

At temperatures around 400 °C, nitrogen trifluoride (NF₃) readily reacts with alkanes and benzene as well as ethers. In all cases, products were N,N-difluoroamines. This is in contrast to difluoroamination of benzylic substrates where the initial N,N-difluoroamines underwent eliminations or rearrangements and were not isolated. Cyclic and acyclic alkanes generated N,N-difluoroaminoalkanes. Benzene substituted on the ring to form N,N-difluoroaniline. Ethers reacted to generate α-N,N-difluoroamino ethers. Little direct fluorination was observed.

Full text of DOI:10.1016/j.jfluchem.2011.07.024

Journal of Fluorine Chemistry 132 (2011) 961–964
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Difluoroalkylamines from high temperature vapor phase reactions of nitrogen
trifluoride with alkanes, ethers and benzene
Randolph K. Belter *
Y-Not Chemical Consulting, Zachary, LA, 70791, United States
A R T I C L E I N F O
A B S T R A C T
Article history:
At temperatures around 400 8C, nitrogen trifluoride (NF ) readily reacts with alkanes and benzene as
well as ethers. In all cases, products were N,N-difluoroamines. This is in contrast to difluoroamination of
3
Received 1 July 2011
Received in revised form 15 July 2011
Accepted 19 July 2011
Available online 26 July 2011
benzylic substrates where the initial N,N-difluoroamines underwent eliminations or rearrangements
and were not isolated. Cyclic and acyclic alkanes generated N,N-difluoroaminoalkanes. Benzene
substituted on the ring to form N,N-difluoroaniline. Ethers reacted to generate
ethers. Little direct fluorination was observed.
a-N,N-difluoroamino
Keywords:
ß 2011 Elsevier B.V. All rights reserved.
Nitrogen trifluoride
Alkyl substitution
Aromatic substitution
Radical abstraction
Difluoroalkylamines
1
. Introduction
positions are equivalent and selectivity should not be an issue. In
3
light of the results seen for the reaction of NF with benzylic
1.1. Organic reactions of nitrogen trifluoride
substrates, we expected an initial difluoroamination to 2, followed
by elimination and Beckmann rearrangement. After hydrolysis
We have previously shown that nitrogen trifluoride (NF
3
) can
during work-up, we expected to isolate e-caprolactam, 3, as the
be reacted in a controlled manner with benzylic substrates in a
00 8C vapor phase reactor [1]. Each substrate tested underwent
N,N-difluoroamination at the benzylic position. In every case, the
initial N,N-difluoroamine was unstable and converted to another
functionality. Specifically, toluene produced benzonitrile via HF
elimination. Ethylbenzene also produced benzonitrile, but via
principle product (Scheme 1). In fact, we expected lactams and
amides to be the products of all reactions with alkanes, cyclic and
acyclic respectively.
4
3
Gas chromatography of the crude cyclohexane + NF reaction
mixture immediately indicated that our suppositions were not
correct as the main product was of too short a retention time to be a
lactam. After isolation and NMR analysis the product was
Beckmann rearrangement. Cumene produced
a-methylstyrene via
HNF elimination. Diphenylmethane produced benzanilide, again
2
identified as N,N-difluoraminocyclohexane, 2! Compound 2
via Beckmann rearrangement. In addition, little or no direct
fluorination or radical dimerization was observed.
comprised 65% of GC observable products along with 15%
cyclohexene. Though difluoroamines were unstable intermediates
in the reactions of benzylic substrates at least one difluoroamine is
now a stable main product for an alkane.
To further investigate the scope of reactivity of nitrogen
3
trifluoride, we have now investigated NF reactions with acyclic
and cyclic aliphatic compounds, cyclic and acyclic ethers, and
benzene. The results contrast starkly with the results of reaction
with benzylic substrates and we report those results now.
The reaction sequence we envisioned in Scheme 1 has been
stopped short. For a Beckmann rearrangement to occur, an N,N-
difluoroamine must first eliminate HF to become an N-fluoroimine.
Clearly, this is not occurring and must be the result of the pKa of the
2
. Results and discussion
a
-proton not being of sufficient acidity to support an elimination.
For eliminations of -NF nitriles see references [2,3]. Elimination
a
2
2
.1. Reaction of NF with cyclic alkanes
3
did not occur under the high temperature, acidic conditions of
reaction, nor did it occur during the aqueous and basic (10% KOH)
work-up.
These results were duplicated with cyclopentane, 4, where
N,N-difluoroaminocyclopentane, 5, comprised 56% of products.
Interestingly, while some fluorocyclohexane was observed for the
The first substrate chosen for evaluation was cyclohexane, 1.
This compound would be expected to yield a single product as all
*
Tel.: +1 225 658 8792.
E-mail address: randolphbelter@gmail.com.
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.07.024

9
62
R.K. Belter / Journal of Fluorine Chemistry 132 (2011) 961–964
3
Scheme 1. Expected reaction of NF with cycloalkanes.
3
Scheme 2. Reaction of NF with n-pentane and n-hexane.
cyclohexane reaction, fluorocyclopentane was not observed in the
cyclopentane reaction.
3
2.2. Reaction of NF with acyclic alkanes
3
Scheme 4. Reaction of NF with diethyl ether.
Acyclic alkanes such as n-pentane and n-hexane produced a
mixture of the possible N,N-difluoramines as 60–75% of products.
The exact regioisomeric ratios have not been determined as two of
the isomers coincide on GC and H-NMR does not clearly
1
(Schemes 4). The compound 10 has been reported along with H
NMR spectra [7].
1
1
3
distinguish between those isomers.
C-NMR does show the
3
Under the NF reaction conditions, methyl t-butyl ether (MTBE)
19
existence of all 3 isomers for each substrate. The F NMR exhibits
one singlet at +55.9 ppm and overlapping quintets at +39.2 ppm.
NMR literature for 1-N,N-difluoroaminobutane [4] and 2-N,N-
difluoraminobutane [5] indicate a single resonance for each
produced both methanol and t-butyl fluoride. This product pair is
clearly the result of HF lysis. However, any HF had to come from
difluoroamination, but as no difluoroaminated products were
isolated or observed on GC, it is apparent that they are unstable.
(+54.6 ppm and +52.5 ppm respectively). Our spectra indicate
one isomer to have a single resonance while the other two behave
more like N-fluorodialkylamines [6], which show predictable F–H
splitting. While one may suspect that we have isolated N-
fluorodialkylamines, electrospray high resolution mass spectros-
copy indicates that the compounds are monoalkyl in nature. The
anomalous nature of these F spectra will be the subject of future
study, pending isolation of the individual isomers. Minor amounts
of fluoropentanes and fluorohexanes were observed, respectively
2.5. Reaction of NF
3
with benzene
Benzene readily reacted with NF
3
at 400–410 8C. N,N-difluor-
oaniline, 11, was accompanied by an almost equal amount (by GC)
of fluorobenzene, the two making up 79% of the observed products
(Scheme 5). These products were more difficult to separate from
the parent reactant (benzene) than the other difluoroalkylamines.
19
(
Scheme 2).
2.6. General reaction behavior
2
Isobutane (2-methylpropane) produced t-butyl-NF , 8, with
accompanying t-butyl fluoride when treated with NF
3
.
3
In contrast to the reactions of NF with benzylic substrates, the
reaction of aliphatics, ethers and benzene were not accompanied
by heavy by-products. In fact, the organic fraction of the product
stream was generally clear and only slightly colored. The HF layers
were generally dark, but lightened upon neutralization, depositing
only small amounts of dark insoluble material.
2
.3. Reaction of NF with a cyclic ether
3
The high temperature reaction of tetrahydrofuran with NF
3
was
surprisingly clean. The principle product (57% of GC) was the
a
-
substituted THF, 9 (Scheme 3). Though this compound might
appear susceptible to anomeric elimination, it is clearly stable and
isolated in the best yield of this study. Compound 9 is previously
The exotherm of reaction was much milder and more
controllable for these reactions, clearly because there were no
HF eliminations occurring. There were no pre-heater detonations
as were common for the benzylic substrates and higher
1
reported along with H NMR spectra [7]. Also known are bis- and
tetra-difluoramino substituted furans, which are used in rocket
propellants [8–13].
concentrations of NF
Conversions are low (ꢀ5%) versus the excess organic substrate.
Most NF passes through the reactor unused. Equilibrium
calculations show that NF only dissociates to one part per million
3
could be used.
3
2
.4. Reaction of NF
3
with an acyclic ether
3
at 400 8C [14], in which case, our observed reactivity is fairly good.
These reactions are, with all intent, uncatalysed. It is not yet
understood why these reactions, which exotherm in the front half
The reaction of diethyl ether was as clean as that of THF. Again,
the main product observed (87%) was a -substituted ether, 10
a
Scheme 3. Reaction of NF
3
with tetrahydrofuran.
3
Scheme 5. Reaction of NF with Benzene.

R.K. Belter / Journal of Fluorine Chemistry 132 (2011) 961–964
963
of the reactor, do not continue reacting through the rest of the
reactor bed. It is possible that the generation of HF may inhibit
downstream reaction. None-the-less, these conversions are
4.3. Spectral details
N,N-difluoroaminocyclohexane [2] clear, colorless liquid, b.p.
1
comparable to those attainable for vapor phase O
2
oxidations [15].
22 8C (ꢀ1 mmHg); H-NMR (250 MHz CDCl
1.67 (1H), 1.8–2.0 (5H), 3.34 (m, 1H); C-NMR (62 MHz
CDCl ): 24.0 (s), 25.5 (s), 26.8 (t, J = 7.2 Hz), 73.1 (t, J = 6.0 Hz);
F-NMR (235 MHz CDCl ): + 42.3 (s); IR 2958, 2866, 1446, 995,
3
/TMS): d 1.2–1.5 (6H),
1
3
d
d
d
3
d
3
. Conclusion
1
9
3
d
9
43, 920, 850; GC/MS 70 eV, m/z (rel. int.): 81(100).
N,N-difluoroaminocyclopentane [5] clear, colorless liquid, b.p.
3
At 400 8C, NF reacts with n-pentane, n-hexane, isobutane,
cyclopentane, cyclohexane, diethyl ether, tetrahydrofuran and
benzene to generate N,N-difluoroalkylamines. There is no reason
to believe that this reaction cannot be generalized to include all
volatile alkanes and cycloalkanes, ethers and cyclic ethers and
substituted benzenes that are stable to HF exposure and high
temperatures.
1
2
1
2
CDCl
7
0 8C (ꢀ1 mmHg); H-NMR (250 MHz CDCl
3
/TMS):
d
1.67 (m, 4H),
):
5.2 (s), 28.2 (t, J = 6.4 Hz), 75.6 (t, J = 5.6 Hz); F-NMR (235 MHz
): + 52.9 (s); IR 2958, 2864, 1446, 995, 938, 920, 850; GC/MS
1
3
.87 (m, 4H), 3.93 (tp, 1H, J = 29.6, 6.5); C-NMR (62 MHz CDCl
3
d
1
9
3
d
0 eV, m/z (rel. int.): 69 (100).
N,N-difluoroaminopentanes [6] clear, colorless liquid, b.p. 94–
It is the continuing goal of this project to find a means by which
1
9
5 8C (760 mmHg); H-NMR (250 MHz CDCl
3
/TMS):
d
0.9–1.1
3
waste NF can be utilized in a manner in which valuable products
(
(
3.7H), 1.21 (d, 2H, J = 6.5 Hz), 1.40 (m, 2.4H), 1.68 (mm, 2H), 3.17
tp, 0.22H, J = 26.2, 6.1 Hz), 3.42 (tm, 0.78H, J = 28.1 Hz);
might be generated. In this study, we have discovered a method for
the direct and continuous generation of N,N-difluoroamino
compounds. While conversions are low, yields are good and
products are readily isolated. The easy generation of these N,N-
difluoroamino compounds opens the possibility of attempting
further substitution of the nitrogen as well as other reactions and
we look forward to investigating those possibilities.
1
3
C-NMR (1-N,N-difluoroaminopentane) (62 MHz CDCl
3
): d
1
3.7 (s, C-5), 22.5 (s, C-4), 23.8 (t, J = 7.8 Hz, C-2), 29.1 (s, C-3), 66.2
(
t, J = 6.3 Hz, C-1);
1
3
C-NMR (2-N,N-difluoroaminopentane) (62 MHz CDCl
3
): d
1
4.0 (s, C-1), 13.2 (t, J = 10.0 = Hz, C-2), 21.2 (t, J = 6.6 Hz, C-1), 33.3
(
t, J = 6.8 Hz, C-3), 70.2 (t, J = 6.2 Hz, C-2);
1
3
C-NMR (3-N,N-difluoroaminopentane) (62 MHz CDCl
10.2 (s, C-5), 19.1 (s, C-4), 77.0 (t, J = 5.3 Hz, C-3);
3
): d
4
. Experimental
1
9
F-NMR (235 MHz CDCl
3
):
d
+ 55.9 (s),
d + 39.2 (p,
4.1. General
J = 579.3 Hz); IR 2958, 2875, 1462, 1370, 953, 860, 844, 810; GC/
MS 70 eV, m/z (rel. int.): 71(100), 55(40).
Benzene, cyclopentane, and methyl t-butyl ether were from
N,N-difluoroaminohexanes [7] clear, colorless liquid, b.p. 25–
1
Aldrich. Cyclohexane, diethyl ether, n-hexane, n-pentane and
tetrahydrofuran were from Aaper. Isobutane was from Bismar, Inc.
All substrates were used without further purification or drying.
Nitrogen trifluoride was from Fluoromar.
28 8C (ꢀ20 mmHg); H-NMR (250 MHz CDCl
3
/TMS): d 0.9–1.1
(3.7H), 1.25 (d, 1.9H, 1.7H, J = 5.6 Hz), 1.3–1.5 (m, 4.0H), 1.6-1.9
(mm, 1.7H), 3.30 (tp, 0.21H, J = 26.8, 6.0 Hz), 3.46 (tm, 0.79H,
1
3
3
J = 26.0 Hz); C-NMR (62 MHz CDCl ): d 10.3 (s), 13.3 (t, J = 9.9 Hz),
0
0
Reactions were performed in a single 1 (2.5 cm) diameter
14.0 (s), 14.1 (s), 14.2 (s), 19.4 (s), 21.8 (t, J = 8.4 Hz), 22.6 (s), 22.8
(s), 24.1 (t, J = 7.8 Hz), 26.6 (s), 27.9 (s), 30.3 (t, J = 7.8 Hz), 30.8 (t,
0
0
tubular reactor, 24 (61 cm) long, as described in our previous
publication [1]. A backpressure of 1 atm was maintained for each
reaction except for the isobutane reaction where the backpressure
of 3 atm was maintained. Product was collected through a cold
water condenser, washed with water to remove HF, neutralized
J = 6.9 Hz), 31.6 (s), 66.2 (t, J = 6.3 Hz, 1-NF
NF ), 75.7 (t, J = 5.4 Hz, 3-NF );
): d + 55.9 (s), +39.3 (p, J = 574.0 Hz);
2
), 70.4 (t, J = 6.3 Hz, 2-
2
1
2
9
F-NMR (235 MHz CDCl
3
IR 2958, 2939, 2866, 1462, 1379, 953, 855, 839, 810; GC/MS 70 eV,
with saturated NaHCO
3
and dried over Na
2
SO
4
. Unreacted starting
m/z (rel. int.): 85(100), 57(70).
material and product fractions were separated by vacuum
fractional distillation.
Products were identified by H and C and F NMR performed
on a Bruker DPX-250. MS was performed on an Agilent 6210 Time-
of–Flight spectrometer.
2-N,N-difluoroamino-2-methylpropane [8] clear, colorless liq-
1
uid, b.p. 25 8C (ꢀ260 mmHg); H-NMR (250 MHz CDCl
3
/TMS): d
22.8 (t, J = 7.2 Hz), 69.6 (t,
1
13
19
13
1.25 (s, 9H); C-NMR (62 MHz CDCl
3
):
):
d
1
9
J = 7.3 Hz); F-NMR (235 MHz CDCl
3
d
+ 28.3 (s); IR 2958, 2875,
1462, 1370, 953, 860; GC/MS 70 eV, m/z (rel. int.): 194 (100), 179
100), 164 (72), 149 (25), 119 (18), 91 (34), 77 (22).
-N,N-difluoroaminotetrahydrofuran [9] clear, colorless liquid,
(
4.2. Cautionary notes
a
1
b.p. 39 8C (ꢀ60 mmHg); H-NMR (250 MHz CDCl
3
/TMS): d 2.00 (m,
Nitrogen trifluoride is toxic by inhalation and should only be
2H), 1.19 (m, 2H), 4.05 (m, 2H), 5.01 (ddt, 1H, J = 23.5, 18.9, 4.6);
1
3
used in a well ventilated environment. It is apparent to us that the
N,N-difluoroamino products are toxic as well. In addition, trace by-
products may be toxic and concentrated during distillation. The
benzene reaction had particularly noxious light by-products.
C-NMR (62 MHz CDCl
100.0 (t, J = 10.3 Hz);
3
):
d
24.0 (s), 27.7 (t, J = 4.6 Hz), 70.7 (s),
1
9
F-NMR (235 MHz CDCl ): + 31.9 (d,
3
d
J = 66.5 Hz); IR 2975, 2865, 1726, 1461, 1184, 1070, 1032, 912, 865;
GC/MS 70 eV, m/z (rel. int.): 82 (65), 71 (100), 42 (100).
NF
outside the explosivity limits of the NF
advisable that all metal surfaces be fluoride passivated. In our
previous study where the NF ratio exceeded 50 mol% and/or
reactor inlet temperatures rose much beyond the boiling point of
the substrate detonations were observed in the preheater system
3
is an oxidant and care must be taken to ensure operations
a-N,N-difluoroaminodiethylether [10] clear, colorless liquid,
1
3
/hydrocarbon mixture. It is
b.p. 13 8C (ꢀ30 mmHg); H-NMR (250 MHz CDCl
3
/TMS): d 1.24 (t,
3H, J = 7.0 Hz), 1.40 (dm, 3H, J = 5.9), 3.72 (dt, 1H, J = 8.2, 7.1), 3.99
1
3
3
(dt, 1H, J = 8.2, 7.1), 4.58 (dq, 1H, J = 18.5, 5.9); C-NMR (62 MHz
19
CDCl
3
):
d
14.8 (t, J = 7.9 Hz), 15.3, 67.8, 97.5 (t, J = 9.4 Hz); F-NMR
): + 26.5 (q, J = 523.9 Hz); IR 2984, 2941, 1446,
(235 MHz CDCl
3
d
[
16].
Anhydrous HF is a by-product of these reactions. Anhydrous HF
1382, 1336, 1182, 1149, 1099, 1051, 952, 865; IR 2975, 2865, 1726,
1461, 1184, 1070, 1032, 912, 865; GC/MS 70 eV, m/z (rel. int.): 80
(65), 73 (100), 61 (21).
causes instantaneous severe burns to the skin and mucous
membranes. HF should be handled with full PPE protection. An
ample supply of HF antidote gel should be kept on hand before
handling HF. See the reference for burn treatment procedures [17].
N,N-difluoroaminobenzene [11] clear, colorless liquid, b.p. 25 8C
1
(60 mmHg); H-NMR(250 MHzCDCl
3
/TMS):
d
7.50(m,3H,J = 6.9 Hz),
1
3
7.70 (d, 2H, J = 7.2); C-NMR (62 MHz CDCl
3
): d 125.4 (q, J = 3.7 Hz),

9
64
R.K. Belter / Journal of Fluorine Chemistry 132 (2011) 961–964
1
9
[8] K. Baum, J. Am. Chem. Soc. 90 (1968) 7083.
9] A.J. Passannante, J.R. Lovett, P.A. Argabright, US Patent 3,347,872 (1967).
10] R.J. Leary, US Patent 3,347,873 (1967).
1
1
28.6, 128.9, 140.0; F-NMR (235 MHz CDCl
3
):
d
ꢁ63.2; IR 3036,
[
480, 1036, 860, 673, GC/MS 70 eV, m/z (rel. int.): 77 (100).
[
[11] J.R. Michael, R.J. Leary, P.A. Argabright, A.J. Passannante, US Patent 3,346,599
(1967).
References
[
[
[
[
12] P.A. Argabright, US Patent 3,350,414 (1967).
13] H. Bieber, H.M. Yaylor, L. Spenadel, US Patent 3,376,318 (1968).
14] A.J. Woytek, J.T. Lileck, J.A. Barkanic, Solid State Technol. (1994) 172.
15] P.J. Chenier, Survey of Industrial Chemistry, 2nd ed., Wiley-VCH, New York, 1992,
p. 202.
[
[
[
[
[
[
[
1] R.K. Belter, J. Fluorine Chem. 132 (2011) 318.
2] A.L. Logothetis, G.N. Sausen, J. Org. Chem. 31 (1966) 3689.
3] H.M. Marsden, J.M. Shreeve, Inorg. Chem. 26 (1987) 169.
4] R.C. Petry, J. Am. Chem. Soc. 89 (1967) 4600.
5] C.L. Bumgardner, Tetrahedron Lett. 48 (1964) 3683.
6] O.D. Gupta, R.L. Kirchmeier, J.M. Shreeve, J. Am. Chem. Soc. 112 (1990) 2383.
7] M.J. Cziesla, K.F. Mueller, O. Jones, Tetrahedron Lett. 8 (1966) 813.
[
16] For details of NCl
2002) 241.
17] D. Peters, R. Methchen, J. Fluorine Chem. 79 (1996) 161.
3
flame, see: N. Rubtsov, V. Kotelkin, Mendeleev Commun. 12
(
[