Dioxanes, Prins reaction

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. 

A commercial process based on the Prins reaction is the synthesis of isoprene from isobutylene and formaldehyde through the intermediacy of 4,4-dimethyl-l,3-dioxane (49—51) ... 

The acid-catalyzed addition of an aldehyde—often formaldehyde 1—to a carbon-carbon double bond can lead to formation of a variety of products. Depending on substrate structure and reaction conditions, a 1,3-diol 3, allylic alcohol 4 or a 1,3-dioxane 5 may be formed. This so-called Prins reaction often leads to a mixture of products. 

The addition of an alkene to formaldehyde in the presence of an acid catalyst is called the Prins reaction.Three main products are possible which one predominates depends on the alkene and the conditions. When the product is the 1,3-diol or the dioxane, the reaction involves addition to the C=C as well as to the C=0. The mechanism is one of electrophilic attack on both double bonds. The acid first protonates the C=0, and the resulting carbocation attacks the C=C ... 

The limitation on this simple dioxan synthesis is that unbranched olefins are unreactive. Nevertheless, the method offers advantages over the alternative acid-catalyzed (Prins) reaction in regard to both product yield and selectivity. 

Simple mono- and disubstituted alkenes react to yield 1,3-diols, when the Prins reaction is carried out at elevated temperature. Diols originate from the attack of water on carbocation 18, or through the acidolysis of dioxanes under the reaction conditions. When the reaction is conducted in acetic acid, monoacetates are formed by acetate attack on 18. Dienes resulting from the dehydration of intermediate diols are the products of the transformation of more substituted alkenes. Monoacetates and diols may react further to yield 1,3-diol diacetates. When the Prins reaction... 

Dioxacyclohexanes can be produced in excellent yields from aliphatic or aryl-substituted alkenes.64 Dilute sulfuric acid at or above room temperature with paraformaldehyde appears to give the best results. Dioxane-water or acetic acid as solvent was found to afford increased yields in the Prins reaction of arylalkenes. 

The stereochemistry of the Prins reaction is complex. In the transformation of cyclohexene and 2-butenes anti stereoselective addition was observed,67-69 whereas syn addition of two formaldehyde units takes place in the formation of 1,3-dioxanes from substituted styrenes.70 Most of the transformations are, however, nonstereo-selective,71 72 accounted for by carbocation 18. 

The method ZC3Z + C is used for the preparation of reduced pyrimidines, oxazines and thiazines as well as for dioxanes, dithianes and oxathianes as mentioned above (e.g. 258 — 257, 259 Z, Z = NH, O, S). The Prins reaction yields 1,3-dioxanes (77S661) it involves the acid-catalyzed condensation of alkenes with aldehydes with 1,3-diols as intermediates. 

Keywords styrene, TaCls-Si02, paraformaldehyde, microwave irradiation, Prins reaction, 1,3-dioxane derivative... 

Dioxanes can be efficiently synthesized from styrenes using formalin as the formaldehyde source (Prins reaction) with triflic acid as catalyst717 [Eq. (5.267)]. 

Prins reaction (cf 10, 186-187). Dimethylaluminum chloride is an effective catalyst for the ene addition of formaldehyde (as trioxane or paraformaldehyde) to mono- and 1,2-disubstituted alkenes.5 When 1.5-2.0 equiv. of the Lewis acid is used, homoallylic alcohols are obtained, usually in high yield. y-Chloro alcohols, formed by cis-addition of -Cl and -CH2OH to the double bond, are sometimes also observed when only 1 equiv. of the Lewis acid is present. The advantage of this reaction over the Prins reaction (using HC1) is that m-dioxanes are not formed as by-products, because formaldehyde no longer functions as a nucleophile when complexed to the Lewis acid. 

In an early step in an enantioselective total synthesis of certain prostaglandins <88T4989,92T10345>, application of the Prins reaction conditions to an unsaturated bicyclic lactone or ether (Equation (11)) afforded tricyclic heterocycles (31) containing cyclopentane-fused tetrahydrofuran and 1,3-dioxane units in 4-10% yield. The major products in each case were bicyclic diacetate derivatives of the starting material. 

Terpenoid Synthesis from Isoprene.—Interest continues in new syntheses of iso-prene and its derivatives the dioxan (37) is obtained108 in good yield by the Prins reaction of methylallyl chloride with formaldehyde (cf. Vol. 5, p. 8) free-radical addition of isopropyl alcohol to vinyl acetate yields compound (38) which gives isoprene by acid-catalysed reaction over alumina.109 (Z)-2-Methylbut-2-en-l-ol and dimethylallyl alcohol are readily available from frans-crotyl alcohol.110... 

The principal develo naents achieved in this area, some of which have cohnfnated in industrial production, are those of Bayer, Davy Powergas, IFP, Kuraray and the Soviet Union. Using a C4 cut containing isobutene, these processes manufacture isoprene by the addition of fommldehyde in a first step (Prins reaction), followed by cat ytk cracking of the dioxane formed in a second step ... 

It may be clear that this reaction involves the formation of one C-C and one C-0 bond during the linking of three molecules I, II, and methanol from the solvent. The combination of an expectedly strong electrophile such as the pyrrolinium ion (I) and a very mild nucleophile represented here by isopropylene, falls within the familiar framework of a Prins -type reaction. That process has a protonated form of a carbonyl derivative as the electrophile, usually an aldehyde of which the iminium ion would be a nitrogen homolog. However, in contrast with the classical Prins reaction whereby 1,3-dioxanes result by the inclusion of a second mole of the electrophile, in the present reaction 1 mol of methanol is incorporated instead. 

Some data have been reported for another reaction of formaldehyde, the Prins reaction, with a-methylstyrene. With water or 40 60 watei dioxane mixture as solvent, the reaction was reported to be first order kinetically in each reactant. A direct relation between the log of the rate coefficient and the acidity function Hq of the mineral acid catalyst was found [204]. 

Prins reaction. Very rapid formation of 1,3-dioxanes is accomplished by microwaving a mixture of alkenes and paraformaldehyde in the presence of TaClj/SiOj. 

Prins reaction. 4-Phenyl-/n-dioxane was prepared first by H. J. Prins in 1919 by reaction of styrene and formaldehyde in the presence of sulfuric acid, but the correct structure was inferred only in 1930. A modern procedure calls for stirring a mixture of formalin, coned, sulfuric acid, and styrene under gentle reflux for 7 hrs. The mixture is cooled, and the product collected by extraction with benzene. 

Prins reaction. Acid-catalyzed addition of olefins to formaldehyde to give 1,3-diols, allylic alcohols, or meta-dioxanes. 

Bi(III) is an efficient catalyst for the formation of tetrahydropyran-4-ols from homoallylic alcohols by the Prins reaction application to styrenes leads to 1,3-dioxanes <05SC1177> cr i-2,6-Disubstituted tetrahydropyrans are selectively formed in a Bi-mediated intramolecular oxa-conjugate addition of a,P-unsaturated ketones 10 the actual catalyst is considered to be the Bronsted acid derived from the Bi salt <05TL5625>. cat. BiXa... 

The Prins reaction involves the addition of an alkene 1 to an aldehyde 2 under acidic conditions. The major products of this reaction are often a 1,3-dioxane 3, a diol 4, or a homoallylic alcohol 5.1-5... 

While several mechanisms for the Prins reaction have been proposed,7,10 there is general agreement that the mechanism shown below is reasonable.7 Attack of olefin 1 on protonated aldehyde 10 gives carbocation 11. This carbocation can then be trapped with another molecule of aldehyde, generating adduct 12. Cyclization of 12 affords dioxane 3. Carbocation 11 can also be captured with water giving diol 4. Finally, elimination of a proton from carbocation 11 affords homoallylic alcohol 5. It is possible that the formation of 5 could also proceed via an ene-type mechanism.8... 

Dioxans - Several syntheses of this ring are notable. In a modification of the Prins reaction, self-condensation of aliphatic aldehydes with styrene has given 4-phenyl-1,3-dioxans [such as ( 195)] in which the alkyl group is in the equatorial position.203 Good yields of the 1,3-dioxin-4-ones (196 R1 and R2 alkyl or aryl) have been obtained by reaction of aldehydes or ketones with diketene and Aliquat 336 (MeN[ (CH2 bMe] 3C1). 20 Condensation of aryl aldehydes with the diol (197) also gave good yields of the... 

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