Formation of Urea, Isourea, and Triazine Derivatives from Diisopropylcyanamide with Trifluoroacetic Anhydride and Trifluoromethanesulfonic Anhydride: Thermal Instability of Urea and Isourea Derivatives

Article abstract of DOI:10.1021/jo9710184

Diisopropylcyanamide reacts exothermically with trifluoroacetic anhydride to give 2, an equilibrium mixture, in C₆D₆ solution, of 1:1 adducts, N,N-diisopropyl-N', O-bis(trifluoroacetyl)isourea, 2a (10%), and N,N-diisopropyl-N',N'-bis(trifluoroacetyl)urea, 2c (90%), at 27°C. Compound 2c is a colorless solid, mp 49-51°C. Thermolysis of 2, at 117°C, shows first-order kinetics with the intital products being trifluoroacetonitrile, 4, and diisopropylcarbamic trifluoroacetic mixed anhydride, 3. Trifluoroacetonitrile trimerizes to 2,4,6-tris(trifluoromethyl)-1,3,5-triazine, and 3 is thermally labile giving diisopropyltrifluoroacetamide and CO₂. In the thermolysis reaction 4 reacts with 2a to give a small amount of 4-(diisopropylamino)-4-(trifluoroacetoxy)-2,6-bis(trifluoromethyl)-4H-1,3,5- oxadiazine, 7. A related compound, 4,4-bis(diisopropylamino)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 8, is formed from 7 and 2c going through a concentration maximum at 4000 s in the kinetic run. Compound 8 thermolytically dissociates to generate 4 and tetraisopropylurea. Compound 2 is a trifluoroacetylating agent with methanol giving methyl trifluoroacetate in 97% yield. Accompanying this reaction is a methanol displacement of diisopropylamine giving a 1.7% yield of methyl-N-(trifluoroacetyl)urethane. Diisopropylcyanamide also reacts exothermically with trifluoromethanesulfonic anhydride to give 2,4,6-tris(diisopropylamino)-l-(trifluoromethanesulfonyl)triazinium trifluoromethanesulfonate, 15, in 96% yield. X-ray crystallographic structure drawing of 15 shows N1 (attached to CF₃SO₂) is pyramidal while N2, N4, and N6 (all diisopropylamino nitrogens) are sp²-planar. A small amount of O-ethyl-N,N-diisopropyl-N'-(trifluoromethanesulfonyl)isourea was also recovered, produced by the reaction of the initially formed intermediate, N,N-diisopropyl-N',O-bis(trifluoromethanesulfonyl)isourea, with ethanol contaminant in absolute ethyl ether solvent. Treatment of 15 with methanol, in the presence of K₂CO₃, gave a 90% yield of 2,4,6-tris-(diisopropylamino)-1-(trifluoromethanesulfonyl)-4-methoxy-1,4- dihydrotriazine.

Full text of DOI:10.1021/jo9710184

9070
J . Org. Chem. 1997, 62, 9070-9075
F or m a tion of Ur ea , Isou r ea , a n d Tr ia zin e Der iva tives fr om
Diisop r op ylcya n a m id e w ith Tr iflu or oa cetic An h yd r id e a n d
Tr iflu or om eth a n esu lfon ic An h yd r id e: Th er m a l In sta bility of Ur ea
a n d Isou r ea Der iva tives
William P. Norris,* Lawrence H. Merwin, and Gregory S. Ostrom
Chemistry and Materials Branch, Research and Technology Division, Naval Air Warfare Center Weapons
Division, China Lake, California 93555-6100
Richard D. Gilardi
Laboratory for the Structure of Matter, Naval Research Laboratory, Washington, D.C. 20375-5000
Received J une 6, 1997X
Diisopropylcyanamide reacts exothermically with trifluoroacetic anhydride to give 2, an equilibrium
mixture, in C6D6 solution, of 1:1 adducts, N,N-diisopropyl-N′,O-bis(trifluoroacetyl)isourea, 2a (10%),
and N,N-diisopropyl-N′,N′-bis(trifluoroacetyl)urea, 2c (90%), at 27 °C. Compound 2c is a colorless
solid, mp 49-51 °C. Thermolysis of 2, at 117 °C, shows first-order kinetics with the intital products
being trifluoroacetonitrile, 4, and diisopropylcarbamic trifluoroacetic mixed anhydride, 3. Trifluo-
roacetonitrile trimerizes to 2,4,6-tris(trifluoromethyl)-1,3,5-triazine, and 3 is thermally labile giving
diisopropyltrifluoroacetamide and CO2. In the thermolysis reaction 4 reacts with 2a to give a small
amount of 4-(diisopropylamino)-4-(trifluoroacetoxy)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 7.
A related compound, 4,4-bis(diisopropylamino)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 8, is
formed from 7 and 2c going through a concentration maximum at 4000 s in the kinetic run.
Compound 8 thermolytically dissociates to generate 4 and tetraisopropylurea. Compound 2 is a
trifluoroacetylating agent with methanol giving methyl trifluoroacetate in 97% yield. Accompanying
this reaction is a methanol displacement of diisopropylamine giving a 1.7% yield of methyl-N-
(trifluoroacetyl)urethane. Diisopropylcyanamide also reacts exothermically with trifluoromethane-
sulfonic anhydride to give 2,4,6-tris(diisopropylamino)-1-(trifluoromethanesulfonyl)triazinium
trifluoromethanesulfonate, 15, in 96% yield. X-ray crystallographic structure drawing of 15 shows
N1 (attached to CF3SO2) is pyramidal while N2, N4, and N6 (all diisopropylamino nitrogens) are
sp2-planar. A small amount of O-ethyl-N,N-diisopropyl-N′-(trifluoromethanesulfonyl)isourea was
also recovered, produced by the reaction of the initially formed intermediate, N,N-diisopropyl-N′,O-
bis(trifluoromethanesulfonyl)isourea, with ethanol contaminant in absolute ethyl ether solvent.
Treatment of 15 with methanol, in the presence of K2CO3, gave a 90% yield of 2,4,6-tris-
(diisopropylamino)-1-(trifluoromethanesulfonyl)-4-methoxy-1,4-dihydrotriazine.
In tr od u ction
to add chloride on the carbon and the remainder on the
nitrogen of the cyano group, as demonstrated with phos-
phorus trichloride:
The chance observation that diisopropylcyanamide, 1,
reacted vigorously and exothermically with trifluoroacetic
anhydride (TFAA) prompted the initial investigation
which indicated the formation of a 1:1 adduct, 2. Search
of the literature disclosed a number of examples of dial-
kylcyanamides reacting with acyl chlorides with the acyl
group adding to nitrogen and the chloride adding to the
carbon of the cyano group, as shown in the illustra-
tion:1-3
There was one reference8 to the reaction of dialkylcy-
anamides with phthalic anhydride which required several
hours of heating at 150 °C as opposed to the exothermic
reaction of TFAA with diisopropylcyanamide, 1, at low
Phosphorus trichloride,4 sulfuryl chloride,5-7 and thio-
nyl chloride5,7 react with dialkylcyanamides, similarly,
temperature. Very recently a reference appeared on the
reaction of trifluoromethanesulfonic anhydride (triflic
anhydride) with dimethylcyanamide9 which proceeded
X Abstract published in Advance ACS Abstracts, December 1, 1997.
(1) Bredereck, K.; Richter, R. Chem. Ber. 1966, 99, 2454-2460.
(2) Lebedev, V. N.; Yurechko, V. V.; Vishnyakova, T. P. Zh. Vses.
Khim. Ova. 1981, 26, 465-466.
(3) Tocker, S. Ger. Offen. 2708024, 1977; Chem. Abstr. 1977, 87,
201591p.
(4) Shevchenko, V. I.; Pisanenko, N. P.; Kosinskaya, I. M. Zh.
Obshch. Khim. 1978, 48, 1179.
(5) Markovskii, L. N.; Shermolovich, Yu. G.; Shevchenko, V. I. Zh.
Org. Khim. 1973, 9, 633-634.
(6) Schindler, N. Chem. Ber. 1973, 106, 56-61.
(7) Markovskii, L. N.; Shermolovich, Yu. G.; Nuzhdina, Yu. A.;
Shevchenko, V. I. Zh. Org. Khim. 1974, 10, 1000-1006.
(8) (a) Grigat, E. Angew. Chem., Int. Ed. Engl. 1972, 11, 949-963
(see p 955). (b) Grigat, E.; Pu¨tter, R. Ger. Offen. 1936127, 1971; Chem.
Abstr. 1971, 74, 87642k.
(9) Martinez, A. G.; Fernandez, A. H.; J imenez, F. M.; Ruiz, P. M.;
Subramanian, L. R. Synlett 1995, 161-162.
S0022-3263(97)01018-9 This article not subject to U.S. Copyright. Published 1997 by the American Chemical Society

Thermal Instability of Urea and Isourea Derivatives
J . Org. Chem., Vol. 62, No. 26, 1997 9071
quite differently from the reaction of triflic anhydride
with 1 in the present work.
Research discussed in this work includes reaction of 1
with TFAA to give 2, kinetics of the thermolysis of 2,
reactions of the thermolysis fragments of 2, and 2 as a
trifluoroacetylating agent with methanol. In addition,
the quite different reaction of 1 with triflic anhydride will
be discussed.
Discu ssion a n d Resu lts
but may be present in sufficient concentration, particu-
larly at higher temperature (117 °C), to account for the
thermolysis. As mentioned later, the equilibrium con-
centration of 2a probably more than triples going from
27 to 117 °C.
The mixed anhydride 3 is also thermally labile and can
expel CO2 to give diisopropyltrifluoroacetamide, 6.10
Trifluoroacetonitrile, 4, trimerizes to give 2,4,6-tris-
(trifluoromethyl)-1,3,5-triazine, 5.11 Monomeric 4 is never
detected by NMR in the thermolysis products of 2, even
when conducted in sealed NMR tubes.
Rea ction of Diisop r op ylcya n a m id e w ith Tr iflu o-
r oa cetic An h yd r id e. Diisopropylcyanamide, 1, reacts
exothermically with trifluoroacetic anhydride in ether to
give a high yield (98%) of a 1:1 adduct, 2. The reaction
presumably proceeds by addition of TFAA to the nitrile
triple bond, similar to the way acyl chloride adds to
dialkylcyanamides1-3 (with the acyl group on the nitrogen
and the chloride on the carbon), to give N,N-diisopropyl-
N′,O-bis(trifluoroacetyl)isourea, 2a , which rearranges
largely to N,N-diisopropyl-N′,N′-bis(trifluoroacetyl)urea,
2c, by O f N acyl group migration.
Phthalic anhydride adds to dialkylcyanamide in a
similar way, rearranging to give a phthalimide deriva-
tive.8 N,N-Diisopropyl-N′-[2,2,2-trifluoro-1-(trifluoroacet-
oxy)ethylidene]urea, 2b, and N-trifluoroacetyl O-(N′,N′-
diisopropylcarbamyl)trifluoroacetimidate, 2d , also could
be formed by the appropriate acyl group migrations. The
Rea ction s of Th er m olysis F r a gm en ts. In the ther-
molysis reaction mixture some additional compounds
have been detected by NMR and GC-MS. One is a
compound with a mass of 431 which could be formed by
the reaction of 4 with 2a to give 4-(diisopropylamino)-4-
(trifluoroacetoxy)-2,6-bis(trifluoromethyl)-4H-1,3,5-oxa-
diazine, 7. It is consumed in the thermolysis reaction
reaction product 2, according to NMR in C6D6 solution,
consists of 2c as the principal component, along with
about 10% of an isomeric material, which could be either
2a , 2b, or 2d , all of which have nonequivalent CF3
groups. Because the N f O migrating acyl group of 2c,
seemingly, would prefer the more electron-rich oxygen
of the diisopropylcarbamyl group to the oxygen of a tri-
fluoroacetyl group, compound 2a could represent the 10%
isomeric material. Conceivably, low concentrations of 2b
and/or 2d , undetectable by NMR, could also exist. In the
course of kinetic analysis of the thermal decomposition
of 2, a dynamic equilibrium between 2c and 2a was
observed. Compound 2c exists as a colorless solid, mp
49-51 °C. The structure of the solid was not determined
directly, but considering the structural symmetry of 2c
versus that of the other isomers, 2c would probably be
higher melting and, therefore, is considered the structure.
Th er m olysis of 2. Thermal decomposition of 2 leads,
initially, to dissociation into two fragments: diisopropyl-
carbamic trifluoroacetic mixed anhydride, 3, and triflu-
oroacetonitrile, 4. Isomeric structures 2b,d would seem
to readily accommodate the thermal fragmentation, while
2a ,c would not. Equilibrium concentrations of 2b and/
or 2d , at 27 °C, may be small and undetectable by NMR
by reverse reaction and/or by conversion to 8 since it is
reduced to very low concentration in the reaction mixture
in the 9 half-lives thermolysis experiment with 2.
Another compound detected by NMR and GC-MS is
one with a mass of 418. 4,4-Bis(diisopropylamino)-2,6-
bis(trifluoromethyl)-4H-1,3,5-oxadiazine, 8, is suggested
for the structure. The trifluoroacetoxy group of 7 could
be replaced by a diisopropylamino group from 2c to give
8. The other product, N,N-bis(trifluoroacetyl)carbamic
trifluoroacetic mixed anhydride, 9, was never detected.
In the kinetic run at 117 °C the concentration of 8 reaches
(10) Robson, J . H.; Reinhart, J . J . Am. Chem. Soc. 1955, 77, 498-
499.
(11) Pyrolysis of pentafluoropropionamidine gives 2,4,6-tris(pen-
tafluoroethyl)-1,3,5-triazine, presumably passing through the mono-
meric RfCN. Reilly, W. L.; Brown, H. C. J . Org. Chem. 1957, 22, 698-
699.

9072 J . Org. Chem., Vol. 62, No. 26, 1997
Norris et al.
Rea ction of 2 w ith Meth a n ol. Equilibrium mixture,
2a +2c, reacts with methanol as a trifluoroacetylating
agent giving a 97% yield (19F NMR) of methyl trifluoro-
acetate, 12, along with N,N-diisopropylurea, 13.14 In
addition there is a 1.7% yield of methyl-N-(trifluoro-
acetyl)urethane, 14.15 The fate of the displaced diiso-
propylamine was not determined. Reaction of 2 with an
alcohol is quite different from the reaction of the triflic
anhydride-dimethylcyanamide addition product, N,N-
dimethyl-N′,N′-bis(trifluoromethanesulfonyl)urea, with
alcohol as reported in ref 9. This latter compound, with
ethanol, gives N,N-dimethyl-O-ethyl-N′-(trifluoromethane-
sulfonyl)isourea and, presumably, triflic acid.9
Rea ction of Diisop r op ylcya n a m id e w ith Tr iflu o-
r om eth a n esu lfon ic An h yd r id e (Tr iflic An h yd r id e).
Triflic anhydride was chosen as another acid anhydride
to react with 1. It reacts exothermically with 1 in ether
to give a high yield (96%) of isolated, very pure 2,4,6-
tris(diisopropylamino)-1-(trifluoromethanesulfonyl)triaz-
inium trifluoromethanesulfonate, 15, which is a white
F igu r e 1. Plot of concentration versus time of principal
thermolysis products of 2 at 117 °C plus a calculated plot
(theory) for a thermolysis product.13
a maximum at about 4000 s (Figure 1). In the 9 half-
lives thermolysis experiment with 2 there is still 6.3% of
8. There is 0.75% of tetraisopropylurea, 11,12 suggesting
that some of the thermal decompostion reaction of 8 could
proceed as indicated. There was never any N′′-(trifluo-
roacetyl)-N,N,N′,N′-tetraisopropylguanidine, 10, detected.
Monomeric 4 was never detected and would have been
incorporated in the trimer 5.
solid that endures normal laboratory handling without
noticeable reaction with atmospheric moisture. An X-ray
crystallographic structure drawing of the cation of 15 is
shown in Figure 2.16 There are several consistent
structural cues that point to the structure being best
represented by the three-part hybrid 15a -c. The only
Kin etics of Th er m olysis of 2. Kinetic analysis of
the thermolysis of 2 in C6D6 at 117 °C shows it to follow
first-order kinetics, k ) 2.15 × 10-4 s-1. While a major
part of 2 is consumed by fragmentation to 3 and 4, there
is a reaction occurring between 2a and the fragmentation
product 4. Nevertheless, the plot of log [2a +2c] (19F
NMR integral) versus time gives a good straight line, r2
) 0.9983. The concentration (19F NMR integral) versus
time plots of products 5, 3+6, and 8 are shown in Figure
1 along with the theoretical (theory) plot13 of a first-order
fragmentation product. The plot of 5, in the beginning,
lags behind the theory plot, because some of 4 (precursor
to 5) is reacting with 2a to give 7 (which largely converts
to 8), but after about 3 half-lives 5 approaches to 95% of
the theoretical value. The belated concentration increase
of 5 derives from the thermal decomposition of 8, which
generates the 5 precursor, 4. The plot of 8 goes through
a maximum at about 4000 s. Also, the 19F NMR integral
plot of 3+6, the other half of the thermal fragmentation
process of 2, similarly lags behind the theory plot because
the concentration of 2 is being decreased by reaction of
2a with 4. At 3 half-lives the 19F NMR integral plot of
3+6 is 81% of the theoretical value.
nitrogen atom which is significantly nonplanar is N1,
with average bond angles of 115.1°. The three bonds of
(14) van der Zand, M. K. H. M. Recl. Trav. Chim. Pays-Bas 1889,
8, 221-247.
(15) Boiko, V. I.; Samari, L. I. Ukr. Khim. Zh. 1992, 58, 797-798.
(16) Crystals of 15 belong to monoclinic space group P21. Crystal
data: a ) 10.181(2), b ) 15.393(2), c ) 11.238(2) Å; â ) 109.47(2)°, Z
) 2, Dx ) 1.322 mg mm-3; R ) 0.0554, R2w ) 0.1557 for 2126 unique
observed [I >2σ(I)] reflections. The authors have deposited X-ray
crystallographic data for the structure of compound 15 with the
Cambridge Crystallographic Data Center. The data can be obtained,
upon request, from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.
(12) Barton, D. H. R.; Elliott, J . D.; Gero, S. D. J . Chem. Soc., Perkin
Trans. 1 1982, 2085-2090.
(13) Theoretical plot: y ) 1/2{[2]0 - [2]t}, or y ) 1/2(102.761
-
-5
102.761-9.351×10 ), where y ) 19F NMR integral and t ) 0-9000 s.
t

Thermal Instability of Urea and Isourea Derivatives
J . Org. Chem., Vol. 62, No. 26, 1997 9073
methyl and methine protons of the isopropyl groups are
not well-resolved but integrate satisfactorily for the
required number. The methoxide proton peak is clearly
evident at δ 3.24.
Con clu sion
Trifluoroacetic anhydride adds to 1 to give 2 which, in
C6D6 solution, is an equilibrium mixture of a 10%
concentration of the initial adduct 2a with 90% rear-
1
ranged 2c at 27 °C as evidenced by H and 19F NMR.
Compound 2c is a colorless solid, mp 49-51 °C. Ther-
molysis of 2 at 117 °C shows first-order kinetics. The
initial thermolysis products are 3 and 4. Compound 3
is thermally unstable and fragments to 6 and CO2, and
4 trimerizes to 5. In the thermolysis reaction mixture 4
F igu r e 2. Drawing of the structure observed in the crystal
for the cation of 15.16 The nitrogen atom N1 is pyramidal,
with its three bond angles averaging 115.1°; nitrogen atoms
N2, N4, and N6 are essentially planar; each displays average
bond angles of 119.9°. The hydrogen atoms are omitted for
visibility.
reacts with 2a to give an adduct, 7, of mass 431.
A
related compound, 8, of mass 418 is formed from 7 and
2c in the thermolysis going through a concentration
maximum at 4000 s in the kinetic run at 117 °C (see
Figure 1). The formation of 8 consumes 4 (5 precursor)
which causes the plot of 5 to initally lag behind the
theoretical plot but to largely recover after 3 half-lives
as concentration of 8 thermolytically decreases with
release of 4. Similarly, formation of 8 consumes 2 which
causes the 3+6 plot to lag behind the theoretical plot.
With methanol, 2 is a trifluoroacetylating agent giving
a 97% yield of methyl trifluoroacetate. In addition
methanol displaces diisopropylamine from 2 to give 1.7%
of methyl-N-(trifluoroacetyl)urethane, 14. Triflic anhy-
dride reacts with 1 in quite a different way to give a 96%
yield of 15, a triazine derivative. Ethanol contaminant
in the absolute ether solvent trapped intermediate 1:1
adduct 16 as O-ethylisourea derivative 17. Compound
15 reacts with methanol in the presence of K2CO3 to give
a 90% yield of 2,4,6-tris(diisopropylamino)-1-(trifluo-
romethanesulfonyl)-4-methoxy-1,4-dihydrotriazine, 18.
N1 are all quite long indicating full single-bond character.
The CN bonds are 1.458 and 1.464 Å, typical single-bond
values, and the NS bond at 1.674 Å matches single NS
bonds found in the X-ray crystallographic structural
database. Atoms N2, N4, and N6 are sp2-planar; each
of them has the same average bond angle, 119.9°. The
CN bonds along the N2‚‚‚N4 and N4‚‚‚N6 pathways
range from 1.309 to 1.386 Å; thus, all fall in the aromatic
single/double-hybrid-bond category.
Triflic anhydride reacts quite differently with 1 com-
pared to TFAA (which gives the 1:1 adduct 2), and
compared to 1, dimethylcyanamide reacts quite differ-
ently with triflic anhydride, as recently reported.9 Lit-
erature NMR data were consistent with N,N-dimethyl-
N′,N′-bis(trifluoromethanesulfonyl)urea as the structure
of their isolated, 1:1, adduct.9
Besides 15 there was a small amount of O-ethyl-N,N-
diisopropyl-N′-(trifluoromethanesulfonyl)isourea, 17, iso-
lated. The initially formed intermediate 16 reacts with
C2H5OH, contaminant in the absolute ether, to give 17.
This parallels the literature-reported reaction of N,N-
dimethyl-N′,O-bis(trifluoromethanesulfonyl)isourea with
ethanol.9
Exp er im en ta l Section
Melting points were determined on a Mel-Temp II apparatus
and are uncorrected. GC-MS analyses were performed on a
Hewlett-Packard 5890 Series II gas chromatograph, with a
temperature-programmed 30-m Restek XTI-5 column, helium
gas, and a 250 °C injection port temperature, connected to a
Fisons TS-250 Tribrid high-resolution mass spectrometer, 70
eV ionization energy.
Rea ction of Diisop r op ylcya n a m id e, 1, w ith Tr iflu o-
r oa cetic An h yd r id e. Trifluoroacetic anhydride, 23.1 g (0.110
mol), dissolved in 25 mL of anhydrous ether was added, with
stirring, to 12.6 g (0.100 mol) of diisopropylcyanamide, 1,
dissolved in 25 mL of anhydrous ether at -20 ( 5 °C, protected
from atmospheric moisture. When addition was complete the
reaction mixture was warmed to 25 °C and volatiles were
removed under reduced pressure (1 mm/25 °C) to give 33.0 g
(98% yield) of a liquid 1:1 addition product, 2. Chilling and
scratching induced crystallization. Recrystallization from
hexane (1 g of 2 to 2 mL of hexane) gave colorless crystals of
2c, mp 49-51 °C. Filtration was done in a drybox, dewpoint
) -109 °C. NMR analyses were run on solutions prepared
from the crystalline material in the drybox using carefully
dried equipment and solvent. NMR spectra for 2c: 1H NMR
(400 MHz, C6D6/TMS, 27 °C) δ 0.62 [d, J ) 6.6 Hz (2 CH3)],
1.21 [d, J ) 6.8 Hz (2 CH3)], 2.84 [septet, J ) 6.8 Hz (CH)],
Rea ction of 15 w ith Meth a n ol. Compound 15 is
stable to exposure to moisture in laboratory air and at
least to brief solution in pure methanol. In methanol,
in the presence of K2CO3, methoxide adds in the 4-posi-
tion of 15 to give a 90% yield of 2,4,6-tris(diisopropyl-
amino)-1-(trifluoromethanesulfonyl)-4-methoxy-1,4-dihy-
drotriazine, 18. In the 1H NMR spectrum of 18 the

9074 J . Org. Chem., Vol. 62, No. 26, 1997
Norris et al.
3.43 [septet, J ) 6.6 Hz (CH)]; 19F NMR (188 MHz, C6D6/CFCl3,
27 °C) δ -70.11 (s, 2 CF3). NMR spectra for 2a : 1H NMR
(400 MHz, C6D6/TMS, 27 °C) δ 0.72 [d, J ) 6.8 Hz (2 CH3)],
0.85 [d, J ) 6.8 Hz (2 CH3)], 3.33 [septet, J ) 6.8 Hz (2 CH)];
19F NMR (188 MHz, C6D6/CFCl3, 27 °C) δ -73.81 (s, CF3),
Hyd r olysis P r od u ct of Diisop r op ylca r ba m ic Tr iflu o-
r oa cetic An h yd r id e, 3. (This was an attempt to prepare and
isolate 3, but instead the hydrolysis product, diisopropylam-
monium trifluoroacetate, was obtained.) Diisopropylcarbamyl
chloride, 1.64 g (0.0100 mol), dissolved in 25 mL of acetonitrile
was added to 2.43 g (0.0110 mol) of silver trifluoroacetate
dissolved in 25 mL of acetonitrile and stirred for 30 min at 25
°C. Silver chloride, 1.43 g (0.0100 mol), was filtered off, and
volatiles were removed from the filtrate on the rotary evapora-
tor to leave 2.0 g (95% yield) of diisopropylammonium trifluo-
roacetate. Recrystallization from hexane gave 1.2 g: mp 122-
1
-72.50 (s, CF3). The H and 19F NMR spectra obtained show
that 2 consists of N,N-diisopropyl-N′,N′-bis(trifluoroacetyl)-
urea, 2c, as the predominant component (90%), with a single
19F signal (equivalent CF3 groups), and about a 10% concen-
tration of N,N-diisopropyl-N′,O-bis(trifluoroacetyl)isourea, 2a ,
which shows two equivalent (by integration) 19F signals
(nonequivalent CF3 groups). As demonstrated later, 2 is an
equilibrating mixture of 2c,a . 2: MS (m/z) 336 (M+), 321 (100),
279, 267, 236, 210, 165, 154, 140, 128, 113, 97, 86, 70, 58. Anal.
Calcd for C11H14F6N2O3: C, 39.29; H, 4.20; N, 8.33. Found:
C, 39.49; H, 4.15; N, 8.37. The reaction product is very reactive
toward atmospheric moisture, and the solid, 2c, within min-
utes becomes a colorless liquid when exposed to laboratory air
(30% relative humidity).
Th er m olysis of 2. Sixty-six grams (0.20 mol) of 2 was
heated in a distillation flask (condenser cooled to 0 °C) at 97
°C at 162 Torr for 2 h and then at 110 °C for 30 min. There
was 16.4 g of distillate, bp 47-90 °C. Combining this with
4.7 g, recovered from the dry ice-acetone trap, and redistil-
lation gave 14.6 g (77% yield), bp 92-102 °C/700 Torr (lit.11
bp 95-96 °C), of 2,4,6-tris(trifluoromethyl)-1,3,5-triazine, 5:11
19F NMR (188 MHz, CDCl3/CFCl3, 27 °C) δ -70.04 (s, CF3);
13C NMR (100 MHz, CDCl3/TMS, 27 °C) δ 117.7 [q, J ) 276
Hz (CF3)], 168.2 [q, J ) 42 Hz (C, ring)]; MS (m/z) 285 (M+),
266, 190, 121, 76, 69 (100).
Distillation of the distillation residue, from recovery of 5,
gave 31.7 g (80% yield) of N,N-diisopropyltrifluoroacetamide,
6: bp 85-90 °C/50 Torr, mp 49-52 °C (lit.10 mp 52-52.5 °C).
Another thermolysis of 2 was observed when a CH2Cl2
solution of 2 was injected into the 250 °C injection port of the
GC-MS instrument. The GC plot indicated about 40% of 2
passed through unchanged [MS (m/z) 336 (M+)], 55% of the
plot consisted of 3 (from loss of CF3CN from 2) [MS (m/z) 241
(M+)], and 5% consisted of 6 (from loss of CO2 from 3) [MS
(m/z) 197 (M+)]. Compound 5 was not detected in the GC plot
because it exited too close to the solvent front.
Kin etics of Th er m olysis of 2. A 0.216 M solution of 2 in
C6D6, prepared in a drybox and sealed in a 5-mm NMR tube,
was heated at 117 ( 1 °C over successive 30-min (1800-s)
intervals and thermally quenched, and concentration changes
of 2c,a , 5, 3, 6, and 8 were determined, relative to an internal
standard of C6H5CF3, by 19F NMR integration. A least-squares
plot of log of 19F NMR integration values of 2 (2c+2a ) versus
time gave log y ) -9.351 × 10-5x + 2.761, r2 ) 0.9983. The
reaction rate constant, at 117 °C, for thermolysis of 2, is k )
2.15 × 10-4 s-1. The concentrations (19F NMR integrals) of 5,
3+6, and 8, plotted against time, are shown in Figure 1.
A significant observation, in this kinetic run, was that the
concentration of 2a , in the thermally quenched sample at 1800
s, was 26% of the concentration of 2. This indicates that at
117 °C the equilibrium concentration of 2a shifts to something
greater than 26% (greater, because of some time delay between
thermal quenching and 19F NMR analysis) and is kinetically
slow in returning to the 10% equilibrium concentration at 27
°C. After the sample stands at 27 °C for several hours
(minimum time not determined) the 2a value returns to 10%
of 2. Similar results were observed when the other quenched
samples were analyzed. It was also observed that a sample
of 2 in C6D6 in a sealed NMR tube stored at -10 °C for an
extended period, then thawed and an 19F NMR quickly run,
had a 6% concentration of 2a .
1
123 °C; H NMR (400 MHz, C6D6/TMS, 27 °C) δ 0.94 [d, J )
6.5 Hz (4 CH3)], 2.65 [septet, J ) 6.3 Hz (2 CH)]; 19F NMR
(188 MHz, C6D6/CFCl3, 27 °C) δ -73.81 (s, CF3); MS (m/z) (solid
probe, 70 eV) 114, 101, 97, 95, 86 (100), 69 (90), 58, 51. Anal.
Calcd for C8H16NF3O2: C, 44.64; H, 7.49; N, 6.51. Found: C,
44.56; H, 7.51; N, 6.45.
P r ep a r a tion of Diisop r op ylca r ba m ic Tr iflu or oa cetic
Mixed An h yd r id e, 3. In a drybox, dew point -111 °C, 16.7
mg (0.102 mmol) of diisopropylcarbamyl chloride dissolved in
0.7 mL of dry C6D6 was added to 22.7 mg (0.103 mmol) of silver
trifluoroacetate dissolved in 0.3 mL of dry C6D6 and thoroughly
mixed. Silver chloride was filtered off, and the filtrate was
sealed in a dried 5-mm NMR tube. 1H and 19F NMR and GC-
MS were run on the filtrate. 1H NMR showed, by integration,
that 94% of the product was 3, 4.6% was the previously
described hydrolysis product, diisopropylammonium trifluo-
roacetate, and there was 1.6% of 6 (thermolysis product of 3).
The 1H NMR spectrum of 3 shows a multiplet at δ 3.33 for
the isopropyl methines which is due to a 6.8-Hz overlap of the
septets of the two methine protons: 1H NMR (400 MHz, C6D6/
TMS, 27 °C) δ 0.68 [d, J ) 6.8 Hz (2 CH3)], 0.98 [d, J ) 6.8 Hz
(2 CH3)], 3.33 [septet, J ) 6.8 Hz (CH)], 3.34 [septet, J ) 6.8
Hz (CH)]; 19F NMR (188 MHz, C6D6/CFCl3, 27 °C) δ -73.89
(s, CF3); MS (m/z) 241 (M+), 226, 141, 128, 97, 86, 84, 70 (100),
69, 58, 56.
4-(Diisop r op yla m in o)-4-(tr iflu or oa cetoxy)-2,6-bis(tr i-
flu or om eth yl)-4H-1,3,5-oxa d ia zin e, 7.17 In the thermolysis
reaction mixture of 2, 7 was detected by NMR and GC-MS:
19F NMR (188 MHz, C6D6/CFCl3, 27 °C) δ -73.54 (s, 2 CF3),
-73.25 (s CF3); MS (m/z) 431 (M+), 416, 331, 318, 303, 274,
260, 249, 234, 187, 165, 140, 128, 112, 97, 84, 70, 69 (100), 58.
4,4-Bis(d iisop r op yla m in o)-2,6-bis(tr iflu or om eth yl)-4H-
1,3,5-oxa d ia zin e, 8.17 Compound 8 was detected in the
thermolysis reaction mixture of 2 by NMR and GC-MS. It
reached maximum concentration at about 4000 s in the 117
°C kinetic thermolysis run (see Figure 1): 19F NMR (188 MHz,
C6D6/CFCl3, 27 °C) δ -73.76 (s, 2 CF3); MS (m/z) 418 (M+),
349, 318, 276, 234, 128, 100, 86 (100), 70, 58.
Rea ction of 2 w ith Meth a n ol. In a drybox, 16.6 mg
(0.0494 mmol) of compound 2 was dissolved in 0.5 mL of dry
C6D6 and treated with 30 µL (0.74 mmol) of CH3OH and 1 drop
of CF3C6H5 19F NMR standard. The reaction mixture was
analyzed by 19F NMR and GC-MS. 19F NMR (188 MHz, C6D6/
CFCl3, 27 °C) integration showed a 97% yield of CF3CO2CH3,
12, δ -73.50 (s, CF3), and a 1.7% yield of methyl-N-(trifluo-
roacetyl)urethane, 14,15 δ -74.58 (s, CF3). GC-MS showed a
trace of unknown material, MS (m/z) 224 (M+). 14:15 1.7%
yield; MS (m/z) 171 (M+), 140, 112, 102, 97, 69 (100), 57, 58.
N,N-Diisopropylurea 13:14 95% yield; 1H NMR (400 MHz,
C6D6/TMS, 27 °C) δ 1.03 [d, J ) 6.8 Hz (4 CH3)], 3.46 [septet,
J ) 6.8 Hz (2 CH)], 4.90 (s, NH2); MS (m/z) 144 (M+), 129,
101, 86 (100), 70, 58.
P r ep a r a tion of 2,4,6-Tr is(d iisop r op yla m in o)-1-(tr iflu -
or om eth an esu lfon yl)tr iazin iu m Tr iflu or om eth an esu lfon -
a te, 15. Triflic anhydride, 5.64 g (0.0200 mol), dissolved in
Th er m olysis of 2 for 9 Ha lf-Lives a t 117 ° C. A 0.119 M
solution of 2 along with C6H5CF3 in C6D6 in a sealed 5-mm
NMR tube was placed in a 117 °C bath for 8 h. 19F NMR
analysis of the reaction mixture gave the following yields based
on the starting amount of 2: 2, 0.0%; 5, 79%; 3, 55%; 6, 35%;
8, 6.3%. GC-MS analysis of the reaction mixture, using
uncalibrated response of the GC, gave the following yields
based on the sum of the components detected: 2, 0.0%; 3, 56%;
6, 32%; 7, 1.4%; M+ ) 316 (unidentified), 2.4%; 8, 7.1%;
N,N,N′,N′-tetraisopropylurea, 11,12 0.75%.
(17) Compounds 7 and 8 were not isolated (except GC-MS), and
no elemental analyses were obtained. The structures were deduced
from mass spectral data, mass spectral cracking patterns, and syn-
thetic components available in the thermolysis reaction mixture.
Thermolysis products 4 and 11 are consistent with structure 8. 19F
NMR data, obtained from the thermolysis reaction mixtures, are
compatible with the structures.

Thermal Instability of Urea and Isourea Derivatives
J . Org. Chem., Vol. 62, No. 26, 1997 9075
20 mL of dry ether18 was added, with stirring, to 2.52 g (0.0200
mol) of 1 dissolved in 20 mL of dry ether keeping the reaction
temperature at 25 ( 5 °C. White solid began separating from
the reaction mixture as soon as triflic anhydride was added.
When triflic anhydride addition was completed, the white solid
was filtered off, washed with two 50-mL portions of ether, and
dried to give 4.22 g (96% yield) of 15: mp 189-191 °C dec; 1H
NMR (400 MHz, CD3CN/TMS, 77 °C) δ 1.35 [d, J ) 6.7 Hz (2
CH3)], 1.41 [d, J ) 6.9 Hz (2 CH3)], 1.46 [d, J ) 6.4 Hz (4 CH3)],
1.54 [d, J ) 6.8 Hz (2 CH3)], 1.59 [d, J ) 6.8 Hz (2 CH3)], 4.13
[septet, J ) 6.8 Hz (2 CH)], 4.58 [broad, (2 CH)],19 4.68 [septet,
J ) 6.5 Hz (2 CH)]; 13C NMR (100 MHz, CD3CN/TMS, 77 °C)
δ 19.6 (s, 4 CH3), 21.0 (s, 2 CH3), 21.5 (s, 2 CH3), 21.8 (s, 2
CH3), 22.3 (s, 2 CH3), 51.5 (s, 2 CH), 52.0 (s, 2 CH), 57.3 (s, 2
CH), 120.7 (q, J ) 325 Hz, CF3), 122.9 (q, J ) 319 Hz, CF3),
149.7 (s, 2 C), 158.3 (s, C); 19F NMR (75 MHz, CDCl3/CFCl3,
27 °C) δ -77.16 (s, CF3), -66.82 (s, CF3); MS (m/z) 511 (M+),
447, 378, 335, 209, 100 (100), 68, 58. Anal. Calcd for
C23H42N6F6S2O5: C, 41.80; H, 6.41; N, 12.72. Found: C, 41.72,
41.68; H, 6.49, 6.32; N, 12.59, 12.66.
-79.01 (s, CF3). Anal. Calcd for C10H19N2F3SO3: C, 39.46; H,
6.29; N, 9.21. Found: C, 39.55; H, 6.35; N, 9.22.
Rea ction of 2,4,6-Tr is(d iisop r op yla m in o)-1-(tr iflu or o-
m eth an esu lfon yl)tr iazin iu m Tr iflu or om eth an esu lfon ate,
15, w ith Meth a n ol in th e P r esen ce of P ota siu m Ca r bon -
a te. To 100 mL of CH3OH containing 0.33 g of K2CO3‚1.5H2O
(2.0 mmol) was added 0.66 g (1.0 mmol) of 15 at 25 °C.
Removal of volatiles on the rotary evaporator followed by
treatment of the residue with 25 mL of H2O and 25 mL of
CH2Cl2, separation of the CH2Cl2 phase, drying over MgSO4,
and removal of the CH2Cl2 on the rotary evaporator left 0.49
g (90% yield) of 2,4,6-tris(diisopropylamino)-1-(trifluoromethane-
sulfonyl)-4-methoxy-1,4-dihydrotriazine, 18. Recrystallization
from 30 mL of hexane gave 0.40 g of 18, mp 151-152 °C.
Another recrystallization from hexane raised the melting point
to 153-154 °C: 1H NMR (400 MHz, C6D6/TMS, 27 °C) δ 0.89-
1.39 (multiplet, 12 CH3), 3.24 (s, CH3O), 3.70 (unresolved, 2
CH), 4.12 (unresolved, 2 CH), 4.53 (unresolved, 2 CH); 19F
NMR (188 MHz, C6D6/CFCl3, 27 °C) δ -76.11 (s, CF3); MS (m/
z) 542 (M+), 499, 473, 457, 442, 409, 358, 310 (100), 217, 184,
142, 100, 58. Anal. Calcd for C23H45N6F3SO3: C, 50.90; H, 8.36;
N, 15.49. Found: C, 51.09; H, 8.41; N, 15.75.
Volatiles were removed from the ether wash filtrate, from
isolation of 15, on a rotary evaporator, and the residue was
chromatographed on a silica gel column, CH2Cl2 solvent, to
give 0.15 g of material, mp 60-64 °C. Recrystallization from
n-hexane gave 90 mg of O-ethyl-N,N-diisopropyl-N′-(trifluo-
Ack n ow led gm en t. We wish to thank A. P. Chafin
and E. D. Erickson for many helpful discussions, R. D.
Chapman for editing the manuscript, and M. P. Nadler
for plotting and drawing Figure 1.
1
romethanesulfonyl)isourea, 17: mp 68-69 °C; H NMR (400
MHz, CDCl3/TMS, 55 °C) δ 1.33 [d, J ) 6.8 Hz (4 CH3)], 1.45
[t, J ) 7.1 Hz (CH3)], 4.18 [broad band (2 CH)],19 4.61 [q, J )
7.1 Hz (CH2)]; 19F NMR (188 MHz, CDCl3/CFCl3, 300 K) δ
Su p p or tin g In for m a tion Ava ila ble: 1H and 19F NMR
spectra for 3 (3 pages). This material is contained in libraries
on microfiche, immediately following this article in the micro-
film version of the journal, and can be ordered from the ACS;
see any current masthead page for ordering information.
(18) Lindner, E.; von Au, G.; Eberle, H.-J . Chem. Ber. 1981, 114,
810-813. This refers to the cleavage of the cyclic ether tetrahydro-
2H-pyran by triflic anhydride. However, in the present work diethyl
ether solvent is not cleaved by triflic anhydride.
(19) The isopropyl methine proton signal, at 27 °C, was so broad as
to be undetectable. At the higher temperature used, an unresolved
broad band developed, indicating its position in the spectrum.
J O9710184