Nucleophilic activation of a nitrile group: Synthesis of trifluoromethyl substituted 4H-1,3,5-dioxazines

Article abstract of DOI:10.1016/j.jfluchem.2011.12.013

The negatively charged carbon atom of phosphorus ylides is capable of increasing the nucleophilicity of the triple CN bond. The nitrile group activated in this way can add two equivalents of hexafluoroacetone with the formation of trifluoromethyl substituted 4H-1,2,3-dioxazines. Due to delocalization of the ylidic negative charge one of the C-C bonds acquires a double bond character, the consequence of which is the existence of E/Z-isomerism in these compounds.

Full text of DOI:10.1016/j.jfluchem.2011.12.013

Journal of Fluorine Chemistry 135 (2012) 379–382
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Short communication
Nucleophilic activation of a nitrile group: Synthesis of trifluoromethyl substituted
4H-1,3,5-dioxazines
*
Kostiantyn V. Turcheniuk, Igor V. Shevchenko
Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Murmanskaya str. 1, 02660 Kiev, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
The negatively charged carbon atom of phosphorus ylides is capable of increasing the nucleophilicity of
the triple CN bond. The nitrile group activated in this way can add two equivalents of hexafluoroacetone
with the formation of trifluoromethyl substituted 4H-1,2,3-dioxazines. Due to delocalization of the ylidic
negative charge one of the C–C bonds acquires a double bond character, the consequence of which is the
existence of E/Z-isomerism in these compounds.
Received 6 September 2011
Received in revised form 23 December 2011
Accepted 26 December 2011
Available online 13 January 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
Nitriles
Dioxazines
Ylides
Hexafluoroacetone
Imines
1. Introduction
which is absolutely coplanar. Both carbon atoms in this fragment
C7-C11 also have ideal flat geometry, and the bond length between
´
˚
Due to high energy of the triple CBB N bond (224 kcal/mol) the
nitrile group is chemically rather stable. On the other hand, there
are several examples of nitriles X-CN (where X = NR2, SR, SeR, PR2,
Cl) which display the increased nucleophilicity and can add two
equivalents of hexafluoroacetone (HFA) to the CN group with the
formation of 4H-1,3,5-dioxazines (Scheme 1) [1].
As the cyanide anion itself (CN)À does not react with HFA in this
way [2], one can conclude, that the conjugation of the electrons of
the substituents with CN triple bond is the necessary condition for
such reactions.
them is only 1.396 A. This value is abnormally short for a single C–C
bond and it is comparable with the length of a double C55C bond.
This testifies to the considerable level of conjugation between the
pn orbital of the ylidic carbon atom and the p-system of the C55N
double bond as well as to the delocalization of the ylidic negative
charge. Apparently the delocalization is promoted by the
electronegative atoms and groups forming the six-member ring
and stabilizing the zwitterionic structure (Scheme 3). Because of
the double bond character of the C7–C11 bond, compound 4a can
be represented by E- and Z-isomers. According to the X-ray data
the crystal lattice of this compound consists of only E-isomers. E-
and Z-isomers are well distinguishable in the NMR spectra. Since
all NMR data show the presence in the reaction solution of only one
compound, one can conclude that the interaction of HFA with the
nitrile group of ylide 3a proceeds stereoselectively with the
formation of E-isomer.
Unlike the abovementioned example the reactions of ylides 3b
and 3c with HFA are not stereoselective and result in the
formation of a mixture of E- and Z-isomers (Scheme 3). This is
probably accounted for by lower degree of double bond character
between the two carbon atoms in the PCCN chain and
consequently by lower energetic barrier separating the isomers.
The NMR data of E-isomers in compounds 4a–c are similar which
allows clear assignment. In solution there is a dynamic equilibri-
um between the isomers. For instance, the E/Z ratio in chloroform
for 3b and 3c is 2:1 and 4:1, respectively. The position of the
equilibrium depends also on the solvent used. It is interesting that
2. Results and discussion
We have found that the negatively charged carbon atom of
phosphorus ylides is also capable of increasing the nucleophilicity
of the triple CN bond. For example, CN group in ylides 3 easily adds
two equivalents of HFA with the formation of appropriate 4H-
1,2,3-dioxazines 4a–c (Scheme 2). The reactions proceed almost
quantitatively to give NMR spectroscopically rather pure products,
which can also be isolated in crystalline form. The molecular
structure of dioxazine 4a containing dimethylamino groups at the
phosphorus atom has been investigated by X-ray analysis (Fig. 1). A
peculiarity of this molecule is the structure of the PCCN fragment,
* Corresponding author. Tel.: +380 44 573 25 89; fax: +380 44 558 25 52/732552.
E-mail address: igorshevchenko@yahoo.com (I.V. Shevchenko).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.12.013

380
K.V. Turcheniuk, I.V. Shevchenko / Journal of Fluorine Chemistry 135 (2012) 379–382
X
R3P
N
F3C
F3C
CH(CF3)2
O
CF3
CF3
R3P
N
F3C
F3C
CH(CF3)2
O
CF3
CF3
(F3C)2HC
N
F3C
F3C
PR3
O
CF3
CF3
C
O
C
O
C
O
X
C
N
N
O
CF3
CF3
2(CF3)2CO
F3C
F3C
O
1
2
Z-isomer
E-isomer
4a-c
4a-c
4b-c
X = NR2 ; SR ; SeR ; PR2 ; Cl
R: NMe2, i-PrO, n-Bu
Scheme 1.
Scheme 3.
R3P
CH(CF3)2
C
O
R3P
CH(CF3)2
R3P
N
F3C
F3C
CH(CF3)2
C
C
N
R3P
N
CH(CF3)2
O
C
O
2(CF3)2CO
N
O
CF3
CF3
F3C
F3C
O
CF3
CF3
-(CF3)2CO
F3C
CF3
5b-c
H2O
3a-c
4a-c
4b-c
E/Z-isomer
R = NMe2 (a); i-PrO (b); n-Bu (c)
R: i-PrO, n-Bu
Scheme 2.
CH(CF3)2
R3P
CH(CF3)2
O
n-Bu3P O
in the solid phase after crystallization only the E-isomer is
present, which in 15–20 min after dissolution comes again to the
equilibrium with Z-isomer.
H2O
7
R: n-Bu
HN
O
HN
F3C
F3C
F3C
Analogously to the examples described earlier, dioxazines 4a–c
slowly eliminate one equivalent of HFA even in solution [1a]. This
process accelerates in the presence of water. We have studied the
hydrolysis of dioxazines 4b and 4c. In both cases the process is
slow and includes the successive formation of acylimines 5b–c and
amides 6b–c during several days at 25 8C. The intermediate
compounds 5b–c cannot be isolated under these reaction
conditions, but they are detectable in the 31P NMR and in the
mass spectra. For example, 5c in the reaction mixture showed M+1
signal at 558.2 (APCI). Unlike iso-propoxy compound 6b which is
stable, the butyl-substituted derivative 6c is capable of further
hydrolyses with the cleavage of the PC bond to give tributylpho-
sphine oxide 7 and amidoalcohol 8. As the rates of all these stages
are approximately equal, the reaction mixture before completion
OH
OH
6b-c
F3C
8
Scheme 4.
of the hydrolysis contains a mixture of these intermediate
compounds in different proportions (Scheme 4).
3. Conclusions
The negatively charged carbon atom of phosphorus ylides
activates the nucleophilicity of the adjacent nitrile group. Such
nitriles can add two equivalents of hexafluoroacetone to the CN
triple bond to give trifluoromethyl substituted 4H-1,3,5-dioxa-
zines. Because of delocalization of the negative charge one formally
single C–C bond acquires a double bond character and such
compounds can exist as E- and Z-isomers. Depending on the
substituents at phosphorus atom this reaction can go stereo-
selectively with the formation of only one isomer.
4. Experimental
All operations were performed under nitrogen in a dry box.
Solvents were dried and purified according to common procedures.
The 1H, 13C, 19F and 31P NMR spectra were recorded with Varian
Gemini 400 MHz, Bruker Avance 400 and JEOL FX-90Q spectro-
meters. The
tetramethylsilane (TMS), the d 31P values were measured relative
d d
1H and 13C chemical shifts are referenced to
to 85% aqueous H3PO4 and the
relative to CCl3F.
d
19F chemical shifts are given
4.1. Ylides 3a–c: common procedure
A solution of (CF3)2C55C(H)CN (1.05 equiv.) in hexane (1 mL)
was added to solution of the corresponding phosphorus
compound [(Me2N)3P, (i-PrO)3P, (n-Bu)3P] (0.5 mmol) in hexane
(1 mL) at room temperature. The reaction completed in 20 min for
3a, c and in ca. 1 week (31P NMR control) for 3b. The products
crystallized from the reaction mixture during 2 days at À16 8C.
Fig. 1. Ortep drawing of 4a (ellipsoids are drawn at the 30% probability level, bonds
a
´
˚
to H atoms are missed for clarity). Selected bond lengths [A] and angles [8]: C7–C11
1.397, C7–P1 1.747, C11–N4 1.295, C7–C8 1.512, C11–O2 1.399, C12–O2 1.392,
C12–O1 1.398; C8–C7–P1 118.8, C11–C7–P1 117.0, C11–C7–C8 124.1, C7–C11–O2
113.6, N4–C11–C7 125.4, N4–C13–O1 117.9, O2–C12–O1 115.8, O2–C11–C7–C8
0.56, N4–C11–C7–P1 0.82.

K.V. Turcheniuk, I.V. Shevchenko / Journal of Fluorine Chemistry 135 (2012) 379–382
381
4.1.1. 4,4,4-Trifluoro-3-(trifluoromethyl)-2-
4.2.2. (E)-2,2,4,4-Tetrakis(trifluoromethyl)-6-[3,3,3-trifluoro-2-
(trifluoromethyl)-1-(triisopropoxyphosphoranylidene)propyl]-4H-
1,3,5-dioxazine (4b)
[tris(dimethylamino)phosphoranylidene]-butanenitrile (3a)
White solid (148.5 mg, 84.3%), mp 184–186 8C. 1H NMR
(400 MHz, CDCl3):
d
2.7 (1H, m, CH(CF3)2), 2.7 (18H, d,
11.0 (1C, dm,
Colorless crystals (59.1 mg, 40.5%), mp 48–50 8C. 1H NMR
J = 9.3 Hz, CH3); 13C{1H} NMR (100 MHz, CDCl3):
d
(400 MHz, CDCl3):
J = 20.0 Hz, J = 9.3 Hz, CH(CF3)2), 4.9 (1H, oct, J = 6.4 Hz); 13C{1H}
NMR (100.6 MHz, CDCl3): 23.2 (6C, d, J = 5 Hz, CH3), 43.3 (1C, dm,
d 1.4 (18H, d, J = 6.4 Hz, CH3), 3.9 (1H, dsept,
J = 232 Hz, P55C), 37.3 (6C, d, J = 4 Hz, CH3), 46.4 (1C, dsept,
J = 30 Hz, J = 15 Hz, CH(CF3)2), 123.8 (2C, q, J = 284 Hz, CF3), 124.9
(1C, d, J = 14 Hz, CN); 19F NMR (84 MHz, CDCl3):
J = 9 Hz, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3):
APCI-MS m/z: 353.1 [M+H]+.
d
d
d
67.4 (6F, d,
64.1 (1P, s);
J = 237 Hz, P55C), 48.2 (1C, dsept, J = 32 Hz, J = 11 Hz, CH(CF3)2),
76.1 (3C, d, J = 8 Hz, P–C), 83.4 (1C, m, C(CF3)2), 91.5 (1C, m,
C(CF3)2), 118.7 (2C, q, J = 290 Hz, CF3), 120.5 (2C, q, J = 290 Hz, CF3),
123.3 (2C, q, J = 282 Hz, CF3), 159.6 (1C, d, J = 18 Hz, C55N); 19F NMR
4.1.2. 4,4,4-Trifluoro-3-(trifluoromethyl)-2-
(84 MHz, CDCl3):
d
À83.2 (6F, br s, CF3), À82.5 (6F, br s, CF3), À67.4
(triisopropoxyphosphoranylidene)butanenitrile (3b)
(6F, br s, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3): 41.2 (1P, s).
White needless (196.7 mg, 99%), mp 44–46 8C. 1H NMR
(400 MHz, CDCl3):
J = 15.6 Hz, J = 8.3 Hz, CH(CF3)2), 4.8 (1H, oct, J = 6.34 Hz); 13C{1H}
NMR (100.6 MHz, CDCl3): 9.2 (1C, dm, J = 270 Hz, P55C), 23.3 (6C,
d, J = 5 Hz, CH3), 46.5 (1C, dsept, J = 30 Hz, J = 11 Hz, CH(CF3)2), 75.5
(3C, d, J = 6 Hz, CH), 122.0 (1C, d, J = 18 Hz, CN), 123.5 (2C, q,
d
1.4 (18H, d, J = 6.3 Hz, CH3), 3.1 (1H, dsept,
4.2.3. (Z)-2,2,4,4-Tetrakis(trifluoromethyl)-6-[3,3,3-trifluoro-2-
(trifluoromethyl)-1-(triisopropoxyphosphoranylidene)propyl]-4H-
1,3,5-dioxazine (4b)
d
1H NMR (400 MHz, CDCl3):
d
1.4 (18H, d, J = 6.4 Hz, CH3), 4.4
(1H, dsept, J = 29.3 Hz, J = 9.3 Hz, CH(CF3)2), 4.8 (1H, oct, J = 6.4 Hz,
CH(CH3)2); 13C{1H} NMR (100.6 MHz, CDCl3):
23.0 (6C, d, J = 5 Hz,
J = 282 Hz, CF3); 19F NMR (84 MHz, CDCl3):
d
À67.8 (6F, d, J = 8 Hz,
46.7 (1P, s); ESI-MS
d
CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3):
d
CH3), 44.3 (1C, dm, J = 233 Hz, P55C), 46.8 (1C, dsept, J = 31 Hz,
J = 8 Hz, CH(CF3)2), 84.3 (1C, m, C(CF3)2), 90.9 (1C, m, C(CF3)2),
118.8 (2C, q, J = 290 Hz, CF3), 120.6 (2C, q, J = 290 Hz, CF3), 123.4
(2C, q, J = 282 Hz, CF3), 159.3 (1C, d, J = 18 Hz, C55N); 19F NMR
m/z: 398.2 [M+H]+.
4.1.3. 4,4,4-Trifluoro-2-(tributylphosphoranylidene)-3-
(trifluoromethyl)butanenitrile (3c)
(84 MHz, CDCl3):
d
À83.4 (6F, br s, CF3), À82.1 (6F, br s, CF3), À66.7
White needless (160.5 mg, 82%), mp 94–96 8C. 1H NMR
(6F, d, J = 9 Hz, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3): 39.0
(400 MHz, CDCl3):
(CH2)2), 1.8–1.9 (6H, m, CH2), 2.9 (1H, dsept, J = 15.6 Hz, J = 6.2 Hz,
CH(CF3)2); 13C{1H} NMR (100.6 MHz, CDCl3):
0.3 (1C, dm,
J = 135 Hz, P55C), 13.2 (3C, s, CH3), 22.0 (3C, d, J = 55 Hz, P–C), 23.1
(3C, d, J = 3 Hz, CH2), 23.7 (3C, d, J = 15 Hz, CH2), 46.6 (1C, dsept,
J = 29 Hz, J = 11 Hz, CH(CF3)2), 123.6 (2C, q, J = 286 Hz, CF3), 125.0
d
0.9 (9H, t, J = 6.8 Hz, CH3), 1.4–1.6 (12H, m,
(1P, s).
d
4.2.4. (E)-2,2,4,4-Tetrakis(trifluoromethyl)-6-[3,3,3-trifluoro-1-
(tributylphosphoranylidene)-2-(trifluoromethyl)propyl]-4H-1,3,5-
dioxazine (4c)
Colorless crystals (67 mg, 46.3%), mp 84–86 8C. 1H NMR
(1C, d, J = 13 Hz, CN); 19F NMR (84 MHz, CDCl3):
d
À67.4 (6F, d,
d 30.5 (1P, s);
(400 MHz, CDCl3):
(CH2)2), 2.0–2.1 (6H, m, P–CH2), 2.86 (1H, dsept, J = 16.1 Hz,
J = 8.3 Hz, CH(CF3)2); 13C{1H} NMR (100.6 MHz, CDCl3):
13.1 (3C,
d 0.9 (9H, t, J = 6.8 Hz, CH3), 1.4–1.5 (12H, m,
J = 7 Hz, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3):
APCI-MS m/z: 392.3 [M+H]+.
d
s, CH3), 19.7 (3C, d, J = 56 Hz, P–C), 23.3 (3C, d, J = 4 Hz, CH2), 23.6
(3C, d, J = 15 Hz, CH2), 34.0 (1C, d, J = 120 Hz, P55C), 47.9 (1C, dsept,
J = 31 Hz, J = 10 Hz, CH(CF3)2), 83.8 (1C, m, C(CF3)2), 91.1 (1C, m,
C(CF3)2), 118.9 (2C, q, J = 290 Hz, CF3), 120.2 (2C, q, J = 290 Hz, CF3),
123.2 (2C, q, J = 282 Hz, CF3), 158.1 (1C, d, J = 20 Hz, C55N); 19F NMR
4.2. Dioxazines 4a–c: common procedure
Hexafluoroacetone (2.5 equiv.) was condensed in a solution
of ylide (0.2 mmol) in CDCl3 (2 mL) in a small autoclave (10 mL).
The reaction mixture was heated at 50 8C for 2 h and then left at
room temperature for 4 days. As the reaction goes almost
quantitatively, CDCl3 was used as a solvent to record the NMR
spectra of the reaction solutions. In the case of R = NMe2 the
formation of only E-isomer was observed in the reaction
solution. Compounds 4a, 4c crystallized from the reaction
mixture in 3 days at À16 8C. Compound 4b crystallized from
hexane at À16 8C during 3 days. In all cases the solvent could
slowly evaporate from the crystallization flask through a needle
to provide the slow concentration of the solution during
crystallization. In crystalline form the compounds exist as E-
isomers.
(84 MHz, CDCl3):
d
À80.7 (6F, br s, CF3), À80.5 (6F, br s, CF3), À64.3
(6F, br d, J = 8 Hz, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3):
d
28.9 (1P, s).
4.2.5. (Z)-2,2,4,4-Tetrakis(trifluoromethyl)-6-[3,3,3-trifluoro-1-
(tributylphosphoranylidene)-2-(trifluoromethyl)propyl]-4H-1,3,5-
dioxazine (4c)
1H NMR (400 MHz, CDCl3):
d
0.9 (9H, t, J = 7.2 Hz, CH3), 1.3–1.5
(12H, m, (CH2)2), 2.1–2.2 (6H, m, P–CH2), 4.6 (1H, dsept, J = 23.5 Hz,
J = 9.8 Hz, CH(CF3)2); 13C{1H} NMR (100.6 MHz, CDCl3):
13.3 (3C,
d
s, CH3), 19.5 (3C, d, J = 55 Hz, P–CH2), 23.5 (3C, d, J = 4 Hz, CH2), 23.9
(3C, d, J = 14 Hz, CH2), 36.2 (1C, d, J = 114 Hz, P55C), 46.4 (1C, dsept,
J = 31 Hz, J = 6 Hz, CH(CF3)2), 84.4 (1C, m, C(CF3)2), 90.4 (1C, m,
C(CF3)2), 118.9 (2C, q, J = 290 Hz, CF3), 120.2 (2C, q, J = 290 Hz, CF3),
123.2 (2C, q, J = 282 Hz, CF3), 157.8 (1C, d, J = 18 Hz, C55N); 19F NMR
4.2.1. (E)-2,2,4,4-Tetrakis(trifluoromethyl)-6-{3,3,3-trifluoro-2-
(trifluoromethyl)-1-[tris(dimethylamino)phosphoranylidene]-
propyl}-4H-1,3,5-dioxazine (4a)
(84 MHz, CDCl3):
d
À80.9 (6F, br s, CF3), À80.3 (6F, br s, CF3), À64.0
Yellow crystals (63.4 mg, 46.3%), mp 99–101 8C. 1H NMR
(6F, d, J = 10 Hz, CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3):
d 26.9
(400 MHz, CDCl3):
J = 20.5 Hz, J = 8.8 Hz, CH(CF3)2); 13C{1H} NMR (100 MHz, CDCl3):
37.2 (6 C, d, J = 5 Hz, CH3), 44.0 (1 C, d, J = 200 Hz, P55C), 48.2 (1C,
dsept, J = 31 Hz, J = 14 Hz, CH(CF3)2), 83.8 (1C, m, C(CF3)2), 90.7
(1C, m, C(CF3)2), 118.8 (2C, q, J = 290 Hz, CF3), 120.1 (2C, q,
J = 289 Hz, CF3), 123.8 (2C, q, J = 282 Hz, CF3), 157.8 (1C, d,
d
2.7 (18H, d, J = 9.3 Hz, CH3), 3.2 (1H, dsept,
(1P, s).
d
4.3. 4,4,4-Trifluoro-N-[2,2,2-trifluoro-1-hydroxy-1-
(trifluoromethyl)ethyl]-3-(trifluoromethyl)-2-
(triisopropoxyphosphoran-ylidene)butanamide (6b)
J = 25 Hz, C55N); 19F NMR (84 MHz, CDCl3):
d
À80.8 (6F, s, CF3),
To dioxazine 4b (E/Z = 2:1) (30 mg, 0.041 mmol) in CDCl3
(0.5 mL) water (0.3 mL) was added. The reaction was conducted at
25 8C in a NMR tube to monitor the hydrolysis. After completion of
À79.9 (6F, s, CF3), À63.9 (6F, br s, CH(CF3)2); 31P{1H} NMR
(36.2 MHz, CDCl3):
d 64.8 (1P, s).

382
K.V. Turcheniuk, I.V. Shevchenko / Journal of Fluorine Chemistry 135 (2012) 379–382
3
˚
the reaction (ca. 24 h) water (1 mL) was additionally added and
then separated from the mixture to remove the hexafluoroacetone
hydrate. The solvent was evaporated in vacuo to give a light-yellow
V = 2537.2(2) A , T = 296(2) K, space group P 2(1)/c; Z = 4,
m
(Mo-
˚
Ka
) = 0.266 mmÀ1
5310 unique (Rint = 0.0570). Final
wR(F2) = 0.0875 (for 3782 reflections with I/
,
l
= 0.71073 A, 27184 reflections measured,
R
indices R1 = 0.0432,
(I) > 2.0). The
solid (20 mg, 83.9%); mp 63–65 8C. 1H NMR (400 MHz, CDCl3):
d
1.3
s
(18H, d, J = 5.9 Hz, CH3), 3.8 (1H, dsept, J = 22.0 Hz, J = 9.8 Hz,
CH(CF3)2), 4.8 (1H, dsept, J = 8.3 Hz, J = 5.9 Hz, CH(CH3)2), 5.8 (1H,
structure was solved by direct methods and refined by full-matrix
least-squares on F2 using the SHELX-97-program system [3].
Crystallographic data (excluding structure factors) for the struc-
ture reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation nos. CCDC-820011. Copies of the data can be obtained, free
of charge, on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK, fax: +44 1223 336033; deposit@ccdc.cam.ac.uk or via
www.ccdc.cam.ac.uk/conts/retrieving.html.
br s, NH), 11.3 (1H, br s, OH); 13C{1H} NMR (100.6 MHz, CDCl3):
d
23.3 (6C, d, J = 5 Hz, CH3), 44.9 (1C, dm, J = 239 Hz, P55C), 46.9 (1C,
dsept, J = 30 Hz, J = 12 Hz, CH(CF3)2), 79.0 (3C, d, J = 7 Hz, CH), 84.3
(1C, sept, J = 32 Hz, C(CF3)2), 121.4 (2C, q, J = 289 Hz, CF3), 123.8
(2C, q, J = 285 Hz, CF3), 173.6 (1C, d, J = 17 Hz, C55O); 19F NMR
(84 MHz, CDCl3):
d
À83.1 (6F, s, CF3), À64.7 (6F, d, J = 10 Hz,
CH(CF3)2); 31P{1H} NMR (36.2 MHz, CDCl3): 43.0 (1P, s); ESI-MS m/
z = 582.0 [M+H]+.
Acknowledgments
4.4. Hydrolysis of 4c
The authors thank Professor A. Chernega and Dr. E. Rusanov for
the X-ray diffraction study of compound 4a.
To dioxazine 4c (E/Z = 4:1) (30 mg, 0.041 mmol) in CDCl3
(0.5 mL) water (0.3 mL) was added. The reaction was conducted at
25 8C in a NMR tube to monitor the hydrolysis. After completion of
the reaction (ca. 10 d) water (1 mL) was additionally added and
then separated from the mixture to remove the hexafluoroacetone
hydrate. The NMR and mass-spectroscopic study of the reaction
mixture revealed tris(n-butylphosphine)oxide 7 and compound 8.
References
[1] (a) M.E. Hermes, R.A. Braun, J. Org. Chem. 31 (1966) 2568–2571;
(b) U. Utebaev, E.M. Rokhlin, I.L. Knunyants, Bull. Acad. Sci. USSR Div. Chem. Sci.
(Engl. Transl.) 23 (1974) 2177–2180;
(c) A.V. Davydov, J. Gen. Chem. USSR (Engl. Transl.) 51 (1981) 2362–2368;
(d) J. Lucas, D. Amirzadeh-Asl, H. Djarrah, H.W. Roesky, Phosphorus Sulfur Relat.
Elem. 18 (1983) 69–72;
(e) R. Richter, B. Tucker, H. Ulrich, J. Org. Chem. 48 (1983) 1694–1700;
(f) H.W. Roesky, N.K. Homsy, M. Noltemeyer, G.M. Sheldrick, Angew. Chem. 96
(1984) 1002–1003;
(g) H.W. Roesky, J. Lucas, K.-L. Weber, H. Djarrah, E. Egert, M. Noltemeyer, G.M.
Sheldrick, Chem. Ber. 118 (1985) 2396–2406;
(h) H.W. Roesky, J. Fluorine Chem. 30 (1985) 123–140;
(i) N.K. Homsy, H.W. Roesky, J. Lucas, V.W. Pogatzki, J. Fluorine Chem. 29 (1985)
93;
4.4.1. 4,4,4-Trifluoro-N-[2,2,2-trifluoro-1-hydroxy-1-
(trifluoromethyl)ethyl]-3-(trifluoromethyl)butanamide (8)
1H NMR (400 MHz, CDCl3):
d
2.7 (2H, d, J = 5.9 Hz, CH2), 3.9 (1H,
m, CH(CF3)2), 5.9 (1H, br, NH), 10.1 (1H, br, OH); 13C{1H} NMR
(100.6 MHz, CDCl3): 29.2 (1C, s, CH2), 44.2 (1C, sept, J = 29 Hz,
d
CH(CF3)2), 90.4 (1C, sept, J = 33 Hz, C(CF3)2), 123.0 (2C, q,
J = 279 Hz, CF3), 123.1 (2C, q, J = 279 Hz, CF3), 174.1 (1C, s, CO);
19F NMR (84 MHz, CDCl3):
d
À83.0 (6F, s, CF3), À68.2 (6F, d, J = 9 Hz,
CH(CF3)2); ESI-MS m/z: 374.0 [MÀH]À.
(i) H.W. Roesky, V.W. Pogatzki, K.S. Dhathathreyan, A. Thiel, H.G. Schmidt, M.
Dyrbusch, M. Noltemeyer, G.M. Sheldrick, Chem. Ber. 119 (1986) 2687–2697;
(k) I.V. Martynov, A.Yu. Aksinenko, A.N. Chekhlov, O.V. Korenchenko, I.N. Torgun,
V.B. Sokolov, J. Gen. Chem. USSR (Engl. Transl.) 59 (1989) 1397–1400.
[2] (a) T. Mill, J.O. Rodin, R.M. Silverstein, C. Woolf, J. Org. Chem. 29 (1964)
3715–3716;
(b) Yu.V. Zeifman, S.A. Postovoi, A.F. Aerov, E.I. Mysov, J. Fluorine Chem. 65 (1993)
189–194.
[3] G.M. Sheldrick, SHELX-97, University of Go¨ttingen, 1997.
4.5. Crystal data for 4a
Data were collected on Bruker Smart Apex II Enraf-Nonius CAD4
difractometer. C17H19F18N4O2P, M = 684.33, monoclinic,
˚
a = 10.6750(5), b = 16.2543(7), c = 15.3661(7) A,
b
= 107.899(2)8,