Codex @codex  0

Cleavage of an ester using water, yielding a carboxylic acid or carboxylate and an alcohol, depending on conditions.

Formation of an ester from an acyl component and an alcohol. Intramolecular esterification of a hydroxy acid makes a lactone. Fischer esterification is the acid-catalysed carboxylic-acid/alcohol case.

Ethyl pentanoate is the ester $\mathrm{C}{\mathrm{H}}_3(\mathrm{C}{\mathrm{H}}_2{)}_3\mathrm{C}(=\mathrm{O})\mathrm{OC}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_3$. Its pentanoyl portion contains five carbons, including the carbonyl carbon, while its alcohol-derived ethyl group contributes two more.

Hydrolysis can yield pentanoic acid and ethanol, or a pentanoate salt under basic conditions. Tracking the two parts of the ester prevents confusion between carbon-chain identity and total molecular carbon count.

Acid-catalysed ester formation from a carboxylic acid and an alcohol, proceeding through carbonyl addition and elimination with net water formation.

Geraniol is an acyclic, ten-carbon primary alcohol with molecular formula ${\mathrm{C}}_{10}{\mathrm{H}}_{18}\mathrm{O}$. Its carbon skeleton contains two double bonds and a terminal hydroxyl group. It is chemically distinct from geranyl diphosphate, the activated diphosphate ester of that alcohol.^[ref]

A 2004 study by Yoko Iijima and colleagues connected this structure to a plant reaction. They purified geraniol synthase activity from leaf glands of sweet basil and showed conversion of geranyl diphosphate into geraniol. Expression of the identified gene produced an enzyme with similar activity.^[ref]

The motivating mechanistic experiment used isotope labelling. Supplying water containing oxygen-18 led to oxygen-18-labelled geraniol. That result tracked the origin of the product's oxygen and supported a synthase-type mechanism rather than simple removal of phosphate groups by a phosphatase.^[ref]

The distinction is experimentally powerful: two proposed routes can yield the same unlabelled product yet predict different atom origins. Measuring how much geraniol appears answers a yield question; locating the label addresses a mechanistic question. The isotope observation complements product identification rather than replacing it.

A hemiketal is the addition product of an alcohol and a ketone, with hydroxy group and alkoxy substituents on the former carbonyl carbon. Intramolecular formation can temporarily tether an alcohol to a ketone before another chemical reaction changes the carbon skeleton.

Addition of a nitroalkane-derived nitronate to an aldehyde or ketone gives a beta-nitro alcohol after protonation. Subsequent dehydration is possible under some conditions but is a separate step.

A compound containing $\mathrm{R}-\mathrm{O}-\mathrm{O}-\mathrm{H}$. Its oxygen–oxygen bond distinguishes it from the corresponding alcohol.

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.

$\mathrm{LiAl}{\mathrm{H}}_4$, a strong hydride donor capable of reducing ketones to alcohols and amides to amines, with oxygen removal in the latter transformation.

A cerium(III)-assisted borohydride reduction often used to favour 1,2-reduction of an enone to an allylic alcohol. Actual selectivity remains substrate- and condition-dependent.

Evolutionary biologist who, with John H. McDonald, developed a comparison of within-species variation and between-species divergence to test neutral evolution. Their 1991 study compared synonymous and amino acid-changing differences at the alcohol-dehydrogenase locus in Drosophila, finding an excess of fixed amino acid changes consistent with natural selection.^[ref]

Methanol is the one-carbon alcohol $\mathrm{C}{\mathrm{H}}_3\mathrm{OH}$. Its hydroxyl group can donate and accept hydrogen bonds, making its behavior different from that of the similarly small methane molecule.

It mixes readily with water and participates in reactions characteristic of alcohols, including formation of methyl esters. The methyl group and hydroxyl group together determine its polarity and chemical reactivity; an alcohol is not simply a hydrocarbon dissolved in water.

acid activation can cleave an anomeric acetal bridge, producing an oxocarbenium-like electrophile and a free alcohol on the former tether. methanol capture produces a methyl acetal; anomeric stereochemistry and chair preference must be distinguished.

Substitution of an alcohol using a phosphine and an azodicarboxylate reagent with a suitable acidic nucleophile. Carboxylate displacement normally inverts a stereogenic alcohol carbon; subsequent ester hydrolysis can unveil the inverted alcohol.

The methoxy groups activate the aromatic ring by electron donation through chemical resonance and direct electrophilic substitution ortho and para. Their para positions are already occupied by one another, so the first alkylation occurs at an available ortho position; the four initially vacant positions are equivalent by symmetry.

After placing the first tert-amyl group at position 2, position 5 is favored for the second substitution. It is para to that bulky group and ortho to the other methoxy group. Position 3 is crowded between methoxy and tert-amyl substituents, while position 6 is near the first tert-amyl group across the intervening methoxy-bearing carbon. The 2,5 arrangement distributes the bulky groups on opposite parts of the ring and preserves the equivalence seen in the spectrum.

Alkyl groups do not electronically deactivate the ring, so the stopping point needs a steric explanation. After two such substitutions the remaining positions are much more congested, each adjacent to a bulky tert-amyl group and a methoxy group. Two large substituents are accommodated much more readily than a third, despite excess alcohol. The formula and NMR identify this sterically favored disubstitution; they do not imply that a Friedel-Crafts reaction always stops after two alkylations.

protonation of the alcohol converts its OH group into a water leaving group. Departure of water initially gives the secondary carbocation $\mathrm{C}{\mathrm{H}}_3-\mathrm{C}{\mathrm{H}}^{+}-\mathrm{CH}(\mathrm{C}{\mathrm{H}}_3{)}_2$. A 1,2-hydride shift from the neighboring methine group transfers its C–H bonding pair to the electron-deficient carbon:The resulting tertiary carbocation is the tert-amyl electrophile. An aromatic $\pi$ bond of the dimethoxybenzene attacks that carbon, producing a Wheland intermediate. Removal of the proton from the attacked ring carbon restores aromaticity and regenerates acid. Repeating this Friedel-Crafts alkylation at the symmetry-related second site gives the disubstituted product.

The hydride migration explains the new ethyl group and the absence of a benzylic methine group proton. Simply attaching the original alcohol skeleton at its OH-bearing carbon would not explain the twelve-proton NMR singlet.

The product is 1,4-dimethoxy-2,5-bis(2-methylbutan-2-yl)benzene. Each new substituent is $-\mathrm{C}(\mathrm{C}{\mathrm{H}}_3{)}_2\mathrm{C}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_3$, a tert-amyl group, rather than the unrearranged secondary alkyl group of the alcohol. The two substituents are related by the symmetry of the ring.

The proton assignments are:

The integrals add to 30 H. The unusually shielded terminal ethyl methyl signal is compatible with an aryl-containing environment; its NMR quartet–NMR triplet partner and integral are the decisive assignment evidence. The molecular formula and degree of unsaturation, $\mathrm{DBE}=4$, fit a benzene ring with saturated side chains.

The new ring is formed by intramolecular Friedel-Crafts addition to the ketone. titanium tetrachloride coordinates the ketone oxygen of the cyclic beta-ketoester, increasing electrophilicity at that carbonyl carbon. The nearby electron-rich aryl ring attacks this activated ketone at the available position ortho to its ethyl tether.

The electron-flow sequence is: an aromatic $\pi$ bond forms the new aryl–carbonyl-carbon bond, the ketone $\pi$ bond moves onto oxygen, and loss of the aromatic proton restores aromaticity. The two-carbon tether and the shared quaternary carbon make the newly closed carbocycle six-membered. Hydrolytic work-up converts the titanium-bound alkoxide into the tertiary alcohol.

The lactone carbonyl survives. This is an addition to the ketone with retention of its oxygen as OH, rather than an acyl substitution that removes that oxygen. The pendant terminal alkene is not involved. These bond changes account for the fused aromatic ring system and the alcohol in C without needing to assign the new stereochemistry.

copper(I) converts the methyl grignard reagent into a softer organocopper nucleophile. Methyl undergoes 1,4 addition to the beta carbon of the cycloheptenone, giving a metal enolate rather than direct 1,2 addition to the ketone carbonyl.

The carbon nucleophilic site of this enolate, at the alpha carbon, attacks the aldehyde carbonyl in the second reagent. Its C=O $\pi$ electrons move to oxygen; protonation of the resulting alkoxide gives the beta-hydroxy ketone side chain. The cyclic acetal is a protected ketone and survives these nucleophilic conditions.

The beta methyl group shields one face of the cyclic enolate. Aldol bond formation from the less crowded opposite face places the new alpha side chain trans to the beta methyl group. Thus the two starred ring centers have an anti relationship; the two mirror-related products are possible from achiral starting materials and reagents. This argument does not assign the separate, unstarred alcohol center, for which the question gives no specified configuration.