Reaction with dimethylformamide acetals

Azadiene 157, which is prepared by aza-Wittig reaction of diethyl azidomethylphosphonate followed by reaction with dimethylformamide (DMF) diethyl acetal, is hydrolyzed with hydrochloric acid to produce a-amino ketone 159, affording the unusual pyrazine phosphonate 158 (Scheme 43) <2003T2617>. 

An analogous scheme is used to prepare a more highly nitrogenated compound. Thus, reaction of acylpyridine (22-1) with dimethylformamide acetal gives enamide (22-2). Condensation of that with the somewhat more complex pyrrazole (22-3) leads to the soporihc agent ocinaplon (22-4) [23]. 

A powerful oxidizer. Explosive reaction with acetaldehyde, acetic acid + heat, acetic anhydride + heat, benzaldehyde, benzene, benzylthylaniUne, butyraldehyde, 1,3-dimethylhexahydropyrimidone, diethyl ether, ethylacetate, isopropylacetate, methyl dioxane, pelargonic acid, pentyl acetate, phosphoms + heat, propionaldehyde, and other organic materials or solvents. Forms a friction- and heat-sensitive explosive mixture with potassium hexacyanoferrate. Ignites on contact with alcohols, acetic anhydride + tetrahydronaphthalene, acetone, butanol, chromium(II) sulfide, cyclohexanol, dimethyl formamide, ethanol, ethylene glycol, methanol, 2-propanol, pyridine. Violent reaction with acetic anhydride + 3-methylphenol (above 75°C), acetylene, bromine pentafluoride, glycerol, hexamethylphosphoramide, peroxyformic acid, selenium, sodium amide. Incandescent reaction with alkali metals (e.g., sodium, potassium), ammonia, arsenic, butyric acid (above 100°C), chlorine trifluoride, hydrogen sulfide + heat, sodium + heat, and sulfur. Incompatible with N,N-dimethylformamide. 

ReckendorP< > < >) reported that the closely related compound (ISl), on reaction with sodium acetate in 95% ethanol, sodium methoxide in N, N-dimethylformamide, or sodium benzoate in iV,iV-dimethylformamide, gave a product that contained (152), as it could be hydrolyzed to 2,6-di-... 

The production of a 2-unsubstituted chromone by this route requires the use of triethyl orthoformate. Reaction with dimethylformamide dimethyl acetal, followed by an electrophile, bromine in the example, gives 3-substituted chromones. ... 

The methyl group in ethyl 5-methylpyridazine-4-carboxylate can be converted by reaction with dimethylformamide dimethyl acetal to the 2-(dimethylamino)vinyl group (see Houben-Weyl, Vol. E9a, p 649), which may serve as a C-C unit for the annulation of a pyridine ring. Thus, ethyl 5-[2-(dimethylamino)-l-phenylvinyl]pyridazine-4-carboxylate reacts with ammonia or benzylamine in acetic acid/ethanol at elevated temperatures to give 8-phenylpyrido[3,4-r/]-pyridazin-5(6//)-one (4a) or the 6-benzyl derivative 4b.67 Similar condensations have been carried out with ethyl 5-[2-(dimethylamino)vinyl]pyridazine-4-carboxylate and ammonia or butylamine.131... 

FIGURE 9.16 Ammonia derivatization process involving benzene sulfonylation with benzenesulfonyl chloride and subsequent reaction with dimethylformamide dimethyl acetal to form benzesulfonyldimethyl-aminomethylene derivative. 

Z)-Allylic alcohols (162) can be converted into /3y-unsaturated amides (163) with virtually complete chiral transmission by a high-temperature reaction with dimethylformamide dimethyl acetal, the crucial step being a stereospecific [2,3]sigmatropic rearrangement. By contrast, the corresponding (S)-(E )-alco-hols give rise to mixtures. 

Miscellaneous Reactions.—second method for the oxidative decarboxylation of acids has appeared this year see also ref. 335. Thus, 5-cndo-norborn-2-ene carboxylic acid on conversion to its dianion and reaction with molecular oxygen affords the a-hydroperoxide. The hydroperoxide is decomposed to 5-norbomen-2-one by reaction with p-toluenesulphonic acid or by reaction with dimethylformamide dimethyl-acetal. 

With this diacid in hand, the synthesis of 4 can be completed by reaction with dimethylformamide di-tert-butyl acetal to afford the bis tert-butyl ester, followed by dihydroxylation (cat. OsClj and MCjNO) [41]. 

Multzer s group has applied the dehydrative decarboxylation of (3-hydroxy-acids to the synthesis of buta-l,3-dienes. Thus, the addition of acetate anion to the a -unsaturated ketone (204) followed by reaction with dimethylformamide dimethyl acetal affords the ( )-dienes (205) stereospecifically, in high yields... 

However, 17a,21-acetonides (103), as well as acetals of other ketones or aldehydes, can be easily prepared by acid-catalyzed exchange reaction with dimethoxypropane or other alkyl acetals in dimethylformamide or benzene. Enol etherification of the A -S-ketone also occurs with the former procedure. 

A solution of 3.55 parts of L-trypTtophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate in 30 parts of dimethylformamide is cooled to 0 C, and 1.01 parts of tri-ethylamine are added. The mixture is stirred while 1.84 parts of N-tert-butyloxycarbonyl-(3-alanine 2,4,5-trichlorophenyl ester are added at 0 C. The reaction mixture is kept at 0°C for 48 hours and then at 20°-23°C for 24 hours. The mixture is added to a mixture of 100 parts of ice-water, 0.37 part of concentrated hydrochloric acid (SG 1.18), 1.2 parts of acetic acid and 20 parts of ethyl acetate. The mixture is stirred for 15 minutes at 0°-10°C and is then filtered. The solid residue is washed with water and then with ethyl acetate, and is dried at 40°-50°C under reduced pressure. There is thus obtained N-tert-butyloxycarbonyl-)3-alanyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide, MP 213°C with decomposition. 

A suspension of 30 g of sodium hydride in benzene (30 ml) was added dropwise to 52 g of 8-chlorodibenzo[b,f] thiepin-10(11 H)-one dissolved in dimethylformamide (800 ml), and the mixture was heated at 100°C for 2 hours. To this, there were added 68 g of 2-dimethylamino-ethyl chloride, and the mixture was heated at 60°C for 39 hours. The reaction mixture, after cooled, was poured into ice-water, and the solution was extracted with ethyl acetate. The ethyl acetate layer, after washed with water, was extracted with 10% hydrochloric acid, when oil was precipitated. The aqueous layer, in which oil was precipitated, was washed with ether, made neutral with concentrated sodium hydroxide solution and then extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over magnesium sulfate, and concentrated to give oil, which was allowed to stand to provide solid. The solid was washed with petroleum ether and recrystallized from cyclohexane to yield 42.5 g of 8melting point 90°C to 91°C. Male-ate as colorless needle, melting point 204°C to 204.5°C. 

Triazinethiones have been used frequently for the syntheses of triazino-triazines in the literature. Reaction of 6-methyl-5-[substituted styryl]-2/7-[l,2,4]triazine-3-thiones 39 with thiourea or acetylthiourea in dimethylformamide (DMF) led to the formation of N,N -disubstituted thioureas 40. Heating the compound 40b with glacial acetic acid and fused sodium acetate under reflux led to the formation of the compounds 4,7-dimethyl-8-[2-ethenylfuran]-2-thioxo-l,3,5-triazino[5,6- ][l,2,4]triazine 22 (Scheme 6) <2003PS279>. 

As these acetals could be converted into the 4,6-O-ethylidene derivatives on treatment with acid, it was reasoned that use of a cyclic vinyl ether, namely, 3,4-dihydro-2H-pyran, might prevent this second process, thus leading to a more useful method of selective acetalation.338 An equimolar reaction with methyl a-D-glu-copyranoside for 4 days in N,N-dimethylformamide led to utilization of 88% of the glycoside, and the 6-(tetrahydropyran-2-yl) ether constituted —85% of the crude reaction-product. In contrast to the steric control apparent in this instance, reaction of 3,4-dihydro-2H-pyran with the axial and equatorial hydroxyl groups in dl-1,4,5,6-tetra-O-acetyl-mi/o-inositol was completely unselective,339 a fact that has been rationalized310 in terms of the probable mechanism of these reactions. 

The coupling of Naphtol AS or its phenyl-substituted derivatives with diazonium salts from variously substituted anilines in aqueous alkaline solution (section 4-11) gave incomplete reactions and impure products in some instances, probably because these coupling components have inadequate solubility in aqueous media. Pure dyes in ca. 90% yields were obtained by reaction in dimethylformamide in the presence of sodium acetate. Metallisation of these o,o -dihydroxyazo ligands with sodium chromium salicylate or a cobalt(II) salt gave metal-complex dyes in 80-100% yields [22]. Specific structural isomers of these complexes were identified by i.r., n.m.r., Raman and UV/visible spectroscopy [23]. 

Heating 101 with aqueous sodium hydroxide in diethyleneglycol monomethyl-ether or with alkali acetate, a reaction which may also be performed in other polar organic solvents, such as dimethylformamide, N-methylpyrrolidone, or di-methylacetamide at 150°C to 210°C, also provides pyranthrone. As an alternative, 101 may be cyclized to form pyranthrone in a two-phase reaction, carried out in the presence of quarternary ammonium salts in a phase-transfer system comprising an aqueous and an organic phase [20]. 

Activated esters of A-alkoxycarbonylamino acids are prepared by two approaches, activation of the acid followed by reaction with the hydroxy compound, and trans-esterification. Most of the products are stable enough to be purified by washing a solution of the ester in an organic solvent with aqueous solutions. A few that are not crystalline are purified by passage through a column of silica. The commonly used method for their preparation is addition of dicyclohexylcarbodiimide to a cold mixture of the reactants in dimethylformamide or ethyl acetate. The first Boc-amino acid nitrophenyl esters were obtained using pyridine as solvent. Pyridine generates the nitrophenoxide ion that is more reactive. For one type of ester, 2-hydroxypyridino... 

The Schrock catalyst shown in Figure 16.12 does react cleanly with benzaldehyde according to the equation shown in Figure 16.21, a Wittig- type reaction [19], The compound did not react with ethyl acetate or N,N-dimethylformamide for several weeks at room temperature. 

The reaction of 1-amino-4,6-diphenylpyridine-2(l//)-thione (147) with dimethylformamide dimethyl acetal or triethyl orthoformate afforded 2-phenyl-4//-pyrido[2,l-a]phthalazine-4-thione (148) [81AQ(C)248],... 

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