Dimethylformamide dimethyl acetal

Amino-pyridazines and -pyridazinones react with monomethyl- or iV,A-dimethyl-formamide and other aliphatic amides in the presence of phosphorus trichloride, thionyl chloride, phosgene or benzenesuUonyl chloride to give mono- or di-alkylaminomethyl-eneamino derivatives. The same compounds can be prepared conveniently with A,iV-dimethylformamide dimethyl acetal in high yield (Scheme 50). 

In 1971, Batcho and Leimgruber introduced a new method for the synthesis of indoles. For example, condensation of o-nitrotoluene (5) with N,N-dimethylformamide dimethyl acetal (6) (DMFDMA) was followed by reduction of the rrans-P-dimethylamino-2-nitrostyrene (7) which resulted to provide the indole (8). ... 

Fewer procedures have been explored recently for the synthesis of simple six-membered heterocycles by microwave-assisted MCRs. Libraries of 3,5,6-trisubstituted 2-pyridones have been prepared by the rapid solution phase three-component condensation of CH-acidic carbonyl compounds 44, NJ -dimethylformamide dimethyl acetal 45 and methylene active nitriles 47 imder microwave irradiation [77]. In this one-pot, two-step process for the synthesis of simple pyridones, initial condensation between 44 and 45 under solvent-free conditions was facilitated in 5 -10 min at either ambient temperature or 100 ° C by microwave irradiation, depending upon the CH-acidic carbonyl compound 44 used, to give enamine intermediate 46 (Scheme 19). Addition of the nitrile 47 and catalytic piperidine, and irradiation at 100 °C for 5 min, gave a library of 2-pyridones 48 in reasonable overall yield and high individual purities. 

The condensation between enaminones and cyanoacetamide is a well-established method for the synthesis of 2-pyridones (see c, Scheme 2, Sect. 2.1), and the use of malonodinitrile instead of the amide component has also been shown to yield 2-pyridones [39-41]. Recently, Gorobets et al. developed a microwave-assisted modification of this reaction suitable for combinatorial synthesis, as they set out to synthesize a small library of compounds containing a 2-pyridone scaffold substituted at the 3, 5, and 6-positions [42]. The 2-pyridones were prepared by a three-component, two-step reaction where eight different carbonyl building blocks were reacted with N,N-dimethylformamide dimethyl acetal (DMFDMA) to yield enaminones 7 (Fig. 2). The reactions were performed under solvent-free conditions at el-... 

Phenols and primary alcohols form ethers when heated with dicyclohexylcarbo-diimide (DCC see 10-23). 1,2-Diols can be converted to epoxides by treatment with dimethylformamide dimethyl acetal, (MeO)2CHNMc2, with diethyl azodi-carboxylate, EtOOCN=NCOOEt, and Ph3P with a diaUcoxytriphenylphospho-rane, ° or with TsCl-NaOH-PhCH2NEt3+ CP. ... 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

We also investigated reaction of 4-hydroxycoumarin with an excess of Ar,Ar-dimethylformamide dimethyl acetal (DMFDMA) which afforded the corresponding 3-(dimethylaminomethylene)-chromane-2,4-dione derivative 72. The structure was again confirmed by IR, NMR, and MS analyses. 

The groups of Giacomelli and Taddei have developed a rapid solution-phase protocol for the synthesis of 1,4,5-trisubstituted pyrazole libraries (Scheme 6.194) [356]. The transformations involved the cyclization of a monosubstituted hydrazine with an enamino-/8-ketoester derived from a /8-ketoester and N,N-dimethylformamide dimethyl acetal (DMFDMA). The sites for molecular diversity in this approach are the substituents on the hydrazine (R3) and on the starting j3-keto ester (R1, R2). Subjecting a solution of the /8-keto ester in DMFDMA as solvent to 5 min of microwave irradiation (domestic oven) led to full and clean conversion to the corresponding enamine. After evaporation of the excess DMFDMA, ethanol was added to the crude reaction mixture followed by 1 equivalent of the hydrazine hydrochloride and 1.5 equivalents of triethylamine base. Further microwave irradiation for 8 min provided - after purification by filtration through a short silica gel column - the desired pyrazoles in >90% purity. 

In Scheme 6.230, the multistep synthesis of 2,3-dihydro-4-pyridones is highlighted [411]. The pathway described by Panunzio and coworkers starts from a dioxin-4-one precursor, which is readed with 2 equivalents of benzyl alcohol under solvent-free microwave conditions to furnish the corresponding /1-diketo benzyl esters. Subsequent treatment with 1 equivalent of N,N-dimethylformamide dimethyl acetal (DMFDMA), again under solvent-free conditions, produces an enamine, which is then cyclized with an amine building block (1.1 equivalents) to produce the desired 4-pyridinone produds. All microwave protocols were conducted under open-vessel conditions using power control. 

A ,A"-/i/. s,(dimcthylaminomcthylenc)thiourea (prepared by double condensation of AAY-dimethylformamide dimethyl acetal with thiourea) has been reacted with a-haloketones or acrylic dienophiles to give thiazolic and thiazinic diazadienes, respectively. These undergo cyclization reactions to yield imidazo[2,1-/ ][1,3] thiazoles, 5H-1,3-thiazolo[3,2-a]pyrimidines, 72/-imidazo[2,1 -/ ][ 1,3]thiazines and 2//,6//-pyrimido[2,l -/)][1,3]thiazines without any regioisomeric ambiguity (Scheme 61).144,145... 

Use of dimethoxydiphenylsilane in combination with N,N-dimethylformamide-p-toluenesulfonic acid to introduce silicon into the sucrose molecule has been exploited.27 On treatment with this combination of reagents, sucrose gave, after chromatographic fractionation of the acetylated mixture, 3,4,6,3, 4, 6 -hexa-0-acetyl-2,l -0-(diphenylsilyl)sucrose (10) and 3,4,3, 4 -tetra-0-acetyl-2,l 6,6 -di-0-(diphenylsilyl)sucrose (33) in 45 and 10% yield, respectively.27 With a view to introducing other heteroatoms, such as phosphorus or nitrogen, into the sucrose molecule, such reagents as dimethoxy-phenylphosphine, N,N-dimethylformamide dimethyl acetal, and 3,3-dimethoxypropylamine in combination with 2V,N-dimethylfor-mamide-p-toluenesulfonic acid are of interest. 

Alkenes from vie -diols.2 The 2-dimethylamino-l,3-dioxolanes 1, obtained by reaction of a 1,2-diol with N,N-dimethylformamide dimethyl acetal in quantitative yield, when treated with ethyldiisopropylamine (4 equiv.) and triflic anhy-... 

Numerous procedures for the preparation of butenolides have been developed. Font and coworkers (234-236) prepared the 5-O-substituted derivatives 223a-c of D-ribono-1,4-lactone. The cw-glycol system of223a reacted with ATjV-dimethylformamide dimethyl acetal and then with iodomethane to give the trimethylammonium methylidene intermediate 224. Pyrolysis of 224 gave the butenolide 225. 

Dimethylformamide dimethyl acetal was reacted with malonic acid derivatives at room temperature for 6 hr (84TL3743) or at 110°C for 1-2 hr (780PP67) to afford /V.N-dimethylaminomethylene derivatives (331) in 75-96% yields. 

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],... 

Treatment of 2-amino-5-nitrothiobenzamide with iV,iV-dimethylformamide dimethyl acetal gives 2-amino-iV-((dimethylamino)methylene)-5-nitrobenzothioamide 191 in excellent yield <2004TL5913>. Cycloaddition reaction of 191 with DMAD results in formation of dimethyl 2-(2-amino-5-nitrophenyl)-4-(dimethylamino)-4//-l,3-thiazine-5,6-dicarboxylate 192 in low yield when R = H. This is caused by cycloreversion of thiazine 192 to give dimethyl 2-((dimethylamino)methylene)-3-thioxosuccinate 193 and 2-amino-5-nitrobenzonitrile 194 (Scheme 19). When W((dimethylamino)methylene)-2-(alkylamino)-5-nitrothiobenzamides 191 (R = Me, Bn) are reacted with DMAD, the expected 4//-l,3-thiazine-5,6-dicarboxylates 195 are produced as stable compounds. 

Scheme 7.49). The requisite activated double bond is generated in situ from the 1,3-dicarbonyl compound and a one-carbon synthon such as a trialkyl orthoformate, diethoxymethyl acetate or Al,Al-dimethylformamide dimethyl acetal. 

The reactivity of amino functions on diazotization and condensation with dimethylformamide dimethyl acetal has been discussed in CHEC-II <1996CHEC-II(7)431>. The diamine 220 is readily converted into a variety of tricyclic pyrazolo[3,4-r/ pyrimidines under a variety of conditions <2004T5093>. Thus with chloroacetyl chloride the chlor-oacetyl derivative 221 was formed. This could not be further cyclized into 222. Refluxing 220 with diethyl oxalate afforded 223 while 224 was formed when the reaction was conducted at 40 °C. Treatment of 224 with POCI3 afforded 223. Reacting 220 with carbon disulfide afforded 225 (Scheme 14) <2004T5093>. 

Amidines formed by condensation of 4-aminouracils with dimethylformamide dimethyl acetal are effective dienophiles, and form pyrimido[4,5-rflpyrimidines by [4-I-2] cycloaddition with isocyanates, isothiocyanates (Equation 83) <2005TL1433> and imines (Equation 84), A similar process has also been reported, using a nitrone as the dienophile (Equation 85) <2006BMCL3537>. 

The formation of a pyrimido[5,4-f][l,2]thiazine by annulation of a pyrimidine ring onto a benzoH[l,2]thiazin-4-one has been reported, involving condensation with dimethylformamide dimethyl acetal followed by Bredereck s reagent (Scheme 90), and reaction of the resultant vinylogous amide with guanidine <2005W02005/037843>. Essentially, the same approach has been used to prepare annulated forms of the isomeric pyrimido[4,5-< ][l,2]thiazines, as outlined in Scheme 91 <1998W098/28281>. 

N,N-Dimethylformamide dimethyl acetal, obtained from Aldrich Chemical Company, Inc., is redistilled before use. 

Phenanthrenequinone (8) 9,10-Phenanthrenedione (9) (84-11-7) Lithium aluminum hydride Aluminate (1-), tetrahydro, lithium (8), Aluminate (1-), tetrahydro-, lithium, (T-4)- (9) (16853-85-3) N,/V-Dimethylformamide dimethyl acetal Trimethylamine, 1,1-dimethoxy- (8) Methanamine, 1,1-dimethoxy-(V,N-dimethyl- (9) (4637-24-5)... 

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