Phosphorus oxychloride/DMF

The stabilized phosphonium ylide (601) reacts with aromatic aldehydes to give N-phenacylpyrazoles (602) in good yields (73CC7). Ketone semicarbazones and ketazines react with two moles of phosphorus oxychloride-DMF, the Vilsmeier-Haack reagent, with the formation of 4-formylpyrazoles (603 R = H or PhC=CH2) (70JHC25, 70TL4215). 

In the absence of phosphorus oxychloride, DMF or its acetal yields chromone itself with... 

Other variations include formamide (57JA6421), sodium dithioformate or phosphorus oxychloride-DMF (69RTC1263), a thioamide (78MI41000) and acetylacetone (77JHC813). Reduction of 2,6-dibenzamido-3-(2-butoxypyrid-5-ylazo)pyridine with iron and hydrochloric acid resulted in ring closure to 5-benzamido-2-phenylimidazo[4,5-f>]pyridine (60AC(R)125). 

Aromatic compounds are formylated using triphosgene/DMF [1300], phosphorus oxychloride/DMF, or oxalyl chloride/DMF [1301],... 

An efficient synthesis of 2,4-dihydroxybenzaldehyde 1775 from resorcinol 1773 by a Vilsmeier-Haack reaction using either phosphorus oxychloride/DMF or oxalyl chloride/DMF, working below room temperature in acetonitrile, has been reported [1301]. 

In an initial step the reactive formylating agent is formed from N,N-dimethylformamide (DMF) 2 and phosphorus oxychloride. Other N,N-disubstituted formamides have also found application for example A -methyl-A -phenylformamide is often used. The formylating agent is likely to be a chloromethyl iminium salt 4—also called the Vilsmeier complex (however its actual structure is not rigorously known)—that acts as the electrophile in an electrophilic substitution reaction with the aromatic substrate 1 (see also Friedel-Crafts acylation reaction) ... 

The entire product from the previous reaction (calculated to contain about 46 mmol of 6) is combined with phosphorus oxychloride (8.53 mL, 91.6 mmol). The viscous mixture is mechanically stirred (note 2) at 0°C, and DMF (5.31 mL, 68.7 mmol) is added portionwise over 1 h. The reaction mixture is stirred for an additional 20 h at 25°C, and then quenched by addition of ice (200 g). The very acidic aqueous solution is washed with ethyl ether (3 x 75 mL) to remove 4 carried over from the previous reaction, after which the pH is adjusted to 6.0 with 19 N aqueous NaOH. Sodium acetate (40 g) is also added, and the solution is extracted with EtOAc (3 x 75 mL). The combined organic phases are washed with saturated aqueous... 

The major absorption in the 31P n.m.r. spectrum of an equimolar solution of penta-phenoxyphosphorane and sodium phenoxide in DMF-acetonitrile is due to the hexaphenoxyphosphate anion, as predicted from the low equilibrium constant estimated for equation (2) (page 35).27 Catechol and phosphorus oxychloride in refluxing benzene gave the spirophosphorane(108), which with triethylamine gave the salt (109).45 On the basis of its 31P chemical shift in DMF solution, (108) was formulated86 as the free six-co-ordinate acid (110), but it seems probable that DMF is... 

Treatment of hydrazide 22 with cuprous chloride in dimethyiformamide (DMF) affords 23 (85IZV1367), whereas treatment of 24 with K2CO3 and Ni(N03>2 at 130°C in DMF gives 25 (80KGS1524). The cyclization of hydrazinopyridazine (26) with phosphorus oxychloride in DMF afforded either 28 or 29 depending on reaction conditions 27 is a common intermediate (Scheme 4) (85CPB982). 

Unsubstituted thienothiophenes 1 and 2 are smoothly formylated in the 2-positions by DMF-phosphorus oxychloride in dchloro-ethane. The site of substitution in thienothiophene 2 was confirmed by preparing the corresponding formyl derivative from 2-lithiothieno-[3,2-6]thiophene and DMF, and in the case of 1, by oxidizing the formyl derivative to thieno[2,3-h]thiophene-2-carboxylic acid, as well as the NMR spectra [Eqs. (66) and (67)]. 

By DMF and phosphorus oxychloride, dithieno[3,2-6 2, 3 -d]-thiophene (6) was converted into the 2-formyl derivative in 93% yield. The production of 2,6-diformyldithieno[3,2-6 2, 3 -[Pg.193]

When DMF and phosphorus oxychloride are reacted together in the Vilsmeier reaction, the A,A-dimethylamino(chloro)methyleniminium cation is generated, and this reacts with indole at 5 °C to give 3-(A,A-dimethylaminomethylene)indolenine (see Section 6.1.2). When hydrolysed by treatment with dilute sodium hydroxide, this gives an excellent yield of 3-formylindole (Scheme 7.5). 

In connection with the aminocarbonylation processes described above, an apparent CO-free aminocarbonylation reaction of aryl and alkenyl iodides was reported using A, Wdimethylformamide (DMF) as the ammonia substitute in the presence of phosphorus oxychloride (POCI3) (Scheme 23). This reaction is so far restricted to DMF at present. 

The Vilsmeier-Haack formylation procedure (Scheme 24) provides the most effective synthesis of formylpyrroles and indoles. Reaction of the heterocycles with the immonium cation (72), derived from DMF or (V-methylformanilide with an acid chloride, such as phosphorus oxychloride, thionyl chloride, phosgene, oxalyl chloride, benzoyl chloride or bromotriphenylphosphonium bromide, yields the intermediate heteroarylimmonium salt (73). Under suitable reaction conditions, this salt may be isolated from the reaction involving phosphorus oxychloride as an impure chlorophosphate (78TH30500) or precipitated from the reaction system as the thermally unstable perchlorate by the addition of sodium... 

The reaction of 2,3-dihydro-1//- pyrrolizin-1 -one with phosphorus oxychloride and DMF at -50 °C results in the formation of (77) but, at 0°C with an excess of the Vilsmeier reagent, further reaction yields (78) (79CB2465). In contrast, the benzopyrrolizinone (79) reacts only with difficulty under similar reaction conditions to give the monoformyl derivative... 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

Russian workers (74KGS58) carried out Vilsmeier reactions on 4,5-disubstituted 2-acylthienylamines and cyclized the resulting 3-formyl compounds with substances containing active methylene groups (Scheme 60). A versatile new synthesis of thieno[2,3-6]pyridines is also based on the Vilsmeier formylation of 2-acetamidothiophenes. Whereas with equimolar amounts of DMF and phosphorus oxychloride 3-formyl derivatives are obtained,... 

The Schiff base 134 with the mixture of phosphorus oxychloride and dichloroacetic acid in DMF led to the triazolopyrimidinone 135 instead of the expected 3,3-dichloroazetidinone derivative (88JHC173) (Scheme 25). 

Reaction of Schiff bases 422 with a mixture of phosphorus oxychloride and dichloroacetic acid in DMF gave triazolopyrimidinones (423) instead of the expected 3,3-dichloroazetidinones (424) (88JHC173). 1,4-Cycloaddition of 422 (R = SMe R1 = Ph) with phenoxyacetyl chloride in the presence of triethylamine gave the dihydro-1,2,4-triazolo[4,3-ajpyrimidinone 425 (88JHC173) (Scheme 82). 

The transformation of one hetero substituent into another is a reaction frequently observed in the 1,2,4-triazine series. Oxo group transformations are indicated in Scheme 8. They can be transformed into thioxo groups by phosphorus pentasulfide or Lawesson s reagent. Pyridine seems to be the best solvent for the phosphorus pentasulfide reaction and a small amount of water (0.1% or less) seems to improve results. An oxygen in the 5-position is more easily replaced than one in the 3- or 6-position. Transformation of the oxo (hydroxy) group into a chloro substituent is achieved by phosphorus oxychloride, phosphorus penta-chloride, or thionyl chloride and DMF. In this reaction also the oxygen is most reactive in the 5-position. 

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