Phosphorus esters reactions with

Phosphorus pentachloride, for conversion of pentaacetylgluconic add to add chloride, 41, 80 for oxidation of cycloheptatriene to tropylium fluoborate, 43, 101 with cyanoacetic acid, 41, 5 Phosphorus tribromide, reaction with l,5-hexadien-3-ol, 41, 50 Phthalic acids from thioimides, 44, 93 Phthalic anhydride, reaction with L-phenylalanine to yield N-phthaiyi-L-phenylalanine, 40, 82 Phthalic monoperacid, 42, 77 Phthaionic acid, 44, 63 N-Phthalyl-L-alanine, 40, 84 N-Phthalyl-0-alanine, 40, 84 N-Phthalylglydne, 40,84 N-Phthalyl-l-/3-phenylalanine, 40,82 PlMELIC ACID, (S-OXO-, DIETHYL ESTER, 42,41... 

The reaction of a-aminonitriles and carbon disulphide was stated by Cook and Heilbron to give 5-amino-2-mercaptothiazoles however, they later found that the same reaction with aminoacetonitrile was more complex. When aminoacetonitrile sulphate in ethanolic solution was treated with carbon disulphide, the dithiodicarbamate 9 was formed. Benzylation was then carried out treatment of the resulting ester 10 with phosphorus tribromide with subsequent loss of water gave 5-amino-2-benzylthiothiazole 11 in a quantitative fashion. The rapid reaction was thought to be the first example of the formation of a 5-aminothiazole from an a-aminoamide. 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

A piridazine ring forms the nucleus for a rather unusual nontricyclic antidepre.ssant. Condensation of the keto ester 136 with hydrazine leads to the cyclic hydrazide 137. Oxidation, for example with bromine, gives the corresponding pyridazone 138. The oxygen is then replaced by chlorine by reaction with phosphorus oxychloride. Displacement of the halogen in 139 with N-ethylami-nomorpholine affords minaprine 140 [30]. 

Sulfinic esters, aromatic, by oxidation of disulfides in alcohols, 46, 64 Sulfonation ot d,l camphor to d,l-10-camphorsulfomc acid, 45,12 Sulfoxides, table of examples of preparation from sulfides with sodium metapenodate, 46,79 Sulfur dioxide, reaction with styrene phosphorus pentachlonde to give styrylphosphomc diclilonde, 46,... 

Dialkylphosphonoacetic acid esters react with p-aminobenzoic acid to anilides. The potassium salt of the diamyl ester is said to be surface-active [126]. Phosphorus organic carbonic acid amides can also be obtained by the following reaction [127] see Eq. (76). 

Another general method for converting alcohols to halides involves reactions with halides of certain nonmetallic elements. Thionyl chloride, phosphorus trichloride, and phosphorus tribromide are the most common examples of this group of reagents. These reagents are suitable for alcohols that are neither acid sensitive nor prone to structural rearrangement. The reaction of alcohols with thionyl chloride initially results in the formation of a chlorosulfite ester. There are two mechanisms by which the chlorosulfite can be converted to a chloride. In aprotic nucleophilic solvents, such as dioxane, solvent participation can lead to overall retention of configuration.7... 

Highly stabilized phosphorus ylides are prepared from acetylenic esters, a carbon-based nucleophile, and triphenylphosphine in aqueous media.40 In acetone-water (2 1) solvent, the reaction proceeds via the conjugate addition of triphenylphosphine to dialkyl acetylenedicarboxy-lates the resulting vinyl triphenylphosphonium salts undergo Michael addition reaction with a carbon-nucleophile to give the corresponding highly stabilized phosphorus ylides. 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

Inmost instances, a haloorganic subject to either SN2 displacement reaction or SN1 substitution is heated at reflux with the trivalent phosphorus ester with the concomitant formation of the valence-expanded organophosphorus compound and haloorganic by-product, as illustrated with an example in Equation 3.1. 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

As with other reactions, silyl esters of phosphorus acids constitute an important and useful category of reagents for conjugate addition reactions. With aldehydes, ketones, and esters, the silyl ester linkage is transferred to the carbonyl oxygen, facilitating the completion of the reaction, generating the free carbonyl or ester upon workup with a protic solvent (Equation 3.25). 

A further selectivity is found with the preferential displacement of aromatic ester linkages compared to alkyl ester linkages using Grignard reagents.41 In the reaction of the chiral mixed-ester phosphonite shown in Equation 4.17, preferential displacement of the aromatic ester compared to the alkyl ester occurs with inversion of configuration at phosphorus.42... 

The reaction is performed most simply by the addition of the propargylic alcohol to a solution of the phosphorus halide. Rearrangement of the phosphorus ester proceeds at ambient temperature or with mild heating. When phosphorus trihalides are used, the product can be isolated as the phosphonic dichloride.168169 Aqueous workup provides the phosphonic acid.162 In most instances, however, a dialkyl phosphorochloridite with only a single halogen on phosphorus available for reaction with alcohol has been used.165 170 174... 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

The reaction depended upon the marked difference in reactivity between the chlorine atoms and the fluorine atom in phosphorus oxydichlorofluoride. In general, the reaction with alcohols waa clear-cut, and most of the phosphorofluoridic esters were obtained in excellent yield and uncontaminated with the phosphoric triester. For example, when ethyl alcohol and phosphorus oxydichlorofluoride were allowed to react in the odd, diethyl phosphorofluoridate (VII, R = Et) was obtained in 93 per cent yield. No tertiary base was necessary to remove the hydrogen chloride produced in the reaction. The general process was patented during the war.1... 

---