Guanidinophosphazenes: Synthesis, Application

and Basicity in THF and in the Gas Phase

Alexander A. Kolomeitsev

Team

• Dr. Jan Barten

• Dr. Alexander Kolomeitsev

• Falko Przyborowski

• Prof. Dr. Gerd-Volker Röschenthaler

• Dr. Dmitrij Sevenard

HFC Company Profile1

• 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.

HFC Company Profile2

• The core product list encompasses compounds in the following categories:• F- and RF-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

HFC Company Profile3

• 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 fluorine-containing compounds

EWG

Cl

P N

N

NR1

R2

R1 R2

R1

R2

NR2R1

F

EWG

F- source

catalyst

Cl (Br)

R1, R2 = different Alkyl, cycloalkyl; -(CH2)4-

A.A. Kolomeitsev, S.V. Pazenok. DE 19631854/WO 9805610/EP 9704284 /US 6184425; B. Schiemenz, T. Wessel, R. Pfirmann; DE19934595.

(R2N)4PX PT Catalysts

• (R2N)4PX 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

EWG EWG

F

N

R2N

R2N NR2

NR2

Cl

N

R2N

R2N

P

NR2

NR2

NR2

Cl

fluoride source

+

CNC+

+

PNC+

catalyst

Cl(Br)n n

1 2

R2N

R2NN S

NR2

NR2

3

SNC+

Br-

+

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.

Carbsulfiminium Salts

6 equiv. HMG

ClS NN

NC

NMe2

NMe2

C

NMe2

Me2N

CNMe2

Me2N

SCl4CH2Cl2, -70°C

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

Me2N

Me2N F

FMe2N

Me2NN

NMe2

NMe2

TMG-H

HF2

Me2N

Me2NN

NMe2

NMe2

Me3SiF2

CH3CN, -30°C

TMG-SiMe3

____(Et2N)3P=NSiMe3

Me3SiF2

Me2N

Me2NN P

NEt2NEt2

NEt2

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

CNC Catalysts

  Temp.[°C]

Cl3 Benzene

15

Cl2F

" 18

ClF2

" 17

F3

" 16

Rest (side reactions, decomposition)

First step (12 h)   GC area %  

CNC+ (5 mol%) 230 1 20 61 18 1

(NMe2)3PNPPh3Br 3

(5 mol%)

230 1 20 60 15 5

Second step (24 h)      

CNC+ (5 mol%) 230 0 1 8 87 4

(NMe2)3PNPPh3Br 3 (5

mol%)

230 0 2 46 46 6

Cl Cl

Cl

F F

F

F F

Cl

Cl F

Cl

+ +KF, catalyst

sulfolane

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=NRMeMeMe Me2N

Me2NMe2N

P=NR

P-alkyl-phosphazenes, Appel P-dialkylamino-phosphazenes, P1 bases, Issleib, Marchenko

Schwesinger`s P2-P4 phosphazo-phosphazene bases

(Me2N)3P=N(Me2N)3P=N

Me2NP=NRP=NR

Me2NMe2N

(Me2N)3P=NP=NR

(Me2N)3P=N(Me2N)3P=N(Me2N)3P=N

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.

Designations of the "Classical" Phosphazenes and Some Other Bases1

No Compound Measurement Resultsa pK ip(THF)b pK (THF)b

8b (tmg)3P=N-Et 29.0 c,d 29.7 c,d

8c (tmg)3P=N-t -Bu 28.4 c 29.1 c

8 (tmg)3P=N-H 27.9 28.6

40b [(pyrr)3P=N-]3P=N-C6H4-4-OMe 27.8 28.9

40a [(pyrr)3P=N-]3P=N-Ph 27.1 28.1

39d [(dma)3P=N-]3P=N-C6H4-4-OMe 27.0 27.7

11 (tmg)2(NEt2)P=N-t -Bu 26.3 26.8

39c [(dma)3P=N-]3P=N-Ph 26.3 27.0

33a (pyrr)3P=N-(pyrr)2P=N-Et 25.9 26.6

40c [(pyrr)3P=N-]3P=N-C6H4-4-Br 25.8 26.9

[(pyrr)3P=N-]3P=N-C6H4-2-Cl 25.6 e 26.6 e

36b [(pyrr)3P=N-]2(pyrr)P=N-C6H4-4-OMe 24.8 e 25.7 e

36a [(pyrr)3P=N-]2(pyrr)P=N-Ph 24.2 e 25.0 e

8d (tmg)3P=N-Ph 23.7 24.3

35b [(dma)3P=N-]2(dma)P=N-C6H4-4-OMe 23.6 e 24.0 e

35a [(dma)3P=N-]2(dma)P=N-Ph 23.0 e 23.5 e

[(pyrr)3P=N-]2(pyrr)P=N-C6H4-4-CF3 22.3 e 23.2 e

[(dma)3P=N-]2(dma)P=N-C6H4-4-CF3 21.2 e 21.7 e

10 (tmg)2(dma)P=N-Phf 21.1 21.5

(pyrr)3P=N-(pyrr)2P=N-C6H4-4-OMe 20.9 e 21.5 e

(dma)3P=N-(dma)2P=N-Ph 19.4 e 19.9 e

[(pyrr)3P=N-]2(NEt2)P=N-C6H3-2,5-Cl2 19.3 e 20.2 e

33b (pyrr)3P=N-(pyrr)2P=N-C6H4-4-Br 19.3 20.0

MTBDg 18.7 e 18.0 e

DBUg 18.1 e 16.9 e

9 (tmg)(dma)2P=N-Ph 18.1 18.4

(pyrr)3P=N-C6H4-4-OMe 16.8 e 16.8 e

TMGNg 16.5 16.8

(pyrr)3P=N-Ph 16.0 e 16.0 e

32d (dma)3P=N-(dma)2P=N-C6H4-2-Cl 15.8 16.3

(Me)(dma)2P=N-Ph 15.4 e 15.4 e

30b (pyrr)3P=N-C6H4-4-NO2 13.2 13.3

(pyrr)3P=N-C6H4-2-Cl 13.2 e 13.2 e

(dma)3P=N-C6H4-2-Cl 12.5 e 12.5 e

0.52

0.11 0.70

1.200.10

0.23

1.08 1.25

0.10

1.44

0.13

0.58

0.98

0.51

0.80 0.01

0.36 0.66

0.27

0.97 0.27 1.05

0.35

0.02

0.77

0.67

1.17

0.08 0.70

0.75

1.50

0.85 0.07

0.6

0.6

No Compound Measurement Resultsa pK ip(THF)b pK (THF)b

8b (tmg)3P=N-Et 29.0 c,d 29.7 c,d

8c (tmg)3P=N-t -Bu 28.4 c 29.1 c

8 (tmg)3P=N-H 27.9 28.6

40b [(pyrr)3P=N-]3P=N-C6H4-4-OMe 27.8 28.9

40a [(pyrr)3P=N-]3P=N-Ph 27.1 28.1

39d [(dma)3P=N-]3P=N-C6H4-4-OMe 27.0 27.7

11 (tmg)2(NEt2)P=N-t -Bu 26.3 26.8

39c [(dma)3P=N-]3P=N-Ph 26.3 27.0

33a (pyrr)3P=N-(pyrr)2P=N-Et 25.9 26.6

40c [(pyrr)3P=N-]3P=N-C6H4-4-Br 25.8 26.9

[(pyrr)3P=N-]3P=N-C6H4-2-Cl 25.6 e 26.6 e

36b [(pyrr)3P=N-]2(pyrr)P=N-C6H4-4-OMe 24.8 e 25.7 e

36a [(pyrr)3P=N-]2(pyrr)P=N-Ph 24.2 e 25.0 e

8d (tmg)3P=N-Ph 23.7 24.3

35b [(dma)3P=N-]2(dma)P=N-C6H4-4-OMe 23.6 e 24.0 e

35a [(dma)3P=N-]2(dma)P=N-Ph 23.0 e 23.5 e

[(pyrr)3P=N-]2(pyrr)P=N-C6H4-4-CF3 22.3 e 23.2 e

[(dma)3P=N-]2(dma)P=N-C6H4-4-CF3 21.2 e 21.7 e

10 (tmg)2(dma)P=N-Phf 21.1 21.5

(pyrr)3P=N-(pyrr)2P=N-C6H4-4-OMe 20.9 e 21.5 e

(dma)3P=N-(dma)2P=N-Ph 19.4 e 19.9 e

[(pyrr)3P=N-]2(NEt2)P=N-C6H3-2,5-Cl2 19.3 e 20.2 e

33b (pyrr)3P=N-(pyrr)2P=N-C6H4-4-Br 19.3 20.0

MTBDg 18.7 e 18.0 e

DBUg 18.1 e 16.9 e

9 (tmg)(dma)2P=N-Ph 18.1 18.4

(pyrr)3P=N-C6H4-4-OMe 16.8 e 16.8 e

TMGNg 16.5 16.8

(pyrr)3P=N-Ph 16.0 e 16.0 e

32d (dma)3P=N-(dma)2P=N-C6H4-2-Cl 15.8 16.3

(Me)(dma)2P=N-Ph 15.4 e 15.4 e

30b (pyrr)3P=N-C6H4-4-NO2 13.2 13.3

(pyrr)3P=N-C6H4-2-Cl 13.2 e 13.2 e

(dma)3P=N-C6H4-2-Cl 12.5 e 12.5 e

0.52

0.11 0.70

1.200.10

0.23

1.08 1.25

0.10

1.44

0.13

0.58

0.98

0.51

0.80 0.01

0.36 0.66

0.27

0.97 0.27 1.05

0.35

0.02

0.77

0.67

1.17

0.08 0.70

0.75

1.50

0.85 0.07

0.6

0.6

Designations of the "Classical" Phosphazenes and

Some Other Bases2

Einsatzmöglichkeiten: Aminophosphazene und

Phosphazenium Salze, Guanidinophosphazene?

- Polyepoxiden- Polyurethanen- Polysiloxanen- Polymethacrylaten

als metallfreie Katalysatoren zur Polymerisation von

Vorteile:- geruchsfrei- scharfes Molekulargewicht- spezielle Eigenschaften- keine Kontamination, keine Spuren des cancerogenen HMPTA (Guanidophosphazene) oder seiner Derivaten im Produkt enthalten- kleine Katalysatormengen- vereinfachte IsolierungAnwendung in Kondensatoren

als Polymerisationskatalysator in der Halbleitertechnikals Katalysator zur Synthese von 2-Oxazolidonen (aus Epoxiden und Carbamaten)

Ring-opening polymerization of siloxanes

using Phosphazene P4 base catalysts Phosphazene bases have been reported in the literature to be strongly basic materials with basicities up to 1 x 1018 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. Tomake 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.

Cl

PNMe2Me2N

P N

N

N

P

NMe2

NMe2

PNMe2Me2N

NP

Me2N

Me2N

NMe2

NMe2

NMe2Me2N

Mitsui, Rhodia, Clariant

+

Cl-

R2N

P

R2N

N P

NR2

NR2

NR2R2N

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.

Extremely base-rasistant organic cations:

Phosphazenium Halex Catalysts

For properties of extremely base-rasistant organic cations see: Schwesinger et al.,Chem. Eur. J. 2006, 12, 429-437.

Immobilised Iminophosphatranes Useful for Transesterification

PN

N

N

R

R

N

NSiO2

Verkade et al. US 2005 0176978

An active geterogeneous catalyst for production of biodiesel

Our Idea:Guanidino-, Biguanidino- and

Triguanidinophosphazenes

(IV)

(III)(II)(I)

P N C(NAlk NN

N

Me

Me

)2[ ] 3

P

N

N

N

C

C

C

NAlk NNMe2

NMe2

(

(

(

) 2

2)N

NMe2

NMe2

2)NNMe2

NMe2

P NAlk

N

N

N

NMe

MeN

NMe

Me

N

N

MeMe

N

Me

MeMe

Me

Me

Me

P NAlk

N

N

N

N

N

N

N

N

N

Me

MeMe

Me

Me

Me

Alk = Me, Et, i-Pr, t-Bu

(V)

P

N

N

N

C

C

C

NAlk

NNMe2

NMe2

Me2N

NNMe2

NMe2NMe2

NNMe2

NMe2

Me2N

Ionic precursors: synthesis

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.

2 equiv. RNH2P N

N

N

CNMe2

NMe2

CNMe2Me2N

CNMe2Me2N

Cl ClToluene, -30 - 20°C

PCl5 Cl6 equiv. TMGH

P N

N

N

CNMe2

NMe2

CNMe2Me2N

CNMe2Me2N

N

H

R

Cl (BF4)

NMe2

t-Bu N P

H

N

N

N

Me2N

NMe2

NMe2

NMe2Me2N

Toluene NH

Me2N

Me2N

t-BuN PCl3+

Liberation of Guanidinophosphazene Bases

ClP N

N

N

CNMe2

NMe2

CNMe2Me2N

CNMe2Me2N

NH

R t-BuOK, glymeP N

N

N

C

NMe2

NMe2

CNMe2Me2N

CNMe2Me2N

NR

-30 : 60°C

R = H, Et, t-Bu, Ph

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.

N6C6

N8

N4

C11

N5

N7

N9

P1N10N3

N1

C1

N2

.

Figure 1. Molecular structure of [(dma)2C=N]3P=N-t-Bu

N-C 138.3 pm N=C 128.8 pm

Figure 2. Molecular structure of [(dma)2C=N]3P+-N(H)Bu-t BF4

-

C10

C9

N5

C14

C6

N6

N4

C8

C7

H39

N9

C15

N10

C17

P1

C11

N7

C16

C18

C2

C13

N1

N8

C19

N2

C1

C12

C3

N3 C4

C5

F2

F4B1

F1

F3

„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

PN

N

N

NPh

N

N

N

N

N

N

24.3pK

pK 2.8

PN

N

N

NPh

N

N

N

N

21.53.1

PN

N

N

NPh

N

N

18.43.1

PN

N

N

NPh

15.3

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)

NN

NN

NH

NH

NNH

NH

N

dma pyrr tmg

imenim

NNH2

NH2

N

g

N

NN

imme

Results of Basicity Calculations at DFT B3LYP 6-311+G** Level of Guanidinophosphazenes

and Related Bases 4Guanidines

Guanidinec 230.6 237.5

234.3 241.2

235.5 242.4

239.6 -246.2

Tetramethylguanidinec 240.7 248.2

[(H2N)2C=N]2C=NH 248.4 255.1

Phosphines

[(H2N)2C=N-]3Pb 258.9 263.7

[(dma)2C=N-]3Pb 267.1 276.7

[(H2N)3P=N-]3P 275.0 283.3

NH

NH

NH

NH

NH

NH

N

NNH

Results of Basicity Calculations at DFT B3LYP 6-311+G** Level of Guanidinophosphazenes

and Related Bases 1Base GB PA

Guanidinophosphazenes

(H2N)2[(H2N)2C=N]P=NHb 253.1 259.1

H2N[(H2N)2C=N]2P=NH 261.7 267.7

[(H2N)2C=N]3P=NHb 266.5 272.6

[(H2N)2C=N]3P=N-Me 271.7 278.0

[(H2N)2C=N]3P=N-t-Bu 273.0 278.6

[(H2N)2C=N]3P=N-Ph 264.3 269.6

(dma)2[(H2N)2C=N]P=NH 260.1 264.8

(dma)[(H2N)2C=N]2P=NH 265.0 270.4

[(dma)2C=N](H2N)2P=NH 258.4 266.1

[(dma)2C=N]2(H2N)P=NH 269.7 278.1

[(dma)2C=N]3P=NH 276.1 283.9

[im](H2N)2P=NH 254.3 261.4

[im]2(H2N)P=NH 261.5 267.9

[im]3P=NH 270.5 277.6

Results of Basicity Calculations at DFT B3LYP 6-311+G** Level of Guanidinophosphazenes

and Related Bases 2Base

(H2N)2(imen)P=NH

GB

253.8

PA

261.4

(H2N)(imen)2P=NH 260.2 267.5

(imen)3P=NH 271.5 279.2

(H2N)2[imme]P=NH 257.9 265.7

(imme)2(H2N)P=NH 267.9 275.0

(imme)3P=NH 280.8 287.0

(imen)[(H2N)2C=N]2P=NH 266.8 273.1

(im)[(H2N)2C=N]2P=NH 267.7 273.6

[((H2N)2C=N)3P=N](H2N)2P=NH 276.2 281.9

[(H2N)2C=N]3P=N-P[(H2N)2C=N]2=NH 290.8 296.7

(H2N)2[((H2N)2C=N)2C=N]P=NH 272.6 278.3

[((H2N)2C=N)2C=N]3P=NH 296.2 302.3

Results of Basicity Calculations at DFT B3LYP 6-311+G** Level of Guanidinophosphazenes

and Related Bases 3

Other bases

Phosphazenes

(H2N)3P=NH 241.7 249.7

(H2N)3P=N-Mec 245.6 253.8

(H2N)3P=N-Ph 238.9 246.9

(dma)3P=NHc 249.6 256.3

(dma)3P=N-Mec 252.3 260.3

(dma)3P=N-Ph 245.3 252.7

(H2N)2(pyrr)P=NH 246.8 254.9

(pyrr)3P=NH 255.0 262.8

(H2N)3P=NP(NH2)2(=NH) 257.0 262.9

[(dma)3P=N](dma)2P=N-Ph 259.2 266.9

[(H2N)3P=N-]2P(NH2)(=NH) 269.3 276.2

[(H2N)3P=N]P(NH2)2=N-P(NH2)2(=NH) 264.8 271.9

[(H2N)3P=N]3P=NH 273.2 279.1

[(dma)3P=N]3P=NH ca 290

Promising TMG-ligands1

PN

N

N

NMe2

NMe2

NMe2Me2N

NMe2

Me2N

still unknowna

a obtained as dihydrochloride, HCl2-,

by Schmutzler, R. et al. Phosphorus, Sulphurand Silicon 1997,123, 57 - 74.

GB ca. 267 kcal/mol GB ca. 255 kcal/mol

Proazaphosphotranes pKa ca. 33 (CH3CN)

PN

N

NR

R

R

N

Promising TMG-ligands2: Tris(triguanido)phosphine

TMG2C NH (Me2N)3P NH

GB 268.4 kcal/mol GB 249.6 kcal/mol

PN

N

N

TMG2

TMG2

TMG2TMG2

TMG2

TMG2

Has to be the most basic and hindered phosphine

PN

N

NP

P

P

NMe2Me2N

Me2N

NMe2

NMe2

NMe2

NMe2

Me2NNMe2

GB ca. 280 kcal/mola,b

a DFT calculations: this work. bSynthesis: Marchenko, A. et al. Zh. Obsch. Khim. 1984, 54,1774-1782.

Biodiesel Catalysts

Catalyst: TMG3P=NH (0.5% mol., 30 min, 90%; 1% mol., 30 min. quantitative)

Biodiesel

+O CH33 R C

O

CH2

CH

CH2

HO

HO

HO

3 MeOH, Catalyst

Triglyceride

CH2

CH

CH2

O

O

O

C

C

C

O

O

O

R

R

R

Mesoporous neutral superbase catalysts

N

NN

Me

Me

P

N

NMe

MeN

C

N

NMe

Me

N

N Spacer-Si(OMe)3 N Spacer-Ti(OAlk)3

NN

N

Me Me

N N

N

MeMe

N

NMe

MeN

C

N

NMe

Me

N

N SiO2

N N

N

MeMe

NN

N

Me Me

NN

NN

Me

Me

P TiO2

Mesoporous ionic ctalysts for transesterification (Cl- and OH- form)

TiO2

N

NN

Me

Me

P N

Me

NN

N

Me Me

N N

N

MeMe

SiO2

N

NMe

MeN

C

N

NMe

Me

N

N

Me

OHOH

OH

N

Me

TiO2N PR

RN

RR

NR R

Ionic Liquids for Halex and other Organic

Reactions Proceeding under Extreme Conditions?

R = Alkyl, Aryl, Heteroaryl

R FF-

R X

BF4-/ PF6

-

N

N

Problems: - Hoffmann-degradation, nucleophilic dealkylation at elevated temperature - low yields (even with CsF) of R-F

C NN

NC

NMe2

NMe2

C

NMe2

Me2N

CNMe2

Me2N

Cl, PF6

N

N

C NN

N

Alk

AlkN

N

Cl, PF6

Novel Robust Ionic Liquids, Chiral Ionic Reaction Media or dopants?

NN

N

N

NN

O

C2F5

Ar

X

NN

N

N

NN

N

Me

XCF3

Heteroaryl

X = Cl, Br, BF4, PF6, CF3SO3; R = H, Me; R1 = Alk

N

N

N

N

N

N

N

N

N

N

N

N

N

2X

( )n

N CH2 CH

R

O CH2 CH

R

Novel organic metals?

aChem. Rev. Molecular Conductors. 2004, 104, issue N 11.

S

SMe

Me

S

S

Me

Me

Tetramethyltetrathiofulvalenea

BA

C

N

NMe2N

Me2N

Me2N

Me2NN

C

N

NMe2N

Me2N

Me2N

Me2N

C

N

NMe2

NMe2

NMe2

NMe2

Tetrakis(tetramethylguanidino)tetrathiofulvalene

S

S

TMG

TMGS

STMG

TMG

Grubbs Ruthenium Catalysts for Alkene Metathesis?

Ru

NN

Cl

Cl

PCy3

N

NN NN

N

..

To be used instead of PCy3 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.

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.

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.

Ph3PMe+Cl-

R-OCF3 Derivatives

• The occurrence of R-O-CF3 compounds has significantly increased in recent years.

Some 30 000 OCF3 containing structures

are presently compiled in chemical databases.1

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

Oxidative Desulfurization-Fluorination

50 % HF/Py (40 mol)NBS (5.0 mol)CH2Cl2, 0 °C, 1h

25-42 %OCF3R

OCS2MeR73-95 %

i) NaH (1.2 mol)ii) CS2 (2.0 mol)iii) MeI (2.0 mol)

OHR

Kuroboshi, M.; Kanie, K.; Hiyama, T. Adv. Synth. Catal., 2001, 343, 235-250.

CF3OSO2CF3: Synthesis and Properties

(70 %)

CF3SO3CF3 + H3PO4CF3SO3H + P2O5

CF3SO3H(CF3SO2)2O

(100 %)

CF3SO3CF3

Oudrhiri-Hassani, M.; Germain, A.; Brunel, D. Tetrahedron Lett., 1981, 22, 65.

-+OSO2CF3N CF3N+CF3OSO2CF3

25°C

Olah, G. A.; Ohayama, T. Synthesis, 1976, 319.

CF3OSO2CF3: Properties2

(25 %)

OH

SO2CF3

OSO2CF3

H3O+

H3O+

(Not formed)

CF3

O

XN+CF3OSO2CF3

Kobayashi, Y.; Yoshida, T.; Kumadaski, I. Tetrahedron Lett. 1979, 40, 3865.

Adducts of RFOH with triethylamine

+ Et3N 3HF+2Et3NRFCOF RFCF2OH NEt3 RFCF2O - HNEt3 +

RF : F, C2F5, i-C3F7

CF3OHCOF2 3HF+2/3Et3N1/3Et3N+ NEt3

NEt3CF3OH + (CH3)2SO4 CF3OCH3

49% (Purity 84%)

70°C, 17 h

Cheburkov, Y.; Lillquist, G. J. Fluorine Chem., 2002, 118, 123-126.

Trifluoromethanol CF3OH and Trifluoromethoxide

CF3OH, b.p. –20°C, > -20°C dec.

Kloeter, G.; Seppelt, K.; J. Am. Chem. Soc., 1979,101, 347-349.

CF3SH, b.p. 36.7°C

CF3OCl + HCl -120°C

CF3OH + Cl2

F2C=O + F-CF3O-

Adducts of RFOH with triethylamine

+ Et3N 3HF+2Et3NRFCOF RFCF2OH NEt3 RFCF2O - HNEt3 +

RF : F, C2F5, i-C3F7

CF3OHCOF2 3HF+2/3Et3N1/3Et3N+ NEt3

NEt3CF3OH + (CH3)2SO4 CF3OCH3

49% (Purity 84%)

70°C, 17 h

Cheburkov, Y.; Lillquist, G. J. Fluorine Chem., 2002, 118, 123-126.

Trifluoromethanol CF3OH and Trifluoromethoxide

CF3OCl + HCl -120°C

CF3OH + Cl2

CF3OH, b.p. –20°C, > -20°C dec.

Kloeter, G.; Seppelt, K.; J. Am. Chem. Soc., 1979,101, 347-349.

CF3SH, b.p. 36.7°C

F2C=O CF3O-F-

Trifluoromethyl triflate

CF3-O-S-CF3

O

O

CF3OSO2CF3, (TMFT, 1) is stable and easy to handle liquid, b. p. 20°C. TMFTIs resistant to hydrolysis by water , but does hydrolyse at 100°C by 0.1 N NaOH.

O

OAlk-O-S-CF3

There are very few reports dealing with TMFT reactions, though Alk-OTf belonging to the most powerfull alkylating agentsare widely used in organic synthesis.

CF3OSO2CF3: Properties3

25 °C

1 atm

Sealedtube

COF2 + C5H5N+N

CF2O-

+CF3SO2FCF3OSO2CF3 + C5H5N

CF3OSO2CF3 + CsF CF3SO2F +

Sealedtube

COF2

Taylor, S. L.; Martin, J. C. J. Org. Chem., 1987, 52, 4148-4156

Splitting of Trifluoromethyl Triflate

Kolomeitsev, A. A. Tetrahedron Lett., 2006, in press.

Q+ F-

Q+ F- = (Me2N)3C+ Me3SiF2

-, Me4NF,

(Me2N)4P+ F-, Et3N/3HF, CsF, KF (s.d.), AgF

Q+ CF3O- (97-100%) CF3SO2OCF3

Trifluoromethoxylation with (Me2N)3C+ CF3O-

HMG+CF3O-

Me COOEt

Me OTf

COOEt

Me

OTf

CH2Br

COOEt

Me

Ph

OTf (in situ)

Me COOEt

OCF3

CH2OCF3

COOEt

Ph Me

OCF3

Me COOEt

Me OCF3

85% 77%

90%90%

Straightforward C-Trifluoromethoxylation with TFMT1

Et3N ( 0.5% ), Py ( - ), (Et2N)3P=N-Me, CH3CNpKa ca. 28 ( 17%)

[(Me2N)3P=N](NMe2)2P=N-Bu-t, CH3CNpKa ca. 33 ( 42%)

[(Me2N)2C=N]3P=NH (ca. 40%)

Ph Me

OH

+ CF3OSO2CF3Ph Me

OCF3

Base,pentane

-30 - +20°C

+

Straightforward Transformation of alcohols into trifluoromethyl ethers

NN

F

X = BF4-, OSO2CF3, OSO2CH3

X AlkOH, Et3N

THF, 0 - 20°CXNN

OAlk

+ Et3NH+ F- (ca. 100%)

Et3NH+ F-+ NN

OAlk

X + CF3OSO2CF3THF, -30 -20°C AlkOCF3

66% (1); 87% (2)

Alk = CH(COOEt)CH3 (1); CH(CH3)Ph(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-2-yliden)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)3P=N-t-Bu (pK =18.9) to (tmg)3P=N-t-Bu (pK 29.1) is almost ten orders of magnitude.

• 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.