Formaldehyde with alkenes

The reaction of formaldehyde with alkenes is of industrial interest and has been extensively studied. Reaction of excess formaldehyde as formalin with an alkene and aqueous acid gives 1,3-dioxanes (2) in 40-90% yield. Reaction of 2-butenes with paraformaldehyde and hydrogen chloride at -65 C gives a mixture of diastereomeric y-chloro alcohols rich in the isomer formed by trans addition to the alkenyl double bond. For example frans-2-butene gives an 85 15 mixture of erythro- and fAreo-3-chloro-2-methyl-1-butanol (equation 2). Reaction of 1-alkenes under similar conditions gives 3-alkyl-4-chlorotet-rahydropyrans (5) in 50-80% yield (Scheme 2). Initial reaction occurs via addition of formaldehyde to the terminal carbon of the double bond, followed by loss of a proton to give the 3-alken-l-ol. Reaction of... 

The copolymerization of carbonyl monomes with alkenes has been even less studied than that between different carbonhyl monomers. The radiation-initiated copolymerization of styrene with formaldehyde proceeds by a cationic mechanism with a trend toward ideal behavior, r = 52 and r2 = 0 at —78°C [Castille and Stannett, 1966]. Hexafluoroacetone undergoes radiation-initiated copolymerization with ethylene, propene, and other a-olefins [Watanabe et al., 1979]. Anionic copolymerizations of aldehydes with isocyanates have also been reported [Odian and Hiraoka, 1972]. 

The theoretical studies showed that the [2 4-2] cydoaddition reactions with alkenes or alkynes were almost barrierless and very exothermic. The exothermicity for alkynes (—42.8 kcal mol ) was found to be greater than that for alkenes (—21.3 kcal mol ). Scheme 4.21b shows the calculated [2 4- 2] cydoaddition with polar unsaturated molecules, formaldehyde and FICN. The barriers (3.6kcalmol for formaldehyde and 9.0 kcal mol for HCN) are slightly higher than those in the reactions with alkenes and alkynes. The exothermicity is also significant (—26.5 for formaldehyde and —37.4 for HCN). 

Alkylation with Carbonyl Compounds The Prins Reaction. Carbonyl compounds react with alkenes in the presence of Brpnsted acids to form a complex mixture of products known as the Prins reaction. The use of appropriate reaction conditions, solvents, and catalysts allows one to perform selective syntheses. Characteristically formaldehyde is the principal aldehyde used. Mineral acids (sulfuric acid, phosphoric acid), p-toluenesulfonic acid, and ion exchange resins are the most frequent catalysts. Certain Lewis acids (BF3, ZnCl2, SnCl4) are, however, also effective. 

Organic Materials. Violent reaction with formaldehyde, benzaldehyde, and aniline3 vigorous reaction with alkenes.4... 

The reactions of alkenes with carbon electrophiles have already been mentioned in the cyclization of 1,5-dienes. However, carbon electrophiles may be generated in other ways. Protonation of formaldehyde (methanal) leads to a carbocation that may be stabilized by the oxygen lone pair (Scheme 3.12a). This may react with alkenes with the formation of 1,3-glycols or unsaturated alcohols, depending upon the way in which the intermediate carbocation is discharged (the Prins reaction, Scheme 3.12b). 

Formaldehyde, benzaldehyde and aniline react violently with 90% performic acid (Ref 1). An unspecified organic compd was added to the acid, and soon after the initial vigorous reaction had subsided, the mixt expld violently (Ref 3). Reaction with alkenes is vigorously exothermic, and adequate cooling is necessary. Reactions with performic acid can be more safely accomplished by the slow addition of hydrogen peroxide to a soln of the compd in formic acid (Ref 4)... 

They also applied this method to the intermolecular ene reactions of aliphatic and aromatic aldehydes with alkenes containing a disubstituted vinylic carbon, a potentially valuable route to homoallylic alcohols [50]. Proton-initiated rearrangements do not take place, because the alcohol-Lewis acid complex formed in the ene reaction reacts readily to give methane and a non-acidic aluminum alkoxide. Formaldehyde and excess Me2AlCl gave good yield of ene adducts with all types of alkene, as exemplified in Sch. 26. 

Excellent yields of ene adducts can be obtained from BF3-Et20- or SnCU- catalyzed addition of formaldehyde to alkenes that can give a tertiary carbocation. Limonene reacts selectively at the 1,1-disub-stituted double bond to give ene adduct (9) in 80% yield (equation 6). SnCU- catalyzed addition of formaldehyde to 2,6-dimethyl-2,3-heptadiene gives lavandulol (10) in 35% yield (equation 7). BF3-Et20-catalyzed ene reaction of formaldehyde with (11) occurs exclusively from the less-hindered a-face to give ene adduct (12) with the correct stereochemistry at C-20 and functionality suitable for construction of the vitamin D side chain (equation 8). ... 

Halide anions have also been employed to facilitate the cyclization of weakly nucleophilic terminal vinyl ir-nucleophiles. For example, the butenylamine (85) undergoes Mannich cyclization in the presence of excess Nal to provide the 4-iodopiperidine (87) in excellent yield. The success of this cyclization should be contrasted with the failure of related amines to cyclize in formic acid with formaldehyde (Scheme 25). A detailed study " of the effect that nucleophile concentration has on the outcome of Mannich cyclizations provides deilnitive evidence that the cyclization of iminium ions with alkenes is not a concerted process, but rather proceeds via a cationic intermediate capable of partitioning between product formation and reversal to the starting iminium ion. A bridged cation or ir-complex, e.g. (86) in equation (8), is a reasonable description of this intermediate. 

Synthesis of 5,6-dihydro-4 H-l,3-oxazines. Acid-catalyzed depolymerization and condensation of the resulting formaldehyde with an amide gives the acyliminium ion, which is capable of undergoing a formal Diels-Alder reaction with alkenes. 

Oxyselenation. In the presence of hydrogen peroxide the selenide reacts with alkenes to form acctoxyselenated products yith loss of formaldehyde. The reaction apparently involves formation of the selenoxide, and indeed no reaction occurs in the absence of H2O2. Presumably the selenoxide then loses formaldehyde to form methaneselenenyl acetate, CHaSeOAc, which is the actual reagent. Examples ... 

Ozone reacts rapidly with alkenes to give a chemiluminescence emission from several excited-state species. Excited species identified as emitters in the ozone oxidation of ethene include formaldehyde at 350-520nm ( A2) and hydroxyl radicals at 700-1100 nm (X n, v<9) and 306 nm (A E ). In addition, phosphorescence is observed from glyoxal and methyl glyoxal ( Au are oxidized. 

The ene reaction of carbonyl compounds with alkenes is a potentially valuable route to homoallylic alcohols. With reactive, i.e., electron deficient aldehydes such as chloral or methyl glyoxylate, these reactions can be carried out thermally at 100-200 °C or with Lewis acid catalysis at ambient temperature. 1 Formaldehyde undergoes ene reactions with alkenes at 180 C and undergoes Lewis acid catalyzed ene reactions at ambient temperatures with alkenes which can give a tertiary carbocation.3 In the presence of Br0nsted acids, aldehydes and alkenes undergo the Prins... 

The side products obtained in Lewis acid catalyzed ene reactions of formaldehyde with mono-and 1,2-disubstituted alkenes are consistent with the mechanistic scheme shown in Figure 2. When only 1 equivalent of Me2AlQ is used chloro alcohols are formed as by products. When excess Lewis acid is used chloroalcohols are fonned as transient intermediates which are converted to ene adducts and other products. The chloroalcohols formed from 1,2-disubstituted alkenes result from the stereospecifically cis addition of the hydroxymethyl and chloride groups to the double bond. This result was unexpected since all previous Prins additions have been shown to proceed predominantly by trans addition. 4 Cis addition of chloride and hydroxymethyl groups would be expected from intermediates such as 4 or 5 and 6. 

Figure 6. EtAlQ2 catalyzed reaction of formaldehyde with functionalized alkenes.

The Prins reaction has been modelled using DFT (density functional theory), using an alkene (RCH=CH2, R = Me or Ph), a formaldehyde dimer, and a proton-water cluster, H30" (H20)i3. Both alkenes feature a concerted path to give the 1,3-diols. An unprecedented hemiacetal intermediate, H0-CH2-0-CH(R)-CH2CH2-0H, was then identified it undergoes ring closure to the 1,3-dioxane product. Gas-phase Prins reaction of formaldehyde dimer with alkene has been studied computationally it proceeds via a r-complex (without formation of any intermediate rr-complex). ... 

In water dihydropirans become a major product of Prins reaction only in interaction of formaldehyde monomer with alkenes with exo-double bond [12,13],... 

It is shown lhat interaction of formaldehyde oligomers with alkenes in gas phase or nonpolar solvents, accompanied by 1,3-dioxane formation must occur as a pseudo synchronous syn-addition. Only formaldehyde oligomers addition to ethylene can be considered as a synchronous interaction. 

According to the scheme, formaldehyde dimers preliminary form the corresponding 71-cations (2b-5b) with alkenes (2a-5a), which are isomer-ized into a-cations (2i-5i). These a-cations are transformed through the transition states (2j-5j) into oxetanes (2k-5k). The calculated values of the thermodynamic parameters are represented in Table 11.3. 

Other Unsaturated Alcohols. Dimethylaluminium chloride has been found to be a useful catalyst for the ene reaction of aliphatic and aromatic aldehydes with alkenes (Scheme 16) to produce homoallylic alcohols/ by acting as a mild Lewis acid and proton scavenger rapid decomposition of the product alcohol-Lewis acid complex (42), a strong proton acid species, gives methane and a non-acidic alkoxide, thus avoiding protonation of the carbon-carbon double bond in the alkene or ene adduct, 1,1-Disubstituted alkenes are the most reactive under these conditions, and the yields of ene additions to formaldehyde are also improved. 

In addition to the iminium-salt-based chemistry and to cross-coupling processes, aqueous formaldehyde can also be used as the carbonylated substrate in the Prins reaction, an intermolecular ene-type acid-catalyzed reaction with alkenes providing 1,3-dioxanes (Adams and Bhatnagar, 1977). 

Certain carbonyl compounds also react with alkenes according to the ene reaction pattern. Formaldehyde in acidic solution reacts to form homoallylic alcohols or the corresponding esters as in entry 3. 

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