A New Preparation of gem-bis(Difluoramino)-alkanes via Direct Fluorination of Geminal Bisacetamides

Article abstract of DOI:10.1081/SCC-120026361

A fundamentally new preparation of internal and terminal gem-bis-(diflouramino)alkanes has been demonstrated by the direct flourination of corresponding gem-bisacetamides, specifically, 1,1-bisacetamidocyclohexane and 1,1-bisacetamidopropane, leading to 1,1-bis(diflouramino)cyclohexane and 1,1-bis(diflouramino)-propane, respectively.

Full text of DOI:10.1081/SCC-120026361

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A New Preparation of gem -bis(Difluoramino)- alkanes
via Direct Fluorination of Geminal Bisacetamides
Robert D. Chapman a , Matthew C. Davis a & Richard Gilardi b
a Research Department (Code 4T4200D) , Naval Air Warfare Center Weapons Division , Naval
Air Systems Command , China Lake, California, USA
b Laboratory for the Structure of Matter (Code 6030) , Naval Research Laboratory ,
Washington, DC, USA
Published online: 16 Aug 2006.
To cite this article: Robert D. Chapman , Matthew C. Davis & Richard Gilardi (2003) A New Preparation of gem -
bis(Difluoramino)- alkanes via Direct Fluorination of Geminal Bisacetamides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 33:23, 4173-4184, DOI: 10.1081/SCC-120026361
To link to this article: http://dx.doi.org/10.1081/SCC-120026361
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 23, pp. 4173–4184, 2003
A New Preparation of gem-bis(Difluoramino)-
alkanes via Direct Fluorination of
Geminal Bisacetamides
1
Robert D. Chapman,1, Matthew C. Davis,
*
and Richard Gilardi2
1Research Department (Code 4T4200D), Naval Air
Warfare Center Weapons Division, Naval Air Systems
Command, China Lake, California, USA
2Laboratory for the Structure of Matter (Code 6030),
Naval Research Laboratory, Washington, DC, USA
ABSTRACT
A fundamentally new preparation of internal and terminal gem-bis-
(difluoramino)alkanes has been demonstrated by the direct
fluorination of corresponding gem-bisacetamides, specifically,
1,1-bisacetamidocyclohexane and 1,1-bisacetamidopropane, leading
to 1,1-bis(difluoramino)cyclohexane and 1,1-bis(difluoramino)-
propane, respectively.
*Correspondence: Robert D. Chapman, Research Department (Code 4T4200D),
Naval Air Warfare Center Weapons Division, Naval Air Systems Command,
China Lake, CA 93555, USA; Fax: (þ1) 760-939-1617; E-mail: robert.chapman@
navy.mil.
4173
DOI: 10.1081/SCC-120026361
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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4174
Chapman, Davis, and Gilardi
Key Words: Difluoramines; Geminal bisacetamides; Fluorination.
There has recently been a resurgence of interest in the class of
(difluoramino)alkane derivatives due to the prospect of preparing
gem-bis(difluoramino)-substituted analogs of conventional cyclic
nitramines.[1] For example, this interest has prompted the development
of a new route to alkyl fluoramines and difluoramines by electrophilic
fluorination of nucleophilic primary and secondary amines with an NꢀF
fluorinating agent (SelectfluorTM).[2] Also, the utility of trityldifluoramine
(Ph3CNF2)—a known source of difluoramine via acidic hydrolysis[3]—for
effecting in situ difluoramination of ketones[4] has been recently
rediscovered.[5] The latter system invokes the mechanism of difluoramine
alkylation by carbenium ions generated in strong acids, as traditionally
employed in conventional difluoraminations of ketones with added
difluoramine.[6] Trityldifluoramine as an indirect difluoramine source
suffers an economic disadvantage of a preparation requiring the radical
reaction of trityl chloride with N2F4, itself prepared via oxidation of
difluoramine.[7]
Conventional difluoramination of ketones has heretofore been the
only practical preparation of gem-bis(difluoramino)alkane derivatives,
but it has suffered some disadvantages with respect to the recent applica-
tions of interest. Although the historical hazards of handling difluoramine
in such reactions[8] have been mitigated by improvements in experimental
methodology,[9] the successful difluoramination of b,b0-diaminoketones—
i.e., cyclic derivatives of 1,3-diaminoacetone—to b,b-bis-(difluoramino)-
substituted nitrogenous heterocycles requires relatively exotic
N-protection of heterocyclic nitrogens—e.g., by 4-nitrobenzenesulfonyl
(nosyl)—in order to allow generation of the requisite b-carbenium ion in
preference to simple N-protonation.[9] Suitable N-protecting groups for
this transformation tend to result in particularly difficult nitrolytic depro-
tection to make corresponding nitramines.[10] A superior method leading
to gem-bis(difluoramino)alkanes that obviates alkylation of difluoramine
by heterocyclic carbenium ions is therefore needed.
Our premise for such an alternative method involves the direct
fluorination of protected aminals, especially ketoaminals which would
be the basis of internal gem-bis(difluoramino)alkanes. A model for this
transformation was recognized in another electrophilic substitution of
protected aminals: namely, the nitrolysis of variously N-protected hexa-
hydro-1,3,5-triazines, reported by Gilbert et al.[11] In this system, simple
acyl-protected hexahydrotriazines were efficiently nitrolyzed: triacetyl

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New Preparation of gem-bis(Difluoramino)alkanes
4175
and tripropionyl derivatives in 80–95% yield by HNO3–P2O5, 80–98%
yield by HNO3–(CF3CO)2O. In contrast, carbamate derivatives
(trialkyl hexahydro-1,3,5-triazine-1,3,5-tricarboxylates), electronegatively
substituted acyl derivatives—e.g., 1,3,5-tris(2-chloroacetyl)hexahydro-
triazine—and derivatives with protecting groups subject to electrophilic
attack themselves (1,3,5-triacryloylihexahydrotriazine) showed no
conversion to the corresponding nitramine (RDX).
Our initial attempt to effect electrophilic deprotection of a geminal
biscarbamate was consistent with the similar finding of Gilbert et al.[11]
our direct fluorination (F2/N2) of diethyl cyclohexylidene biscarbamate
resulted only in cleavage of the aminal linkage rather than fluorinolysis
of the carbamate substituents.[12] Although geminal bisacylamides then
appeared to offer the best prospect of a protected aminal amenable to
electrophilic fluorinolysis to difluoramines, there was no general
method to prepare that class of ketoaminal, so we developed potentially
general methodology to produce such derivatives.[13] This method
provided 1,1-bisacetamidocyclohexane (1) as a model compound
expected to lead to a ‘‘typical’’ internal gem-bis(difluoramino)alkane,
1,1-bis(difluoramino)cyclohexane.
We have now confirmed that simple fluorination (5–20 vol% F2/N2)
of 1 under a variety of mild conditions proceeds via 1-acetamido-1-
(difluoramino)cyclohexane (2) to the desired 1,1-bis(difluoramino)cyclo-
hexane (3), although the latter stages of fluorination are complicated by
competing side reactions, as shown in Sch. 1.
The fluorination of 1 in acetonitrile solvent was generally conducted
at low temperature (ꢁꢀ40ꢂC). The presence or absence of various
Brønsted bases (NaF, KF, K2CO3) generally did not affect the course
or product distribution of the reaction. The first stage of fluorinolysis of 1
showed concomitant generation of acetyl fluoride, as expected, as well as
its subsequent fluorination to 2-fluoroacetyl fluoride and 2,2-difluoroace-
1
tyl fluoride, according to comparison to published H and 19F NMR
data.[14] Intermediate 2 could be isolated by workup after monitoring
aliquots of the mixture (1H, 19F NMR) for its formation, but isolation
of 2 was not necessary to carry it on to 3.
Crystals of 2 suitable for X-ray diffraction were obtained by
crystallization from n-pentane–chloroform. The X-ray analysis results[15]
completely corroborated the expected structure and provided another
accurate determination of the geometry of the NF2 group, which is
consistently found to be extremely pyramidal in both aromatic[16]
and aliphatic[10,17,18] situations. The bond angles in 2 (Fig. 1) are
CꢀNꢀF(1A) ¼ 105.6(2)ꢂ,CꢀNꢀF(1B) ¼ 105.2(2)ꢂ,andFꢀNꢀF¼ 99.8(1)ꢂ,
all significantly less than ‘‘tetrahedral’’ (109.5ꢂ). The corresponding

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4176
Chapman, Davis, and Gilardi
Scheme 1.
Figure 1. A drawing of 1-acetamido-l-(difluoramino)cyclohexane (2) as it occurs
in the crystalline state. The difluoramino group is equatorial and the acetamido
group is axial to the cyclohexane ring.

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New Preparation of gem-bis(Difluoramino)alkanes
4177
averages for all fifteen previously published NF2 geometries[18] are
<CꢀNꢀF>¼ 105.2(7)ꢂ and <FꢀNꢀF>¼ 100.4(8)ꢂ.
Continued fluorination of 2 produced two major products based on
the cyclohexane skeleton: 3 is formed, probably via 1-(difluoramino)-
1-(N-fluoroacetamido)cyclohexane (4), a minor intermediate apparent
by 19F NMR during the course of the reaction; and, by elimination of
N-fluoroacetamide from 2, N-fluorocyclohexylimine (5) and, to a minor
extent, similar, substituted derivatives (6) are formed, identified by
comparison to literature 19F NMR data.[19] The elimination of N-fluoro-
acetamide, via aminal cleavage of 2, is apparent by the formation of N,N-
difluoroacetamide.
We confirmed the identity of N,N-difluoroacetamide by simple direct
fluorination of acetamide. Although other researchers[20] have reported
difficulty in its preparation by this method,[21] we observed an interesting
course of reaction by fluorinating acetamide in acetonitrile (5% F2/N2,
ꢀ40ꢂC) in the presence of NaF (Sch. 2).
The initial product is unfluorinated N,N0-diacetylhydrazine—by
comparison to literature data[22]—which undergoes fluorination to
N,N-difluoroacetamide and HF by-product, a mixture that is observed
subsequently to degrade to acetyl fluoride and difluoramine, as previously
reported.[20] This behavior of coupling by the carbamoyl group of
acetamide is analogous to that reported for urea by Glemser and
Ludemann,[23] forming hydrazodicarbonamide from fluorination (1:2
F2/N2) of urea in a temperature range of ꢀ30ꢂC to r.t. This course of
fluorination of a primary amide is distinctly different from that of
secondary amides, which proceed simply to N-alkyl-N-fluoroamides
and alkyldifluoramines.[24]
In Sch. 1, another minor side reaction that is apparent by 19F NMR
is the fluorination of the acetyl protecting group remaining in 4. This
reaction leaves the N-(2-fluoroacetyl) group unamenable to fluorinolysis
under mild conditions, a result also consistent with the observations
of Gilbert et al.[11] about the lack of reactivity of electronegatively
substituted protecting groups (e.g., 2-chloroacetyl) toward nitrolytic
deprotection.
Scheme 2.

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4178
Chapman, Davis, and Gilardi
The yield of 1,1-bis(difluoramino)cyclohexane (3) observed in our
runs of the Sch. 1 reaction appears to maximize at ꢁ10%, measured
via an internal standard for quantitative integration of the NF region
of 19F NMR and confirmed by isolation of 3 by removal of solvent as the
low-boiling n-pentane–acetonitrile azeotrope (ꢁ31ꢂC) followed by
purification by chromatography. It should be recognized, however, that
conventional difluoramination of cyclohexanone also produces an
atypically low yield of 3 (31%) compared to other ketones; thus, in
contrast, conventional difluoramination of even 1,4-cyclohexanedione
produces a yield of 1,1,4,4-tetrakis(difluoramino)cyclohexane of 75%.[6a]
Another anomalous property of 3 is the chemical shift of NF2 in its
19F NMR spectrum: a reported ꢀ 22.79[6a] and our measurement of
ꢀ 22.61 (CFC13 solvent) put it far upfield of all other ‘‘typical’’ internal
gem-bis(difluoramino)alkane derivatives, which are predominantly in the
range of ꢀ 26–30.[25] This property as well as the low yield of 3 by
conventional difluoramination may suggest unusual electronic or steric
effects in 3 (and perhaps in 2) that contribute to the susceptibility of
cyclohexylidene aminals to the side reactions that occur, as in Sch. 1.
Although terminal gem-bis(difluoramino)alkanes are of less interest
for practical applications, the fluorination of terminal gem-bisaceta-
mides—aldoaminals readily prepared from aldehydes plus amides[26]
—
proceeds more efficiently than that of 1. Thus, fluorination (5% F2/N2) of
1,1-bisacetamidopropane at ꢁꢀ40ꢂC in acetonitrile (no added base)
proceeds, via 1-acetamido-1-(difluoramino)propane, to 1,1-bis(difluora-
mino)propane in ꢁ45 min with ꢁ40% yield according to 19F NMR anal-
ysis—closer to a yield of 65% obtained by conventional difluoramination
of propionaldehyde.[6a]
In conclusion, we have demonstrated the technical feasibility of the
first fundamentally new preparation of gem-bis(difluoramino)alkanes
since conventional difluoramination of ketones: namely, via direct
fluorination of suitable gem-bisacylamides. The cyclohexylidene system
may not be an ideal model for this transformation, in hindsight, due to
unusual aspects of its spectral and chemical properties, summarized
above. b,b-Bisacylamides of suitably N-protected heterocycles should
be less susceptible to aminal cleavage than the simple cyclohexylidene
system. Other technical modifications are apparent that should provide
improved behavior of the protected aminal system. For example, gem-
bispropionamides formed from corresponding ketones should still be
amenable to fluorinolysis even following competitive terminal fluori-
nation of the propionyl protecting group. This new methodology
would eliminate a requirement for expensive N-protecting groups in
order to prepare products based on 1,3-diaminoacetone derivatives,

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New Preparation of gem-bis(Difluoramino)alkanes
4179
since alkylation of difluoramine via heterocyclic carbenium ions is
obviated. (The N-protecting groups in such systems need not be as
exotic as nosyl, merely removable by nitrolysis and less readily displaced
than simple N-acyl, e.g., methanesulfonyl.) Of course, a requirement for
difluoramine generation (even in situ) is also avoided.
EXPERIMENTAL
Reagents were commercially available and used as received.
Multinuclear NMR spectra were obtained on a Bruker AC-200 spectrom-
eter (200 MHz 1H) and referenced to solvent or tetramethylsilane.
Microanalysis was performed by Galbraith Laboratories (Knoxville, TN).
Typical Experimental Procedure
1-Acetamido-1-(difluoramino)cyclohexane, 2. To a magnetically-
stirred solution of 1.02 g (5.14 mmol) of 1[13] in 100 mL CH3CN–CFC13
(1:1) in a 2-neck round-bottom flask was added 2.16 g anhydrous
NaF (51.4 mmol). The flask was cooled in a dry ice–CH3CN bath
(ꢁꢀ40ꢂC) while a fluorine mixture (20 vol% F2 in N2) was very slowly
bubbled through the reaction solution via ‘‘spaghetti’’ fluoropolymer
tubing. After 4 h, no starting material remained, according to GC-MS
analysis. Then N2 was bubbled through the mixture briefly, and the reac-
tion mixture was filtered through Celite 521. The filtrate was evaporated at
r.t. to obtain a yellow oil that slowly solidified. This was dry-column
chromatographed (silica; CHCl3; Rf ¼ 0.4) with fractions analyzed by
19F NMR to obtain the title compound as a white solid; yield 0.25 g
(25%). The solid recrystallized from n-pentane–chloroform as colorless
needles. M.p.: 95–110ꢂC (dec). H NMR (CDC13) ꢀ 1.22–1.55 (m, 3H),
1
1.62–1.85 (m, 5H), 2.08 (s, 3H), 2.35–2.55 (m, 2H), 5.43 (bs, 1H). 13C NMR
3
(CDC13) ꢀ 21.79, 24.93, 25.07, 30.31 (t, JCF ¼ 3.95 Hz), 84.69 (t,
2JCF ¼ 7.75 Hz), 170.61. 19F NMR (<5% CDCl3 in CFCl3) ꢀ 21.53.
(CDCl3) ꢀ 22.47. (CD3CN) ꢀ 23.54. (CD3CN, 70ꢂC) ꢀ 23.49. IR (KBr):
ꢁ(NF2) 841.5 cmꢀ1. Analysis calcd. for C8H14N2F2Oꢃ0.11H2O: C, 49.47;
H, 7.38; N, 14.42. Found: C, 49.53; H, 7.44; N, 14.24. EIMS: m/z 140
(Mþ ꢀ NF2), 98 (140 – C2H2O), 81 (140 – H2NAc).
1,1-bis(Difluoramino)cyclohexane, 3. Fluorine in nitrogen (20 vol%)
was diluted with a threefold excess flow of N2 and slowly bubbled through
a cooled (ꢁꢀ40ꢂC), magnetically stirred solution of 0.10 g (0.50 mmol) of 1

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4180
Chapman, Davis, and Gilardi
in 9 mL CD3CN in
a
25 mL 2-neck pear-shaped flask which
contained 0.10 g dry KF. After 30 min, an aliquot was withdrawn, and
1H NMR showed intermediate 2 still present. Apparent by 19F NMR
at this stage were minor amounts of intermediate 1-(difluoramino)-1-
(N-fluoroacetamido)cyclohexane (4) and side product 1-(difluoramino)-
1-(2,N-difluoroacetamido)cyclohexane. Fluorination of the reaction
solution was continued for a total of 1 h, when 1H NMR showed no resi-
dual 2. The content of 3 was quantified by integration of the 19F NMR
signal of 3 vs. that of 3,3,7,7-tetrakis(difluoramino)octahydro-1,5-dinitro-
1,5-diazocine (HNFX) in a solution made from measured quantities of
HNFX stock solution and of reaction solution. Yields of 3 were typically
8–10% at the time of consumption of intermediate 2. Product 3 could be
isolated by adding excess n-pentane to distill off acetonitrile as a low-boil-
ing azeotrope (ꢁ31ꢂC). The pot residue was dissolved in a minimum
volume of CCl4 and chromatographed (silica gel/pentane); fractions
were monitored by 19F NMR. Excess pentane was easily distilled from
higher-boiling 3. 1H NMR of 3 (CD3CN) ꢀ 1.5–1.9 (m), 2.08 (t).
13C NMR (CD3CN) ꢀ 21.5, 25.0, 27.0, 96.8. 19F NMR (1 : 10 CDCl3–
CFCl3) ꢀ 22.61; (CH2Cl2–CDCl3) ꢀ 23.22. (CD3CN) ꢀ 23.56. (CD3CN,
70ꢂC) ꢀ 24.11.
1-(Difluoramino)-1-(N-fluoroacetamido)cyclohexane, 4, and 1-
(difluoramino)-1-(2,N-difluoroacetamido)cyclohexane. Bisacetamide
1
was fluorinated similarly to the example above, but with NaF instead of
KF. After 1 h, no residual intermediate 2 was apparent. Solid NaHCO3
was added to the mixture, which was stirred at r.t. overnight. Volatiles,
including some of product 3 and of N-fluorocyclohexylimine (5), were
removed by rotary evaporation at reduced pressure. The residue was
eluted through silica gel with chloroform, and the combined eluates
were rechromatographed (silica gel–chloroform, eluted successively with
n-pentane and dichloromethane). The final fraction, containing the
title compounds, was concentrated to dryness by rotary evaporation.
1-(Difluoramino)-1-(N-fluoroacetamido)cyclohexane
4
(4):
1H NMR
(CDCl3) ꢀ 1.52–1.94 (m), 2.29 (d, JHF ¼ 9.8 Hz), 2.69 (b), 2.75 (b).
4
19F NMR (CDCl3) ꢀ 26.76 (d, JFF ¼ 17.0 Hz, NF2), ꢀ71.1 (b, NF).
4
{1H}19F NMR (CDCl3) ꢀ 26.76 (d, JFF ¼ 17.0 Hz, NF2), ꢀ71.11 (t,
4JFF ¼ 17.0 Hz, NF). 1-(Difluoramino)-1-(2,N-difluoroacetamido)cyclo-
1
hexane: H NMR (CDCl3) ꢀ 1.52–1.94 (m), 2.69 (b), 2.75 (b), 5.16 (dd,
4
2JHF ¼ 46.9 Hz, JHCCNF ¼ 3.5 Hz). 19F NMR (CDCl3) ꢀ 27.42 (d,
4JFF ¼ 18.7 Hz, NF2), ꢀ92.7 (bt, NF), ꢀ234.66 (t of d, JHF ¼ 46.9 Hz,
2
4JFCCNF ¼ 7.8 Hz). {1H}19F NMR (CDCl3) ꢀ 27.42 (d, JFF ¼ 18.7 Hz,
4
4
4
NF2), ꢀ92.68 (t of d, JFNCNF ¼ 18.7 Hz, JFCCNF ¼ 7.8 Hz, NF),
ꢀ234.66 (t of d, 2JHF ¼ 46.9 Hz, 4JFCCNF ¼ 7.8 Hz).

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New Preparation of gem-bis(Difluoramino)alkanes
4181
Typical Experimental Procedure
N,N-Difluoroacetamide. Fluorine in nitrogen (20 vol%) was diluted
with a threefold excess flow of N2 and slowly bubbled through a cooled
(ꢁꢀ40ꢂC), magnetically stirred solution of 0.10 g of acetamide in
8 mL CD3CN in a 25 mL 2-neck pear-shaped flask. After 10 min,
NMR analysis showed that N,N0-diacetylhydrazine [1H NMR (CD3CN)
ꢀ 1.85 (s), 1.88 (s). Lit.[22] (DMSO-d6) (Z,Z)—ꢀ 1.83, (E,E)—ꢀ 1.86]
was the major solute besides starting material acetamide and HF
by-product. After 40 min, N,N-difluoroacetamide was the major
solute, and degradation products acetyl fluoride and difluoramine were
significant. N,N-Difluoroacetamide: 1H NMR (CD3CN) ꢀ 2.42 (t,
4JHF ¼ 3.0 Hz). 19F NMR (CD3CN) ꢀ 26.2 (b).
1,1-bis(Difluoramino)propane. Fluorine in nitrogen (20 vol%) was
diluted with a threefold excess flow of N2 and slowly bubbled through
a cooled (ꢁꢀ40ꢂC), magnetically stirred solution of 0.1023 g of 1,1-bis-
acetamidopropane[26] in 8 mL CD3CN in a 25 mL 2-neck pear-shaped
flask. After 15 min, 1-acetamido-1-(difluoramino)propane was the predo-
minant fluorinated component, according to 19F NMR, apparent as an
AB quartet of doublets: ꢀ 23.31, 26.39 (3JHF ¼ 28.0 Hz); 35.09, 38.16
(3JHF ¼ 12.9 Hz). After 45 min, starting material and this intermediate
were gone, and 1,1-bis(difluoramino)propane was the most prevalent
1
difluoramine derivative, according to H and 19F NMR. Yield ꢁ40%
by integration of the NF region of 19F NMR [ꢀ 35.3 (b). Lit[6a] ꢀ 36.3].
ACKNOWLEDGMENTS
Financial support, managed by Dr. Judah Goldwasser, of the Office
of Naval Research is gratefully acknowledged.
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>NF compounds. Chem. Comm. 2001, 1196–1197.
3. Graham, W.H.; Parker, C.O. The reaction of trityldifluoramine
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J. Org. Chem. 1963, 28, 850.

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4182
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4. Fokin, A.V.; Kosyrev, Yu.M.; Shevchenko, V.I. Certain examples
of difluoroamine alkylation reactions. Bull. Acad. Sci. USSR, Div.
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New Preparation of gem-bis(Difluoramino)alkanes
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15. Crystal data for 2: Orthorhombic space group Pbca, with
a ¼ 10.325(3), b ¼ 9.722(3), c ¼ 19.175(6) A (at data collection
T ¼ ꢀ180ꢂC), V ¼ 1924(1) A3, Z ¼ 8. R ¼ 0.0422 for 1010 observed
[I>2ꢂ(I) reflections, R ¼ 0.0669 for all 1390 reflections. Additional
crystal and molecular data have been deposited as supplementary
publication CCDC 207557 with the Cambridge Crystallographic
Data Centre; copies can be obtained on application to CCDC, 12
Union Road, Cambridge CB2 1 EZ, UK (or e-mail to deposit@
ccdc.cam.ac.uk).
16. (a) Batail, P.; Louer, M.; Grandjean, D.; Dudragne, F.; Michaud, C.
Etude structurale de fluoramines aromatiques. III. Structure cristal-
line et moleculaire du (N,N-difluoroamino) dinitro-2,4 benzene,
C6H3O4N3F2. Acta Cryst. Sect. B 1976, 32, 2780–2786; (b)
Batail, P.; Grandjean, D.; Dudragne, F.; Michaud, C. Etude struc-
turale de fluoramines aromatiques. II. Structure cristalline et
moleculaire du (N,N-difluoroamino) trinitro-2,4,6 benzene,
C6H2O6N4F2. Acta Cryst. Sect. B 1975, 31, 1367–1372; (c)
Dalinger, I.L.; Vinogradov, V.M.; Shevelev, S.A.; Kuz0min, V.S.
N-(Difluoroamino)azoles—a new class of N-substituted azoles.
Mendeleev Commun. 1996, 13–15.
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structure of para-bromophenyldiphenylcarbinyl difluoramine. J.
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18. Values cited are from Tables 6 and 7 in: Butcher, R.J.; Gilardi, R.;
Baum, K.; Trivedi, N.J. The structural chemistry of energetic
compounds containing gem-difluoramino groups. Thermochim.
Acta 2002, 384, 219–227.
19. (a) Sharts, C.M. N,N-Difluoroalkylamines by direct fluorination of
alkylamines. J. Org. Chem. 1968, 33, 1008–1011; (b) Smith, H.F.;
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3,479,404, November 18, 1969.
20. Davydov, A.V.; Stolyarov, V.P. Fluorination of acetamide by
elementary fluorine. Mendeleev Chem. J. 1977, 22, 21–22; and
references therein.
21. N,N-Difluoroacetamide was first prepared by radical reaction of
N2F4 with acetaldehyde. Petry, R.C.; Freeman, J.P.
Tetrafluorohydrazine: a versatile intermediate for the synthesis of
N-fluoro compounds. J. Am. Chem. Soc. 1961, 83, 3912.
22. Fritz, H.; Kristinsson, H.; Mollenkopf, M.; Winkler, T. 15N and
13C NMR study of acylated hydrazines. The instability of trifluoro-
acethydrazide in the solid state. Magn. Reson. Chem. 1990, 28,
331–336.

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Chapman, Davis, and Gilardi
23. Glemser, O.; Ludemann, H. Uber die einwirkung von fluor auf
harnstoff. Z. Anorg. Allg. Chem. 1956, 286, 168–173.
24. Grakauskas, V.; Baum, K. Direct fluorination of amides. J. Org.
Chem. 1970, 35, 1545–1549.
25. (a) Jones, K.; Mooney, E.F. Fluorine-19 nuclear magnetic reso-
nance spectroscopy. Annu. Rep. NMR Spectrosc. 1970, 3,
261–421; (b) Emsley, J.W.; Phillips, L. Fluorine chemical shifts.
Prog. Nucl. Magn. Reson. Spectrosc. 1971, 7, 1–520.
26. Fernandez, A.H.; Alvarez, R.M.; Abajo, T.M. Improved synthesis
of symmetrical N,N0-alkylidene bisamides. Synthesis 1996,
1299–1301.
Received in the USA June 2, 2003