Replacement of methylene hydrogen by alkyl

As we have seen, the replacement of one hydrogen atom in a halomethane by a methyl group (Figure 6-8B) causes significant steric hindrance and reduction of the rate of Sn2 reaction. Chloroethane is about two orders of magnitude less reactive than chloromethane in Sn2 displacements. Will elongation of the chain of the primary alkyl substrate by the addition of methylene (CH2) groups further reduce Sn2 reactivity Kinetic experiments reveal that 1-chloropropane reacts about half as fast as chloroethane with nucleophiles such as I. ... 

Ethylmalonic Acid.—Like acetoacetic ester (see p. 83), diethylmalonate contains the gioup CO.CHj.CO. By the action of sodium or sodium alroholate, the hydrogen atoms of the methylene group are successively replaceable by sodium. The sodium atoms are in turn replaceable by alkyl or acyl groups. Thus, in the present preparation, ethyl malonic ester is obtained by the action of ethyl iodide on the monosodium compound. If this substance be treated with a second molecule of sodium alcoholate and a second molecule of alkyl iodide, a second radical would be in roduced, and a compound formed of the general formula... 

This section lists examples of the replacement of hydrogen by ketonic groups, R-H R(C=0)-R . For the oxidation of methylenes, R2CH2 -> R2C=0, see section 170 (Ketones from Alkyls). 

The anti selectivity increases as the disubstituted side of the double bond becomes more crowded (Scheme 8). This is illustrated with the trisubstituted alkenes 16, 17 and 13. Alkene 16 shows the normal cis effect selectivity where only 10% of the anti ene adduct is formed. However, as the size of the cis alkyl substituent increases from methyl in 16, to isopropyl in 17 and ferf-butyl in 13, the anti selectivity increases from 10% to 42% and to >97%, respectively. The same trend is also noted in substrate 19. A substantial deviation from cis effect selectivity is observed by replacing one methyl group in 18 with a ferf-butyl group in 19. The totally unreactive methylene hydrogens in 18 (cis effect) become reactive in 19, producing the exo ene adduct in 38% yield. 

A second radicle R may be caused to replace the second hydrogen of the methylene group, by repeating the treatment with sodium ethylate and an alkyl iodide RXI. 

Among the aryl-aliphatic nitriles subject to alkylation, phenylaceto-nitrile, CjHjCHjCN, is especially reactive and its methylene hydrogens are readily replaced by one or two alkyl groups. Alkylation of this substance has been performed with alkyl halides or dialkyl sulfates. ... 

V) The ester of malonic acid, like acetacetic ester, possesses the property in virtue of which one of the two methylene hydrogen atoms can be replaced by sodium, in consequence of the acid properties imparted by the two neighbouring carbonyl (CO) groups. When the sodium compound is treated with organic halides, like alkyl halides, halogen derivatives of add-esters, acid-chlorides, etc., the sodium is replaced by alkyl residues, add residues, etc-, just as in the case of the dosely related acetacetic ester. In the above-mentioned examples, the sodium salt of the malonic ester is first formed from sodium alcoholate and the ester ... 

Replacing a hydrogen atom in any of the methylene groups by a hydroxide function significantly reduces the retention time. The position of the hydroxide function exerts a noticeable influence on the resulting retention time. Fig. 5-35 shows the separation of two Ci6-hydroxyalkane sulfonates, which are hydroxy-substituted in the 2- and 3-pos-ition of the alkyl chain. In comparison to non-substituted alkane sulfonates, the retention decrease corresponds to the loss of 2 to 3 methylene groups from the solvophobic alkyl groups. 

The replacement of an a hydrogen of an alkyl halide by halogen decreases Sn2 reactivity. Chloroform, however, is about one thousandfold more reactive in basic hydrolysis than methylene chloride . Every bromine-containing halo-form studied (Table 7) is at least 600 times as reactive toward hydroxide ions in 66.7% aqueous dioxan as methylene bromide ". Toward weakly basic nucleophiles, such as thiophenoxide ion, the predicted reactivity order is obeyed haloforms have been found to be less reactive than the corresponding methylene halides . The reaction of haloforms with sodium thiophenoxide is strongly accelerated, however, by the presence of hydroxide ions - . These observations are quite unexplainable in terms of scheme (22). 

This section lists examples of the replacement of hydrogen by olefinic groups. For the dehydrogenation of alkyl groups, e.g. RCH2CH2R — RCH=CHR, see section 200 (Olefins from Alkyls, Methylenes and Aryls)... 

Branched alkanes are derived from the straight-chain systems by removal of a hydrogen from a methylene (CH2) group and replacement with an alkyl group. Both branched and straight-chain alkanes have the same general formula, C H2 +2. The smallest branched alkane is 2-methylpropane. It has the same molecular formula as that of butane (C4H10) but different connectivity the two compounds therefore form a pair of constitutional isomers (Section 1-9). 

The second hydrogen on the methylene unit of acetoacetic ester can also be replaced by an alkyl group, creating a disubstituted acid. To accomplish this conversion, the reaction product in step 2 above would be reacted with a very strong base to create a carbanion. 

---