Phosphorus(III) Chloride1

PCl3

[7719-12-2]  · Cl3P  · Phosphorus(III) Chloride  · (MW 137.32)

(reactive chlorinating agent;1,2 strong oxo, aza, thio, and dienophilicity; reactive with organometallics and metal salts; phosphorus source for metal ion ligand synthesis28)

Alternate Name: phosphorus trichloride.

Physical Data: mp -112 °C; bp 76 °C; d 1.586 g cm-3.

Solubility: sol benzene, CHCl3, CH2Cl2 ether, CS2; dec in water or alcohols.

Form Supplied in: water-white liquid; widely available.

Purification: generally used as received without further purification. To purify, heat under reflux to expel dissolved hydrogen chloride, then distill at atmospheric pressure under N2. Further purification is possible by vacuum fractionation several times through a -45 °C trap into a -78 °C receiver.

Handling, Storage, and Precautions: the liquid is highly toxic by ingestion and slightly toxic by single dermal applications. Inhalation can cause delayed, massive, acute pulmonary edema and death. Contact with water will be violent and result in sufficient gas evolution to rupture closed or inadequately vented containers. Acids produced by contact with water can evolve hydrogen on contact with metals. This reagent must be used in a fume hood.

Chlorinations.

Alcohols, aldehydes, ketones, and carboxylic acids have been chlorinated with PCl3. The alternative phosphorochloridites, SOCl2, HCl, PCl5, Ph3PCl2, Ph3P-hexachloroacetone, Ph3P-CCl4, and NCS-SEt2,1,2 have been used to convert alcohols to chlorides. Aldehydes and ketones are converted to phosphites by PCl3. Conversion of a carboxylic acid to the acid chloride has been accomplished using PCl3, PCl5, POCl3, and SOCl2. In some cases, these reactions tend to be sluggish and substrate, solvent, and temperature dependent. Modified phosphorus halides, i.e. 2,2,2-trichloro-1,3,2-benzodioxaphospholes or Ph3PCl2, are superior phosphorus reagents for acid chloride formation.1 Carboxylic acids are a-brominated with a combination of PCl3 and Br2.3 Imidoyl halides, generated from amides, thioamides, or hydroxamic acid derivatives with PCl3, are valuable synthetic intermediates and provide access to a wide range of heterocycles, e.g. quinazolinones and oxadiazoles.4

Preparation of Phosphites.

Alcohols, diols, and phenols are readily converted to phosphites. Analogous reactions are seen with thiols1 and amines.5 Diaryl phenols react to form medium-sized heterocyclic ring systems (eq 1).6

Dihydroxyarenes yield dioxaphospholes with PCl3.7 A special subclass of phosphite reactions are phosphitylations. Dichlorophosphite derived from PCl3 and an alcohol, epoxide, or P(OMe)3 are common phosphitylation reagents. Replacement of the alcohol by an amine leads to dialkylaminodichlorophosphites and subsequent phosphoramidation of the substrate.8 Direct phosphitylation with PCl3 is useful with sterically hindered axial hydroxy functions which fail to phosphorylate with other reagents (eq 2).9

Oxidations.

Oxidation of PCl3 with ozone,10 diazomethane/chlorine,11 or oxygen/ethylene,12 produces POCl3 or, in the latter two cases, phosphate esters.

Deoxygenations.

Sulfoxides,13 amine N-oxides,14 and hydroxy amides15 are readily reduced with PCl3 to the corresponding sulfides, amines, and amides. Alternative sulfoxide reducing agents include AcCl, RCOCl, I-, Sn2+, Fe2+, SiHCl3, Si2H2Cl2, LiAlH4, NaBH4/CoCl2, BHCl2 (aliphatic >> aryl), Rh/H2, Pd/C/H2, Fe(CO)5, TiCl3, TMSI, TMSBr, I2, and PhSiMe3. The presence of active hydrogens will complicate attempts to reduce amine N-oxides. Amine N-oxides can also be reduced using H2SO3, Raney Ni, Pd/C/H2, and R3P (R = alkyl or aryl).

Amines.

Reaction of PCl3 with quaternary ammonium salts yields phosphaindolizines and thiazolodiazaphospholes.16 Imines produce phosphonates17 whereas hydrazones are converted to pyrazoles, indoles, and nitriles.18 Nitrones undergo rearrangement to secondary or tertiary amides19 and primary alkylnitro compounds are reduced to nitriles (eq 3).20 Diazonium salts are transformed to phosphonic acids.21

Reaction with Organometallic Compounds.

Organomagnesium (eq 4),22,23 lithium,24 and other main group metals25 readily undergo ligand transfer with PCl3 to form mono-, di-, or trialkyl(aryl) phosphines. A subclass of reactions include Aluminum Chloride-assisted transformations to form phosphetanes (eq 5).26

Enols and Ketene Silyl Acetals.

Reaction of a silyl enol ether with PCl3/Zinc Chloride leads to the formation of dichlorophosphine addition products (see also Phosphorus(III) Chloride-Zinc(II) Chloride). Ketene silyl acetals react directly with PCl3 under very mild conditions to form similar addition products (eq 6).27

Ligands.

Synthesis of some phosphorus-containing ligand molecules have utilized PCl3 as a key reagent for introduction of the phosphorus atom.28

Related Reagents.

Acetyl Chloride; Bromotrimethylsilane; N-Chlorosuccinimide-Dimethyl Sulfide; Dichloroborane Diethyl Etherate; Hydrogen Chloride; Iodine; Iodotrimethylsilane; Lithium Aluminum Hydride; Pentacarbonyliron; Phosphorus(V) Chloride; Phosphorus Oxychloride; Sodium Borohydride; Thionyl Chloride; Titanium(III) Chloride; Trichlorosilane; Triphenylphosphine Dichloride; Triphenylphosphine-Hexachloroacetone.


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17. Lukanov, L. K.; Venkov, A. P. S 1992, 263.
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19. Brever, E.; Aurich, H. G.; Nielson, A. Nitrones, Nitronates, and Nitroxides; Wiley: New York: 1989.
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Kenneth P. Moder

Eli Lilly and Company, Lafayette, IN, USA



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