The Hammett equation in organic chemistry describes a linear free-energy relationship relating reaction rates and equilibrium constants for many reactions involving benzoic acid derivatives with meta- and para-substituents to each other with just two parameters: a substituent constant and a reaction constant. This equation was developed and published by Louis Plack Hammett in 1937 as a follow-up to qualitative observations in a 1935 publication; the basic idea is that for any two reactions with two aromatic reactants only differing in the type of substituent, the change in free energy of activation is proportional to the change in Gibbs free energy. This notion does not follow from elemental thermochemistry or chemical kinetics and was introduced by Hammett intuitively; the basic equation is: log K K 0 = σ ρ relating the equilibrium constant, K, for a given equilibrium reaction with substituent R and the reference K0 constant when R is a hydrogen atom to the substituent constant σ which depends only on the specific substituent R and the reaction constant ρ which depends only on the type of reaction but not on the substituent used.
The equation holds for reaction rates k of a series of reactions with substituted benzene derivatives: log k k 0 = σ ρ. In this equation k0 is the reference reaction rate of the unsubstituted reactant, k that of a substituted reactant. A plot of log for a given equilibrium versus log for a given reaction rate with many differently substituted reactants will give a straight line; the starting point for the collection of the substituent constants is a chemical equilibrium for which both the substituent constant and the reaction constant are arbitrarily set to 1: the ionization of benzoic acid or benzene carboxylic acid in water at 25 °C. Having obtained a value for K0, a series of equilibrium constants are now determined based on the same process, but now with variation of the para substituent—for instance, p-hydroxybenzoic acid or p-aminobenzoic acid; these values, combined in the Hammett equation with K0 and remembering that ρ = 1, give the para substituent constants compiled in table 1 for amine, ethoxy, methyl, bromine, iodine and cyano substituents.
Repeating the process with meta-substituents afford the meta substituent constants. This treatment does not include ortho-substituents; the σ values displayed in the Table above reveal certain substituent effects. With ρ = 1, the group of substituents with increasing positive values—notably cyano and nitro—cause the equilibrium constant to increase compared to the hydrogen reference, meaning that the acidity of the carboxylic acid has increased; these substituents stabilize the negative charge on the carboxylate oxygen atom by an electron-withdrawing inductive effect and by a negative mesomeric effect. The next set of substituents are the halogens, for which the substituent effect is still positive but much more modest; the reason for this is that while the inductive effect is still negative, the mesomeric effect is positive, causing partial cancellation. The data show that for these substituents, the meta effect is much larger than the para effect, due to the fact that the mesomeric effect is reduced in a meta substituent.
With meta substituents a carbon atom bearing the negative charge is further away from the carboxylic acid group. This effect is depicted in scheme 3, where, in a para substituted arene 1a, one resonance structure 1b is a quinoid with positive charge on the X substituent, releasing electrons and thus destabilizing the Y substituent; this destabilizing effect is not possible. Other substituents, like methoxy and ethoxy, can have opposite signs for the substituent constant as a result of opposing inductive and mesomeric effect. Only alkyl and aryl substituents like methyl are electron-releasing in both respects. Of course, when the sign for the reaction constant is negative, only substituents with a negative substituent constant will increase equilibrium constants; because the carbonyl group is unable to serve a source of electrons for -M groups, for reactions involving phenol and aniline starting materials, the σp values for electron-withdrawing groups will appear too small. For reactions where resonance effects are expected to have a major impact, a modified parameter, a modified set of σp– constants may give a better fit.
This parameter is defined using the ionization constants of para substituted phenols, via a scaling factor to match up the values of σp– with those of σp for "non-anomalous" substituents, so as to maintain comparable ρ values: for ArOH ⇄ ArO– + H+, we define σ p − = 1 2.11 log 10 . The carbonyl carbon of a benzoic acid is at a nodal position and unable to serve a s sink for +M groups, thus for reactions involving carbocations at the α-position, the σp values for electron-donating groups will appear insufficiently negative. Based on similar considerations, a set of σp+ constants give better fit for r
An allyl group is a substituent with the structural formula H2C=CH−CH2R, where R is the rest of the molecule. It consists of a methylene bridge attached to a vinyl group; the name is derived from the Latin word for Allium sativum. In 1844, Theodor Wertheim isolated an allyl derivative from garlic oil and named it "Schwefelallyl"; the term allyl applies to many compounds related to H2C=CH−CH2, some of which are of practical or of everyday importance, for example, allyl chloride. A site adjacent to the unsaturated carbon atom is called allylic site. A group attached at this site is sometimes described as allylic. Thus, CH2=CHCH2OH "has an allylic hydroxyl group". Allylic C−H bonds are about 15% weaker than the C−H bonds in ordinary sp3 carbon centers and are thus more reactive; this heightened reactivity has many practical consequences. The industrial production of acrylonitrile by ammoxidation of propene exploits the easy oxidation of the allylic C−H centers: 2CH3−CH=CH2 + 2NH3 + 3O2 → 2CH2=CH−C≡N + 6H2OUnsaturated fats spoil by rancidification involving attack at allylic C−H centers.
Benzylic and allylic are related in terms of structure, bond strength, reactivity. Other reactions that tend to occur with allylic compounds are allylic oxidations, ene reactions, the Tsuji–Trost reaction. Benzylic groups are related to allyl groups. A CH2 group connected to two vinyl groups is said to be doubly allylic; the bond dissociation energy of C−H bonds on a doubly allylic centre is about 10% less than the bond dissociation energy of a C−H bond, allylic. The weakened C−H bonds reflect the high stability of the resulting pentadienyl radicals. Compounds containing the C=C−CH2−C=C linkages, e.g. linoleic acid derivatives, are prone to autoxidation, which can lead to polymerization or form semisolids. This reactivity pattern is fundamental to the film-forming behavior of the "drying oils", which are components of oil paints and varnishes; the term homoallylic refers to the position on a carbon skeleton next to an allylic position. In but-3-enyl chloride CH2=CHCH2CH2Cl, the chloride is homoallylic because it is bonded to the homoallylic site.
The allyl group is encountered in organic chemistry. Allylic radicals and cations are discussed as intermediates in reactions. All feature three contiguous sp²-hybridized carbon centers and all derive stability from resonance; each species can be presented by two resonance structures with the charge or unpaired electron distributed at both 1,3 positions. In terms of MO theory, the MO diagram has three molecular orbitals: the first one bonding, the second one non-bonding and the higher energy orbital is antibonding. Allylation is any chemical reaction. Allylation refers to the addition of an allyl anion equivalent to an organic electrophile: Carbonyl allylation is a type of organic reaction in which an activated allyl group is added to carbonyl group producing an allylic tertiary alcohol. A typical allylation of an aldehyde is represented by the following two-step process that begins with allylation followed by hydrolysis of the intermediate: RCHO + CH2=CHCH2M → CH2=CHCH2RCH CH2=CHCH2RCH + H2O → CH2=CHCH2RCH + MOHA popular reagent for asymmetric allylation is the "Brown reagent", allyldiisopinocampheylborane.
The introduction of allylic groups into molecular frameworks generates many opportunities for downstream diversification. A common method to introduce allyl moieties into organic molecules is through 1,2-allylation of carbonyl groups; the homoallylic alcohol products can undergo a variety of diversity-generating reactions such as ozonolysis and olefin metathesis. Allylmetal reagents such as allylboranes and allylindium compounds are used by organic chemists to introduce allyl groups. Allylstannanes are stable reagents in the allylmetal family, have been employed in a variety of complex organic syntheses. In fact, allylstannane addition is one of the most common methods for producing polypropionates and other oxygenated molecules with a contiguous arrays of stereocenters. Ley and coworkers used an allylstannane to allylate a threose-derived aldehyde en route to the macrolide antascomicin B, which structurally resembles FK506 and rapamycin, is a potent binder of FKBP12. Allylboration is often used to add allyl groups in a 1,2 fashion to aldehydes and ketones.
Thanks to decades of research, there is now a wide variety of organoboron reagents available to the synthetic chemist, including organoboranes that predictably yield products in high diastereo- and enantioselectivity. If a one-pot metal insertion and allylation procedure is required, indium- mediated allylation is an attractive option for generating homoallylic alcohols directly from allyl halides and carbonyl compounds. In general, the method is called the Barbier reaction, can employ a variety of metals such as magnesium, zinc and tin; the reaction is used as a milder form of the Grignard addition reaction, can tolerate aqueous solvents Organotantalum reagents are useful for conjugate addition to enones. Of particular interest is the ability of certain organotantalum reagents to promote the conjugate allylation of enones. Although the direct allylation of carbonyl groups is prevalent throughout the literature, little has been reported on the conjugate allylation of enones. Prior to Shibata and Baba's report, only three methods existed to selectively allylate enones, via: Hosomi Sakurai reaction, allylbarium reagents, allylcopper reagents.
Transmetalation of allyltin, alkynyltin, α-stannyl esters, allenyltin compounds with TaCl5 a
An allene is a compound in which one carbon atom has double bonds with each of its two adjacent carbon centres. Allenes are classified as polyenes with cumulated dienes; the parent compound of allene is propadiene. Compounds with an allene-type structure but with more than three carbon atoms are called cumulenes. Allenes are much more reactive than most other alkenes. For example, their reactivity with gaseous chlorine is more like the reactivity of alkynes than that of alkenes; the central carbon atom of allene forms two pi bonds. The central carbon is sp-hybridized, the two terminal carbon atoms are sp2-hybridized; the bond angle formed by the three carbon atoms is 180°, indicating linear geometry for the carbon atoms of allene. It can be viewed as an "extended tetrahedral" with a similar shape to methane; the symmetry and isomerism of allenes has long fascinated organic chemists. For allenes with four identical substituents, there exist two twofold axes of rotation through the center carbon, inclined at 45° to the CH2 planes at either end of the molecule.
The molecule can thus be thought of as a two-bladed propeller. A third twofold axis of rotation passes through the C=C=C bonds, there is a mirror plane passing through both CH2 planes, thus this class of molecules belong to the D2d point group. Because of the symmetry, an unsubstituted allene has no net dipole moment. An allene with two different substituents on each of the two carbon atoms will be chiral because there will no longer be any mirror planes. Where A has a greater priority than B according to the Cahn-Ingold-Prelog priority rule, the configuration of the axial chirality can be determined by considering the substituents on the front atom followed by the back atom when viewed along the allene axis. For the bottom, only the group of higher priority need be considered. Chiral allenes have been used as building blocks in the construction of organic materials with exceptional chiroptical properties. Although allenes require specialized syntheses, the parent, propadiene is produced on a large scale as an equilibrium mixture with methylacetylene: H2C=C=CH2 ⇌ CH3C≡CHThis mixture, known as MAPP gas, is commercially available.
Laboratory methods for the formation of allenes include: from geminal dihalocyclopropanes and organolithium compounds in the Skattebøl rearrangement from reaction of certain terminal alkynes with formaldehyde, copper bromide, added base from dehydrohalogenation of certain dihalides from reaction of a triphenylphosphinyl ester with an acid halide, a Wittig reaction accompanied by dehydrohalogenation Allenes function as ligands, not unlike alkenes. A typical complex is Pt2. Ni reagents catalyze the cyclooligomerization of allene. Using a suitable catalyst, it is possible to reduce just one of the double bonds of an allene. Many rings or ring systems are known by semisystematic names that assume a maximum number of noncumulative bonds. To unambiguously specify derivatives that include cumulated bonds, a lowercase delta may be used with a subscript indicating the number of cumulated double bonds from that atom, e.g. 8δ2-Benzocyclononene. This may be combined with the λ-convention for specifying nonstandard valency states, e.g. 2λ4δ2,5λ4δ2-Thienothiophene.
Compounds with three or more adjacent carbon–carbon double bonds are called cumulenes. The allene motif is encountered in carbo-mers. IUPAC, Compendium of Chemical Terminology, 2nd ed.. Online corrected version: "allenes". Doi:10.1351/goldbook. A00238 Allene chemistry Kay M. Brummond Thematic Series in the open-access Beilstein Journal of Organic Chemistry Stereochemistry study guide Synthesis of allenes
In molecular biology, the five-prime cap is a specially altered nucleotide on the 5′ end of some primary transcripts such as precursor messenger RNA. This process, known as mRNA capping, is regulated and vital in the creation of stable and mature messenger RNA able to undergo translation during protein synthesis. Mitochondrial mRNA and chloroplastic mRNA are not capped. In eukaryotes, the 5′ cap, found on the 5′ end of an mRNA molecule, consists of a guanine nucleotide connected to mRNA via an unusual 5′ to 5′ triphosphate linkage; this guanosine is methylated on the 7 position directly after capping in vivo by a methyltransferase. It is referred to as a 7-methylguanylate cap, abbreviated m7G. In multicellular eukaryotes and some viruses, further modifications exist, including the methylation of the 2′ hydroxy-groups of the first 2 ribose sugars of the 5′ end of the mRNA. Cap-1 has a methylated 2'-hydroxy group on the first ribose sugar, while cap-2 has methylated 2'-hydroxy groups on the first two ribose sugars, shown on the right.
The 5′ cap is chemically similar to the 3′ end of an RNA molecule. This provides significant resistance to 5′ exonucleases. Small nuclear RNAs contain unique 5'-caps. Sm-class snRNAs are found with 5'-trimethylguanosine caps, while Lsm-class snRNAs are found with 5'-monomethylphosphate caps. In bacteria, also in higher organisms, some RNAs are capped with NAD+, NADH, or 3'-dephospho-coenzyme A. In all organisms, mRNA molecules can be decapped in a process known as messenger RNA decapping; the starting point for capping with 7-methylguanylate is the unaltered 5′ end of an RNA molecule, which terminates at a triphosphate group. This features a final nucleotide followed by three phosphate groups attached to the 5′ carbon; the capping process is initiated before the completion of transcription, as the nascent pre-mRNA is being synthesized. One of the terminal phosphate; this results in the 5′–5′ triphosphate linkage, producing 5'n. The mechanism of capping with NAD+, NADH, or 3'-dephospho-coenzyme A is different.
Capping with NAD+, NADH, or 3'-dephospho-conenzyme A is accomplished through an "ab initio capping mechanism," in which NAD+, NADH, or 3'-desphospho-coenzyme A serves as a "non-canonical initiating nucleotide" for transcription initiation by RNA polymerase and thereby directly is incorporated into the RNA product. Both bacterial RNA polymerase and eukaryotic RNA polymerase II are able to carry out this "ab initio capping mechanism." For capping with 7-methylguanylate, the capping enzyme complex binds to RNA polymerase II before transcription starts. As soon as the 5′ end of the new transcript emerges from RNA polymerase II, the CEC carries out the capping process; the enzymes for capping can only bind to RNA polymerase II, ensuring specificity to only these transcripts, which are entirely mRNA. Capping with NAD+, NADH, or 3'-dephospho-coenzyme A is targeted by promoter sequence. Capping with NAD+, NADH, or 3'-dephospho-coenzyme A occurs only at promoters that have certain sequences at and upstream of the transcription start site and therefore occurs only for RNAs synthesized from certain promoters.
The 5′ cap has four main functions: Regulation of nuclear export. Nuclear export of RNA is regulated by the cap binding complex, which binds to 7-methylguanylate-capped RNA; the CBC is recognized by the nuclear pore complex and exported. Once in the cytoplasm after the pioneer round of translation, the CBC is replaced by the translation factors eIF4E and eIF4G of the eIF4F complex; this complex is recognized by other translation initiation machinery including the ribosome. Capping with 7-methylguanylate prevents 5′ degradation in two ways. First, degradation of the mRNA by 5′ exonucleases is prevented by functionally looking like a 3′ end. Second, the CBC and eIF4E/eIF4G block the access of decapping enzymes to the cap; this increases the half-life of the mRNA, essential in eukaryotes as the export and translation processes take significant time. Decapping of a 7-methylguanylate-capped mRNA is catalyzed by the decapping complex made up of at least Dcp1 and Dcp2, which must compete with eIF4E to bind the cap.
Thus the 7-methylguanylate cap is a marker of an translating mRNA and is used by cells to regulate mRNA half-lives in response to new stimuli. Undesirable mRNAs are sent to P-bodies for temporary storage or decapping, the details of which are still being resolved; the mechanism of 5′ proximal intron excision promotion is not well understood, but the 7-methylguanylate cap appears to loop around and interact with the spliceosome in the splicing process, promoting intron excision. Messenger RNA decapping Eukaryotic initiation factor 4F "RNA Caps". PubMed Medical Su
In chemistry, vinyl or ethenyl is the functional group with the formula −CH=CH2. It is the ethylene molecule less one hydrogen atom; the name is used for any compound containing that group, namely R−CH=CH2 where R is any other group of atoms. An industrially important example is vinyl chloride, precursor to PVC, a plastic known as vinyl. Vinyl is one of the alkenyl functional groups. On a carbon skeleton, sp2-hybridized carbons or positions are called vinylic. Allyls and styrenics contain vinyl groups. Vinyl groups can polymerize with the aid of a radical initiator or a catalyst, forming vinyl polymers. Vinyl polymers contain no vinyl groups. Instead they are saturated; the following table gives some examples of vinyl polymers. Many vinylidene and vinylene compounds polymerize in the same manner; those polymers are analogously referred to as polyvinylidenes and polyvinylenes, reflecting the monomeric precursors. Vinyl derivatives are alkenes. If activated by an adjacent group, the increased polarization of the bond gives rise to characteristic reactivity, termed vinylogous: In allyl compounds, where the next carbon is saturated but substituted once, allylic rearrangement and related reactions are observed.
Allyl Grignard reagents can attack with the vinyl end first. If next to an electron-withdrawing group, conjugate addition occurs. Vinyl organometallics, e.g. vinyl lithium, participate in coupling reactions such as in Negishi coupling. The etymology of vinyl is the Latin vinum = "wine", the Greek word "hylos"'υλος, because of its relationship with alcohol; the term "vinyl" was coined by the German chemist Hermann Kolbe in 1851. Acetylenic Allylic/Homoallylic Benzylic Propargylic/Homopropargylic Vinylogous
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group on the periodic table, a reactive nonmetal, an oxidizing agent that forms oxides with most elements as well as with other compounds. By mass, oxygen is the third-most abundant element in the universe, after helium. At standard temperature and pressure, two atoms of the element bind to form dioxygen, a colorless and odorless diatomic gas with the formula O2. Diatomic oxygen gas constitutes 20.8% of the Earth's atmosphere. As compounds including oxides, the element makes up half of the Earth's crust. Dioxygen is used in cellular respiration and many major classes of organic molecules in living organisms contain oxygen, such as proteins, nucleic acids and fats, as do the major constituent inorganic compounds of animal shells and bone. Most of the mass of living organisms is oxygen as a component of water, the major constituent of lifeforms. Oxygen is continuously replenished in Earth's atmosphere by photosynthesis, which uses the energy of sunlight to produce oxygen from water and carbon dioxide.
Oxygen is too chemically reactive to remain a free element in air without being continuously replenished by the photosynthetic action of living organisms. Another form of oxygen, ozone absorbs ultraviolet UVB radiation and the high-altitude ozone layer helps protect the biosphere from ultraviolet radiation. However, ozone present at the surface is a byproduct of thus a pollutant. Oxygen was isolated by Michael Sendivogius before 1604, but it is believed that the element was discovered independently by Carl Wilhelm Scheele, in Uppsala, in 1773 or earlier, Joseph Priestley in Wiltshire, in 1774. Priority is given for Priestley because his work was published first. Priestley, called oxygen "dephlogisticated air", did not recognize it as a chemical element; the name oxygen was coined in 1777 by Antoine Lavoisier, who first recognized oxygen as a chemical element and characterized the role it plays in combustion. Common uses of oxygen include production of steel and textiles, brazing and cutting of steels and other metals, rocket propellant, oxygen therapy, life support systems in aircraft, submarines and diving.
One of the first known experiments on the relationship between combustion and air was conducted by the 2nd century BCE Greek writer on mechanics, Philo of Byzantium. In his work Pneumatica, Philo observed that inverting a vessel over a burning candle and surrounding the vessel's neck with water resulted in some water rising into the neck. Philo incorrectly surmised that parts of the air in the vessel were converted into the classical element fire and thus were able to escape through pores in the glass. Many centuries Leonardo da Vinci built on Philo's work by observing that a portion of air is consumed during combustion and respiration. In the late 17th century, Robert Boyle proved. English chemist John Mayow refined this work by showing that fire requires only a part of air that he called spiritus nitroaereus. In one experiment, he found that placing either a mouse or a lit candle in a closed container over water caused the water to rise and replace one-fourteenth of the air's volume before extinguishing the subjects.
From this he surmised that nitroaereus is consumed in both combustion. Mayow observed that antimony increased in weight when heated, inferred that the nitroaereus must have combined with it, he thought that the lungs separate nitroaereus from air and pass it into the blood and that animal heat and muscle movement result from the reaction of nitroaereus with certain substances in the body. Accounts of these and other experiments and ideas were published in 1668 in his work Tractatus duo in the tract "De respiratione". Robert Hooke, Ole Borch, Mikhail Lomonosov, Pierre Bayen all produced oxygen in experiments in the 17th and the 18th century but none of them recognized it as a chemical element; this may have been in part due to the prevalence of the philosophy of combustion and corrosion called the phlogiston theory, the favored explanation of those processes. Established in 1667 by the German alchemist J. J. Becher, modified by the chemist Georg Ernst Stahl by 1731, phlogiston theory stated that all combustible materials were made of two parts.
One part, called phlogiston, was given off when the substance containing it was burned, while the dephlogisticated part was thought to be its true form, or calx. Combustible materials that leave little residue, such as wood or coal, were thought to be made of phlogiston. Air did not play a role in phlogiston theory, nor were any initial quantitative experiments conducted to test the idea. Polish alchemist and physician Michael Sendivogius in his work De Lapide Philosophorum Tractatus duodecim e naturae fonte et manuali experientia depromti described a substance contained in air, referring to it as'cibus vitae', this substance is identical with oxygen. Sendivogius, during his experiments performed between 1598 and 1604, properly recognized that the substance is equivalent to the gaseous byproduct released by the thermal decomposition of potassium nitrate. In Bugaj’s view, the isolation of oxygen and the proper association of the substance to that part of air, required for life, lends sufficient weight to the discovery of oxygen by Sendivogius.
Phenol is an aromatic organic compound with the molecular formula C6H5OH. It is a white crystalline solid, volatile; the molecule consists of a phenyl group bonded to a hydroxy group. It requires careful handling due to its propensity for causing chemical burns. Phenol was first extracted from coal tar, it is an important industrial commodity as a precursor to useful compounds. It is used to synthesize plastics and related materials. Phenol and its chemical derivatives are essential for production of polycarbonates, Bakelite, detergents, herbicides such as phenoxy herbicides, numerous pharmaceutical drugs. Phenol is an organic compound appreciably soluble in water, with about 84.2 g dissolving in 1000 mL. Homogeneous mixtures of phenol and water at phenol to water mass ratios of ~2.6 and higher are possible. The sodium salt of phenol, sodium phenoxide, is far more water-soluble. Phenol is weakly acidic and at high pHs gives the phenolate anion C6H5O−: PhOH ⇌ PhO− + H+ Compared to aliphatic alcohols, phenol is about 1 million times more acidic, although it is still considered a weak acid.
It reacts with aqueous NaOH to lose H+, giving the salt sodium phenoxide, whereas most alcohols react only partially. One explanation for the increased acidity over alcohols is resonance stabilization of the phenoxide anion by the aromatic ring. In this way, the negative charge on oxygen is delocalized on to the ortho and para carbon atoms through the pi system. An alternative explanation involves the sigma framework, postulating that the dominant effect is the induction from the more electronegative sp2 hybridised carbons. In support of the second explanation, the pKa of the enol of acetone in water is 10.9, making it only less acidic than phenol. Thus, the greater number of resonance structures available to phenoxide compared to acetone enolate seems to contribute little to its stabilization. However, the situation changes. A recent in silico comparison of the gas phase acidities of the vinylogues of phenol and cyclohexanol in conformations that allow for or exclude resonance stabilization leads to the inference that about 1⁄3 of the increased acidity of phenol is attributable to inductive effects, with resonance accounting for the remaining difference.
The phenoxide anion has a similar nucleophilicity to free amines, with the further advantage that its conjugate acid does not become deactivated as a nucleophile in moderately acidic conditions. Phenolate esters are more stable toward hydrolysis than acid anhydrides and acyl halides but are sufficiently reactive under mild conditions to facilitate the formation of amide bonds. Phenol exhibits keto-enol tautomerism with its unstable keto tautomer cyclohexadienone, but only a tiny fraction of phenol exists as the keto form; the equilibrium constant for enolisation is 10−13, which means only one in every ten trillion molecules is in the keto form at any moment. The small amount of stabilisation gained by exchanging a C=C bond for a C=O bond is more than offset by the large destabilisation resulting from the loss of aromaticity. Phenol therefore exists entirely in the enol form. Phenoxides are enolates stabilised by aromaticity. Under normal circumstances, phenoxide is more reactive at the oxygen position, but the oxygen position is a "hard" nucleophile whereas the alpha-carbon positions tend to be "soft".
Phenol is reactive toward electrophilic aromatic substitution as the oxygen atom's pi electrons donate electron density into the ring. By this general approach, many groups can be appended to the ring, via halogenation, acylation and other processes. However, phenol's ring is so activated—second only to aniline—that bromination or chlorination of phenol leads to substitution on all carbon atoms ortho and para to the hydroxy group, not only on one carbon. Phenol reacts with dilute nitric acid at room temperature to give a mixture of 2-nitrophenol and 4-nitrophenol while with concentrated nitric acid, more nitro groups get substituted on the ring to give 2,4,6-trinitrophenol, known as picric acid. Aqueous solutions of phenol are weakly acidic and turn blue litmus to red. Phenol is neutralized by sodium hydroxide forming sodium phenate or phenolate, but being weaker than carbonic acid, it cannot be neutralized by sodium bicarbonate or sodium carbonate to liberate carbon dioxide. C6H5OH + NaOH → C6H5ONa + H2OWhen a mixture of phenol and benzoyl chloride are shaken in presence of dilute sodium hydroxide solution, phenyl benzoate is formed.
This is an example of the Schotten-Baumann reaction: C6H5OH + C6H5COCl → C6H5OCOC6H5 + HClPhenol is reduced to benzene when it is distilled with zinc dust, or when phenol vapour is passed over granules of zinc at 400 °C: C6H5OH + Zn → C6H6 + ZnOWhen phenol is reacted with diazomethane in the presence of boron trifluoride, anisole is obtained as the main product and nitrogen gas as a byproduct. C6H5OH + CH2N2 → C6H5OCH3 + N2When phenol reacts with iron chloride solution, an intense violet-purple solution is formed; because of phenol's commercial importance, many methods have been developed for its production. The dominant current route, accounting for 95% of production, is the cumene process, which uses benzene and propene as feedstock and involves the partial oxidation of cumene vi