Formaldehyde reaction with alkenes

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

Aminobenzothiazoles undergo reaction with formaldehyde and electron-rich alkenes such as cyclopentadiene (Scheme 8) to give a cyclic isothiourea 61 with regio- and stereoconttol <1996TL2619>. 

Rodini and Snider demonstrated that dimethylaluminium chloride catalyses an ene reaction between aldehydes and alkenes. As a follow-up they showed that terminal alkynes give a similar reaction with formaldehyde". ... 

Enol ethers are more reactive toward formaldehyde and MesAl than simple alkenes. Reaction with dihydropyran gives a 75% yield of a 92 8 mixture of 33 and 34 (See Figure 10). The major product is again formed by cis addition of hydroxymethyl and methyl groups. Quite different results are obtained with acyclic enol ethers. 20 Reaction of ethyl propenyl ether, as a 78 22 cis-trans mixture, with 2 equivalents of paraformaldehyde and 2 equivalents of MesAl at 0 in CH2CI2 gives a 65% yield of an 18 1 mixture of threo- and c yr/ir< -3-ethoxy-2-meAyl-l-butanol (37 and 38). Identical results are obtained from either pure stereoisomer of ethyl propenyl ether. 

PdCb-CuCb catalyzes the condensation of branched-chain alkenes with formaldehyde to give the l,3-dioxanes 96a and 96b (Prins reaction)[73]. The yields are much higher than in the conventional acid-catalyzed Prins reaction. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

The ene reaction is strongly catalyzed by Lewis acids such as aluminum chloride and diethylaluminum chloride204 Coordination by the aluminum at the carbonyl group increases the electrophihcity of the conjugated system and allows reaction to occur below room temperature, as illustrated in Entry 6. Intramolecular ene reactions can be carried out under either thermal (Entry 3) or catalyzed (Entry 7) conditions 205 Formaldehyde in acidic solution can form allylic alcohols, as in entry 1. Other carbonyl ene reactions are carried out with Lewis acid catalysts. Aromatic aldehydes and acrolein undergo the ene reaction with activated alkenes such as enol ethers in the presence of Yb(fod)3 206 Sc(03SCF3)3 has also been used to catalyze ene reactions.207... 

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). 

Di-tert-butyl methylenemalonate was originally prepared by phenyl-sulfenylation of di-tert-butyl methylmalonate and thermal elimination of the related sulfoxide.8 Because methylenemalonate esters are customarily prepared by Knoevenagel-type condensation of malonic esters with formaldehyde equivalents, the considerably more convenient procedure described herein was subsequently adapted from Bachman and Tanner s study using paraformaldehyde under metal ion catalysis.39 The approximately 6% di-tert-butyl malonate accompanying the product has presented no interference in the aforementioned reactions with nucleophilic alkenes under neutral or acidic conditions, but its presence should be taken into consideration in other applications. 

Amino-3-chloro-5-trifluoromethylpyridine with electron-rich alkenes and formaldehyde in the presence of trifluoroacetic acid in boiling acetonitrile for 1 h yielded 6a,7,8,9,10,10a-hexahydro-6//-pyrido[l,2-a]-quinazolines (326) (96TL2615). The regiochemistry is dictated by the reaction of formaldehyde at the primary amino group. 

More typical for angle strained cycloalkynes is the dehydrogenation of alcohols, amines and thiols208. The reaction of (31) with methanol to yield the alkene (63) and formaldehyde was investigated in detail. On the basis of rate laws and H/D kinetic isotope effects the following reaction mechanism was proposed 208,212>. 

A major aspect of the chemistry of both Rh1 and Ir1 is the formation of tertiary phosphine complexes. Much used are the phosphines PPh3, PPr 3, PMe3 and mixed phosphines such as PMe2Ph. Triphenylphosphine is used in catalytic hydrofor-mylations of alkenes, while water soluble phosphines, notably P(QH4S03H)3, are used in two-phase systems. The important fra s,-chlorocarbonylbis(triphenylphos-phine)rhodium(I) is obtained as yellow crystals on reduction of RhCl3(aq) in EtOH with formaldehyde. It can also be made by the reactions... 

Except in a few cases,cyclic Mannich ba.scs derived from alkenes arc produced by the reaction of unsaturated amino derivatives with formaldehyde. Intramolecular aminomethylation (Fig. 65) takes place with aminoalkenes (184, X = H path a) or with analogous silyl allyl derivatives (184, X = SiMc , path b) ... 

Biological systems overcome the inherent unreactive character of 02 by means of metalloproteins (enzymes) that activate dioxygen for selective reaction with organic substrates. For example, the cytochrome P-450 proteins (thiolated protoporphyrin IX catalytic centers) facihtate the epoxidation of alkenes, the demethylation of Al-methylamines (via formation of formaldehyde), the oxidative cleavage of a-diols to aldehydes and ketones, and the monooxygenation of aliphatic and aromatic hydrocarbons (RH) (equation 104). The methane monooxygenase proteins (MMO, dinuclear nonheme iron centers) catalyze similar oxygenation of saturated hydrocarbons (equation 105). ... 

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