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The Prins reaction is an organic reaction consisting of an electrophilic addition of an aldehyde or
ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
to an alkene or alkyne followed by capture of a nucleophile or elimination of an H+ ion. The outcome of the reaction depends on reaction conditions. With water and a protic acid such as
sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...
as the reaction medium and formaldehyde the reaction product is a 1,3-diol (3). When water is absent, the cationic intermediate loses a proton to give an allylic alcohol (4). With an excess of formaldehyde and a low reaction temperature the reaction product is a dioxane (5). When water is replaced by
acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main compone ...
the corresponding
esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...
are formed.


History

The original reactants employed by Dutch
chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a graduated scientist trained in the study of chemistry, or an officially enrolled student in the field. Chemists study the composition of ...
in his 1919 publication were styrene (''scheme 2''), pinene, camphene, eugenol, isosafrole and anethole. These procedures have been optimized. Hendrik Jacobus Prins discovered two new organic reactions during his doctoral research in the year of 1911–1912. The first one is the addition of polyhalogen compound to olefins and the second reaction is the acid catalyzed addition of aldehydes to olefin compounds. The early studies on Prins reaction are exploratory in nature and did not attract much attention until 1937. The development of petroleum cracking in 1937 increased the production of unsaturated hydrocarbons. As a consequence, commercial availability of lower olefin coupled with an aldehyde produced from oxidation of low boiling paraffin increased the curiosity to study the olefin-aldehyde condensation. Later on, Prins reaction emerged as a powerful C-O and C-C bond forming technique in the synthesis of various molecules in organic synthesis. In 1937 the reaction was investigated as part of a quest for di-olefins to be used in
synthetic rubber A synthetic rubber is an artificial elastomer. They are polymers synthesized from petroleum byproducts. About of rubber is produced annually in the United States, and of that amount two thirds are synthetic. Synthetic rubber, just like natural ru ...
.


Reaction mechanism

The
reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical reaction occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage ...
for this reaction is depicted in scheme 5. The carbonyl reactant (2) is protonated by a protic acid and for the resulting oxonium ion 3 two resonance structures can be drawn. This
electrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively Electric charge, charged, have an ...
engages in an electrophilic addition with the alkene to the carbocationic intermediate 4. Exactly how much positive charge is present on the secondary carbon atom in this intermediate should be determined for each reaction set. Evidence exists for neighbouring group participation of the hydroxyl oxygen or its neighboring carbon atom. When the overall reaction has a high degree of concertedness, the charge built-up will be modest. The three reaction modes open to this oxocarbenium intermediate are: * in blue: capture of the carbocation by water or any suitable nucleophile through 5 to the 1,3-adduct 6. * in black: proton abstraction in an elimination reaction to unsaturated compound 7. When the alkene carries a methylene group, elimination and addition can be concerted with transfer of an allyl proton to the carbonyl group which in effect is an ene reaction in ''scheme 6''. * in green: capture of the carbocation by additional carbonyl reactant. In this mode the positive charge is dispersed over oxygen and carbon in the resonance structures 8a and 8b. Ring closure leads through intermediate 9 to the dioxane 10. An example is the conversion of styrene to 4-phenyl-m-dioxane. * in gray: only in specific reactions and when the carbocation is very stable the reaction takes a shortcut to the oxetane 12. The photochemical Paternò–Büchi reaction between alkenes and aldehydes to oxetanes is more straightforward.


Variations

Many variations of the Prins reaction exist because it lends itself easily to cyclization reactions and because it is possible to capture the oxo-carbenium ion with a large array of nucleophiles. The halo-Prins reaction is one such modification with replacement of protic acids and water by lewis acids such as stannic chloride and boron tribromide. The halogen is now the nucleophile recombining with the carbocation. The cyclization of certain ''allyl pulegones'' in ''scheme 7'' with titanium tetrachloride in dichloromethane at −78 °C gives access to the decalin skeleton with the hydroxyl group and chlorine group predominantly in cis configuration (91% cis). This observed cis diastereoselectivity is due to the intermediate formation of a trichlorotitanium alkoxide making possible an easy delivery of chlorine to the carbocation ion from the same face. The trans isomer is preferred (98% cis) when the switch is made to a tin tetrachloride reaction at room temperature. The Prins-pinacol reaction is a cascade reaction of a Prins reaction and a pinacol rearrangement. The carbonyl group in the reactant in ''scheme 8'' is masked as a dimethyl
acetal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments n ...
and the hydroxyl group is masked as a triisopropylsilyl ether (TIPS). With lewis acid stannic chloride the oxonium ion is activated and the pinacol rearrangement of the resulting Prins intermediate results in ring contraction and referral of the positive charge to the TIPS ether which eventually forms an aldehyde group in the final product as a mixture of cis and trans isomers with modest diastereoselectivity. The key oxo-carbenium intermediate can be formed by other routes than simple protonation of a carbonyl. In a key step of the synthesis of exiguolide, it was formed by protonation of a vinylogous ester:


See also

* Heteropoly acid


References

{{reflist


External links

* Prins reaction in Alkaloid total synthesi
Link
* Prins reaction
organic-chemistry.org
Addition reactions Carbon-carbon bond forming reactions Name reactions