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910 Journal of Chemical Education • Vol. 77 No. 7 July 2000 • JChemEd.chem.wisc.edu

“Acid” is derived from the Latin acidus, to be sour; oftenany compound (organic or inorganic, with or without thecarboxyl group) that provided a sour taste to its discovererwas termed an acid. However, modern IUPAC rules associatethis organic nomenclature specifically with carboxylic acids.It could be misconstrued that all organic “acids” must contain acarboxyl group, but certain acidic organic compounds do notformally contain this functionality. Their names can belietheir structures. In this article, instead of surveying all acidsthat are not carboxylic acids, we will concentrate on thosecommon organic compounds that provide a simple name yetlack an easily discernible acidic proton. We have divided thereview into three parts, into which most of these compoundscan be distributed: phenolic-type acids, vinylogous carboxylicacids, and carbon acids.

Group I: Phenolic-Type Acids

The acidity of phenols is greater than that of normalalcohols; for example, unsubstituted phenol (pKa = 9.89) ismore acidic than the saturated alcohol, cyclohexanol (pKa =17) (1). In phenolic-type acids, the OH group is attached toan sp2 hybridized carbon, which by induction withdrawsmore electron density away from the proton (ground statedestabilization) than the sp3 carbon does in cyclohexanol.Moreover, the phenolate anion can be delocalized by resonanceto the ortho and para positions (product stabilization), which islacking in the aliphatic analog (2). As the substitution patternon the aromatic ring changes, the acidity of the OH group onthe phenol changes. For example, nitro groups placed in theortho and para positions are strongly electron-withdrawing andthree of these groups have a large effect on the acidity (seeScheme I and structures below) (3). Some heterocyclic com-pounds with phenolic-type structures also show high acidity.

OH O

ortho ortho

para

O O O

Scheme I. Resonance structures of deprotonated phenol.

OH OH

O2N NO2

NO2

Carbolic AcidpKa = 9.89

Picric AcidpKa = 0.38

OH

O2N NO2

NO2

OH

Styphnic AcidpKa ≈ 0

Many hydroxybenzene compounds (phenols) were iso-lated long before their actual structure was determined andso were named on the basis of their acidity. The “carbolic acid”that Lister used for the sterilization of operating theaters was anaqueous solution of phenol. Picric acid (Greek pikros [bitter])and styphnic acid (Greek styphnos [contracting, astringent])were also obviously named after their properties, not theirstructure. Note that many natural products listed as acids (e.g.,ellagic acid from gallnuts, chrysophanic acid from rhubarb,tannic acid from oak, and usnic acid from lichen) are actuallyphenols (4 ).

O

O

O

O

OH

OH

HO

HO

Ellagic Acid

O

O

OH OH

CH3

Chrysophanic Acid

OR

O

HO

HO

OH

Tannic Acid Subunit

O

OH

H3C

HO

CH3O

H3CO

O

CH3

O

Usnic Acid

The cyclic ureides are derivatives of urea (H2NCONH2),one of the building blocks of nature. Interestingly, whereasurea is neutral (or slightly basic, since it forms salts with strongacids), the derivatives shown here are strongly acidic. Part ofthe acidity can be attributed to the production of tautomericforms in solution. The tautomerization between the oxo formand the hydroxy form greatly affects the intramolecular H-bonding and the acidity of the proton. Also, it can be seenfrom the hydroxy structures that they form 6-membered ringsanalogous to phenol, with a hydroxy group attached to anaromatic ring. This tautomer is expected to be deprotonated.

Uric AcidpK = 5.4

Isocyanuric AcidpK = 6.88

Barbituric AcidpK = 4.01

N

N N

N

O

O

H

HH

H

O N

N N

HN

OH

HO

OH

N

N

N

O

O

H

H H

O

N

N

N

OH

OHHO

N

N

OH

HO OH

N

N

O

O

H

H

O

a1

a1

a1

Organic Acids without a Carboxylic Acid Functional GroupG. V. Perez and Alice L. Perez*Department of Chemistry, University of Costa Rica, 2060 San Pedro, San Jose, Costa Rica; *alperez@cariari.ucr.ac.cr

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JChemEd.chem.wisc.edu • Vol. 77 No. 7 July 2000 • Journal of Chemical Education 911

Isolated from human urine independently by Scheele andBergman in 1776, uric acid (also known as lithic acid) is theoldest known of these ureides (5). It is ubiquitous in nature.Aside from being present in some seeds and plant parts, allcarnivorous mammals have a few percent in their urine, blood,and muscle (and too high a concentration in humans leadsto precipitation of the sodium salt as kidney stones or goutydeposits in certain joints). Large amounts of the ammoniumsalt are found in the excrement of birds, scaly reptiles (espe-cially snakes), and some insects (e.g., caterpillars).

Several structures were initially suggested for this com-pound. The correct tricarbonyl structure (purine-2,6,8(1H,3H,9H)-trione) was predicted by Medicus in 1875 and con-firmed by Emil Fischer in 1883. Fischer also discovered thaturic acid formed both a monosodium and a disodium salt (butnot a trianion), which he predicted was due to the deproto-nation of the trienol tautomer at the C2 and C6 hydroxygroups. Contrary evidence was provided when the dianionwas methylated and found to provide the N3, N9 dimethylcompound, indicating that it is the C2–O and C8–O thatare deprotonated (Scheme II). Of all the protons in the trienolstructure, the hydroxy group on C8 (with the imine towardN9) is considered to be the most acidic (6 ).

N

N N

HN

OH

O

ON

N N

N

O

O

Me

HH

Me

O2 Me-I 1

8

3

67

92

Scheme II. Methylation of the dianion of uric acid.

(Iso)cyanuric acid exists as an interconverting mixture ofseveral possible tautomers, including the tricarbonyl (triazine-2,4,6(1H,3H,5H)-trione, also known as isocyanuric acid) andtrienol (2,4,6-trihydroxy-1,3,5-triazine, or cyanuric acid) (7 ).The predominant tautomeric form in the solid state and insolution is isocyanuric acid; in basic solution the enol formis more stable. Undoubtedly, its acidity is due to removal of aproton from the hydroxy group in the enolic (cyanuric) form.

The rich history and the naming of barbituric acid hasbeen reviewed (8). Both in the solid state and in aprotic so-lutions, the trioxo form (2,4,6-(1H,3H,5H)-pyrimidine-trione) is the only structure detected (9). In basic solution,the acidic proton is not removed from the central carbon butrather from the oxygen of the hydroxy tautomer (unlikeMeldrum’s acid, see below). It is believed that deprotonationof the enolic proton is favored owing to the greater resonancedelocalization of the resulting anion.

Group II: Vinylogous Carboxylic Acids

R OH

O

R

O

OH

CarboxylicAcid

VinylogousCarboxylic Acid

A common theme among some acidic compounds canbe viewed through the “vinylogous” principle (10). The juxta-position of a hydroxy group in conjugation with a carbonyl canbe thought of as a “vinylogous carboxylic acid”—the protonbehaves as if it were attached to a carboxylic acid rather than

an alcohol. The acidic proton is on an oxygen connected to anelectronegative sp2 hybridized carbon, increasing its acidityrelative to that of a simple alcohol. Recent calculations (11, 12)indicate that the acidity of these systems increases as thenumber of vinyl groups separating the hydroxy and thecarbonyl groups increases. The calculated increase in aciditycan be thought to arise from the dispersal of the negativecharge between the two oxygens in the anion.

A 6-carbon carbohydrate derivative, originally christenedhexuronic acid due to its acidity, was found to be identical tovitamin C and so was renamed ascorbic acid (13). It wasisolated from the adrenal cortex of oxen and is found in tangyfoods such as citrus fruits, hip berries, and tea leaves, whichprevent scurvy (Latin a scorbutus [without scurvy]).

HO

Ascorbic AcidpK = 4.10

O O

OH

HO

OH

a1

Amazingly, the enol form of 3-oxo-L-gulofuranolactone(to provide a more descriptive name) is a stronger acid thanacetic acid (pKa = 4.75). Note that the structure could bedrawn in at least 3 other tautomeric forms, but X-ray crystalanalysis (14 ) and solution NMR work (15) confirm thatthe structure shown is the predominant (most stable) isomer.This interesting compound and the basis for its acidity havebeen highlighted previously (16 ). Once deprotonated, thenegative charge can be spread out over the molecule byresonance (Scheme III).

O O

OO OH

HO

OH

O O

OH

HO

OH

Scheme III. Resonance structures of deprotonated ascorbic acid.

Named for the 4 carbons it contains and its strong acidity,tetronic acid was another misassigned structure (17 ). Although5-membered ring lactones are not especially prone to disasso-ciation, the presence of a second oxygen at C3 greatly influencesthe acidity. The enolized form is most prevalent in the solid state(18), so the pKa is probably a measure of the O–H acidity atC3. Its enolic structure is reminiscent of ascorbic acid (seeabove) and it shares the same enhanced acidity.

OO

HO

Tetronic AcidpKa = 3.76

OO

O

The oxocarbons are a series of acidic compounds withthe general formula CnH2On, which also fall into this secondgroup (19). The brightly colored dianionic salts of croconicacid (Greek krokos [yellow]) (20) and rhodizonic acid (Greekrhodizein [rose-red]) (21) have been known for more than acentury as unusual compounds. Squaric acid was not prepareduntil 1959 (22) and deltic acid was prepared in 1975 (23).