Methylenation dimethyl acetals

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. 

Methylenebis(oxy) ]bis(2-chloroformaldehyde), see Bis (2-chloroethoxy) methane Methylene chlorobromide, see Bromochloromethane Methylene dichloride, see Methylene chloride Methylene dimethyl ether, see Methylal Methyl 2,2-divinyl ketone, see Mesityl oxide Methylene glycol, see Formaldehyde Methylene glycol dimethyl ether, see Methylal Methylene oxide, see Formaldehyde Methyl ethanoate, see Methyl acetate (1 -Methylethenyl)benzene, see a-Methylstyrene Methyl ethoxol, see Methyl cellosolve 1-Methylethylamine, see Isopropylamine (l-Methylethyl)benzene, see Isopropylbenzene Methylethyl carbinol, see sec-Bntyl alcohol Methyl ethylene oxide, see Propylene oxide ds-Methylethyl ethylene, see cis-2-Pentene frans-Methylethyl ethylene, see frans-2-Pentene Methyl ethyl ketone, see 2-Bntanone Methylethylmethane, see Butane... 

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. 

This method has since been used for synthesis of annelated furanes.2 An example is formulated in equation (II). The masked furane ring is introduced by reaction of an activated methylene group with dimethylformamide dimethyl acetal. 

M. Funabashi, H. Wakai, K. Sato, and J. Yoshimura, Branched-chain sugars. Part 15. Synthesis of l-i.-(l,2,3, 4,5/3,6)-3-hydroxymethyl-4,5-0-isopropylidene-3,3 -0-methylene-6-nitro-2,3,4,5-tetrahydrocyclohexanecarbaldehyde dimethyl acetal, a potential key compound for total synthesis of optically active tetrodotoxin, J. Chem. Soc. Perkin Trans, p. 14 (1980). 

Dimethylaminomethylene derivatives, usually obtained by condensation of the dimethyl acetal or diethyl acetal of dimethylformamide with an active methylene group, can react with carbanions. This results in various heterocyclization reactions including formation of the pyridine ring (91TL1999 95S557). Thus, enamine 176 and the 2-acetylpyridone anion give 2,2 6, 2"-terpyridine (177) (91TL1999). 

H20. Representative acetals include CH2(OCH3)2, methylene dimethyl ether, bp 42°C CH3CH (OCH3)2, ethyhdene dimethyl ether, bp 64°C and CH3CH(OC2H5)2, ethyhdene diethyl ether, bp 104°C. 

The resulting 5-methylene-2-oxa-l-silacyclohexanes are insufficiently Lewis acidic to react with a second equivalent of the carbonyl compound. However, the incipient allylsilane does react with dimethyl acetals in decent yields in the presence of external Lewis acids including BF3-Et20 or AICI3. Based on these results, double allylation of dicarbonyl compounds with 3-methylene-l,l-diphenyl-l-silacyclobutane was examined, leading to the formation of 3-methylene-oxabicyclo[3.2.1]octanes. This transformation proceeded in one pot and in the presence of BF3-Et20 (Scheme 42). 

Testosterone. Introduction of Ja-methyl (S-150), la-ethyl (S-151), la-methyl 17-acetate (S-72), la-chloromethyl 17-acetate (S-74), la-bromomethyl 17-acetate (S-75), la-iodomethyl 17-acetate (S-76), 1,1-dimethyl 17-acetate (S-77), la,2a-methylene 17-acetate (S-78), la-methyl 4-chloro 17-acetate(S-79), la-methyl 7a-methyl 17-acetate (S-80), la-methyl 7/3-methyl 17-acetate (S-81), la-methyl 1 l 6-hydroxy 17-acetate (S-82), 1 a,2a-methylene 11/3-hydroxy 17-acetate (S-83), la-methyl 11-keto 17-acetate (S-84), la-methyl A 17-acetate (S-86), la-methyl A 11 -keto 17-acetate (S-88), 1 a,2a-methylene A 17-acetate... 

Hasegawa and Fletcher25,37 studied the reaction of some aldoses, mainly 2-acetamido-2-deoxyaldohexoses, with 2,2-dimethoxypro-pane-N V-dimethylformamide-p-toluenesulfonic acid at 25 and 80°. The products obtained at the two temperatures differed markedly, and, again, lack of activity at the anomeric hydroxyl group in the presence of N,N-dimethylformamide was noted. To account for this phenomenon, it was postulated that the dimethyl acetal ofA/JV-dimethyl-formamide, presumably formed in situ, reacts to afford highly labile (dimethylamino)methylene acetals which may thereby permit insertion of isopropylidene groups in abnormal positions. 

Condensation with active methylene compounds. One step in the total synthesis of the naturally occurring fulvene fulvoplumierin involved condensation of a mixture of the isomeric diols (1) with dimethylformamide dimethyl acetal.18... 

ENOL ETHERS Trimethylchlorosilane. EPISULFIDES Sulfur monochloride. EPOXIDES Dimethylformamide dimethyl acetal. Dimethyloxosulfonium methylide. Iodine. Methylene bromide-Lithium. Methylphenyl-N-p-toluene-sulfonylsulfoximine. a -EPOXY SULFONES Hydrogen peroxide. 

Wird die Bestrahlung in methanolLscher Essigsaure durchgeiuhrt, so konnen auBer dem Oxetan aueli das primar gebildete 3-(l-Methyl-2-methylen-cyclohexyl)-propanal und dessen Dimethyl-acetal isoliort werden. 

Thus, refluxing 2-aminonicotinonitrile in triethyl orthoformate with26 or without14 acetic anhydride yields the (ethoxymethylene)amino compound, whose cyclization with ammonia yields pyrido[2,3-c/]pyrimidin-4-amine (18),14 while methylaminc affords 3-methylpyrido[2,3- /]pyrimidin-4(3//)-imine (41%).26 Dimethylformamide dimethyl acetal converts 2-aminonicotinonitrile into 2- [(dimethylamino)methylene]amino nicotinonitrile,14 which cyclizes with hy-droxylamine hydrochloride in methanol at room temperature to give pyrido[2,3-rf]pyrimidin-... 

Ring closure between the two amino ends in the 2,3-position of 3-aminopyridine-2-carboxam-ide occurs by using dimcthylformamide dimethyl acetal as the source of the methylene group, the product being pyrido[3,2-r/]pyrimidin-4(3//)-one (5).427... 

The condensation product of malononitrile with methyl cyanoacetate reacts with excess dimethylformamide dimethyl acetal at the amino as well as at the methylene group. The resulting compound cyclizes with arylamines to give l-aryl-4- [(A, JV-dimethylamino)methylene]-amino -2-oxo-l,2-dihydropyridine-3,5-dicarbonitriles which, in turn, with concentrated hydrochloric acid may be cyclized to furnish 6-aryl-4,7-dioxo-3,4,6,7-tetrahydropyrido[4,3-r/]-pyrimidine-8-carbonitriles 4.493... 

The reaction of 2-aminoprop-l-ene-l,l,3-tricarbonitrile ( dimeric malononitrile ) with dimethylformamide dimethyl acetal occurs at both the amino and the methylene group and yields a biscondensation product 1. By heating this compound with aliphatic or aromatic amines, various 6-substituted 4-amino-5-imino-5,6-dihydropyrido[4,3-tf]pyrimidine-8-carboni-triles 2 are obtainable, the presumed mechanism including a Dimroth rearrangement (cf. p 90) in the pyrimidine part of the molecule.494... 

The completion of the total synthesis is described in Scheme 47. The HW reaction of phosphine oxide 320 and 314 efficiently afforded ( )-triene 321. After hydrolysis of dimethyl acetal in 321 followed by aldol reaction, macro-lactamization was carried out under Mukaiyama macrocyclization conditions to give an 1 1 mixture of diastereomers 322. Removal of three allylcarbonates followed by treatment with the Dess-Martin reagent resulted in oxidation of the three alcohols and subsequent oxidation of the C9 methylene. Final deprotection of the resulting tetraketone with HF-py completed the total synthesis of rapamycin (2). 

AI3-16096 Anesthenyi Bis(methoxy)methane Dimeth-oxymethane Dimethyl formal 2,4-Dioxapentane EINECS 203-714-2 Formal Formaldehyde dimethyl-acetal Formaldehyde methyl ketal HSDB 1820 Methane, dimethoxy- Methoxymethyl methyl ether Methylal Methylene dimethyl ether Metylal UN1234, Used as a solvent In organio synthesis perfumes, adhesives, protective coatings special fuel. Liquid mp = -104.8° bp = 42° d = 0.8593 soluble in H2O (30 g/100 ml), very soluble In EtOH, Et20, MezCO, CeHe LD50 (rbt orl) n5708mg/kg. 

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