Hydroxymethyl Phosphine Derivatives

1994 Katti, 1996 Katti et al., 1999). Nucleophiles react with the hydroxymethyl arms by attack on the electron-deficient carbon atom with loss of water to form secondary or tertiary amine bonds (Reaction 16). 

Hydroxymethyl phosphines are susceptible to oxidation to form the phosphine oxide derivative. Therefore, avoid excess oxygen, oxidizing agents, or azide compounds, which react with phosphines in the Staudinger reaction (Chapter 17, Section 5). In addition, metallic surfaces can be modified via the phosphine group to result in hydroxymethyl group substitutions. 

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In addition to the release of carbon monoxide, transition metal carbonyl complexes have also found applications in anticancer chemotherapy [212], radiolabelling [213-216], and as photosensitisers. The cobalt complex shown in Fig. 14 a demonstrates a higher anticancer activity than cis-platin in certain mammary tiunor cells Hnes [217,218]. Complexes such as Tc-99m(I)(CO)3(OH2)3 along with hydroxymethyl phosphine derivatives [219] and the cyclopentadienyl complex shown in Fig. 14b have useful radiopharmaceutical applications, in diagnosis, using Tc, as the metal centre, and in therapy based on Re and Re isotopes [220]. 

Textile Flame Retardants. The first known commercial appHcation for phosphine derivatives was as a durable textile flame retardant for cotton and cotton—polyester blends. The compounds are tetrakis(hydroxymethyl)phosphonium salts (10) which are prepared by the acid-cataly2ed addition of phosphine to formaldehyde. The reaction proceeds ia two stages. Initially, the iatermediate tris(hydroxymethyl)phosphine [2767-80-8] is formed. 

Biocides. Two phosphine derivatives are ia commercial use as biocides. These are tetrakis(hydroxymethyl)phosphonium sulfate [55566-30-8] and tributyl(tetradecyl)phosphonium chloride [8741-28-8]. These compounds are sold by Albright and Wilson Ltd. and EMC, respectively. The preparation... 

Our attempts as well as those of C. C. Price to react 2.4.6-triphenylpyry-lium salts with phosphine, phenylphosphine or tris-hydroxymethyl-phosphine in the hope of isolating phosphorins or their P-substituted derivatives were unsuccessful. In contrast, MarM applying essentially the same principle but using pyridine as base and solvent, succeeded by heating 2.4.6-triphenylpyrylium-tetrafluoro-borate 21 with tris-hydroxymethyl-phosphine 5. He was able to isolate 2.4.6-triphenyl-X -pbosphorin 22, m. p. 171—172 C, as the first X -phosphorin in 20-25% yield. 

Extension to aliphatic aldehydes leads to the 2,4,6-trialkyl-5-phenyl derivatives (342). When H3PO2 is refluxed in toluene with benzaldehyde or isobutyraldehyde the phosphinic acids (343 R = Ph, Pr ) are formed <68IZV397, 92EUP463994>. Di(hydroxymethyl)phosphines (344) react with aldehydes, ketones and acetals to form the 2-mono- or 2,2-disubstituted 1,3,5-dioxaphosphinanes (345) <86IZV2506,86ZOB2256>. With triethyl orthoformate the 2-ethoxy derivatives (346) are obtained (Scheme 70) <86IZV418, 86IZV640>. 

Hydroxymethyl phosphinate 105 was prepared in three steps from hydroxymethyl-//-phosphinic acid 115 [102]. //-Phosphinic acid 115 was silylated to give the P ° intermediate, which reacted in a silyl-Arbusov reaction with the bromoacetyl derivative of aspartic acid to give 116. A deprotective step using hydrogen afforded phosphinic acid 105. From intermediate 116, cyclic phosphinic acid 106 was also accessible in two steps. First, a 5-exo-tet cyclization under... 

Colourless crystals of (6.973a), 3,5,8 trioxa-1-phosphabicyclo (2,2,2)octane, mp=88-89 C, can be made by heating tris(hydroxymethyl)phosphine with trimethyl orthofonnate in the presence of a little triethylamine (6.974). The methyl derivative, P(CH20)3 CMe can be obtained using MeC (OCHPa in this reaction. 

The kinetics of deuterium isotope exchange between diphenyl phosphine and t-butylthiol have been studied by H n.m.r. spectroscopy.274 A negative temperature coefficient was observed for the reaction of a perf1uoroalky1 phosphite with a fluorinated aldehyde.275 The kinetics for the reaction of alcohols with phosphoryl trichloride bore strong similarities to those of carboxylic acid derivatives.276 An interesting report desribed the solvolysis of ary 1 hydroxymethyl-phosphonates. It was shown that a phosphoryl group does not prevent carbocation formation on an immediately adjacent carbon atom.277... 

Treatment of pyrylium salts with aryl-(or alkyl)-phosphines or their bis-hydroxymethyl derivatives. 

On the other hand, some experimental results are in agreement with the predominance of path b (Fig. 24) they arc due in particular to the aptitude of a very large number of substrates to react readily with aldehydes (see references reported for 12 and Ref. 274). Indeed, several successful syntheses of Mannich bases have been carried out starting from the hydroxymethyl derivative of the substrate, as reported for C-Mannich bases obtained from ferrocenyl derivatives,- nitroalkanes. - and hydrogen cyanide as well as for N-, S-, P-Mannich bases of benzimidazoles, sulfonic acids,- phosphines, etc. 

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