Methylene Side Chains

7 Reactivity of Substituents Attached to Ring Carbon Atoms 12.01.7.1 Methylene Side Chains 

---

The final stages of the synthesis of (—)-A-58365B, a Streptomyces metabolite that inhibits the angiotensin-converting enzyme, involve several reactions at substituents attached to ring carbon atoms of a quinolizidine system. Thus, ozonolysis of the exocyclic methylene side chain of compound 107, followed by base-induced elimination and carboxyl deprotection, gave 108 (Scheme 12) <1999JOC1447>. 

Although the pK of the cy-amine group for Lys is within the titratable range and that for Arg would probably become so on coordination, the relatively long methylene chains render any tridentate chelation unlikely, and this appears to be the case.10- 4 The shorter methylene side chains in the synthetic diamine-monocarboxylates ornithine, 2,4-diaminobutanoic acid and 2,3-diamino-propionic acid lead to increased tridentate behaviour in that order. 

Rule 4. Name the side chains by approved radical names and precede these with the correct position numbers. For the acyclics, the complexity order and the alphabetical order of prefixes will be identical, since only methyl and methylene side chains are involved — for example, 2,6-dimethyl in geraniolene (Nos. 1A and IB, Chart 3) and 7-methyl-3-methylene in myrcene (No. 2, Chart 3). 

The remaining a-hydrogen on the side chain ester can then be removed, and the ring opened up to reveal an a,P-unsaturated ester with a carboxylate group on the methylene side chain. Write the mechanism for these remaining steps. 

Some of the preparative methods for alkyl phenols and their reactions are unique to this class and both therefore warrant separate treatment from the parent compound. These features are even more prevalent in the hindered phenols a group of substances first synthesised less than half a century ago. In this account the synthesis of alkylphenols bearing purely methylenic side-chains in the benzenoid, naphthalenic and polycyclic series are considered first. Alkylphenols with side-chains containing oxy or alkoxycarbonyl groups are then reviewed, followed by mention of those containing Si, N or S in the side-chain and finally polycyclic types with saturated and unsaturated rings bearing hetero atoms. As before emphasis has been placed on developments in the last decade. 

TABLE 6.1 SYNTHESIS OF ALKYLPHENOLS WITH METHYLENIC SIDE CHAINS... 

Some of the reactions in this section are summarised in Table 6.4 (refs.41-44) with reference mostly to methylenic side chains. 

Comparison of the Hammett p values for phenylacetic acid ( + 0.47) and benzoic acid (-I-1.00) dissociation constants provides us with a measure of the transmission of the methylene group (0.47) compared with direct coupling. The ratio (0.47) is remarkably constant for attenuation of the polar effect down a methylene side chain and essentially the same value is obtained for the reaction of phenylacetic and... 

Fig. 3.5 Biosynthesis pathway of saxitoxin as proposed by Shimizu et al. [224]. The reaction steps are (1) Claisen-condensation between acetate and arginine (2) amidino transfer from a second arginine to the a-amino group of intermediate B (3) and (4), cyclization (5), introduction of S-adenosyl methionine (SAM) methyl-derived side chain, involving the loss of one methionine methyl hydride (6) 1,2-H shift (7) epoxidation of methylene side chain (8) opening of epoxide to an aldehyde (9) reduction of the aldehyde to hydroxyl (10) carbamoyl transfer and dihydroxylation of C-12...

Ethylene-co-allene polymers, as prepared with (iso-Bu)3Al-VCl3 catalyst, have side-chain methylene, side-chain vinyl, in-chain cis, and in-chain trans unsaturation.The side-chain methylene moiety appears to predominate in the copolymer. The copolymer is easily grafted with MA via the Diels-Alder reaction. Films of the grafted material, in comparison to ungrafted copolymer, exhibited greatly enhanced printability, due to the increased polarity. Polyal-lene has also been treated with MA and maleimides to obtain Diels-Alder type grafting and new polymers for possible use in coatings. Little is known about the properties of these modified polymers and copolymers. 

As noted earlier, hard tissues are composite materials consisting of mineral and organic matrix. In Raman spectroscopic analysis, the organic matrix is identified by methylene side chains (CH2 at 1450 cm" ), amide III ( 1200-1300 cm" ), amide I ( 1620-1700cm ), phenylalanine (1002cm ) or the combined proline (921 and 855 cm ), and hydroxyproline (876 cm ) bands [2, 27, 208-210]. 

---