Phosphorodiamidous esters

The reactions between a,j -unsaturated carboxylic acids and phosphoramidous diesters or phosphorodiamidous esters are, as might be expected, more complex than those with phosphorus(III) triesters. The products from propenoic acid and EtOP(NEt2)2 include the amides 449 and 450 (in 21% total yield), the phosphonic amide 451 (26%) and N,N-... 

Reactions analogous to (7.96) and (7.97) may in some cases be carried out with phosphorochlo-ridate esters, to give phosphoroamidochloridic or phosphorodiamidic esters (7.118) and (7.119). As in the case of (7.120), when mixed halides are used, the P-F bond r ains preferentially intact. 

Many of these compounds were toxic for example, tetra-methyl phosphorodiamidic fluoride (dimethylaminofluorophos-phine oxide (VII)) had a l.c. 50 of 0-1 mg./l. Unlike the phosphorofluoridate esters, however, they were devoid of myotic action. 

We then decided to combine the toxicities of a phosphoro-fluoridic ester with that of a phosphorodiamidic fluoride in a hybrid molecule, and carried out the following synthesis in 1943 3... 

Furyl N,N,N, N -tetramethyld1amidophosphate Phosphorodiamidic acid, tetramethyl-, 2-furanyl ester (12) (105262-58-6)... 

CHLOROETHYL)HYDRAZINO)ACRIDINE MONOHYDROCHLORIDE see BID800 N.N-BIS(2-CHLOROETHYL)-N -(3-HYDROXYPROPYL)PHOSPHORODIAMIDATE, CYCLOHEXYLAMMONIUM SALT see CQNOOO N,N-BIS(2-CHLOROETHYL)-N -(3-HYDROXYPROPYL)PHOSPHORODIAMIDICACID intramol. ESTER see CQC650... 

CYCLIC N, 0-PROPYLENE ESTER of N,N-BIS(2-CHLOROETHYL)PHOSPHORODIAMIDIC ACID MONOHYDRATE see CQC500 CYCLIC PROPYLENE... 

Carboxamides were prepared from acids and amines in the presence of Af,Af -bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride (311) and a tertiary base (84S413). In the first step, an ester (e.g., 313) was formed, which then reacted with amines to give carboxamides. In this way, optically active amide 315 was prepared in 74% yield from 3,3-dimethylacrylic acid (312) and optically active a-methylbenzylamine (314) in the presence of 311 and DBU in dimethylacetamide. 

NTE is an integral membrane protein in neurons and some non-neural cell types of vertebrates [3,27,32] and its activity depends on lipid contents. It is present in all neurons, but is absent from glia [32], NTE can hydrolyze many esters of carboxylic acids. NTE is conveniently detected in vitro by its ability to catalyse OP-sensitive hydrolysis of an artificial substrate, phenyl valerate. Its activity is operationally defined as phenyl valerate hydrolysis resistant to inhibition by 0,0-diethyl-4-nitrophenyl phosphate (paraoxon, non-neuropathic) and sensitive to inhibition by NJ T-diisopropyl phosphorodiamidic fluoride (mipafox, neuropathic), determined under specified conditions [3]. Differential centrifugation of brain homogenates resulted in an enrichment of NTE in microsomal fractions containing elements of endoplasmic reticulum (ER), Goldgi, and plasma membrane [39],... 

Phosphorodiamidic acid, A/,A/ -dimethyI-, phenyl ester Diamidafos ... 

General Synthesis.—/3-Substituted esters can be prepared from a,/3-unsaturated aldehydes by alkylations of the homoenolate anion equivalents (83), formed from the aldehydes by [1, 2] addition of diethyl trimethylsilylphosphite or the corresponding phosphorodiamidate [Et3SiOP(NMc2)2], followed by metallation with lithium di-isopropylamide (Scheme 32). Overall yields are often in the region of 60—80%. 

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