Introduction

Applications of White Phosphorus

White phosphorus is the linchpin synthetic intermediate for the production of virtually all phosphorus-containing non-ferti-lizer chemicals. However, it is produced by the energy-intensive thermal process, and is a toxic and pyrophoric substance. We are targeting methods to produce phosphorus-containing chemicals that bypass P4 as an intermediate, in search of more environmentally friendly, less energy intensive processes for the manufacture of phosphorus-containing chemicals.

Phosphoric Acid as a Precursor to Chemicals Traditionally Derived from White Phosphorus

Michael B. Geeson and Christopher C. Cummins

Preparation of Phosphorus-Containing Compounds

Including P−C, P−F and P−H bonds

One-pot synthesis of primary phosphines

tetrabenzylphosphonium chloride

via: P(SiCl3)H

PH2Cl

[TBA]3[P3O9].2H2OHSiCl3, 110 ℃, 96 h

thenH2O or basic alumina

64%

Conditions: (i): benzyl chloride, MeCN, 70 ℃, 24 h. (ii): methyllithium (3.0 M, THF, 7 equiv). (iii): XeF2 (8 equiv.), DCM, thawing,then Li[BArF20]. (iv): H2O (15 equiv.), DCM, −78 ℃.

Hypothesis: trichlorosilane can protonate phosphide intermediate

− SiCl4

not observed

monoalkylation

Synthesis and Characterization of the Bis(Trichlorosilyl)Phosphide Anion

Sum of single bond covalent radii: 2.27 Å P−Si bond length: 2.143(2) Å

X-ray crystallography

The bis(trichlorosilyl)phosphide anion is prepared by heating the TBA salt of trimetaphosphate and trichlorosilane to 110 ℃ in a steel reactor. It can be recrystallized from DCM/pentane to give a free-flowing white powder.

High temperature and pressure synthesis Determination of byproducts and mass balance

Solid-state structure of [Si(P3O9)2]2−,

determined by X-ray diffraction

Volatile gas from reaction hydrogenates and olefin

cat. [(COD)Ir(py)(PCy3)][PF6]

DCM, 0 °C

HO i-Pr HO i-Pr

Selective Alkylation to give Primary Phosphines

With this work, we have shown it is possible to prepare phosphorus-containing fine chemicals without passing through P4, a toxic and pyrophoric intermediate. Our ongoing studies on this fascinating small anion show promise for further reaction development, especially for P−C bond formation. Finally, reductions in trichlorosilane hold promise for preparing previously known small anions, allowing their utility in chemical synthesis to be demonstrated.

fosinoprilPO

HOH

Lit.6 steps2.2 H2O2

OO

N

OOO

P

CO2H

PH2Ph PhPh Cy

90%

MeCN, 2h, 23 ℃

Application to Sulfur Chemistry: An Alternative to Lawesson's Reagent

Phosphorus Industry Overview

Phosphate

rock

Ca5(PO4)3F

White

phosphorus

P4Phosphoric

acid

H3PO4

Fertilizer

[NH4][H2PO4]Specialist

chemicals

Thermal

Process

Wet

Process

carbon

SiO2

1500 ℃H2SO4

5%95%

-172

.10

-171

.70

-171

.33

-170 -172 -174(ppm)

31P NMR spectroscopy

1JP−Si = 151 Hz

Synthesis from phosphoric acid

Na3P3O9 [TBA]3[P3O9].2H2Oion-exchange

3 H3PO4 + 3 NaCl Na3P3O9 + 3 HCldehydration

− 3 H2O

[TBA]3[P3O9].2H2O [TBA][P(SiCl3)2]HSiCl3

110 ℃, 72 h

70%, 10 g

1/3 [TBA]3[P3O9] [TBA][P(SiCl3)2] + 4 H2 + 4 O(SiCl3)2110 ℃, 72 h

8 HSiCl3

Characterization by 29Si NMR

Industrial synthesis of primary phosphines

hydrophosphinationRPH3 +

radical mechanism

H2P(CH2CH2R)

HP(CH2CH2R)2

P(CH2CH2R)3(neat)

Phosphoric acid used in place of trimetaphosphate

4-phenylbutylphosphine is a precursor to fosinopril

Trichlorosilyl-substituted anions have seen a flurry of activity in recent years, now known for the elements C, Si, Ge, N, P, and S. The sulfur species, [TBA][Cl3SiS], was targeted with the current methodology in order to replace the originally rep-orted synthesis which employed H2S, toxic, flammable, and pungent gas.

Original synthesis:

H2S, SiCl4[TEA][SH]

−78 ℃ [TEA][Cl3SiS]

Sum of single bond covalent radii: 2.19 Å

S−Si bond length: 1.9756(14) Å

Preparation of thiocarbonyl compounds using [TBA][Cl3SiS]

thioketone thioamide

Trichlorosilane is the key to selectivityLonger reaction times for H3PO4 compared to [P3O9]

3−

In the case of [P3O9]3−, a soluble silicophosphate forms

This species can be independently prepared and characterized: [TBA][P(SiCl3)2] + RClHSiCl3

RP

SiCl3

R

dialkylation

toluene

110 ℃96 h R

PSiCl3

H

+ HSiCl3

−[SiCl3]−R

PSiCl3

+ RCl

−Cl−

110 ℃96 h

Conclusions and Acknowledgments

(1) Schipper, W. Phosphorus: Too Big to Fail. Eur. J. Inorg. Chem. 2014, 2014 (10), 1567–1571.(2) Pham Minh, D.; Ramaroson, J.; Nzihou, A.; Sharrock, P. One-Step Synthesis of Sodium Tri-metaphosphate (Na3P3O9) from Sodium Chloride and Orthophosphoric Acid. Ind. Eng. Chem. Res. 2012, 51 (10), 3851–3854.(3) Benkeser, R. A.; Voley, K. M.; Grutzner, J. B.; Smith, W. E. Evidence for the Existence of the Trichlorosilyl Anion. J. Am. Chem. Soc. 1970, 92 (3), 697–698.(4) Anderson, N. G. et. al. Generation and Fate of Regioisomeric Side-Chain Impurities in the Preparation of Fosinopril Sodium. Org. Process Res. Dev. 1997, 1 (4), 315–319.(5) Geeson, M. B.; Cummins, C. C. Phosphoric Acid as a Precursor to Chemicals Traditionally Synthesized from White Phosphorus. Science 2018, 359 (6382), 1383–1385.

The Cummins GroupReferences

X-ray crystallography

Ph Ph

O

Ph Ph

S5 [TBA][Cl3SiS]

CHCl3110 ℃, 96 h 62%

thiol

Br SH1.1 [TBA][Cl3SiS]

DCM40 ℃, 18 h then H2O

62%

Me2N H

O

Me2N H

S

chlorobenzene110 ℃, 6 h

3 [TBA][Cl3SiS]

95%

Li[PF6]PH3

tris(trimethylsilyl)phosphine

lithium hexafluorophosphate

phosphine

(i) (ii)

(iii)(iv)

61%

>65% 70%

P(TMS)3

PhH2CCH2Ph

CH2Ph

ClCH2Ph

P

[TBA]Cl, H3PO4

HSiCl3, 110 ℃, 6 d

thenH2O or basic alumina 41%, 1.3 g

n-octylchloride PH2

Synthesis from bisulfate and trichlorosilane

43%, 3.0 g

Natural Resonance Theory

Sum = 89.2%

ClCl

ClCl

Cl

ClCl

Cl

Cl

39.6% 27.6% 22.0%

S

Si

S

Si

S

Si

HSiCl3, MeCN[TBA][HSO4]

23 ℃, 12 h [TBA][Cl3SiS]

*not all direct transformations

PCl3

PR3

InP

Li[PF6]P4S10

RPO3H2

indium phosphide

phosphonates

phosphorus sulfides

phosphorus trichloride

phosphines

lithium hexafluorophosphate organosulfur compounds,

lubricants

pharmaceuticals, herbicides, chelating agents

electronics

ligands, chemical reagents

battery electrolytes

all-purpose precursor

Science 2018, 359 (6382), 1383–1385.