Groups methylene

Condensations at the 5-Methylene Group.— Thiazolidinones undergo direct heteroarylation under the influence of N-acyl salts of six-membered nitrogen heterocycles. Thus, N-acylisoquinolinium salts convert the appropriate thiazolidinone into products of type (244), or 3-phenyliso-rhodanine into (245). Several other heterocyclic patterns (including quinolinium, pyridinium, and acridinium salts) were employed successfully in the production of analogous structures. 5-(2-Oxo-3-indolinylidene)-3-aryl-2-phenyliminothiazolidin-4-ones (246), of thioindigoid character, are formed by the condensation of thiazolidin-4-ones and isatin.  

Grignard Reagents.—5-Arylidene-4-aryliminothiazolidin-2-ones (247) undergo a 1,4-addition with alkylmagnesium halides, yielding adducts of 

Penicillins.—The condensation of L-4-methoxycarbonylthiazolidine and pyruvic acid in the presence of dicyclohexylcarbodi-imide yields (50%) 3-pyruvoyl-4-methoxycarbonylthiazolidine (251). This may be photolyti-cally cyclized to 3-methoxycarbonyl-6-hydroxy-6-methylpenam (252), i.e. 

In neutral and alkaline aqueous solution, 6-(N-phenylureido)penicillanic 

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Zaera F and Floffmann FI 1991 Deteotion of ohemisorbed methyl and methylene groups surfaoe ohemistry of methyl iodide on Pt(111) J. Phys. Chem. 95 6297-303... 

In this simplified example of phenylalanine, in the first iteration the methyl groups arc given a value of I in the first classification step because they contain a primaiy C-atom, The methylene group obtains a value of 2, and the methine carbon atom a value of 3. In the second step, the carbon atom of the methyl group on the left-hand side obtains an extended connectivity (EC) value of 2 because its neighboring atom had a value of 2 in the first classification step. 

The c arlrnn atoms of the other two methyl groups (on the right-hand side) obtain an EC value of 3 because they arc adjacent to the racthinc carbon atom. The carbon atom of the methylene group obtains an EC value of 4 in the second rcla.xation process, as the sum (1 + 3) of the eonncctivity values of its neighboring atoms in the first iteration. 

This oxidation proceeds readily if the methylene group is activated by linkage to (a) a carbonyl group, (b) an aromatic ring (c) an olefine link also activates adjacent CH2 and CH groups. 

When camphor (I) is heated with selenium dioxide in acetic acid, the methylene group next to the carbonyl group is oxidised also to a carbonyl group, to form camphorquinone (II). Note that the compound (II) is not a true quinone but a 1,2-diketone ... 

The Mannich Reaction involves the condensation of formaldehyde with ammonia or a primary or secondary amine and with a third compound containing a reactive methylene group these compounds are most frequently those in which the methylene group is activated by a neighbouring keto group. Thus when acetophenone is boiled in ethanolic solution with paraformaldehyde and dimethylamine hydrochloride, condensation occurs readily with the formation of... 

Reactions. The methylene group in the 2 position in 5,5-dimethyl-cyclohexan-i,3-dione (V) is strongly activated by the... 

The term Knoevenagel Condensation was originally applied to the base-catalysed condensation of the carbonyl ( CO) group of aldehydes and ketones with the reactive methylene group of malonic acid, with loss of w ater ... 

The role of the base is apparently primarily that of a proton remover from the reactive methylene group thus if B represents the base, reaction (i) gives the carbanion, which then combines with the positive carbon of the carbonyl group (reaction ii) the product regains a proton from the piperidinium ion, and then by loss of water followed by mono-decarboxylation of the malonic acid residue gives the final acid. 

Benzylidene derivatives. Compounds containing the. keto-methylene group (—CH CO) react with benzaldeliyde to yield benzylidene derivatives ... 

The mechanism of the reaction, which is of the aldol type, involves the car-bonyl group of tlie aldehyde and an active methylene group of the anhydride the function of the basic catalyst B (acetate ion 0H3000 or triethylamine N(0,Hb)j) is to form the anion of the active hydrogen component, i.e., by the extraction of a proton from the anhydride ... 

CgHjCOCHj + SeOa —> CgHgCOCHO + Se + H O This is one example of the oxidation by selenium dioxide of compounds containing a methylene group adjacent to a carbonyl group to thecorresponding a-ketoaldehyde or a-diketone (see also Section VII,23). 

Reduction of the ethylenic compound gives a ketone, propiophenone (III), with one more methylene group than the ketone used in the original preparation ... 

The way in which methylene groups interposed between the positive... 

These and other studies of the relative substituent effects of X and CH X in nitration were considered in terms of the transmission factor a of the methylene group. To avoid complications from conjugative interactions, attention was focussed mainly on substitution at the meta-position, and ct was defined in terms of partial rate factors by the equation ... 

The large sulfur atom is a preferred reaction site in synthetic intermediates to introduce chirality into a carbon compound. Thermal equilibrations of chiral sulfoxides are slow, and parbanions with lithium or sodium as counterions on a chiral carbon atom adjacent to a sulfoxide group maintain their chirality. The benzylic proton of chiral sulfoxides is removed stereoselectively by strong bases. The largest groups prefer the anti conformation, e.g. phenyl and oxygen in the first example, phenyl and rert-butyl in the second. Deprotonation occurs at the methylene group on the least hindered site adjacent to the unshared electron pair of the sulfur atom (R.R. Fraser, 1972 F. Montanari, 1975). 

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

The Tebbe reaction, which converts the oxo groups of esters and lactones to methylene groups to give enol ethers, is described in section 2.1.2. 

In a sophisticated variation of the Knoevenagel condensation ("Panizzi ) methyl 3,3-dimethoxypropanoate (from ketene and dimethoxymethenium tetrafluoroborate D.J. Crosby, 1962) is used as a d -reagent. Because only one carbonyl group activates the methylene group, a strong base with no nucleophilic properties (p. 10) has to be used. A sodium-sand mixture, which presumably reacts to form silicate anions in the heat, was chosen... 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

Various terminal allylic compounds are converted into l-alkenes at room temperature[362]. Regioselective hydrogenolysis with formate is used for the formation of an exo-methylene group from cyclic allylic compounds by the formal anti thermodynamic isomerization of internal double bonds to the exocyclic position[380]. Selective conversion of myrtenyl formate (579) into /9-pinene is an example. The allylic sulfone 580 and the allylic nitro compound... 

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