Six-membered rings with one oxygen

What are hexagonal heterocycles with one oxygen?

Because the neutral divalent oxygen atom cannot replace the CH group of the benzene ring (it would need valence 3). Therefore, the existence of neutral oxygenated compounds with a constitution analogous to pyridine is not possible.

The cyclic, unsubstituted, uncharged system with two double bonds is called a pyran.

fig-01

In this structure, the position of the "extra" hydrogen atom must be indicated to distinguish between the two possible isomers.

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In addition, two dihydro-pyrans are possible, using the notation Δ to indicate the position of the double bond (numerical superscript).

On the other hand, α-pyran is not known and γ-pyran is not very stable.

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The oxygenated aromatic nucleus is the pyrilium cation and the 2- and 4-pyrones also occur as derivatives.

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Some pyrones are natural, such as kojic acid.

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On the other hand, oxygenated heterocycles include sugars with a hexagonal ring called pyranoses.

When the pyran or pyrone ring is fused to a benzene ring, the following structures can be formed.

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Simple derivatives of these systems are widely found in nature.

Pyrillium salts

Pyryllium salts, formerly called pyridoxonium salts, were discovered in 1901 by A. Werner, in the form of dibenzopyrillium or xanthanium salts from xanthone.

fig-07

But it was A. von Baeyer, 10 years later, who achieved the synthesis of the first pyrillium salt which presented a simple hexagonal cycle.

This was carried out starting from 2,6-diethyl-pyrone with methyl magnesium chloride (XMgCH3) resulting in the transformation to 2,4,6-trimethyl-pyranol.

fig-08

Intermediate (I) is already one of the possible pseudobases of the pyrillium salt. Furthermore, by the action of strong mineral acids, it loses the OH group producing the 2,4,6-trimethylpyryllium cation.

This cation is formed by the strong aromatization tendency of the pyrranic ring.

Subsequently, their synthesis has been achieved by condensation from simple ketones.

fig-09

The reaction consists of an aldol condensation followed by crotonization by the acidic medium that is induced.

A mixed organic-inorganic anhydride is obtained as an intermediate from HClO4 and CH3COOH.

Acetoxonium perchlorate, acetylates the methyl in gamma (γ) position of the carbonyl of the α,β-unsaturated ketone.

fig-10

Structurally, pyrilium salts have the lack of a proton in the heteroatom, which makes the preparation of the neutral compound impossible. In addition, the existence of the double bond where there is an oxonium ion in the molecule gives it a high reactivity.

Therefore, oxonium salts are very unstable towards bases and rapidly add HO to form pseudobases. Which in acidic media revert to pyrillium salts.

fig-11

Ring formation

Monooxygenated hexagonal heterocycles can be obtained in the ring in several ways:

From pentan-1,5-diones.

fig-12

Normally, pentan-1,5-dione is prepared by aldol condensation or Michael addition.

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From penta-1,2,3-triones

Closure occurs by dehydration obtaining γ-pyrones.

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From substrates that already contain the bonds formed with the heteroatom.

A C—C bond is formed by Dieckman reaction.

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Pyryllium cation reactions

With nucleophilic reagents on a ring carbon.

The charge of oxygen facilitates the attack of nucleophilic reagents at the α or γ positions.

 

fig-16

Thus, it reacts with HO , RO, sulfides, CN and BH4 and certain carbanions, amines and organometallic compounds.

Nucleophilic attack at C2 produces a 2H-pyran which can exist in equilibrium with an open-chain tautomer.

fig-17

This open-chain adduct can be isolated from the reactions of 2,4,6-trimethyl-pyrylium salts with various nucleophiles and can achieve reactions of another type and cyclize, becoming other cyclic compounds.

fig-18

If the reaction is carried out with hydroxylamine (NH2OH), the reaction proceeds as follows.

fig-19

On the other hand, if the reaction is carried out with nitromethane (CH3NO2), a benzene derivative is obtained.

Con reactivos electrófilos

The charge of the oxygen prevents the electrophile reaction on the heteroatom and strongly deactivates the rest of the ring. However a clear example of this type of reaction is the nitration of compounds with activating nuclei in the ring.

Pyrone reactions

The pyrones are usually in unionized form, but the canonical ionic forms are of comparable importance.

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The reactions will be deduced from the electronic displacement in the molecules.

With electrophilic reagents

In the attack on a ring carbon atom, the electrophiles (E) do so in β-position with respect to the ring oxygen.

fig-21

In general, these reactions, e.g. halogenation, proceed better than in benzene. However, others such as nitration or sulfonation, which require very strong acidic conditions, inactivate the ring.

With nucleophilic reagents

In the attack on a ring carbon atom, the electrophiles (Nu) do so in α-γ position with respect to the ring oxygen. Adducts formed by attack on the carbonyl carbon can evolve by opening the ring, such as reactions with HO, NH3 and RNH2.

fig-22

Adducts formed by attack on a carbon other than carbonyl can be followed by addition of a proton (H), i.e. a Michael addition.

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Adducts formed by reaction of γ-pyrones with and amines, at the α-carbon atom, can be opened and often undergo further cyclization.

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If the reaction is carried out with ammonia (NH3) or amines, a pyridone will be obtained.

Benzopiranos y benzopironas

Like pyrans and pyrones, benzopyrans are of little relevance compared to benzopyrans, the latter being aromatic substances while benzopyrans are not.

Of the various benzopyrones, coumarin and chromone deserve special attention.

fig-25

Coumarin

Coumarin can be obtained by Perkin condensation from salicylic aldehyde and acetic anhydride.

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Chromone

Chromone is the basis of a series of yellow plant dyes, the flavones (substituted 2-aryl-chromones).

The chemistry of these heterocycles can be extrapolated from the pyrones. However, these substances do not take their place because of the reactions they may give.

Chromones are not "special or especially reactive reagents", their fundamental characteristic lies in their property as a dye.

As for its synthesis, for example, chromone, which is a colorant of the group, can be obtained by extraction from its natural source before considering a chemical synthesis.

Another example of a chromone is quercetin. This can be prepared from 2,4-dimethoxy-6-hydroxyacetophenone with 3-methoxyanisaldehyde.

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Pyrone dyes

The pyrone ring itself does not possess coloring properties, but constitutes the skeleton of a series of naturally occurring dyes.

Industrial applications are those that are synthetic or those that can be extracted in large quantities from their corresponding natural products.

They are divided into four groups: coumarin, flavone, isoflavone and xanthone dyes.

Coumarin dyes

The most important is ellagic acid, which is often accompanied by gallic acid and industrially obtained from 3,4,5-trihydroxybenzoic acid.

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Flavone dyes

They are subdivided into flavone dyes, properly speaking, and flavonol dyes. Both have several hydroxyls on the benzene rings or only on the benzene ring of the chromone.

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It is seen that the color becomes more intense with increasing λ in the UV/vis spectrum, when there are more phenolic groups.

Isoflavone dyes

Few isoflavone-derived natural dyes have been described, some of them such as daidzein, gacisteina and irigenina are indicated in the figure.

fig-30

Xanthone dyes

The structure of xanthone shows great analogies with that of anthraquinone. Therefore, its hydroxy derivatives are expected to exhibit analogous coloring properties.

However, it shows a clear deviation to yellow, due to the lack of a carbonyl group in the molecule.

The most notable colorant of the group is euxanthone. It has an Indian yellow color used in paint and is obtained by synthesis from hydroquino-carboxylic acid and resorcinol.

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