organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...

, hemithioacetals (or thiohemiacetals) are

organosulfur compound Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.g., saccharin. Nature abounds with organosulfur compounds—sulfu ...

s with the general

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwee ...

. They are the sulfur analogues of the

acetal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments no ...

s, , with an

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

atom replaced by sulfur (as implied by the ''

thio- The prefix thio-, when applied to a chemical, such as an ion, means that an oxygen atom in the compound has been replaced by a sulfur atom. This term is often used in organic chemistry. For example, from the word ''ether,'' referring to an oxyg ...

'' prefix). Because they consist of four differing

substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...

s on a single carbon, hemithioacetals are

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

. A related family of compounds are the dithiohemiacetals, with the formula . Although they can be important intermediates, hemithioacetals are usually not isolated, since they exist in equilibrium with

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

s () and

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

s ().

Formation and structure

Hemithioacetals are formed by the reaction of a

() and an

(): :R-CHO + R'-SH <=> R-CH(OH)S-R' Hemithioacetals usually arise via acid

catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

. They typically are intermediates in the formation of

dithioacetal In organosulfur chemistry, thioacetals are the sulfur (''thio-'') analogues of acetals (). There are two classes: the less-common monothioacetals, with the formula , and the dithioacetals, with the formula (symmetric dithioacetals) or (asym ...

s (): :R-CH(OH)S-R' + R'-SH <=> R-CH(S-R')2 + H2O

Isolable hemithioacetal

Hemithioacetals ordinarily readily dissociate into thiol and aldehyde, however, some have been isolated. In general, these isolable hemithioacetals are cyclic, which disfavors dissociation, and can often be further stabilized by the presence of acid. An important class are S-glycosides, such as octylthioglucoside, which are formed by a reaction between thiols and sugars. Other examples include 2-hydroxy

tetrahydrothiophene Tetrahydrothiophene is an organosulfur compound with the formula (CH2)4S. The molecule consists of a five-membered saturated ring with four methylene groups and a sulfur atom. It is the saturated analog of thiophene. It is a volatile, colorles ...

and the anti-HIV drug

Lamivudine Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typicall ...

. Another class of isolable hemithioacetals are derived from carbonyl groups that form stable hydrates. For example, thiols react with hexafluoroacetone trihydrate to give hemithioacetals, which can be isolated.

Hemithioacetals in nature

Glyoxalase I The enzyme lactoylglutathione lyase (EC 4.4.1.5, also known as glyoxalase I) catalyzes the isomerization of hemithioacetal adducts, which are formed in a spontaneous reaction between a glutathionyl group and aldehydes such as methylglyoxal. :('' ...

, which is part of the glyoxalase system present in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

, catalyzes the conversion of α-oxoaldehyde (RC(O)CHO) and the thiol

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pero ...

(abbreviated GSH) to S-2-hydroxyacylglutathione derivatives CH(OH)CO-SG The catalytic mechanism involves an intermediate hemithioacetal adduct COCH(OH)-SG The spontaneous reaction forms

methylglyoxal Methylglyoxal (MGO) is the organic compound with the formula CH3C(O)CHO. It is a reduced derivative of pyruvic acid. It is a reactive compound that is implicated in the biology of diabetes. Methylglyoxal is produced industrially by degradation ...

-glutathione hemithioacetal and human glyoxalase I. A hemithioacetal is also invoked in the mechanism of prenylcysteine lyase. In catalytic mechanism, S-farnesylcysteine is oxidized by a flavin to a thiocarbenium ion. The thiocarbenium ion hydrolyzes to form the hemithioacetal: After formation, the hemithioacetal breaks into

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...

, farnesal, and

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

References

{{Reflist Acetals Functional groups Organosulfur compounds