Pyridine triester

Asymmetrical triesters of phosphoric acid of the general formula ROPO (OR,)2 (R = C8 i4 alkyl R, = C, 3 alkyl) were obtained in approximately 70% yield by treatment of a higher fatty alcohol and a Ci 3 alcohol with P0C13 in hexane or pyridine at <0°C. The products were soluble in nonpolar organic solvents and partially soluble in polar organic solvents and water. But the foamforming ability and foam stability of the compounds in water were low [11]. 

The rigid, planar pyridine analog 111 was isolated in low yield by first hydrolyzing the known (67) pyridine diethyl phosphonate 109 to the corresponding free acid 110 followed by permanganate oxidation (2). An alternative synthesis of 111 has recently been reported (68). Alkylation of pyridine-2-carboxylate -oxide with dimethylsulfate and subsequent reaction with the sodium salt of diethyl phosphite gave the triester 112, which was readily converted to 111. 

The reaction of pyridines and picolines with acetylenic compounds provides a useful synthesis of indolizines.48 The reaction of such compounds with dimethyl acetylenedicarboxylate (DMAD), originally investigated by Diels and co-workers (see Ref. 4) has been reexamined more recently by several groups.48-52 The two major adducts are now thought to be the quinolizines 26 and 27, although Wiley and Knabeschuh63 obtained the indolizine triester 28 when the reaction was carried out in ether as solvent. The adduct of type 27 is oxidized by nitric acid to 28. 

The chemical basis for the phosphite triester approach is the observation, that dialkyl phos-phorochloridites such as (CjHjOJjPCI react very rapidly at the 3 -OH of nucleosides in pyridine even at low temperatures. In contrast, the reactions of analogous chloridates, e.g. (C2HjO)2POCIi require several hours at room temperature. It was later found that phosphite esters can be oxidized quantitatively to the phosphates by using iodine in water and that clean condensation of phosphorochloridites with nucleosides can be achieved in THF at -78 °C. To develop this chemistry into a useful synthetic procedure it was necessary to establish which... 

Pyridin kann fur bestimmte Phosphorsaure-triester als Entalkylierungsmittel eingesetzt werden109 110 (vgl. Bd. XII/2, S. 262) ... 

Als Chlorwasserstoff-bindendes Mittel ist bei der Umsetzung von Phosphorsiiure-dichlo-rid-estern mit Alkoholen 2,6-Dimethyl-pyridin in Petrolether oder Diethylether (0°) be-sonders geeignet, da dann nur geringe Mengen Phosphorsaure-triester gebildet werden284,... 

Starch propionates, with various degrees of propionation up to the tripropionate, have been prepared by refluxing corn starch with propionic acid and propionic anhydride. The lower propionates are water-soluble, but the tripropionate is soluble only in organic solvents. Starch tripropionate and starch tributyrate are easily prepared by treating swollen starch with pyridine and the acid anhydride. These triesters are more soluble in organic solvents than the starch triacetates. 

Starch palmitate is prepared by treating 1 part of starch in a mixture of 4 parts of benzene and 1.8 parts of pyridine with 6 parts of palmitoyl chloride and 4 parts of benzene for thirty minutes at 60° and precipitating the product with ethanol. Quinoline may be substituted for the benzene and pyridine. Because of the high boiling point of quinoline, an elevated esterification temperature can be used and triesters produced in about three hours. 

Phosphorus oxychloride is a suitable reagent for preparation of the symmetrically substituted phospho-triesters of type (RO)3PO. The preparation is easily achieved by treatment of phosphorus oxychloride with 3 equiv. of alcohols or their metal salts. The reaction is generally promoted by a base or acid. Titanium trichloride is a particularly effective catalyst for the reaction. Conversion of POCI3 to unsymmetri-cally substituted phosphotriesters is achievable with difficulty. Phosphorochloridates and phosphorodichloridates have been used for the preparation of mixed tertiary phosphoric esters of type (ROlmPOfOROn (ffi = 1, n = 2, or m = 2, n = 1) in a very wide variety. Reaction of phosphorus oxychloride and 1 or 2 equiv. of alcohols followed by hydrolysis forms phosphomonoesters or phosphodi-esters, respectively. The hydrolysis may be generally effected by dilute aqueous alkali. Some phosphoFodichlori te intermediates are easily hydrolyzed by water. For example, the phosphorylation of a ribonucleoside (1 equation 4) with phosphorus oxychloride in an aqueous pyridine-acetonitrile mixture furnishes the nucleoside S -monophosphate (2) in excellent yield. ... 

In this case esterification to the tetra ester proceeds well in pyridine solution. Kampouris states that esterification of phloroglucinol in pyridine gives a mixture of the mono-, the di-, and the tri-ester. He esterified this and other polyprotonic phenols in aqueous solution in the presence of calcium hydroxide, added in portions to the reaction mixture until the solution was permanently alkaline to litmus. The yield of catechol dibenzenesulfonate was 96% the yield of the triester from phloroglucinol is not reported. 

Anhydrides of unsaturated acids could react in pyridine, as shown in the preparation of methacrylic esters.1908 1909 As with acetic anhydride, higher aliphatic acyl anhydrides produced triesters,1910 but benzoic anhydride produced only a diester. Subsequent acylation with benzoic and acetic anhydrides provided a mixed acetyldibenzoyl starch.1911... 

A simple approach to pyridazine-substituted pyrimidine nucleosides (52) in the reaction of alkyne derivatives (51) with tetrazine diester (48) was reported by Maggiora and Mertes (Equation (2)) <86JOC950> use of the 1,2,4-triazine triester as diene yields the corresponding pyridine derivatives. A new route to the novel C-nucleosides (55) with substituted pyridazines as aglycones by the reaction of tetrazines (48) and (53) with the sugar alkyne (54) has been described (Equation (3)) <94AP(327)365>. 

As indicated previously in Eq. (68), triester 193 can be hydrolyzed to the tricarboxylic acid 194 which can then be decarboxylated to 195. It has also been reported6 that pyrrolol 1,2-ftlpyridazines of type 195 could not be quaternized under conditions that usually convert pyridines or pyridazines into their quaternary derivatives. 

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