Double bond methylenation

The retention of FAs with more than one double bond depends on the distance between the bonds, the order of decreasing retention being separated double bonds > methylene intermpted double bonds > conjugated double bonds. 

Cyclopropanation. In the presence of copper powder the reagent decomposes to the carbene CHP(=0)(0CH3)2, which adds to double bonds. Methylene chloride is the preferred solvent. 

Lipoxygenase is an enzyme that will attack cis-cis double bonded, methylene interrupted fatty acids (most commonly linoleic and linolenic acids). This enzyme... 

Double-bonded methylenic derivath es are also obtained by iapor-phase reactions of formaldehyde with carbonyl compounds such as acetalde-... 

Polymerizafion of Double-Bonded Methylene Compounds. Some acetone-formaldehyde resins are formed in this way ° ... 

Dehydration to Double-Bonded Methylene Derivatives.. Type reaction H R CHjOH R CH -h H2O. The preparation of methyl vinyl ketone by the distillation of methylolacetone (ketobutanol) in the presence of a trace of iodine or acidic catalyst is representative ... 

Aromatic Aldehydes. As p e dollsly stated, aromatic aldeh des, since they do not contain alpha-hj drogen atoms, cannot react with formalde-liyde toform methylol deri ati es or double-bonded methylene derh -atives. On treatment with fornialdehy-de they are reduced to the corresponding alcohols by means of the crossed Cannizzaro reaction ... 

A -Bromosuccinimide (prepared by the action of bromine on succinimide at o in the presence of sodium hydroxide) is a valuable specific reagent for brominating olefines in the a-methylene position to the double bond without simultaneously adding bromine to this bond. For example, if A -bromosuccini-mide is represented by (C4H40t)NBr —... 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

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... 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

The relative amounts of the two products however are not equal more as 1 2 dimethyl cyclohexane is formed than trans The reason for this is that it is the less hindered face of the double bond that approaches the catalyst surface and is the face to which hydro gen IS transferred Hydrogenation of 2 methyl(methylene)cyclohexane occurs preferen tially at the side of the double bond opposite that of the methyl group and leads to a faster rate of formation of the cis stereoisomer of the product... 

The double bond m 2 methyl(methylene)cyclohexane is prochiral The two faces however are not enantiotopic as they were for the alkenes we discussed m Section 7 9 In those earlier examples when addition to the double bond created a new chirality cen ter attack at one face gave one enantiomer attack at the other gave the other enantiomer In the case of 2 methyl(methylene)cyclohexane which already has one chirality center attack at opposite faces of the double bond gives two products that are diastereomers of each other Prochiral faces of this type are called diastereotopic... 

Methylene transfer from lodo methylzinc iodide converts alkenes to cyclopropanes The reaction is a stereo specific syn addition of a CH2 group to the double bond... 

The a-methylene groups also add to double bonds eg, 1-decene at 160°C gives up to 80% of a-decylbutyrolactone (160). With photochemical initiation similar additions take place at room temperature (161). 

Proton chemical shift data from nuclear magnetic resonance has historically not been very informative because the methylene groups in the hydrocarbon chain are not easily differentiated. However, this can be turned to advantage if a polar group is present on the side chain causing the shift of adjacent hydrogens downfteld. High resolution C-nmr has been able to determine position and stereochemistry of double bonds in the fatty acid chain (62). Broad band nmr has also been shown useful for determination of soHd fat content. 

Measurement of Unsaturation. The presence of double bonds in a fatty acid side chain can be detected chemically or through use of instmmentation. Iodine value (IV) (74) is a measure of extent of the reaction of iodine with double bonds the higher the IV, the more unsaturated the oil. IV may also be calculated from fatty acid composition. The cis—trans configuration of double bonds may be deterrnined by infrared (59) or nmr spectroscopy. Naturally occurring oils have methylene-intermpted double bonds that do not absorb in the uv however, conjugated dienes maybe deterrnined in an appropriate solvent at 233 nm. 

Megestrol acetate (79) is stmcturaHy related to progesterone (1). It has been prepared from medroxyprogesterone acetate (74) by chloranil-mediated dehydrogenation. It also has been prepared from hydroxyprogesterone acetate (42) via 6-methylenation and double-bond migration (109,110). 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

---