Phosphorus methoxide

The compmmd formed may be called methyl phosphite by analogy to sodium phosphite, or better, phosphorus methoxide. In order to keep the rate of side reactions as slow as possible, it is necessary to add the iodine in small portions and to keep the temperature in the beginning below 20°. 

Reduction of the imine with sodium borohydride leads to an intermediate amino-ester that cyclizes spontaneously to the <5-lactam function. Solvolysis of the acetyl group with methoxide followed by acylation of the hydroxyl group thus liberated with trimethoxybenzoyl chloride leads to 38. Bischler-Napieralski cyclodehydration (phosphorus oxychloride) effects closure of the remaining ring. Reduction of the imine thus formed with sodium borohydride gives 39. This, it should be noted, leads to the... 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

The deoxygeneration of nitroarenes by trivalent phosphorus compounds in the presence of amines is a useful route to 3/f-azepin-2-amines (cf. compounds 32, Section 3.1.1.4.2.2.). Subsequently, it has been shown, by carrying out the reaction in strongly basic solution, that the process can be extended to the synthesis of 1H-. 3H- and 5//-2-benzazepines from nitronaph-thalenes 43 For example, 1-nitronaphthalenes 3 with dimethyl phosphite in the presence of sodium methoxide and a primary or secondary aliphatic amine, yield the dimethyl 5//-2-ben-zazepin-3-yl phosphonates 4 accompanied, in some cases, by the isomeric 3//-2-bcnzazepin-3-yl phosphonates 5. 

Methyl P-bromomethyl-A-r-butylphosphonamidate (360) has been found to rearrange upon treatment with methoxide to give dimethyl f-butylaminomethylphosphonate (362) and dimethyl iV-r-butyl-iV-methylphosphoramidate (363). The authors have proposed that the products are derived from an azaphosphiridine oxide intermediate (361) by nucleophilic attack at phosphorus and cleavage of the P-N or P-C bond, respectively. ... 

A First, a reaction with phosphorus oxychloride and phosphorus pentachioride can be used to convert 2-pyridone into 2-chloropy= ridine. and then this compound is subjected to an addition-elimination reaction with methoxide ion (from sodium methoxide) (Scheme 2,26). Note chloride is a much better leaving group than methoxide. 

This method is very useful for the construction of 1-substituted 3,4-dihydroisoquinolines, which if necessary can be oxidized to isoquinolines. A P-phenylethylamine (l-amino-2-phenylethane) is the starting material, and this is usually preformed by reacting an aromatic aldehyde with nitromethane in the presence of sodium methoxide, and allowing the adduct to eliminate methanol and give a P-nitrostyrene (l-nitro-2-phenylethene) (Scheme 3.17). This product is then reduced to the p-phenylethylamine, commonly by the action of lithium aluminium hydride. Once prepared, the p-phenylethylamine is reacted with an acyl chloride and a base to give the corresponding amide (R = H) and then this is cyclized to a 3,4-dihydro-isoquinoline by treatment with either phosphorus pentoxide or phosphorus oxychloride (Scheme 3.18). Finally, aromatization is accomplished by heating the 3,4-dihydroisoquinoline over palladium on charcoal. 

Seven 4-methoxypyridopyrimidines, 182-188, have been prepared by converting the respective 2-/< t/-butylpyr-idopyrimidin-4(3//)-ones using phosphorus oxychloride into their 4-chloro derivatives, which upon reaction with sodium methoxide gave the corresponding 4-methoxy analogues <2004T6353>. 

Treatment of a number of isatin-3-oximes with sodium methoxide at 140°293 or simply thermally274,294 leads to o-aminobenzonitriles. Thermal treatment of isatin-2-oxime gave isatin and 79.294 Beckman rearrangement of isatin-3-oximes resulted in the formation of o-cyano-phenylisocyanates.26,295 With the Vilsmeier reagent, phosphorus... 

Conversion of the phenoxypropanoic acid into the acid chloride enhances the ease of cyclization and the use of phosphorus pentachloride and aluminum chloride provides an example of this technique (51JA4205). The formation of 3-aminochroman-4-one has been achieved in this way starting from 2-amino-3-phenoxypropanoic acid (76TL271). Cyclization of the phenoxyethanoic acid shown in Scheme 234 occurs on reaction with sodium methoxide to give the chroman-3-one (63JCS5322). 

Reaction of enol ether 1 a with sodium methoxidc or ethoxide. or 1 b with sodium methoxide, gives ketene acetals, which rearrange in the presence of triethylamine to give esters 3.3 The phosphorus ylide trimethoxy[2,2,2-trilluoro-l-(trifluoromethyl)cthylidene]-A ,-phosphane f(CF3)2C = P(OMc),] rearranges readily to dimethyl f2.2,2-trifluoro-1-mcthyl-l-(trifluoro-mcthyi)ethyl]phosphonate [(CF,)2C(Me)PO(OMe)2] in a similar 1.3-shift.5-0... 

Alternatively, the alcohol could be treated with hydrogen bromide or with phosphorus tribromide to give the benzylic bromide and the bromide then allowed to react with sodium methoxide. 

An improved method for the conversion of lycorine to hippamine (5) has been developed that commenced with the conversion of 2 to the chloride 175 by the action of phosphorus oxychloride and hydrochloric acid (Scheme 18) (729). The retention of configuration at C-2 was presumably the result of a double inversion sequence involving the participation of the acetate group at C-l. Brief treatment of 175 with sodium methoxide in methanol at 0°C proceeded readily to provide lycorene a-oxide (176), which furnished hippamine (5) when heated with so-... 

Based upon observations made for the CD30-/(CH30)3P system, the tetracoordinate phosphorus anion would be an intermediate rather than a transition state. Finally, it must be noted that an attack on one of the carbon atoms of trimethyl phosphite via an SN2 mechanism can only become competitive with the nucleophilic attack on the phosphorus centre, if displacement of methoxide by the latter is sufficiently endothermic (Anderson et al., 1984). 

Iodination (I2/NaOH) of l,6-naphthyrid-5-one (47) gives the iodo derivative (48) (70% yield). This compound is converted to 5-chloro-8-iodo-l,6-naphthyridine (49) by the action of phosphorus oxychloride (64% yield). Heterocycle (49) undergoes a Heck reaction with ethyl acrylate in the presence of palladium acetate as a catalyst giving compound (51) (47% yield). Similarly, heterocycle (50) (obtained in 98% yield by treating compound (49) with sodium methoxide) gives ester (52) (88% yield) in a Heck reaction <86CPB2018>. 

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