Furans

What are furans?

Furans are heterocyclic organic compounds consisting of a 5-membered aromatic ring with four carbon atoms and one oxygen atom.

furan is a colorless, highly volatile and flammable liquid with a boiling point of 31 ºC. It is also slightly soluble in water, soluble in common organic solvents, and with a dipole moment μ = 0.72 Debye. It has an odor similar to chloroform. The ring system of furan is found in many natural compounds, is toxic and may be carcinogenic in humans. However, other furan derivatives are used as chemotherapeutic agents. Moreover, it is used in synthesis to obtain other value-added derivatives.

Furan-2-carboxaldehyde (furfural) can be prepared by acid-catalyzed hydrolysis of cereal waste.

fig-01

Most natural compounds containing a fully unsaturated furan ring are terpenoid in nature.

Synthesis of the furan ring

The synthesis of the furan ring can be carried out in two steps, starting from the pentoses of oat hulls. The first step consists of a catalyzed dehydration reaction in acidic medium. Followed by a second step of catalyzed distillation with silver oxide (AgO) furan is obtained.

fig-01

Paal-Knorr synthesis of furans

The Paal-Knorr synthesis of furans consists of a cyclization of 1,4-dicarbonyl compounds in acidic media, followed by dehydration.

fig-02

Feist-Benary synthesis of furans

The Feist-Benary synthesis consists of a reaction between an α-haloketone with 1,3-dicarbonyl (β-dicarbonyl) compounds in which an aldol condensation occurs.

fig-03

Garcia-Gonzalez reaction for furan production

The Garcia-Gonzalez reaction< proceeds from α-hydroxy aldehydes or α-hydroxyketones with β-dicarbonylcompounds via an aldol condensation reaction.

fig-04

The reaction is initiated with a base, as shown in the scheme.

fig-05

Electrophilic substitution of furan reactions

Furan is an electron-rich heterocycle and its reactions with electrophiles are similar to those of pyrrole.

However, the main differences with pyrrole can be summarized in the following points:

  • Furan is rather less aromatic than pyrrole and therefore has a much greater tendency to react with electrophiles to give addition rather than substitution products. Although in cases where substitution products are obtained it can be shown that the intermediates are addition products.
  • As with pyrrole, substitution at the C2 position is favored over substitution at the C3 position, but to a greater degree.

Example of nitration

Furan gives with acetyl nitrate an addition compound, which is transformed into 2-nitro furan by addition of pyridine.

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Example of sulfonation

Furan reacts with sulfur trioxide (SO3) and pyridine to yield up to2,5-furan disulfonic acid.

fig-07

 

Example of halogenation

Furan decomposes under most halogenation conditions. That is, it decomposes vigorously with chlorine (Cl2) and bromine (Br2) at room temperature. However, it can be converted to 2-bromo furan, with good yield, by reacting it with the bromo-dioxane complex at a temperature of -5 ºC.

fig-08

If the bromination reaction is carried out at -50 °C, in carbon disulfide (CS2), a series of bromine addition products (Br2) is obtained. This indicates that the intermediate can be attacked by nucleophiles instead of losing a proton.

Example of acylation

Furan reacts very well with acetic anhydride (Ac2O), using a mild catalyst (and in some cases even without catalyst), to give 2-acyl furan.

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Examples of acid reactions

Furan is readily hydrolyzed in acidic media and the reaction proceeds via a protonated intermediate.

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Effect of substituents on electrophilic substitution

The effect of the substituents in the electrophilic substitution reaction occurs in the same way as in the case of benzene.

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The attracting electron groups located in the C2 position of the furan, such as the acid group -COOH or aldehyde group -CHO direct to the C5 position, and those located in the C3 position also direct to the C5 position.

fig-12

However, electron-donating substituents in the C3 position lead in the C2 position, and those in the C2 position lead in the C5 position.

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Furan reactions of nucleophilic substitution

Some furans with electron-attracting substituents can undergo nucleophilic substitution reactions and are generally more reactive than the corresponding benzene derivatives.

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An addition-elimination mechanism has been formulated for the latter reaction. However, it is possible that before the addition complex is formed, there is an electron transfer step.

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[4+2] cycloaddition reactions of furans

Furans have a strong dienic character, since they have a low resonance energy. Therefore, they react with activated dienophiles to give adducts of the Diels-Alder type.

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In the cycloaddition to acetylenes, the reaction proceeds as follows.

fig-17

Adduct I can be converted to phenol upon reaction with an acid.

fig-18

Also, adduct I can be hydrogenated, preferably at the least substituted double bond.

fig-19

Reduction reactions of furans

Furans are readily catalytically hydrogenated to give tetrahydrofuran (THF).

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Ring-opening reactions of furans

Furan ring is much easier to open than the pyrrole one. Therefore, the acid-catalyzed opening is the one that occurs most frequently.

Furan can be considered as a masked 1,4-dicarbonyl system, which can be regenerated by acid-catalyzed hydrolysis. This reaction is the reverse process of the Paal-Knorr synthesis.

fig-21

This reaction can be used to construct 1,4-dicarbonyl compounds with complex side chains.

For example, it has been successfully used in the synthesis of cis-jasmone from 2-methyl furan.

fig-22

On the other hand, the furan ring can also be opened by oxidation. Thus, several 2-monosubstituted and 2,5-disubstituted furans have been successfully converted directly into unsaturated dicarbonyl compounds by oxidation with m-chloroperbenzoic acid (mCPBA) or with pyridinium chlorochromate. This oxidation can also be carried out with bromine (Br2) in methanol (MeOH).

fig-23

Properties of substituted furans

The chemistry of the substituents at the C2 position of furan is strongly influenced by the electron properties of the ring system. Furan is a σ-electron acceptor, but a π-electron donor.

  • The alkyl groups in furan have a reactivity similar to that of benzene.

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  • The same thing happens to hydroxymethyls as to pyrrole, which polymerize.

fig-25

or the cation can give the levulinic acid.

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  • Furanaldehydes (furfural) can be reduced to alcohol or oxidized to acids.
  • The 2-hydroxy furans exist in keto tautomeric forms, such as γ-lactone.

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  • In the case of 3-hydroxy furans the equilibrium is as shown in the scheme.

fig-28

Unless there is a substituent that can stabilize the hydroxy form, such as by hydrogen bonding to the carbonyl of the substituent.

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