Reaction of RF-palmitic acid-F13 with dicyclohexylcarbodiimide

Article abstract of DOI:10.1016/j.jfluchem.2007.05.005

The 1,3-dicyclohexylcarbodiimide (DCC) adduct of R_F-palmitic acid-F₁₃ 1 has been synthesized and characterized. The X-ray crystal structure shows that the product arises from an O- to N-acyl migration of an initially formed N,N′-dicy

Full text of DOI:10.1016/j.jfluchem.2007.05.005

Journal of Fluorine Chemistry 128 (2007) 1026–1028
www.elsevier.com/locate/fluor
Reaction of RF-palmitic acid-F13 with dicyclohexylcarbodiimide
a
b
Gerald W. Buchanan a, , Majid F. Rastegar , Gary Enright
*
a Ottawa-Carleton Chemistry Institute, Department of Chemistry, Carleton University, Ottawa, Canada K1S 5B6
b Steacie Institute for Molecular Sciences, National Research Council, Ottawa, Canada K1A 0R6
Received 15 March 2007; received in revised form 30 April 2007; accepted 8 May 2007
Available online 13 May 2007
Abstract
The 1,3-dicyclohexylcarbodiimide (DCC) adduct of RF-palmitic acid-F13 1 has been synthesized and characterized. The X-ray crystal structure
shows that the product arises from an O- to N-acyl migration of an initially formed N,N0-dicyclohexyl-O-RF-palmitoyl-F13-isourea 2 to give 1-RF-
palmitoyl-F13-1,3-dicyclohexylurea 3. X-ray data for an RF-palmitic acid-F13 unit are reported for the first time. The product of the reaction of DCC
with palmitic acid is also the urea derivative which has been characterized by IR and NMR methods.
# 2007 Elsevier B.V. All rights reserved.
Keyword : Fluorinated palmitic acid derivative
1. Introduction
NMR data were included for either the original or rearranged
products and characterization was made using IR and 1H NMR
only.
Carboxylic acids are known to react with carbodiimides such
as 1,3-dicyclohexylcarbodiimide (DCC) to give acylisourea
intermediates which subsequently rearrange to urea derivatives
[1]. The bulky DCC group can be effectively employed to
function as an end cap for a variety of rotaxanes [2] and the
reagent is particularly useful for the acylation step in the
synthesis of polypeptides from amino acids [3,4]. The acyl
group is highly reactive in this environment because cleavage of
the acyl-oxygen bond converts the C N bond of the isourea to a
more stable C O moiety [5–7]. Although this O-acyl to N-acyl
migration has been reported several times [5–9] little detailed
structural information on the products has been available due to
During the course of our attempted synthesis of glycerol
tripalmitate-F39 [11] we had the occasion to react RF-palmitic
acid-F13 1 with DCC. The X-ray crystal structure of the
resulting product has been determined and is the first available
X-ray crystal structure of this type of urea derivative. Further
characterization via 13C NMR and IR spectroscopic methods is
also included. In order to examine the influence of fluorination
on the reaction, results for palmitic acid itself are compared to
those for those for the terminally perfluorinated system.
2. Results and discussion
the paucity of X-ray crystallographic data. Interpretation of 13
C
NMR data for these compounds is not straightforward, due to
the possibility of geometrical isomers about the C N in the
isoureas [8] and restricted rotation about amide type bonds in
the ureas. The literature contains one clear example of an
acylisourea converting to a urea derivative [10]. In this case,
ferrocene carboxylic acid reacts with DCC in THF at room
temperature to give N,N0-dicyclohexyl-O-ferrocenoylisourea,
which can be converted to N,N0-dicyclohexyl-N-ferroceneoy-
lurea in dioxane at reflux temperature. Unfortunately no 13C
The structure of the initially formed intermediate in the
reaction of 1 with DCC is shown below. In this isourea type
structure 2, the two nitrogen environments would be rendered
equivalent via a 1,3 proton shift (i.e. a tautomerisation) which,
by analogy with imidazole, should be fast on the NMR
timescale. This would lead to the expectation that there should
only be one 13C NMR chemical shift for cyclohexyl carbons
bonded to nitrogen in the region of 50–60 ppm. However, this is
not the case, indeed there are two resonances of equal intensity
at 49.8 and 55.1 ppm. These chemical shifts can be compared to
that observed for the C1 of cyclohexyl amine [12] at 51.4 ppm.
As expected for the rearranged product there are two chemical
shifts in the carbonyl region of the 13C spectrum, with the amide
* Corresponding author. Tel.: +1 613 520 3840.
E-mail address: gerald_buchanan@carleton.ca (G.W. Buchanan).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.05.005

G.W. Buchanan et al. / Journal of Fluorine Chemistry 128 (2007) 1026–1028
1027
type carbon (C14) being the most deshielded at 172.8 ppm.
The urea type carbonyl (C7) resonates at 154.0 ppm, which is
consistent with its lower double bond character due to the
influence of two directly bonded nitrogen atoms. The total
number of observed 13C resonances is 25, indicating that there
is no restricted rotation about bonds involving C7 or C14 on the
NMR timescale at room temperature.
amide carbon (C14) the three bond angles involving this carbon
are 121.48, 121.48 and 117.28 with the N1–C14–C15 angle
being the smallest. In the case of the urea type carbon (C7) the
N2–C7–N1 angle is 112.88, while the two angles involving the
oxygen atom are 121.48 and 125.88.
3. Experimental
The IR spectrum of the adduct shows strong absorptions at
1658 and 1698 cmꢀ1 which are essentially identical to the
values reported for the product of DCC with acetic acid [5]
in which rearrangement to the acetyldicyclohexylurea has
occurred. These findings support the argument that the isolated
product is in fact the rearranged product 3, which is now
confirmed by X-ray crystallography.
RF-palmitic acid-F13 1 was prepared as described previously
[14].
Compound 3 was prepared as follows: Under an argon
atmosphere, 0.98 g (2 mmol) of 1, 0.36 mL (2.6 mmol) triethyl
amine and 24.4 mg (0.2 mmol) of 4-(N,N-dimethylamino)pyr-
idine (DMAP) were added to an oven dried 50 mL round
bottom flask and dissolved in 25 mL of anhydrous dichlor-
omethane (DCM). The reaction mixture was stirred for 15 min
in an ice bath. Subsequently to this was added dropwise over a
period of 10 min a solution of dicyclohexylcarbodiimide
(DCC), 0.41g (2 mmol) in 10 mL of anhydrous DCM. The
For palmitic acid itself, we find similar results. Indeed the
dicyclohexylurea system 4 has been obtained in good yield
ruling out the possibility that the influence of the electro-
negative fluorine atoms in the chain is increasing the propensity
of the molecule to undergo the O-acyl to N-acyl migration.
2.1. X-ray crystallographic structure of 3
reaction mixture was stirred for 4 h in the ice bath and then
overnight at room temperature. The solvent was then removed
by rotary evaporation and the crude product was purified using
column chromatography on silica gel with 90:10 hexane:ethy-
lacetate as eluent. The main component was a white solid which
was dissolved in a minimal amount of toluene and treated with
activated carbon. Upon gradual cooling of the filtrate 0.63 g
(67% yield) of colorless crystals were obtained, mp 84–5 8C.
1H NMR of 3: 5.40 (d, 1H), 3.75 (m, 1H), 2.06 (t, J = 7.6,
2H), 1.98 (m, 2H), 1.82 (m, 3H), 1.60 (m, 10H), 1.23 (m, 18H),
1.04 (m, 4H). 13C NMR of 3: 172.8, 154.0, 120.8 (m), 118.3
(m), 115.7 (m), 113.6 (m), 111.3 (m), 108.6 (m), 55.1, 49.8,
35.5, 32.5, 30.7, 30.7 (t, J = 22.3), 29.2, 29.1 (intensity 2), 28.9,
26.1 (intensity 2), 25.4, 25.3, 25.2, 24.6, 19.9. Mass spec.
C29H41N2F13O2; electrospray ionization with K+: parent ion at
m/z = 734.6, arising from 696.6 + 39 ꢀ 1. Anal. calcd. for
C29H41N2F13O2: C 50.00, H 5.93, N 4.02, F 35.46, O 4.59.
Found: C 50.22, H 6.00, N 3.99, F 34.96.
The ORTEP structure of 3 is depicted below along with the
Crystallographic data and structure refinement in Table 1. Bond
lengths, bond angles, anisotropic displacement factors, hydro-
gen coordinates and torsion angles for 3 are presented in Tables
2–6, respectively and are available as Supplementary Data. The
conformation of the RF-palmitic acid portion of the adduct is of
particular interest, since no literature reports of fluorinated
palmitate X-ray structures have been published. In the non-
fluorinated part of the chain (C15–C23) the conformation is
almost perfectly staggered, with all C–C–C–C angles near
1808. This geometry is somewhat altered in the fluorinated
portion of the chain (C24–C29), with typical C–C–C–C torsion
angles in the range of 160–1658. There is some evidence for a
slight helicity in this part of the chain and the structure is similar
to that observed in the fluorinated portion of hydrated bis(n-
perfluoroalkyl)phosphinic acids [13].
Another point of interest are the bond angles involving the
amide and urea type carbon oxygen double bonds. For the
Compound 4 was prepared as follows: Under an argon
atmosphere, 1.024 g (4 mmol) of palmitic acid, 0.36 mL

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G.W. Buchanan et al. / Journal of Fluorine Chemistry 128 (2007) 1026–1028
1H NMR of 4: 7.20 (bs, 1H), 3.85 (m, 1H), 3.63 (m, 1H),
Table 1
Crystal data and structure refinement for 3
2.35 (t, J = 7.6, 2H), 1.75 (m, 12H), 1.21 (m, 34H), 0.83 (t, 6.6,
3H). 13C NMR of 4: 174.0, 154.1, 56.0, 49.7, 35.9, 32.7, 31.9,
30.9 (intensity 2), 29.8 (intensity 2), 29.7 (intensity 2), 29.6,
29.5, 29.4, 29.3, 29.2, 26.4 (intensity 2), 25.5 (intensity 2), 25.3,
24.7, 22.7, 14.1. Mass spec. C29H54N2O2; electron impact
predicted m/z for parent ion at 462.7, obsd. M ꢀ 1 at 461.7.
Anal. calcd. for C29H54N2O2: C 75.27, H 11.76, N 6.05, O 6.91.
Found: C 75.41, H 11.63, N 5.99, O 6.97.
X-ray crystallographic measurements and structure refine-
ment details are given along with Supplementary Data. The
complete set of X-ray data have been placed in the International
Data Base, reference number CCDC 644471.
Identification code
Empirical formula
Formula weight
Temperature
3
C29H41F13N2O2
696.64
125(1) K
˚
0.71073 A
Wavelength
Elemental analyses were carried out by Canadian Micro-
analytical Service Ltd. Delta B.C. Canada.
Crystal system
Space group
Monoclinic
P12(1)/c1
˚
Unit cell dimensions
a = 15.6192(12) A, a = 908;
˚
4. Conclusions
b = 9.2323(7) A, b = 108.3770(10)8;
˚
c = 23.9898(18) A, g = 908
3
˚
13C NMR and X-ray crystallographic analysis indicates that
the reaction of fluorinated and non-fluorinated fatty acids with
DCC yields rearranged urea derivatives exclusively.
Volume
3282.9(4) A
Z
4
Density (calculated)
Absorption coefficient
F(0 0 0)
1.409 Mg/m3
0.138 mmꢀ1
1448
Crystal size
0.450 mm ꢁ 0.30 mm ꢁ 0.30 mm
Appendix A. Supplementary data
Theta range for data collection
Index ranges
1.37–29.608
ꢀ21 ꢂ h ꢂ 21, ꢀ12 ꢂ k ꢂ 12,
ꢀ33 ꢂ 1 ꢂ 33
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.jfluchem.
2007.05.005.
Reflections collected
39,470
Independent reflections
Completeness to u = 29.608
Absorption correction
Refinement method
9141 [R(int) = 0.0290]
99.0%
Multiscan
Full-matrix least-squares on F2
References
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2s(I)]
R indices (all data)
9141/0/579
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