With dimethylformamide and phosphoryl

Methylpyrazine with dimethylformamide and phosphoryl chloride gave 2-(2 -dimethylamino-l -formylvinyl)pyrazine (717), which was hydrolyzed by alkali to 2-(C,C-diformylmethyl)pyrazine (717). 

In a related reaction, 4-amino-l-methyl-5-(methylthio)carbonyltriazole (27c), when warmed with dimethylformamide and phosphoryl chloride, gave... 

With Dimethylformamide and Phosphoryl Chloride Followed by Ammonia or Amines... 

In this important reaction, which provides the only known means of converting oaminoamides to annelated 4-aminopyrimidines, the amide is acted on with dimethylformamide and phosphoryl chloride the product, a cyanodimethylaminomethyleneamino derivative (see 118), is then cyclized with ammonia or an amine (see Section VI,A,4, where it is treated as a reaction of an o-aminonitrile). 

Amino-2-ethoxycarbonyl-4-methylpyrrole was converted to the di-methylaminomethyleneamino analog (178) with dimethylformamide and phosphoryl chloride. The product, set aside for 3 days with cold methanolic ammonia, gave 7-methylpyrrolo[3,2-rf]pyrimidin-4-one 179) in excellent yield.332 The corresponding reaction with methyl anthranilate gave quina-zolin-4-one quantitatively.333... 

The Vilsmeier reaction has attracted some attention as a route to cyclazines. 3H-pyrrolizine (1) gave the Vilsmeier salt (19a) on treatment with dimethylformamide and phosphoryl chloride at — 60°C. A second formylation to (20a) was achieved by treatment of (19a) with dimethyl-thioformamide and acetic anhydride <80JCS(P1)1319>. Similar products were obtained from a chloro-formylation of the ketone (3a) the Vilsmeier reaction at — 50°C gave the salt (19b) in 65% yield. From a reaction at 0 °C, 91 % of the trisubstituted derivative (21) was obtained, which was hydrolysed... 

Vilsmeier formylation has attracted much attention as a route to cyclazines (see Section III,B,6). Jessep and Leaver have obtained the Vilsmeier salt 263 from 1 by using dimethylformamide and phosphoryl chloride at — 65°C, but the formylpyrrolizine was very unstable, and a second Vilsmeier reaction has not been achieved.128 The salt 263 could be converted to the 3,5-bisaldehyde equivalent 264a by treatment with dimethylthioformamide and acetic anhydride. Flitsch et al. prepared l-chloro-3H-pyrrolizine and treated it in situ at — 60°C with the Vilsmeier reagent to obtain the chloro derivative 259 of compound 263. 7 They also obtained the bis(dimethylaminomethylene) derivative 264b and, at room temperature, the tris(dimethylaminomethylene) derivative 265, which was hydrolyzed to give the dialdehyde 266. Reactions... 

Reaction of dyes containing a primary amino group with dimethylformamide and an inorganic acid chloride, e.g., phosphoryl chloride, permits introduction of the formamidinium group (e.g.,57), which is also scissioned off upon heating in the dye bath [154], A similar reaction occurs with the trialkylhydrazinium moiety obtained by reacting formyl-substituted azo dyes with dialkylhydrazines and subsequent quatemization [155],... 

The combination of tertiary amides, such as dimethylformamide, and phosphoryl chloride generates reactive electrophiles capable of being attacked by electron-rich nucleophiles and is widely used as the Vilsmeier formylation process. The Vilsmeier process has become more general, with the use of more varied amides, and has been particularly successful for the functionalization of pyrroles and indoles. Greater flexibility has been achieved with the replacement of phosphoryl chloride by trifluoromethanesulfonic anhydride. 

Compounds containing activated double bonds can also be formylated by dimethylformamide and phosphoryl chloride styrene thus gives cinnam-aldehyde,852 and chloroformylation to give / -chloro- -unsaturated aldehydes occurs with acetylenes, e.g. 853... 

In the still more 7t-deficient 1,2,3-triazole series (see 20), several 4-amino-5-formyl derivatives resisted both direct acylation and acetal formation. A successful alternative was to form intermediates with side chains conjugated to the nucleus. For example, 1- and 2-methyl-, as well as 3-benzyl-4-amino-l,2,3-triazole-5-aldehydes reacted with a cold mixture of dimethylformamide and phosphoryl chloride to give excellent yields of, e.g., 3-benzyl-4-dimethyl-aminomethyleneamino-l,2,3-triazole-5-aldehyde (84). This was converted to 9-benzyl-8-azapurine (see 21) in excellent yield by refluxing in methanolic ammonium acetate.87 In a variation of this reaction, an imidate (85) replaced the amidine (84) as intermediate. Thus, 4-amino-l-methyl-l,2,3-triazole-5-aldehyde and triethyl orthoacetate, refluxed for 2 hr, gave an excellent yield of 4-ethoxyethylideneamino-l,2,3-triazole-5-aldehyde (85), cyclized, by stirring in cold ethanolic ammonia, to 2,7-dimethyl-8-azapurine (good yield).87... 

The phosphorylation of cellulose with dimethylphosphite was carried out with solvents of different polarity and basicity (dimethyl ether of diethyleneglycol, dimethylsulfoxide, dimethylformamide, dimethylani-line) the highest reaction rate between cellulose and dimethylphmphite, under identical reaction conditions occurs with dimethylformamide. In the presence of other solvents the rate of phosphorylation is much lower. 

Chloro-3-methylpyrazine (101,535) and 2-chloro-5-phenylpyrazine (363, 365a, 377, 824, 825) have been prepared from the corresponding hydroxy compound and phosphoryl chloride, 2-chloro-6-methylpyrazine from 2-hydroxy-6-methylpyrazine and phosphoryl chloride with one drop of dimethylformamide (681), and 2-benzyl(or s-butyl, isobutyl, or isopropyl)-3phosphoryl chloride with a trace of concentrated sulfuric acid (80). 2-Chloro-6-methyl-3-propyl- (826), 3[Pg.99]

Vilsmeyer-Haack formylation of the tricyclic compounds of types 205 and 333 with dimethylformamide-phosphoryl chloride reagent gave the formylated products 390 (For the structures of 390... 

The highly reactive vinamidinium salt (7s) has been prepared starting from N.N-dimethylcanoacetamide by reaction with dimethylformamide diethylacetal, followed by treatment of the acrylamide derivative obtained with phosphoryl chloride and conversion to the stable perchlorate34 ... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

Dichloro-2,3-diphenyl- and 5,8-dichloropyrazino[2,3-t/]pyndazine are obtained by treatment with phosphorus pentachloride/phosphoryl chloride in the presence of a small amount of dimethylformamide (1 drop) at 125 °C for one hour in a yield of 87% [mp 202-204 °C purified by chromatography (silica gel, CH,CI2)],8J or by refluxing for 8 hours in a yield of 34%,86 respectively. 

Quinoxalin-2-ones are readily converted into 2-chloroquinoxalines on treatment with phosphoryl chloride or thionyl chloride containing dimethylformamide, and in view of the highly reactive nature of 2-chloroquinoxalines, quinoxalin-2-ones are much used intermediates in quinoxaline synthesis. 

Arnold and his colleagues have applied the combination of dimethylformamide with phosgene or phosphoryl chloride also to formylation of aliphatic compounds such as acetals,844,845 ketals,846 vinyl ethers,844,845,847 and ketones848,849 (see also Ziegenbein and his co-workers850). Vinyl ethers afford 2-alkyl-3-(dialkylamino) derivatives of acrylaldehyde 844... 

Bredereck and Bredereck,969 however, found that it was unnecessary to start with acetals, and that enamines are formed in about 80% yield when compounds containing reactive methylene groups are treated with dimethylformamide or other amides in the presence of phosphoryl chloride. Eiden970 used acetic anhydride instead of phosphoryl chloride, but the yields then sank to 25-40%. 

Nucleotide derivatives. Dry adenosine-5 -phosphoric acid stirred with -carb-ethoxy-a-ethoxyvinyl diethyl phosphate and tri-n-butylamine in abs. dimethyl-formamide until dissolved after 2-3 days, dil. with acetone and the product precipitated with a soln. of anhydrous Nal in acetone Na P -(5 -adenosyl) P -diethyl diphosphate (Y 87 % as the monohydrate) warmed 3 hrs. at 50° in abs. methanol-pyridine, and the product isolated as the NH4-salt NH4 5 -adenosine methyl phosphate (Y 79.2% as the monohydrate).—Pyrophosphoric acid esters react with alcohols, amines, and acids so that the monoester part appears in the product. The adenosine-5 -phosphoric acid group in the intermediate triester is activated and can be easily combined with various nucleophiles. F. e. without isolation of the intermediate s. F. Cramer and R. Witt-mann. B. 9A, 328 (1961) s. a. B. 94, 322 dimethylformamide as phosphorylation catalyst s. B, 94, 989. 

Nucleophilic processes that generate chloroindoles are largely confined to the displacements of oxy functions and Sandmeyer reactions of diazo-nium salts [81 H( 15)547]. A low yield of 2-chloroindole was obtained by a reaction sequence that involved treatment of oxindole with phosphoryl chloride, and then treatment of the Vilsmeier salt with sodium bicarbonate [66JOC2627 86H(24)2879]. It is, however, much better to prepare this compound from 2-lithioindole (92JOC2495). With phosphoryl chloride and dimethylformamide ethyl l-hydroxyindole-2-carboxylate failed to give the expected 3-formyl derivative. Instead there was a 50% yield of the 3-chloro derivative (84CPB3678). Diazonium salts have been used as precursors in... 

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