Substituted methylene derivatives

The substituted methylene derivative, prepared from a 2-formylpyrrole and a ma-lonic acid derivative, was used in a synthesis of chlorophyll. It is cleaved under drastic conditions (coned alkali). ... 

In the case of the 2-dimethylamino- (or 2-amino-)methylene derivatives, the products were at first thought to be pyrimido[4,5-c]isoquinolines (267), but later work with 6-(N-substituted amino)uracils assigned the structures of the products (268) as belonging to the isomeric pyrimido[4,5-f>]quinoline system (74CB2537), in agreement with the regioselection rules above. 

During the next fifty years the interest in derivatives of divalent carbon was mainly confined to methylene (CHg) and substituted methylenes obtained by decomposition of the corresponding diazo compounds this phase has been fully reviewed by Huisgen. The first convincing evidence for the formation of dichlorocarbene from chloroform was presented by Hine in 1950. Kinetic studies of the basic hydrolysis of chloroform in aqueous dioxane led to the suggestion that the rate-determining step was loss of chloride ion from the tri-chloromethyl anion which is formed in a rapid pre-equilibrium with hydroxide ions ... 

The present procedure is applicable only to bromomalononitrile various a-halogen active methylene derivatives, (e.g., diethyl chloromalonate, methyl bromoacetoacetate) led predominantly to the formation of ring-contracted styrene derivatives. On the other hand, substituted cycloheptatrienylium salts with bromomalononitrile gave the desired dicyanoheptafulvene derivatives in excellent yields. One notable example is the synthesis of 5- and 7-(dicyanomethylene)-2,3-dihydrocyclohepta-1,4-dithiins.6... 

Ketones. Treatment of the diketone (26) with methylenetriphenylphosphorane gave a high yield of 1,6-dimethylenecyclodecane.29 Diphenylcyclobutenedione reacts with ylides, e.g. (27), to yield substituted 4-methylene derivatives.30... 

I. S. Bennett, N. J. P. Broom, K. Coleman, S. Coulton, P. D. Edwards, I. Francois, D. R. J. Griffin, N. F. Osborne, P. M. Woodall, 6-(Substituted Methylene) Penems, Potent Broad Spectrum Inhibitors of Bacterial /3-Lactamase. IV. Kidney Stability, Serum Binding and Additional Biological Evaluation of Racemic Derivatives , J. Antibiot. 1991,44, 338-343. 

Other related reactions involve TV-fluorenylmethyloxycarbonyl (N-Fmoc) AAs and aliphatic aldehydes (83JOC77) or substituted /-butoxycarbonyl (N-Boc) Aas and 2,2-dimethyoxypropane (acetone dimethyl ketal) (84TL5855 87JOC2361 88TL2019), as well as A-(dimethylthio)methylene derivatives of an AA and aromatic aldehydes [89JCS(P1)1577]. 

Not shown in Table I are several adducts obtained by cycloaddition of the acridizinium ion with 5,6-endo-substituted norbomene derivatives. These adducts each have two (imequally shielded) methylene hydrogen atoms which make simple the NMR analysis of mixtures of syn (8) and anti (9). When the 5,6-endo chain (R) was of the type... 

Substitution of the 11-ethoxycarbonylmethylthio group of 64 with anilines, 3-dimethylaminopropylamine, thiosemicarbazide, acetylhydrazine, and dimethyl malonate gave the corresponding 11-amine 65 and ll-bis(di-methoxycarbonyl)methylene derivatives 66 (74JHC125). Deprotonation of the 11-amines 65 gave the 11-imino derivatives 67. 

A further example of the diazaphosphole synthesis by [3 + 2] cycloaddition is given by the reaction of a phosphoranediyl diazomethane (26) (R = NPr j) with P-chloro-bis(trimethylsilyl)-phosphaethene. The adduct loses trimethylchlorosilane and yields a 3-phosphoranediyl-l,2,4-diazaphosphole (or 3-phosphonio-l,2,4-diazaphospholide) (27). The analogous addition to the trimethylsilyl substituted P-chloro-bis(methylene)phosphorane (28) yields a 4-methylene derivative (29) of this diazaphosphole (molecular structure in Table 1). It provides the only fully characterized example of this type up to 1995. Methyl triflate methylates the compound at N-1 and gives a phosphonio methylene diazaphosphole cation (30). 

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