Diethylphosphite Knowpia

Diethylphosphite
Names
	Preferred IUPAC name Diethyl phosphonate
	Other names diethyl phosphonite; DEP; Phosphonic acid, diethyl ester
Identifiers
CAS Number	762-04-9 ;
3D model (JSmol)	Interactive image;
Beilstein Reference	4-01-00-01329
ChemSpider	12437;
ECHA InfoCard	100.010.992
PubChem CID	12977;
UNII	U9X9YBA22W ;
CompTox Dashboard (EPA)	DTXSID9041861 ;
	InChI InChI=1S/C4H11O3P/c1-3-6-8(5)7-4-2/h5H,3-4H2,1-2H3 Key: SULWMEGSVQCTSK-UHFFFAOYSA-N;
	SMILES CCOP(O)OCC;
Properties
Chemical formula	C4H11O3P
Molar mass	138.103 g·mol−1
Appearance	colorless liquid
Density	1.072 g/cm3
Boiling point	50-51 °C at 2 mm Hg
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Diethyl phosphite is the organophosphorus compound with the formula (C₂H₅O)₂P(O)H. It is a popular reagent for generating other organophosphorus compounds, exploiting the high reactivity of the P-H bond. Diethyl phosphite is a colorless liquid.^[1] The molecule is tetrahedral.

Synthesis and properties edit

The compound was probably prepared in the 1850s by combining phosphorus trichloride and ethanol, but intentional preparations came later. It arises as follows:^[2]

PCl₃ + 3 C₂H₅OH → (C₂H₅O)₂P(O)H + 2 HCl + C₂H₅Cl

Under similar conditions but in the presence of base, triethyl phosphite results:^[3]

PCl₃ + 3 EtOH + 3 R₃N → P(OEt)₃ + 3 R₃NH + 3 Cl⁻

Many analogues of diethyl phosphite can be prepared.^[4]^[5] Despite being named as a phosphite the compound exists overwhelmingly in its phosphonate form, (C₂H₅O)₂P(O)H, a property it shares with its parent acid phosphorous acid. Nonetheless many of its reactions appear to proceed via the minor phosphorus(III) tautomer.^[6]

(C₂H₅O)₂P^III(OH) ⇌ (C₂H₅O)₂P^V(O)H, K = 15 x 10⁶ (25°C, aqueous)^[7]

Reactions edit

Hydrolysis and alcoholysis edit

Diethyl phosphite hydrolyzes to give phosphorous acid. Hydrogen chloride accelerates this conversion.:^[2]

Diethyl phosphite undergoes transesterification upon treating with an alcohol. For alcohols of high boiling points, the conversion can be driven by removal of ethanol:^[8]

(C₂H₅O)₂P(O)H + 2 ROH → (RO)₂P(O)H + 2 C₂H₅OH

Similarly amines can displace ethoxide:^[9]

(C₂H₅O)₂P(O)H + RNH₂ → (C₂H₅O)(RN(H)P(O)H + C₂H₅OH

P-alkylation edit

Diethyl phosphite undergoes deprotonation with potassium tert-butoxide. This reactivity allows alkylation at phosphorus (Michaelis–Becker reaction):^[10]

(C₂H₅O)₂P(O)H + KO^tBu → (C₂H₅O)₂P(O)K + HO^tBu

(C₂H₅O)₂P(O)K + RBr → (C₂H₅O)₂P(O)R + KBr

For converting aryl halides, palladium-catalysis can be employed.^[1] The C-P coupling process is reminiscent of the Buchwald-Hartwig amination.

Reaction of diethyl phosphite with Grignard reagents results in initial deprotonation followed by displacement of the ethoxy groups.^[11]^[12] This reactivity provides a route to secondary phosphine oxides, such as dimethylphosphine oxide as shown in the following pair of idealized equations:

(C₂H₅O)₂P(O)H + CH₃MgBr → (C₂H₅O)₂P(O)MgBr + CH₄

(C₂H₅O)₂P(O)MgBr + 2 CH₃MgBr → (CH₃)₂P(O)MgBr + 2 MgBr(OC₂H₅)

(CH₃)₂P(O)MgBr + H₂O → (CH₃)₂P(O)H + MgBr(OH)

Hydrophosphonylation edit

Diethyl phosphite can add across unsaturated groups via a hydrophosphonylation reaction. For example, it adds to aldehydes in a manner similar to the Abramov reaction:

(C₂H₅O)₂P(O)H + RCHO → (C₂H₅O)₂P(O)CH(OH)R

It can also add to imines in the Pudovik reaction and Kabachnik–Fields reaction,^[13] in both cases forming aminophosphonates

References edit

^ ^a ^b Green, Kenneth (2001). "Diethyl Phosphonite". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd211. ISBN 0471936235.
^ ^a ^b Malowan, J. E. (1953). "Diethyl Phosphite". Inorganic Syntheses. Vol. 4. pp. 58–60. doi:10.1002/9780470132357.ch19. ISBN 9780470132357. {{cite book}}: |journal= ignored (help)
^ Ford-Moore, A. H.; Perry, B. J. (1951). "Triethyl Phosphite". Org. Synth. 31: 111. doi:10.15227/orgsyn.031.0111.
^ Pedrosa, Leandro (March 20, 2011). "Esterification of Phosphorus Trichloride with Alcohols; Diisopropyl phosphonate". ChemSpider Synthetic Pages. Royal Society of Chemistry. SyntheticPage 488. doi:10.1039/SP488. Retrieved July 10, 2017.
^ Fakhraian, H.; Mirzaei, A. (2004). "Reconsideration of the Base-Free Batch-Wise Esterification of Phosphorus Trichloride with Alcohols". Org. Process Res. Dev. 8 (3): 401–404. doi:10.1021/op049958v.
^ Doak, G. O.; Freedman, Leon D. (1961). "The Structure and Properties of the Dialkyl Phosphonates". Chem. Rev. 61 (1): 31–44. doi:10.1021/cr60209a002.
^ Guthrie, J. Peter (1979). "Tautomerization Equilibria for Phosphorous Acid and its Ethyl Esters, Free Energies of Formation of Phosphorous and Phosphonic Acids and their Ethyl Esters, and p Ka Values for Ionization of the P—H Bond in Phosphonic Acid and Phosphonic Esters". Canadian Journal of Chemistry. 57 (2): 236–239. doi:10.1139/v79-039.
^ Malowan, John E. (1953). "Dioctyl Phosphite". Inorganic Syntheses. Vol. 4. pp. 61–62. doi:10.1002/9780470132357.ch20. ISBN 9780470132357. {{cite book}}: |journal= ignored (help)
^ John M. Read, Yu-Pu Wang, Rick L. Danheiser (2015). "Synthesis of Phosphoryl Ynamides by Copper-Catalyzed Alkynylation of Phosphoramidates. Preparation of Diethyl Benzyl(oct-1-yn-1-yl)phosphoramidate". Org. Synth. 92: 156. doi:10.15227/orgsyn.092.0156.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Boeckman, Robert K.; Perni, Robert B.; Macdonald, James E.; Thomas, Anthony J. (1988). "6-Diethylphosphonomethyl-2,2-dimethyl-1,3-dioxen-4-one (Phosphonic acid, [(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)methyl]-, diethyl ester)". Organic Syntheses. 66: 194. doi:10.15227/orgsyn.066.0194; Collected Volumes, vol. 8, p. 192.
^ Hays, Hugh R. (1968). "Reaction of diethyl phosphonate with methyl and ethyl Grignard reagents". J. Org. Chem. 33 (10): 3690–3694. doi:10.1021/jo01274a003.
^ Busacca, Carl A.; Lorenz, Jon C.; Sabila, Paul; Haddad, Nizar; Senanyake, Chris H. (2007). "Synthesis of Electron-Deficient Secondary Phosphine Oxides and Secondary Phosphines: Bis[3,5-bis(trifluoromethyl)phenyl]phosphine Oxide and Bis[3,5-bis(trifluoromethyl)phenyl]phosphine". Organic Syntheses. 84: 242. doi:10.15227/orgsyn.084.0242.
^ Keglevich, György; Bálint, Erika (1 November 2012). "The Kabachnik–Fields Reaction: Mechanism and Synthetic Use". Molecules. 17 (11): 12821–12835. doi:10.3390/molecules171112821. PMC 6268146. PMID 23117425.

[eEROS-1] Green, Kenneth (2001). "Diethyl Phosphonite". Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rd211. ISBN 0471936235.

[Malowan-2] Malowan, J. E. (1953). "Diethyl Phosphite". Inorganic Syntheses. Vol. 4. pp. 58–60. doi:10.1002/9780470132357.ch19. ISBN 9780470132357. {{cite book}}: |journal= ignored (help)

[3] Ford-Moore, A. H.; Perry, B. J. (1951). "Triethyl Phosphite". Org. Synth. 31: 111. doi:10.15227/orgsyn.031.0111.

[4] Pedrosa, Leandro (March 20, 2011). "Esterification of Phosphorus Trichloride with Alcohols; Diisopropyl phosphonate". ChemSpider Synthetic Pages. Royal Society of Chemistry. SyntheticPage 488. doi:10.1039/SP488. Retrieved July 10, 2017.

[5] Fakhraian, H.; Mirzaei, A. (2004). "Reconsideration of the Base-Free Batch-Wise Esterification of Phosphorus Trichloride with Alcohols". Org. Process Res. Dev. 8 (3): 401–404. doi:10.1021/op049958v.

[6] Doak, G. O.; Freedman, Leon D. (1961). "The Structure and Properties of the Dialkyl Phosphonates". Chem. Rev. 61 (1): 31–44. doi:10.1021/cr60209a002.

[7] Guthrie, J. Peter (1979). "Tautomerization Equilibria for Phosphorous Acid and its Ethyl Esters, Free Energies of Formation of Phosphorous and Phosphonic Acids and their Ethyl Esters, and p Ka Values for Ionization of the P—H Bond in Phosphonic Acid and Phosphonic Esters". Canadian Journal of Chemistry. 57 (2): 236–239. doi:10.1139/v79-039.

[8] Malowan, John E. (1953). "Dioctyl Phosphite". Inorganic Syntheses. Vol. 4. pp. 61–62. doi:10.1002/9780470132357.ch20. ISBN 9780470132357. {{cite book}}: |journal= ignored (help)

[9] John M. Read, Yu-Pu Wang, Rick L. Danheiser (2015). "Synthesis of Phosphoryl Ynamides by Copper-Catalyzed Alkynylation of Phosphoramidates. Preparation of Diethyl Benzyl(oct-1-yn-1-yl)phosphoramidate". Org. Synth. 92: 156. doi:10.15227/orgsyn.092.0156.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[10] Boeckman, Robert K.; Perni, Robert B.; Macdonald, James E.; Thomas, Anthony J. (1988). "6-Diethylphosphonomethyl-2,2-dimethyl-1,3-dioxen-4-one (Phosphonic acid, [(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)methyl]-, diethyl ester)". Organic Syntheses. 66: 194. doi:10.15227/orgsyn.066.0194; Collected Volumes, vol. 8, p. 192.

[11] Hays, Hugh R. (1968). "Reaction of diethyl phosphonate with methyl and ethyl Grignard reagents". J. Org. Chem. 33 (10): 3690–3694. doi:10.1021/jo01274a003.

[12] Busacca, Carl A.; Lorenz, Jon C.; Sabila, Paul; Haddad, Nizar; Senanyake, Chris H. (2007). "Synthesis of Electron-Deficient Secondary Phosphine Oxides and Secondary Phosphines: Bis[3,5-bis(trifluoromethyl)phenyl]phosphine Oxide and Bis[3,5-bis(trifluoromethyl)phenyl]phosphine". Organic Syntheses. 84: 242. doi:10.15227/orgsyn.084.0242.

[13] Keglevich, György; Bálint, Erika (1 November 2012). "The Kabachnik–Fields Reaction: Mechanism and Synthetic Use". Molecules. 17 (11): 12821–12835. doi:10.3390/molecules171112821. PMC 6268146. PMID 23117425.

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