Methylene and amide

Ruell, J. A., De Clercq, E., Pannecouque, C., Witvrouw, M., Stup, T. L., Turpin, J. A., Buckheit, R. W., Jr., Cushman, M. Synthesis and Anti-HIV Activity of Cosalane Analogues with Substituted Benzoic Acid Rings Attached to the Pharmacophore through Methylene and Amide Linkers. J. Org. Chem. 1999, 64, 5858-5866. 

The most commonly used polyamide fibre in ballistic application prior to the development of aramid fibres was Nylon 6.6. Technically, the basic built-ups of Nylon 6.6 are the methylene and amide groups. 

Best Preparation on a Laboratory and Commercial Scale. A. Methylene diform amide. In a 2fi round bottom 1 neck flask are placed 540g of formamide and 70g of hexamine. The flask is fitted with a wide bore air condenser topped with a w jacketed reflux condenser, and the flask held at 140 for 5 hours. It is chilled in ice, the solid filtered, and washed on the filter with 90g of formamide. The cmde prod may be used in the next step. For a pure sample,- the crude solid is dissolved in et ale, decolorized with charcoal, and the soln chilled, mp 142—43°... 

C. MEDINA. The crude methylenedi(nitro-formamide) is pressed dry on the filter, stirred into lOSml of formic acid, and the paste allowed to stand overnight. The next day the soln is filtered thru an acid-proof flit, the formic acid and w removed by codistn with xylene, and the crude MEDINA, which seps as a sand, filtered and dried over paraffin and NaOH in a vacuum yield 80—100% based on methylene diform-amide, mp 98—103°. The crude MEDINA is recrystd from 2-nitropropane or et chloride iso-Pr ale 9 1, mp 104-059 (Ref 11, p 54). This prepn is also covered in Ref 20... 

SECTION 66 ALKYLS, METHYLENES AND ARYLS FROM AMIDES... 

Chemical degradations have allowed the identification of both extremities of peripentadenine, hexanoic acid (present as an amide) and 2-hydroxy-6-meth-ylacetophenone. 13C NMR showed that the rest of the molecule included two nitrogen atoms, six methylenes, and one methine arranged in a (3-propylami-no)-l-pyrrolidine unit substituted at C-2. This formula was definitively proved by chemical degradations as well as by two total syntheses. As noted before in the cases of hygrine and of the ruspolinone alkaloids, peripentadenine is optically inactive. 

The reaction proceeds via electrogenerated cationic species as its seen with the nonfluorinated amines, carbamates, and amides (Scheme 6.14). However, the regiochemistry of this anodic methoxylation is not governed by the stability of the cationic intermediates B and B (thermodynamic control) since the main products are formed via the less stable intermediates B. Indeed, this remarkable promotion effect and unique regioselectivity can be explained mainly in terms of a-CH kinetic acidities of the cation radicals formed by one-electron oxidation of the amines since the stronger the acidity of the methylene hydrogen, the easier the deprotonation. 

The zinc-mediated reaction tolerates a variety of functionality in the p-keto ester. In fact, the method described above has been applied successfully to p-keto amides and p-keto phosphonates, Unsubstituted p-keto esters, amides and phosphonates have been chain-extended in yields that ranged from 58% to 98% (Table I). The primary limitation to this method is the inefficiency with which a-substituted esters and amides undergo methylene insertion. The zinc carbenoid must be employed in at least a threefold excess h... 

Second, titanium-based reagents are suitable for methylenation or alkylidenation of carbonyl groups of carboxylic acid derivatives such as esters and amides (Equation (7)). ... 

The significance of the amino methylenated amines, ketones, and amides as important compounds and reaction intermediates is well-documented and the use of "Gold s reagent," therefore, provides an efficient, economical, and clean method for obtaining such substances. 

F-Teda BF4 (6) has also been used for the gem-difluorination of active methylene compounds, / -oxo esters and amides.102 The reaction times can be significantly reduced by carrying out the two fluorination steps sequentially and, importantly, with the sodium enolate of the monofluoro intermediate for the second step. 

Reduction of nitriles and amides.1 These compounds are selectively reduced to the corresponding amines by this metal hydride in refluxing methylene chloride. Under the same conditions indoles can be reduced to indolenes in moderate yield. 

The spectra of dry films of intact ghosts prepared by lysis in 20 millios-molal phosphate buffer (21) and of ghost protein prepared by cold butyl alcohol extraction (51) are shown in Figure 6. In both cases the amide I band occurs at 1651 cm. 1 and shows no shoulder near 1630 cm. 1, characteristic of fl structure. The amide II band is also unaffected by removal of lipid and occurs at 1540 cm."1. As expected, extraction of lipid results in removal of the band at 1737 cm. 1 assigned to lipid ester carbonyl stretch and a decrease of the band at about 1455 cm."1 arising from methylene and methyl bending. 

SECTION 66 Alkyls, Methylenes, and Aryl3 from Amides... 

SECTION 80 Amides from Alkyl, Methylenes, and Aryls... 

This section contains dehydrogenations to form olefins and unsaturated ketones, esters, and amides. It also includes the conversion of aromatic rings to olefins. Reduction of aryls to dienes is found in Section 377 (Olefin-Olefin). Hydrogenation of aryls to alkanes and dehydrogenations to form aryls are included in Section 74 (Alkyls, Methylenes, and Aryls from Olefins). 

Further, many amide chlorides having an a-methylene group undergo a selfcondensation to trimethine cyanines. This undesired side-reaction could be exploited synthetically to prepare rare push-pull ynamine salts (40, 41) 75 77) ynamine amidines (41) 76, 78) and amides (41)76 79>. 

Chemical gels are covalently cross-linked polymer networks, featuring very high viscosity and well-defined pore structure. Polyacrylamide is the most widely used chemical gel material, usually cross-linked with N,N-methylene-bisacryl-amide (BIS). The pore size of the gel is determined by the relative concentration of monomer and cross-linker used during polymerization (%T, total monomer concentration and %C, cross-linker concentration as a percent of the total monomer and cross-linker concentration [34]). Highly cross-linked ( 5%C) poly-... 

Gels used for the stationary phase can be hydrophilic, for separations in aqueous and other polar solvents, or hydrophobic, for use in non-polar or weakly-polar solvents. Agar, starch, polyacrylamide and cross-linked dextrans possess hydroxyl or amide groups and are thus hydrophilic. They swell in aqueous media and in such solvents as ethylene glycol and dimethylform-amide. Bio-Cel (a co-polymer of acrylamide and jV.W -methylene-bisacryl-amide) and Sephadex (dextran cross-linked with epichlorhydrin) arc two commercially available gels made in bead form. Cross-linking produces a... 

An unusual feature of their sarcophaginate frameworks is the structure of the cap the amidine and amide fragments are cross-linked with a methylene unit to form a near-planar diazine heterocycle fused to the cap as a subsidiary feature [126]. 

The acid and esters do not isomerize in solvents in the absence of strong adds or bases at temperatures up to 100° or higher. Isomerization of the itaconates through basic abstraction of a proton from the a-methylenic position might be ejq>ected to cause difficulty in anionic polymerization. In fact, attempts to polymerize itaconic esters (7) and amides (6) anionically have given little or no polymar, but considerable isomerization. 

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