Guanidinophosphazenes: Synthesis, Application and Basicity in THF and in the Gas Phase
Alexander A. Kolomeitsev

Team

HFC Company Profile 1
•
Hansa Fine Chemicals GmbH was created as a University of Bremen (Germany) spin-off and was launched as a Limited Company (GmbH) in February 2003. The company’s operating base are state of the art laboratories and offices located within the University of
Bremen Chemistry Department.
• HFC is entirely independent of any other companies or research establishments and is solely owned by its working partners. We are used to working within a strictly controlled, confidential and if desired exclusive environment with our clients that ensures all sensitive data, results and analysis is protected.
• We are a research driven company and offer our clients world leading know-how in the fields of fluoro and phosphorus chemicals, reagents for fluorination, polyfluoroalkylation and fluorinated building blocks for the synthesis of compounds with potential biological activity.
•
These proprietary technologies are new methods that allow the production of complex molecules. It permits the synthesis of novel compounds under commercially accessible conditions for the first time.
•
A key competence is the production of new types of compounds. In many cases complex
F-derivatives, which were either too difficult or impossible to prepare by other fluorination methods, can be designed and synthesised. These compounds are ideally suited for high added-value sectors such as healthcare, pharmaceutical, agro-chemical, additives and microelectronics.

2
• The core product list encompasses compounds in the following categories:
• F- and R
F
-aromatics
• Fluorinated amines, amino acids and related compounds
• Fluorinated and non-fluorinated acids and corresponding esters (acrylic, crotonic, pyruvic, glyoxylic, atrolactic etc.)
• Fluorinated alcohols
• Fluorinated imines, ketones and

,

-enones
• Fluorinated 1,2- and 1,3-diketones, 1,3-ketoesters, 1,3,5-triketones,

aminoenones
• Fluorinated 3-, 5-, 6-, 7-membered N-, O-, S-, P-heterocycles
• Special reagents (for perfluoroalkylation, fluorination etc.)
• Phenacyl bromides
• Thiosemicarbazides
•
Organophosphorus compounds
• In addition, Hansa Fine Chemicals, using a variety of synthesis strategies and analysis techniques, offers services in three main areas:
• Custom fluoro/phosphorus synthesis in gram to kilogram quantities on an ad hoc basis
• Contract research projects
• Process analysis and characterisation

3
• Synthesis techniques using:
– Elemental fluorine
– Sulfur tetrafluoride, DAST, Deoxofluor®
– Bromine trifluoride
– HF/base systems
– Perfluoroalkylating reagents
– Trifluoromethyl Triflate and Difluorophosgene
– Sulfur chloride/bromide pentafluoride
– Hexafluoroacetone
• Special Processes:
• Fluorination
• Polyfluoro- and perfluoroalkylation
• Perfluoroalkoxylation
• Fluorodenitration
• Fluorodesulfurisation
• Halex process
• Phase transfer / Halex catalysts design
• Novel organic bases

Hoechst Patents: Preparation of fluorinecontaining compounds
EWG
EWG
F
-
source catalyst
Cl
F
R
1
R
2
R
1
R
2
N
R
1
N
R
1
P N
R
2
N
R
2
Cl (Br)
R
1
, R
2
= different Alkyl, cycloalkyl; -(CH
2
)
4
-
A.A. Kolomeitsev, S.V. Pazenok. DE 19631854/ WO 9805610/ EP 9704284 / US 6184425; B. Schiemenz, T.
Wessel, R. Pfirmann; DE 19934595.

2
4
• (R
2
N)
4
PX are robust PT catalysts which show their best activity between 170-240 °C. All catalysts of the PN-type exhibit potential dermal toxicity due to traces of HMPT or analogues and are therefore not the best choice for technical purposes.
Similar catalysts containing cyclic amine residues exhibit an improved biological profile

2-Azaallenium, Carbophosphazenium,
Aminophosphonium and Diphosphazenium Salts
Cl(Br) n
EWG fluoride source catalyst
F n
EWG
R
2
N
R
2
N
+
N
Cl
1
CNC +
NR
2
NR
2
R
2
N
R
2
N
+
N
Cl
2
PNC +
P
NR
2
NR
2
NR
2
R
2
N
R
2
N
+
N S
NR
2
Br
-
NR
2
3
SNC
+
M. Henrich, A. Marhold, A. A. Kolomeitsev, G.-V. Röschenthaler. DE 10129057/EP 1266904/US 2003036667
(to Bayer AG), Dec. 18, 2002 ; A. Marhold, A. Pleschke, M. Schneider, A.A. Kolomeitsev, G-V. Röschenthaler.
J. Fluorine Chem.
, 2004 , in press; M.Henrich, A. Marhold, A. A. Kolomeitsev, N. Kalinovich G.-V. Röschenthaler.
Tetrahedron Lett.
, 2003 , 44 , 5795-5798.

SCl
4
6 equiv. HMG
CH
2
Cl
2
, -70°C
Me
2
N
Me
2
N
C
C
NMe
2
N
S N
N
NMe
2
C
NMe
2
NMe
2
Cl
M. Henrich, A. Marhold, A. A. Kolomeitsev, G.-V. Röschenthaler, DE 10129057 /
EP 1266904/ US 2003036667 to Bayer AG), Dec. 18, 2002 ; M.Henrich, A. Marhold,
A. A. Kolomeitsev, N. Kalinovich G.-V. Röschenthaler.
Tetrahedron Lett.
, 2003 , 44 , 5795-5798.

2-Azaallenium, Carbophosphazenium Salts
Me
2
N
N
Me
2
N
HF
2
NMe
2
NMe
2
TMG-H
Me
2
N F
Me
2
N F
TMG-SiMe
3
CH
3
CN, -30°C
Me
2
N
NMe
2
N
Me
2
N
Me
3
SiF
2
NMe
2
(Et
2
N)
3
P=NSiMe
3
Me
2
N
Me
2
N
NEt
2
N P NEt
2
NEt
2
Me
3
SiF
2
M. Henrich, A. Marhold, A. A. Kolomeitsev, G.-V. Röschenthaler, DE 10129057/EP 1266904/
US 2003036667 (to Bayer AG), December, 18, 2002 ; A. Marhold, A. Pleschke, M. Schneider,
A.A. Kolomeitsev, G.-V. Röschenthaler, J. Fluorine Chem.
, 2004 , 125 , 1031-1038.
T. Ishikawa, T. Kumamoto, Guanidines in Organic Synthesis, Synthesis , 2006 , 737-752

Cl
Cl
CNC Catalysts
F Cl
Cl
KF, catalyst sulfolane
F F
+
F F
+
Cl
Cl
F
Temp.
[ °C]
First step (12 h)
CNC + (5 mol%) 230
(NMe
2
)
3
PNPPh
3
Br 3
(5 mol%)
Second step (24 h)
CNC + (5 mol%)
230
230
(NMe
2
)
3
PNPPh
3
Br 3 (5 mol%)
230
0
0
Cl
3
Benzene
15
GC area %
1
1
Cl
2
F
" 18
20
20
1
2
ClF
" 17
61
60
8
46
2
F
"
3
16
18
15
87
46
Rest
1
5
4
6
(side decomposition) reactions,
M. Henrich, A. Marhold, A. A. Kolomeitsev, G.-
V. Röschenthaler.
DE 10129057/ EP 1266904/ US 2003036667 (to Bayer AG). A.
Marhold, A. Pleschke, M. Schneider, A.A. Kolomeitsev,
G-V.
Röschenthaler.
J. Fluorine Chem.
, 2004 , 125 , 1031-1038

A Family of Phosphazene Bases
P-
Me
Me
Me alkyl-
P=NR phosphazenes, Appel
Me
2
N
Me
2
N
Me
2
N
P=NR
Pdialkylaminophosphazenes, P
1 bases, Issleib, Marchenko
Me
2
N
Me
2
N
(Me
2
N)
3
P=N
P=NR
(Me
2
N)
Me
2
N
(Me
2
N)
3
P=N
3
P=N
P=NR
(Me
(Me
(Me
2
2
2
N)
N)
N)
3
3
3
P=N
P=N
P=N
Schwesinger`s P
2
-P
4 phosphazophosphazene bases
For comprehensive review on application of phosphazene bases see:
Strong and Hindered Bases in Organic synthesis. www.sigma-aldrich.com/chemfiles. 2003 , V. 3, No. 1.
P=NR

Designations of the "Classical" Phosphazenes and Some Other Bases 1

No Compound
8b (tmg)
3
P=N-Et
8c (tmg)
3
P=Nt -Bu
8 (tmg)
3
P=N-H
40b [(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-4-OMe
40a [(pyrr)
3
P=N-]
3
P=N-Ph
39d [(dma)
3
P=N-]
3
P=N-C
6
H
4
-4-OMe
11 (tmg)
2
(NEt
2
)P=Nt -Bu
39c [(dma)
3
P=N-]
3
P=N-Ph
33a (pyrr)
3
P=N-(pyrr)
2
P=N-Et
40c [(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-4-Br
[(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-2-Cl
36b [(pyrr)
3
P=N-]
2
(pyrr)P=N-C
6
H
4
-4-OMe
36a [(pyrr)
3
P=N-]
2
(pyrr)P=N-Ph
8d (tmg)
3
P=N-Ph
35b [(dma)
3
P=N-]
2
(dma)P=N-C
6
H
4
-4-OMe
35a [(dma)
3
P=N-]
2
(dma)P=N-Ph
[(pyrr)
3
P=N-]
2
(pyrr)P=N-C
6
H
4
-4-CF
3
[(dma)
3
P=N-]
2
(dma)P=N-C
6
H
4
-4-CF
3
10 (tmg)
2
(dma)P=N-Ph f
(pyrr)
3
P=N-(pyrr)
2
P=N-C
6
H
4
-4-OMe
(dma)
3
P=N-(dma)
2
P=N-Ph
[(pyrr)
3
P=N-]
2
(NEt
2
)P=N-C
6
H
3
-2,5-Cl
2
33b (pyrr)
3
P=N-(pyrr)
2
P=N-C
6
H
4
-4-Br
MTBD g
DBU g
9 (tmg)(dma)
2
P=N-Ph
(pyrr)
3
P=N-C
6
H
4
-4-OMe
TMGN g
(pyrr)
3
P=N-Ph
32d (dma)
3
P=N-(dma)
2
P=N-C
6
H
4
-2-Cl
(Me)(dma)
2
P=N-Ph
30b (pyrr)
3
P=N-C
6
H
4
-4-NO
2
(pyrr)
3
P=N-C
6
H
4
-2-Cl
(dma)
3
P=N-C
6
H
4
-2-Cl
Measurement Results a
pK ip
(THF) b
pK

(THF) b
29.0 c,d
29.7 c,d
0.6
28.4 c
29.1 c
0.6
27.9
28.6
0.07
0.85
27.8
28.9
0.75
27.1
28.1
0.08 1.50
0.70
27.0
27.7
0.67 26.3
26.8
0.02
1.17
0.77
0.35
26.3
25.9
27.0
26.6
0.27
1.20
1.08
1.44
0.98
0.51
0.52
0.70
0.10
0.23
0.13
1.25
0.27
0.66
0.80
1.05
0.11
0.58
0.10
0.36
0.01
0.97
25.8
25.6
e
24.8
e
24.2
e
23.7
23.6
e
23.0
e
22.3
e
21.2
e
21.1
20.9
e
19.4
e
19.3
e
19.3
18.7
e
18.1
e
18.1
16.8
e
16.5
16.0
e
15.8
15.4
e
13.2
13.2
e
12.5
e
26.9
26.6
e
25.7
e
25.0
e
24.3
24.0
e
23.5
e
23.2
e
21.7
e
21.5
21.5
e
19.9
e
20.2
e
20.0
18.0
e
16.9 e
18.4
16.8
e
16.8
16.0
e
16.3
15.4
e
13.3
13.2
e
12.5
e

No Compound
8b (tmg)
3
P=N-Et
8c (tmg)
3
P=Nt -Bu
8 (tmg)
3
P=N-H
40b [(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-4-OMe
40a [(pyrr)
3
P=N-]
3
P=N-Ph
39d [(dma)
3
P=N-]
3
P=N-C
6
H
4
-4-OMe
11 (tmg)
2
(NEt
2
)P=Nt -Bu
39c [(dma)
3
P=N-]
3
P=N-Ph
33a (pyrr)
3
P=N-(pyrr)
2
P=N-Et
40c [(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-4-Br
[(pyrr)
3
P=N-]
3
P=N-C
6
H
4
-2-Cl
36b [(pyrr)
3
P=N-]
2
(pyrr)P=N-C
6
H
4
-4-OMe
36a [(pyrr)
3
P=N-]
2
(pyrr)P=N-Ph
8d (tmg)
3
P=N-Ph
35b [(dma)
3
P=N-]
2
(dma)P=N-C
6
H
4
-4-OMe
35a [(dma)
3
P=N-]
2
(dma)P=N-Ph
[(pyrr)
3
P=N-]
2
(pyrr)P=N-C
6
H
4
-4-CF
3
[(dma)
3
P=N-]
2
(dma)P=N-C
6
H
4
-4-CF
3
10 (tmg)
2
(dma)P=N-Ph f
(pyrr)
3
P=N-(pyrr)
2
P=N-C
6
H
4
-4-OMe
(dma)
3
P=N-(dma)
2
P=N-Ph
[(pyrr)
3
P=N-]
2
(NEt
2
)P=N-C
6
H
3
-2,5-Cl
2
33b (pyrr)
3
P=N-(pyrr)
2
P=N-C
6
H
4
-4-Br
MTBD g
DBU g
9 (tmg)(dma)
2
P=N-Ph
(pyrr)
3
P=N-C
6
H
4
-4-OMe
TMGN g
(pyrr)
3
P=N-Ph
32d (dma)
3
P=N-(dma)
2
P=N-C
6
H
4
-2-Cl
(Me)(dma)
2
P=N-Ph
30b (pyrr)
3
P=N-C
6
H
4
-4-NO
2
(pyrr)
3
P=N-C
6
H
4
-2-Cl
(dma)
3
P=N-C
6
H
4
-2-Cl
Measurement Results a
pK ip
(THF) b
pK

(THF) b
29.0 c,d
29.7 c,d
0.6
28.4 c
29.1 c
0.6
27.9
28.6
0.07
0.85
27.8
28.9
0.75
27.1
28.1
0.08 1.50
0.70
27.0
27.7
0.67 26.3
26.8
0.02
1.17
0.77
0.35
26.3
25.9
27.0
26.6
0.27
1.20
1.08
1.44
0.98
0.51
0.52
0.70
0.10
0.23
0.13
1.25
0.27
0.66
0.80
1.05
0.11
0.58
0.10
0.36
0.01
0.97
19.3
18.7
e
18.1
e
18.1
16.8
e
16.5
16.0
e
15.8
15.4
e
13.2
13.2
e
12.5
e
25.8
25.6
e
24.8
e
24.2
e
23.7
23.6
e
23.0
e
22.3
e
21.2
e
21.1
20.9
e
19.4
e
19.3
e
20.0
18.0
e
16.9 e
18.4
16.8
e
16.8
16.0
e
16.3
15.4
e
13.3
13.2
e
12.5
e
26.9
26.6
e
25.7
e
25.0
e
24.3
24.0
e
23.5
e
23.2
e
21.7
e
21.5
21.5
e
19.9
e
20.2
e

Designations of the "Classical" Phosphazenes and
Some Other Bases 2

Einsatzmöglichkeiten: Aminophosphazene und
Phosphazenium Salze, Guanidinophosphazene?
als metallfreie Katalysatoren zur Polymerisation von
- Polyepoxiden
- Polyurethanen
- Polysiloxanen
- Polymethacrylaten
Vorteile:
- geruchsfrei
- scharfes Molekulargewicht
- spezielle Eigenschaften
- keine Kontamination, keine Spuren des cancerogenen HMPTA
( Guanidophosphazene )
oder seiner Derivaten im Produkt enthalten
- kleine Katalysatormengen
- vereinfachte Isolierung
Anwendung in Kondensatoren als Polymerisationskatalysator in der Halbleitertechnik als Katalysator zur Synthese von 2-Oxazolidonen
(aus Epoxiden und Carbamaten)

4
Phosphazene bases have been reported in the literature to be strongly basic materials with basicities up to 1 x 10 18 times stronger than that of diazabicycloundecene (DBU) a strong hindered amine base widely used in org. reactions. A study of these phosphazene bases as catalysts revealed that they can be activated by small amts. of water, which all silicone feed stocks contain, to form an active ionic base catalyst. The use of these base catalysts, and their analogs, as ring-opening polymn. catalysts for cyclosiloxanes is described. P-base catalysts can be used at low concns. To make high mol. wt. polydimethylsiloxanes with short reaction times over a wide temp. range. Mol. wt. can easily be controlled in the presence of suitably functionalized endblockers. Water and carbon dioxide have been shown to have a significant impact on the polymn. rates. Polymers prepd. show excellent thermal stability by thermogravimetric anal. (TGA), following neutralization of the catalyst, with decompn. onset temps. >500 °C in some cases. As a result of the extremely low levels of catalyst used, the polymers often do not require filtration.
Hupfield, P. et al . (Dow Corning Ltd.) J. Inorg. Organomet. Polymers , 1999, 9, 17-34.

Extremely base-rasistant organic cations:
Phosphazenium Halex Catalysts
Me
2
N
NMe
2
P
NMe
2
Me
2
N
Me
2
N
Me
2
N
P N
Me
2
N
N
P N P
N
NMe
2
NMe
2
Cl
NMe
2
P
NMe
2
NMe
2
Mitsui, Rhodia, Clariant
R
2
R
2
N
R
2
N
N
P
+
N P
NR
2
NR
2
NR
2
Cl
-
For properties of extremely base-rasistant organic cations see: Schwesinger et al.,
Chem. Eur. J . 2006 , 12 , 429-437.
T. Nobori, M. Kouno, T. Suzuki, K. Mizutani, S. Kiyono, Y. Sonobe, U. Takaki, US 5990352 (to Mitsui Chemicals),
Nov. 23, 1999;
V. Schanen, H. J. Cristau, M. Taillefer, WO 02092226 (to Rhodia Chimie), Nov. 21, 2002.

Immobilised Iminophosphatranes Useful for
Transesterification
SiO
2
N
P
N
N
N
R
R
N
An active geterogeneous catalyst for production of biodiesel
Verkade et al. US 2005 0176978

Our Idea:Guanidino-, Biguanidino- and
Triguanidinophosphazenes
Me
N
Me
Me
N
N
Me
Me
N
Me
Me
N
N P NAlk
N
N
Me
Me
Me
N
Me
Me
( I )
N
Me
Me
N
N
Me
N
N P NAlk
N
N
Me
N
Me
N
Me
( II)
Alk N
C ( N
N
P N
N
C ( N
NMe
2
)
2
NMe
2
NMe
2
C ( N
NMe
2
NMe
2
)
2
NMe
2
)
2
( III )
Alk N P
[
N C( N
Me
N
)
2
]
3
N
Me
( IV )
Alk = Me, Et, i-Pr, t-Bu
NMe
2
Alk
Me
2
N
N
N
C
N
P N
N
Me
2
N
C
N
C
NMe
2
NMe
2
N
NMe
2
NMe
2
NMe
2
NMe
2
( V )

Me
2
N
Me
2
N
NH
Ionic precursors: synthesis
+ t-BuN PCl
3
Toluene
Me
2
N
NMe
N t-Bu N P
H N
N
2
NMe
2
NMe
2
Cl (BF
4
)
Me
2
N NMe
2
PCl
5
6 equiv. TMGH
Toluene, -30 - 20°C
Me
2
N
C
NMe
2
Cl
N
P N
N
C
NMe
2
NMe
2
Cl
Me
2
N
C
NMe
2
2 equiv. RNH
2
Me
2
N
C
NMe
2
R N
H
N
P N
N
C
NMe
2
NMe
2
Cl
Me
2
N
C
NMe
2
A. A. Kolomeitsev, I. A. Koppel, T. Rodima, J. Barten, E. Lork, G.V. Röschenthaler, I. Kaljurand,
A. Kütt, I. Koppel, V. Mäemets, I. Leito.. J. Am. Chem. Soc.
, 2005 , 127, 17656-17666 .

Liberation of Guanidinophosphazene Bases
Me
2
N
C
NMe
2
R
H
N
N
P N
N
C
NMe
2
NMe
2
Me
2
N
C
NMe
2
Cl
R = H, Et, t-Bu, Ph
t-BuOK, glyme
-30 : 60°C
Me
R
2
N
C
NMe
N
N
P N
N
NMe
2
C
NMe
2
Me
2
N
C
NMe
2
2
A. A. Kolomeitsev, I. A. Koppel, T. Rodima, J. Barten, E. Lork, G.V. Röschenthaler, I. Kaljurand,
A. Kütt, I. Koppel, V. Mäemets, I. Leito.. J. Am. Chem. Soc.
, 2005 , 127, 17656-17666 .

Figure 1. Molecular structure of
[(dma)
2
C=N]
3
P=N-t-Bu
.
N-C 138.3 pm
N5
N4
C6
N1
N6
N2
N10 P1
N8
N9
C11
N7
C1
N3
N=C 128.8 pm

2
3
+
4
-
F3
B1
F2
F4
C2
N5
C9
C7
N6
C8
C5
C10
N3
C4
C6
C1
N2
N4
N1
P1
N10
H39
C3
F1
N7
C14
C16
C19
C18
C17
C11
C12 N8
N9
C15
C13
„C-N“ 136.5 pm „C=N“ 136.0 pm

Results of Basicity Measurements of
Guanidinophosphazenes and Related Compounds in THF

Results of Basicity Measurements of
Guanidinophosphazenes and Related Compounds in THF

Consecutive Replacement of dma Groups by tmg
Units: Nearly Additive Bacisity Increase
 pK
 pK

N
N
P
N
NPh
15.3
3.1
N
N
N
P
N
NPh
N
3.1
18.4
N
N
N
N
N
P
N
N
NPh
2.8
21.5
N
N
N
N
N
N
N
P
N
NPh
N
24.3
A. A. Kolomeitsev, I. A. Koppel, T. Rodima, J. Barten, E. Lork, G.V. Röschenthaler, I. Kaljurand,
A. Kütt, I. Koppel, V. Mäemets, I. Leito..
J. Am. Chem. Soc.
, 2005 , 127, 17656-17666 .

Designations of the substituents (IUPAC)
N N
H
2
N
H
2
N
N dma
H
N
N
H im
N pyrr g
H
N
N
H imen
N imme
N
N tmg
N
N
N
N

Results of Basicity Calculations at DFT B3LYP
6-311+G** Level of Guanidinophosphazenes and Related Bases 4
Guanidines
Guanidine c
H
N
230.6
234.3
237.5
241.2
NH
N
H
H
N
235.5
242.4
NH
N
H
239.6
-246.2
N
NH
N
Tetramethylguanidine c
[(H
2
N)
2
C=N]
2
C=NH
Phosphines
[(H
2
N)
2
C=N-]
3
P b
240.7
248.4
258.9
248.2
255.1
263.7
[(dma)
2
C=N-]
3
P b
[(H
2
N)
3
P=N-]
3
P
267.1
275.0
276.7
283.3

Results of Basicity Calculations at DFT B3LYP
6-311+G** Level of Guanidinophosphazenes and Related Bases 1
Base GB PA
Guanidinophosphazenes
(H
2
N)
2
[(H
2
N)
2
C=N]P=NH b
H
2
N[(H
2
N)
2
C=N]
2
P=NH
[(H
2
N)
2
C=N]
3
P=NH b
[(H
2
N)
2
C=N]
3
P=N-Me
[(H
2
N)
2
C=N]
3
P=N-t-Bu
[(H
2
N)
2
C=N]
3
P=N-Ph
(dma)
2
[(H
2
N)
2
C=N]P=NH
(dma)[(H
2
N)
2
C=N]
2
P=NH
[(dma)
2
C=N](H
2
N)
2
P=NH
[(dma)
2
C=N]
2
(H
2
N)P=NH
[(dma)
2
C=N]
3
P=NH
[im](H
2
N)
2
P=NH
[im]
2
(H
2
N)P=NH
[im]
3
P=NH
253.1
261.7
266.5
271.7
273.0
264.3
260.1
265.0
258.4
269.7
276.1
254.3
261.5
270.5
278.1
283.9
261.4
267.9
277.6
259.1
267.7
272.6
278.0
278.6
269.6
264.8
270.4
266.1

Results of Basicity Calculations at DFT B3LYP
6-311+G** Level of Guanidinophosphazenes and Related Bases 2
Base GB
(H
2
N)
2
(imen)P=NH
(H
2
N)(imen)
2
P=NH
(imen)
3
P=NH
(H
2
N)
2
[imme]P=NH
(imme)
2
(H
2
N)P=NH
(imme)
3
P=NH
(imen)[(H
2
N)
2
C=N]
2
P=NH
(im)[(H
2
N)
2
C=N]
2
P=NH
[((H
2
N)
2
C=N)
3
P=N](H
2
N)
2
P=NH
253.8
260.2
271.5
257.9
267.9
280.8
266.8
267.7
276.2
[(H
2
N)
2
C=N]
3
P=N-P[(H
2
N)
2
C=N]
2
=NH 290.8
(H
2
N)
2
[((H
2
N)
2
C=N)
2
C=N]P=NH
[((H
2
N)
2
C=N)
2
C=N]
3
P=NH
272.6
296.2
PA
261.4
267.5
279.2
265.7
275.0
287.0
273.1
273.6
281.9
296.7
278.3
302.3

Results of Basicity Calculations at DFT B3LYP
6-311+G** Level of Guanidinophosphazenes and Related Bases 3
Other bases
Phosphazenes
(H
2
N)
3
P=NH
(H
2
N)
3
P=N-Me c
(H
2
N)
3
P=N-Ph
(dma)
3
P=NH c
(dma)
3
P=N-Me c
(dma)
3
P=N-Ph
(H
2
N)
2
(pyrr)P=NH
(pyrr)
3
P=NH
(H
2
N)
3
P=NP(NH
2
)
2
(=NH)
[(dma)
3
P=N](dma)
2
P=N-Ph
[(H
2
N)
3
P=N-]
2
P(NH
2
)(=NH)
[(H
2
N)
3
P=N]P(NH
2
)
2
=N-P(NH
2
)
2
(=NH)
[(H
2
N)
3
P=N]
3
P=NH
[(dma)
3
P=N]
3
P=NH
241.7
245.6
238.9
249.6
252.3
245.3
246.8
255.0
257.0
259.2
269.3
264.8
273.2
ca 290
254.9
262.8
262.9
266.9
276.2
271.9
279.1
249.7
253.8
246.9
256.3
260.3
252.7

Promising TMG-ligands 1
Me
2
N
NMe
2
N
P
N
N
NMe
2
NMe
2
Me
2
N NMe
2 still unknown a
GB ca. 267 kcal/mol a obtained as dihydrochloride, HCl
2
-
, by Schmutzler, R. et al. Phosphorus, Sulphur and Silicon 1997 , 123 , 57 - 74.
R
N
P
N
N
R
R
N
Proazaphosphotranes pK a ca . 33 (CH
3
CN)
GB ca. 255 kcal/mol

Promising TMG-ligands 2:
Tris(triguanido)phosphine
TMG
2
C NH
GB 268.4 kcal/mol
(Me
2
N)
3
P NH
GB 249.6 kcal/mol
TMG
2
TMG
TMG
2
2
N
P
N
N
TMG
2
TMG
2
TMG
2
Has to be the most basic and hindered phosphine
Me
2
N
Me
2
N
NMe
2
P
N
P
N
NMe
2
P
NMe
2
NMe
2
N
Me
2
N
P
NMe
2
NMe
2
GB ca. 280 kcal/mol a,b a
DFT calculations: this work. b
Synthesis: Marchenko, A. et al. Zh. Obsch. Khim . 1984 , 54 ,1774-1782.

Biodiesel Catalysts
R
R
R
O
C
O
C
O
C
O
O
O
CH
2
CH
CH
2
Triglyceride
3 MeOH, Catalyst
O
3 R C
Biodiesel
O CH
3
+
HO CH
2
HO CH
HO CH
2
Catalyst: TMG
3
P=NH (0.5% mol., 30 min, 90%; 1% mol., 30 min. quantitative)

Mesoporous neutral superbase catalysts
N
Me
Me
N
Me
N
N
C
N
N Spacer -Si(OMe)
3
N
Me
Me
Me
N
N
N
N P
N
Me
Me N
N
N Me
N
N Spacer-
Me
Ti(OAlk)
3
N
Me
Me
N
Me
N
N
C
N
N
N
Me
SiO
2
Me
Me
N
N
N
N P
N
Me
Me N
N
N Me
N
N
Me
TiO
2

Mesoporous ionic ctalysts for transesterification
(Cl- and OH- form)
Me
N
Me
N
N
Me
N
C
Me
N
N
N
Me
OH
SiO
2
Me
Me
N
N N Me
N
N
Me
P N
N
Me
Me N
N
N Me
OH
TiO
2
R R
N
Me
R
N P N
R
R
N
R
OH
TiO
2

Ionic Liquids for Halex and other Organic
Reactions Proceeding under Extreme Conditions?
N
N
BF
4
-
/ PF
6
-
R X
F
-
R F
R = Alkyl, Aryl, Heteroaryl
Problems:
- Hoffmann-degradation, nucleophilic dealkylation at elevated temperature
- low yields (even with CsF) of R-F
N
N
N
N
N
C N
N
Alk
Alk
Cl, PF
6
NMe
2
Me
2
N
Me
2
N
C
C
N
C N
N
NMe
2
NMe
2
C
NMe
2
Cl, PF
6

N
N
N
Novel Robust Ionic Liquids, Chiral Ionic Reaction
Media or dopants?
N
N
N
Me
N
Heteroaryl
X
N
O
Ar
N
CF
3 N N
C
2
F
5
N N
X
N
N
N
N
N
N
N
N
N
N ( CH
2
CH
R
O ) n
CH
2
CH
R
N
N
N
N
2X
X = Cl, Br, BF
4
, PF
6
, CF
3
SO
3
; R = H, Me; R
1
= Alk

Me
2
N
Me
2
N
Me
2
N
Me
2
N
N
C
N
A
Novel organic metals?
Me
2
N
Me
2
N
Me
2
N
Me
2
N
N N
N
C C
N
NMe
2
NMe
2
NMe
2
NMe
2
B
Me
S
S
S
S
Me TMG
S
S
S
S
TMG
Me Me TMG TMG
Tetramethyltetrathiofulvalene a Tetrakis(tetramethylguanidino)tetrathiofulvalene a Chem. Rev . Molecular Conductors. 2004 , 104 , issue N 11.

Grubbs Ruthenium Catalysts for Alkene Metathesis?
N
..
N
N
N
N N
Cl
Cl
Ru
PCy
3
N
N
To be used instead of PCy
3 or NHC ligands

DLC ´s as Mitochondriotropics
Mitochondrial research is presently one of the fastest growing disciplines in biomedicine.
Dysfunction contributes to a variety of human disorders such as neurodegenerative diseases, diabetes and cancer. During the last five years, mitochondria, the “power houses” of the cell have become accepted as the “motors of cell death” therefore presenting a priviliged pharmacological target for cytoprotective and cytotoxic therapies.
Mitrochondriotropics are compounds having two structural features in common, they are amphiphilic
, i.e. hydrophilic charged centers with a hydrophobic core, and a π-electron charge density which extends over at least three atoms or more causing delocalization.
Both is crucial for the accumulation in the mitochondrial matrix. Sufficient lipophilicity combined with delocalization if their positive charge to reduce the free energy change when moving from an aqueous to a hydrophobic environment are prerequisites for mitochondrial accumulation.
Ph
3
PMe
+
Cl
-
Targeting of Low-Melecular Weight Drugs to Mammalian Mitochondria, V. Weissig, S. V.
Boddapati, G. G. M. D’Souza, S. M. Cheng,
Drug Design Rev. Online 2004 , 1 , 15-28.

3
3
3
1
1 Leroux, F.; Jeschke, P.; Schlosser, M. Chem. Rev . 2005 , 105 , 827-856.

Oxidative Desulfurization-Fluorination
R OH i) NaH (1.2 mol) ii) CS
2
(2.0 mol) iii) MeI (2.0 mol)
73-95 %
R
50 % HF/Py (40 mol)
NBS (5.0 mol)
CH
2
Cl
2
, 0 °C, 1h
25-42 %
R
OCS
2
Me
OCF
3
Kuroboshi, M.; Kanie, K.; Hiyama, T. Adv. Synth. Catal ., 2001, 343, 235-250.

CF
3
OSO
2
CF
3
: Synthesis and Properties
CF
3
SO
3
H + P
2
O
5
(CF
3
SO
2
)
2
O
CF
3
SO
3
H
CF
3
SO
3
CF
3
(100 % )
CF
3
SO
3
CF
3
+ H
3
PO
4
(70 % )
Oudrhiri-Hassani, M.; Germain, A.; Brunel, D. Tetrahedron Lett ., 198 1, 22, 65.
CF
3
OSO
2
CF
3
+ N
25°C
+
N CF
3
-
OSO
2
CF
3
Olah, G. A.; Ohayama, T. Synthesis , 1976 , 319.

CF
3
OSO
2
CF
3
: Properties 2
CF
3
OSO
2
CF
3
+ N
H
3
O
+
X
O
CF
3
(Not formed)
H
3
O
+
O
SO
2
CF
3
OH
SO
2
CF
3
(25 % )
Kobayashi, Y.; Yoshida, T.; Kumadaski, I. Tetrahedron Lett . 197 9, 40, 3865.

Adducts of R
F
OH with triethylamine
R
F
COF +
Et
3
N 3HF+2Et
3
N R
F
CF
2
OH NEt
3
R
F
CF
2
O
-
HNEt
3
+
R
F
: F, C
2
F
5
, i-C
3
F
7
COF
2
+ 1/3Et
3
N 3HF+2/3Et
3
N CF
3
OH NEt
3
CF
3
OH NEt
3
+ (CH
3
)
2
SO
4
70°C, 17 h
CF
3
OCH
3
49% (Purity 84% )
Cheburkov, Y.; Lillquist, G. J. Fluorine Chem ., 2002 , 118 , 123-126 .

Trifluoromethanol CF
3
OH and Trifluoromethoxide
CF
3
O
-
F
2
C=O + F
-
CF
3
OH, b.p. –20°C, > -20°C dec.
CF
3
SH, b.p. 36.7
°C
CF
3
OCl + HCl
-120°C
CF
3
OH + Cl
2
Kloeter, G.; Seppelt, K.; J. Am. Chem. Soc ., 1979 , 101, 347-349.

Adducts of R
F
OH with triethylamine
R
F
COF +
Et
3
N 3HF+2Et
3
N R
F
CF
2
OH NEt
3
R
F
CF
2
O
-
HNEt
3
+
R
F
: F, C
2
F
5
, i-C
3
F
7
COF
2
+ 1/3Et
3
N 3HF+2/3Et
3
N CF
3
OH NEt
3
CF
3
OH NEt
3
+ (CH
3
)
2
SO
4
70°C, 17 h
CF
3
OCH
3
49% (Purity 84% )
Cheburkov, Y.; Lillquist, G. J. Fluorine Chem ., 2002 , 118 , 123-126 .

Trifluoromethanol CF
3
OH and Trifluoromethoxide
F
-
CF
3
O
-
F
2
C=O
CF
3
OH, b.p. –20°C, > -20°C dec.
CF
3
SH, b.p. 36.7
°C
CF
3
OCl + HCl
-120°C
CF
3
OH + Cl
2
Kloeter, G.; Seppelt, K.; J. Am. Chem. Soc ., 1979 , 101, 347-349.

Trifluoromethyl triflate
O
CF
3
-O-S-CF
3
O
CF
3
OSO
2
CF
3
, (TMFT, 1) is stable and easy to handle liquid, b. p. 20
°C. TMFT
Is resistant to hydrolysis by water , but does hydrolyse at 100
°C by 0.1 N NaOH.
O
Alk-O-S-CF
3
O
There are very few reports dealing with TMFT reactions, though
Alk-OTf belonging to the most powerfull alkylating agents are widely used in organic synthesis.

CF
3
OSO
2
CF
3
: Properties 3
CF
3
OSO
2
CF
3
+ C
5
H
5
N
CF
3
OSO
2
CF
3
+ CsF
Sealed tube
CF
3
SO
2
F +
25 °C
+
N
CF
2
O
-
1 atm
COF
2
+ C
5
H
5
N
Sealed tube
CF
3
SO
2
F + COF
2
Taylor, S. L.; Martin, J. C.
J. Org. Chem ., 1987 , 52 , 4148-4156

CF
3
SO
2
OCF
3
Q
+
F
-
Q
+
CF
Q
+
F
-
= (Me
2
N)
3
C
+
Me
3
SiF
2
-
, Me
4
NF,
(Me
2
N)
4
P
+
F
-
, Et
3
N/3HF, CsF, KF (s.d.), AgF
3
O
-
(97-100%)
Kolomeitsev, A. A. Tetrahedron Lett ., 2006 , in press.

Trifluoromethoxylation with (Me
2
N)
3
C + CF
3
O -
Me
Me COOEt
COOEt
OCF
3
85%
OCF
3
Me
COOEt
OTf
Me
Me
COOEt
Me
OTf
77%
CH
2
Br
HMG
+
CF
3
O
-
COOEt
Ph
Me
OTf (in situ)
CH
2
OCF
3
Ph Me
OCF
3
COOEt
90% 90%

Straightforward C-Trifluoromethoxylation with
TFMT 1
Ph
OH
Me
+ CF
3
OSO
2
CF
3
Base,pentane
-30 - +20°C
Ph
Me
OCF
3
Et
3
N ( 0.5% ), Py ( - ), (Et
2
N)
3
P=N-Me,
CH3CN pK a
ca. 28 ( 17%)
[(Me
2
N)
3
P=N](NMe
2
)
2
P=N-Bu-t,
CH3CN pK a
ca. 33 ( 42%)
[(Me
2
N)
2
C=N]
3
P=NH (ca. 40%)
+

Straightforward Transformation of alcohols into trifluoromethyl ethers
F
N N X
AlkOH, Et
3
N
THF, 0 - 20°C
N
OAlk
N X
+
Et 3
NH
+
F
-
(ca. 100% )
X = BF
4
-
, OSO
2
CF
3
, OSO
2
CH
3
Alk = CH(COOEt)CH
3
(1); CH(CH
3
)Ph(2)
N
OAlk
N X
+ Et
3
NH
+
F
-
+ CF
3
OSO
2
CF
3
THF, -30 -20°C
AlkOCF
3
66% (1); 87% (2)
Kolomeitsev, A. A. Tetrahedron Lett ., 2006 ,submitted

Summary
•
1. A new principle of creating nonionic superbases is presented. It is based on attachment of either tetraalkylguanidino-, 1,3-dimethylimidazolidin-2yliden)amino- or bis(tetraalkylguanidino)carbimino groups to the central tetracoordinated phosphorus atom of the iminophosphorane group using tetramethylguanidine or easily available 1,3-dimethylimidazolidine-2-imine.
•
2. Using this principle, a range of new nonionic superbasic tetramethylguanidinosubstituted at P atom phosphazene bases were synthesized and the base strength of these compounds was established in THF solution by means of spectrophotometric titration and the gas-phase basicity was calculated.
•
3. The enormous basicity-increasing effect has been experimentally verified in the case of the tetramethylguanidino-groups in the THF medium: the basicity increase when moving from (dma)
3
P=N-t-Bu (pK

=18.9) to (tmg)
29.1) is almost ten orders of magnitude.
3
P=N-t-Bu (pK

• 4. The new superbases could be used as auxiliary bases in organic synthesis.
The synthesized and to be synthesized phosphazenes, triguanidino- and tris(triguanido)phosphines a great potential in organic and metal complex chemistry as auxiliary bases and ligands.

Acknowledgement
• I would like to acknowledge my colleagues from the University of
Tartu, Department of Chemistry and Institute of Inorganic & Physical
Chemistry, University of Bremen.
• University of Tartu: Ilmar A. Koppel, Toomas Rodima, Ivari
Kaljurand, Agnes Kütt, Ivar Koppel, Vahur Mäemets, Ivo Leito.
• University of Bremen: Jan Barten, Enno Lork, Gerd-Volker
Röschenthaler
• The support of this work by Professor E. Nicke (Institute of Inorganic
Chemistry, University of Bonn) is also gratefuly acknowledged.