Methylene derivatives

The H C ratio in hydrocarbons is indicative of the hydrogen deficiency of the system. As mentioned, the highest theoretical H C ratio possible for hydrocarbon is 4 (in CH4), although in electron-deficient carbocationic compounds such as CH5 and even CH/, the ratio is further increased (to 5 and 6, respectively, see Chapter 10). On the other end of the scale in extreme cases, such as the dihydro- or methylene derivatives of recently discovered Cgo and C70 fullerenes, the H C ratio can be as low as 0.03. 

Methylene derivatives ate readily formed in the vapor phase with compounds having a hydrogen in the alpha position to an electron-withdrawing group. Acryhc (40,41) and methacrylic (42) acids (or esters) are produced at 300—425°C from acetic and propionic acids (or esters), respectively, using alkafl and... 

The isolation of the 6-deoxytetracyclines (44) led to other chemical modifications of (1). 6P-Deoxytetracycline [5614-03-9] (13), prepared by catalytic hydrogenolysis of tetracycline (1), resulting ia an iaversion (45) of the configuration at the C-6 position, but retention of antibacterial activity. Catalytic reduction (7,8) of the 6-methylene derivative (14) yields both the 6a-methyl (15) and 6P-methyl compound (13). The 6a-isomer (15) is reported (7,45) to be more active than the 6P isomer (13). The a-isomer, doxycycline (6), is an example of a semisynthetic tetracycline that has become commercially useful. 

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. 

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). ... 

According to a detailed mechanistic study, the first step is the abstraction of the relatively acidic hydrazone proton (93- 97). This is followed by hydride attack on the trigonal carbon of the C=N bond, mainly from the a-side at C-3, together with the concomitant loss of the tosylate anion (97 -> 98). Expulsion of nitrogen from the resulting intermediate (98) yields a fairly insoluble anion-metal complex (99) which upon decomposition with water provides the methylene derivative (100). 

Some advantages of this reaction are high yield if the tosylate is in a sterically accessible position excellent isotopic purity of the product (usually higher than-95%) and perhaps most important, access to stereospecifically labeled methylene derivatives. For example, deuteride displacement of 3j -tosylates (183) yields the corresponding Sa-d derivative (185) in 96-98% isotopic purity. Application of this method to the labeled sulfonate (184), obtained. by lithium aluminum deuteride reduction of a 3-ketone precursor (see section HI-A) followed by tosylation, provides an excellent synthesis of 3,3-d2 labeled steroids (186) without isotopic scrambling at the adjacent positions. The only other method which provides products of comparable isotopic purity at this position is the reduction of the tosyl-hydrazone derivative of 3-keto steroids (section IV-B). 

Methyl-3j5-hydroxy-A ° steroids of the racemic and natural series and the corresponding mc-8a-H compounds " give analogous 5, 10)5-methylene derivatives. 

Reactions of potentially tautomeric methyl and methylene derivatives of pyridine with N-electrophiles 98KGS147. 

An aldehyde or ketone 1 can react with hydrazine to give a hydrazone 2. The latter can be converted to a hydrocarbon—the methylene derivative 3—by loss of Na upon heating in the presence of base. This deoxygenation method is called the Wolff-Kishner reduction. ... 

Treatment of hydrazino-compounds with iodine in chloroform can afford iodides which are convertible into methylene derivatives (7,8). An extension of this approach currently being investigated involves reduction of the hydrazones obtainable from glycopyranosiduloses and treatment of the products with iodine. 

Addition of benzoyl chloride to 2.5-dimethyl-3,4,6-triphenyl-3//-azepine (13) in benzene in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) leads to elimination of hydrogen chloride and formation of the 2-methylene-l//-azcpine 14.117 All attempts to isomerize the methylene derivative to 1-benzoyl-2,5-dimethyl-3,4,6-triphenyl-l//-azepine under basic conditions failed. Analogous reactions can occur with 2,5-dielhyl-3,4,6-triphenyl-3//-azepine. 

Various methylene derivatives of spiroorthocarbonates and spiroorthocstcrs have been reported to give double ring-opening polymerization e.g. Scheme 4.36). Like the parent monocyclic systems, these monomers can be sluggish to polymerize and reactivity ratios are such that they do not undergo ready copolymerization with acrylic and styrenic monomers. Copolymerizations with VAc have been reported.170 These monomers, like other acetals, show marked acid sensitivity. 

C. 2-(2-Acetam,idoethyl)A,r)-dimethoxyac.etophenone. A slurry of 31.0 g. (0.125 mole) of the methylene derivative obtained in Part B and... 

Evidently this is a hydrogenation and the source of the hydrogen is benzylamine as indicated by the production of benzaldehyde and ammonia in equivalent amounts presumably the benzylamine is dehydrogenated to the imine C,HjCH =NH, which is then hydrolysed. In the absence of hexamine, the maximum yield of benzaldehyde is 50 per cent. When hexamine is added to the reaction mixture, the yield of aldehyde is increased and that of methylbenzylamine is decreased, and methyl-amine is present at the end of the reaction. Hexamine reacts as the methylene derivative of ammonia, CH2=NH, which is hydrogenated to methylamine. The fundamental stage of the Sommelet reaction may be written as ... 

When a hindered ketone is to be converted to a methylene derivative, the best results are obtained if potassium r-alkoxide is used as the base in a hydrocarbon solvent. Under these conditions the reaction can be carried out at elevated temperatures.243 Entries 10 and 11 illustrate this procedure. 

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

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