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1,4-dioxane is a six-membered cyclic ether with oxygen atoms at positions one and four, formula ${\mathrm{C}}_4{\mathrm{H}}_8{\mathrm{O}}_2$. It can adopt chair-like conformations analogous to those of cyclohexane.

Its ether oxygens can accept hydrogen bonds and coordinate suitable solutes. The positions of those oxygens distinguish it from other dioxane isomers, so the numerical prefix is part of its chemical identity.

Alkylation introduces an alkyl group into a molecule. The new group may attach to carbon, nitrogen, oxygen, sulfur, or another suitable atom; the name alone does not specify the mechanism.

For example, an alkoxide can react with a suitable alkyl halide to form an ether by nucleophilic substitution, while Friedel-Crafts alkylation attaches an alkyl group to an aromatic ring through an electrophilic pathway. Competing elimination, multiple substitution, or rearrangement depends on the particular reacting partners.

Diethyl ether is the ether $\mathrm{C}{\mathrm{H}}_3\mathrm{C}{\mathrm{H}}_2\mathrm{OC}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_3$. Its oxygen has lone pairs that can coordinate metal-containing reagents, while its carbon groups provide a relatively nonpolar environment.

This combination explains its role as a solvent in organometallic chemistry. It is a distinct compound from an ester, which contains a carbonyl group adjacent to oxygen, despite some similarity in their names.

Dimethyl ether, also called methoxymethane, is an ether with an oxygen atom bonded to two methyl groups. Its structural formula is $\mathrm{C}{\mathrm{H}}_3-\mathrm{O}-\mathrm{C}{\mathrm{H}}_3$ and its molecular formula is ${\mathrm{C}}_2{\mathrm{H}}_6\mathrm{O}$. It is a constitutional isomer of ethanol: the atoms have the same inventory but different connectivity.^[ref]

The oxygen connectivity gives a useful molecular comparison. Ethanol contains an oxygen–hydrogen bond; dimethyl ether does not. Thus the two chemical structures present different possibilities for hydrogen bonding, even though weighing equal numbers of their molecules would not distinguish their common elemental formula.

Their physical identity can be tested by measurements beyond composition. NIST tabulates a normal boiling point near $248.3\mathrm{K}$, approximately $-24.9{}^{\circ }\mathrm{C}$, for dimethyl ether. This illustrates why a small carbon-containing molecule can be a gas under ordinary room conditions: phase behavior follows its interactions and external conditions, rather than molecular formula alone.^[ref]

An ether with oxygen directly attached to an alkene carbon. Electrophilic activation and hydrolysis can convert an appropriate enol ether back to a carbonyl compound.

$\mathrm{P}{\mathrm{h}}_3\mathrm{C}-\mathrm{O}-\mathrm{C}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_3$, an ether formed by trapping a triphenylmethyl carbocation with ethanol, followed by deprotonation.

Harald Günther coauthored research on tetrahydrofuran.^[ref]

Tetrahydrofuran is a cyclic ether solvent. Its oxygen can coordinate lithium ions and alter the aggregation of organolithium reagents.

Heike Hausmann coauthored research on tetrahydrofuran.^[ref]

Tetrahydrofuran is a cyclic ether solvent. Its oxygen can coordinate lithium ions and alter the aggregation of organolithium reagents.

Intramolecular capture of an alkene-derived iodonium ion by an alcohol produces a cyclic ether and a carbon–iodine bond. Backside opening gives an anti relationship between the new C–O and C–I bonds.

Isao Oonishi coauthored research on xanthone.^[ref]

A dibenzo-gamma-pyrone framework with two outer benzene rings, an endocyclic ether oxygen and an exocyclic ketone oxygen. The outer rings are strongly aromatic; the central ring has a more polarized, partial aromatic description.

Kinya Iijima coauthored research on xanthone.^[ref]

A dibenzo-gamma-pyrone framework with two outer benzene rings, an endocyclic ether oxygen and an exocyclic ketone oxygen. The outer rings are strongly aromatic; the central ring has a more polarized, partial aromatic description.

Let $\mathrm{Ar}$ denote the 2,5-dimethoxyphenyl group. A is the doubly C-alkylated beta-ketoesterThe central carbon has no hydrogen after the second step. The alkene, ester and tert-butyl ether remain intact.

carbonate reversibly removes a proton from the methylene group between the two carbonyl groups. The resulting resonance-stabilized enolate attacks the primary iodoethyl carbon of the aryl-containing reagent by an $S_{\mathrm{N}}2$ displacement, releasing iodide. The monoalkylated intermediate still has one proton at the same activated carbon. A second deprotonation followed by $S_{\mathrm{N}}2$ attack on the primary bromide introduces the but-3-en-1-yl group.

The beta-dicarbonyl position is much more acidic than the methylene group next to the ketone and ether at the other end, explaining the alkylation site. Counting the retained carbon skeleton gives ${\mathrm{C}}_{24}{\mathrm{H}}_{36}{\mathrm{O}}_6$, including the two carbonyl groups and one terminal alkene. The second panel of the original product drawing specifies this connectivity.

B is 1,3-dibromo-2-hydroxyxanthone: both bromines are on the hydroxy-substituted outer ring, at its two available positions ortho to OH. Define C2 as the OH-bearing carbon; C1 lies between it and the carbonyl-side ring junction, and C3 lies on its other side. These labels specify the substitution independently of the orientation of the printed drawing.

Phenolic lone pair donation strongly activates its ortho and para positions towards electrophilic substitution. The para position is a fused junction and has no replaceable hydrogen, leaving C1 and C3 as the two directly activated sites. C1 also benefits from the conjugative influence of the ring ether oxygen. Although other positions receive some activation from that oxygen, they lack the stronger local phenolic activation of the selected pair. Excess bromine can therefore replace both ortho hydrogens. Replacing two hydrogens in ${\mathrm{C}}_{13}{\mathrm{H}}_8{\mathrm{O}}_3$ gives ${\mathrm{C}}_{13}{\mathrm{H}}_6\mathrm{B}{\mathrm{r}}_2{\mathrm{O}}_3$, consistent with the stated composition. Addition across an outer-ring double bond would sacrifice aromaticity and would not account for the hydrogen loss.

For a monocyclic, approximately planar, continuously conjugated pi system, Hückel's rule predicts aromatic closed-shell filling for $4n+2$ pi electrons, with $n=0,1,2,\dots$. Every atom on the circuit must have an appropriately oriented orbital; counting double bonds without checking pi conjugation is insufficient.

The two outer benzene rings are clearly aromatic; the central pyrone ring has a weaker, polarized six-pi aromatic contribution. Each outer ring has the familiar six-electron circuit. For the central ring, a useful charge-separated contributor moves the exocyclic carbonyl pi pair onto oxygen and donates one endocyclic oxygen lone pair into the ring. Its four fused carbon p centres contribute four electrons and the ring-oxygen lone pair supplies two: a six-pi, pyrylium-like circuit, with positive charge on the ring oxygen and negative charge on the carbonyl oxygen. This does not make three independent benzene rings of equal aromatic stabilization; localized carbonyl bonding and the fused benzene circuits remain important contributors.

The three oxygens play different roles. The endocyclic ether oxygen donates a p-type lone pair to pi conjugation. The carbonyl oxygen accepts pi density in the charge-separated contributor. The phenolic oxygen donates into the outer ring as a substituent. Its in-plane lone pair is not an extra pair to add to every ring's electron count. In particular, neither the external C=O pair nor both lone pairs on a ring oxygen should be counted as independent extra ring electrons. Structural studies of xanthone support a largely planar conjugated framework, while the division into strongly aromatic outer rings and a more polarized central ring is an electronic-structure interpretation.^[ref]

Let $\mathrm{Ar}=4-\mathrm{N}{\mathrm{O}}_2{\mathrm{C}}_6{\mathrm{H}}_4$ and number the carbon substituent from oxygen: $\mathrm{ArO}-\mathrm{C}{\mathrm{H}}_2(1)-\mathrm{C}{\mathrm{H}}_2(2)-\mathrm{C}{\mathrm{H}}_2(3)-\mathrm{CN}$. sodium hydride removes a proton from C3, alpha to the nitrile, forming hydrogen and a nitrile-stabilized carbon anion. That carbon attacks the nitroaryl ipso carbon bearing O. The tether closes a five-membered cyclic Meisenheimer intermediate with sequence C3–C2–C1–O–aryl ipso carbon. The para nitro group stabilizes the negative charge generated by temporary loss of aromaticity.

Rearomatization breaks the aryl–O bond, releasing the tether oxygen as an alkoxide while retaining the new aryl–C3 bond. protonation gives $\mathrm{Ar}-\mathrm{CH}(\mathrm{CN})-\mathrm{C}{\mathrm{H}}_2-\mathrm{C}{\mathrm{H}}_2\mathrm{OH}$. This is a Truce–Smiles rearrangement: the aryl group migrates from oxygen to carbon. The nitrile remains attached to its original side-chain carbon; the original ether oxygen becomes the terminal alcohol oxygen. The substrate and product have identical atomic composition. Ordinary substitution at a saturated chain carbon would not produce this aryl–carbon bond or restore the terminal OH.

protonation of the secondary OH permits water departure. The neighbouring phenylthio sulfur can assist this departure by forming a bond to the adjacent alcohol carbon, generating a thiiranium ion spanning that carbon and the original sulfur-bearing cyclohexane carbon. Label the latter Q and the former L. The temporary Q–S–L bridge transfers the phenylthio attachment from Q to L when its Q–S bond subsequently breaks. sulfur attack opposite the departing OH accounts for the new C–S stereochemistry without requiring a freely rotating carbocation.

For the protected terminal alcohol, no free tethered OH is available to trap the bridge. Removal of a beta hydrogen from a cyclohexane carbon adjacent to Q forms the ring alkene while Q–S breaks. sulfur remains bonded to L, giving the allylic phenyl thioether. acid is regenerated by the deprotonation, so the catalyst need not be consumed.

For the free terminal alcohol, its oxygen attacks Q intramolecularly, opening Q–S instead. Count the new ether ring: O–CH2–CH(Me)–L–Q, a five-membered ring sharing Q with the cyclohexane. deprotonation gives the spirocyclic ether. This is capture of the same neighbouring-group-stabilized intermediate rather than migration of the methyl group. The pre-existing methyl-bearing carbon retains its configuration; its wedge/dash appearance changes when the product is redrawn in a different ring projection. The two substrates differ in whether a suitably placed oxygen nucleophile is available for intramolecular trapping.

base removes an alpha-amide proton from G, giving a carbon nucleophile. Its intramolecular attack on the nitroaryl ipso carbon, which currently bears the ether oxygen, forms a five-membered cyclic Meisenheimer complex. Count its atoms along the existing tether: alpha carbon, the original phenyl carbon bearing the side chain, its adjacent phenoxy carbon, ether oxygen, and attacked nitroaryl ipso carbon. The ortho nitro group again stabilizes the temporarily dearomatized anion.

Rearomatization now breaks the nitroaryl–O bond, leaving phenoxide on the original ring. proton transfer gives $(2-\mathrm{HO}{\mathrm{C}}_6{\mathrm{H}}_4)-\mathrm{CH}(2-\mathrm{N}{\mathrm{O}}_2{\mathrm{C}}_6{\mathrm{H}}_4)-\mathrm{C}(=\mathrm{O}){\mathrm{N}}_{\mathrm{morph}}$. This is a Truce-Smiles rearrangement: the nitroaryl group migrates from oxygen to carbon, while the original phenoxy oxygen stays on its original ring and becomes OH. No nitro-group migration or amide cleavage is needed. G and H have identical formulas; only the bond connections and a proton position change. carbonate need not produce a high equilibrium enolate concentration: a small population can be consumed by favourable intramolecular cyclization and rearomatization. The specified transformation alone does not establish its detailed proton-transfer sequence.

G is the diaryl ether $(2-\mathrm{N}{\mathrm{O}}_2{\mathrm{C}}_6{\mathrm{H}}_4)-\mathrm{O}-(2-\mathrm{C}{\mathrm{H}}_2\mathrm{C}(=\mathrm{O}){\mathrm{N}}_{\mathrm{morph}}{\mathrm{C}}_6{\mathrm{H}}_4)$. Here $N_{morph}$ denotes the nitrogen of the intact morpholine ring; the phenoxy oxygen and phenylacetamide chain are ortho on their original ring. potassium carbonate first generates phenoxide from F. Its oxygen attacks the fluorine-bearing carbon of 1-fluoro-2-nitrobenzene, forming a Meisenheimer complex. Delocalization of its negative charge into the ortho nitro group stabilizes this addition intermediate. Fluoride elimination restores aromaticity and completes nucleophilic aromatic substitution.

This first step forms an O–aryl bond, rather than immediately arylating the less acidic alpha carbon. The neutral product has formula ${\mathrm{C}}_{18}{\mathrm{H}}_{18}{\mathrm{N}}_2{\mathrm{O}}_5$, obtained from the two substrates by net loss of HF. The connectivity is shown beside B in the independently drawn diagram above. The amide-substrate O-to-C migration strategy has direct primary precedent.^[ref]

Write the reacting terminus as $R-\mathrm{C}{\mathrm{H}}_2-\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$, where $R$ includes the pre-existing stereocentres and the intact $\mathrm{OC}{\mathrm{H}}_2\mathrm{C}(=\mathrm{O})\mathrm{NM}{\mathrm{e}}_2$ substituent. ozone undergoes 1,3-dipolar cycloaddition across the terminal alkene to give a molozonide. In a resonance description of ozone as ${\mathrm{O}}^{-}-{\mathrm{O}}^{+}=\mathrm{O}$, the alkene pi pair bonds to one terminal oxygen while the other terminal oxygen forms the second C–O bond and the ozone pi bond shifts onto its central oxygen. Cleavage of this unstable primary ozonide produces a carbonyl compound and a carbonyl oxide, which recombine to form the secondary ozonide. Reductive workup breaks the peroxide bonds and gives the carbonyl fragments $R-\mathrm{C}{\mathrm{H}}_2\mathrm{CHO}$ and formaldehyde.

Excess sodium borohydride also reduces the newly formed aldehyde: hydride attacks its carbonyl carbon, shifting the pi electrons onto oxygen, and the final acidic workup protonates the alkoxide. Thus the retained chain becomes $R-\mathrm{C}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_2\mathrm{OH}$. The terminal alkene carbon becomes formaldehyde and can be reduced to methanol; it is no longer part of the main product. This accounts for the one-carbon shortening of the retained skeleton.

The original amide carbonyl is present in both H and I and is not reduced under the ordinary borohydride workup. The existing stereocenters and benzyl ether are retained. Stopping the mechanism at an aldehyde, or deleting the amide C=O when reading the smaller printed scheme, would give the wrong product. The new terminal alcohol carbon is CH2 and therefore adds no stereocenter.

The initial nucleophile attacks silicon, not the nitrile or an alkene carbon. Each trimethylsilyl group has an electrophilic Si center. A methyl group from methyllithium attacks Si, passing through a pentacoordinate silicon arrangement; Si–O cleavage releases $\mathrm{SiM}{\mathrm{e}}_4$ and the lithium salt of the oxygen-containing fragment. Cleaving the silyl enol ether generates a lithium enolate; cleaving the aryl silyl ether generates a phenoxide. Neither operation needs a new deprotonation at a carbon stereocenter.Here $R-O^{-}$ represents either the phenoxide or the oxygen-centered enolate contributor. Excess reagent permits both cleavages. The pre-existing methyl/nitrile stereocenter retains its configuration: it has no hydrogen to remove, and neither bond attached to that center is broken.

After HMPA is added, each anionic oxygen attacks the carbonyl carbon of allyl chloroformate. The C=O pi electrons move to the carbonyl oxygen, giving a tetrahedral intermediate; collapse expels chloride. The enolate becomes an allyl enol carbonate, and the phenoxide becomes an aryl allyl carbonate, each containing $\mathrm{O}-\mathrm{C}(\mathrm{O})-\mathrm{OC}{\mathrm{H}}_2\mathrm{CH}=\mathrm{C}{\mathrm{H}}_2$. oxygen acylation accounts for preservation of the enol double bond and for the two newly installed carbonate groups. carbon attack would give a different carbon skeleton. The two oxygens are trapped because they were selectively unmasked by desilylation, rather than because every ether oxygen in the molecule is equally reactive.