In chemistry, an ester is a chemical compound derived from an acid (organic or inorganic) in which at least one –OH (hydroxyl) group is replaced by an –O–alkyl (alkoxy) group. Usually, esters are derived from a carboxylic acid and an alcohol. Glycerides, which are fatty acid esters of glycerol, are important esters in biology, being one of the main classes of lipids, and making up the bulk of animal fats and vegetable oils. Esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Phosphoesters form the backbone of DNA molecules. Nitrate esters, such as nitroglycerin, are known for their explosive properties, while polyesters are important plastics, with monomers linked by ester moieties. Esters usually have a sweet smell and are considered high-quality solvents for a broad array of plastics, plasticizers, resins, and lacquers.  They are also one of the largest classes of synthetic lubricants on the commercial market.
Ester names are derived from the parent alcohol and the parent acid, where the latter may be organic or inorganic. Esters derived from the simplest carboxylic acids are commonly named according to the more traditional, so-called "trivial names" e.g. as formate, acetate, propionate, and butyrate, as opposed to the IUPAC nomenclature methanoate, ethanoate, propanoate and butanoate. Esters derived from more complex carboxylic acids are, on the other hand, more frequently named using the systematic IUPAC name, based on the name for the acid followed by the suffix -oate. For example, the ester hexyl octanoate, also known under the trivial name hexyl caprylate, has the formula CH3(CH2)6CO2(CH2)5CH3.
The chemical formulas of organic esters usually take the form RCO2R′, where R and R′ are the hydrocarbon parts of the carboxylic acid and the alcohol, respectively. For example, butyl acetate (systematically butyl ethanoate), derived from butanol and acetic acid (systematically ethanoic acid) would be written CH3CO2C4H9. Alternative presentations are common including BuOAc and CH3COOC4H9.
An uncommon class of organic esters are the orthoesters, which have the formula RC(OR′)3. Triethylorthoformate (HC(OC2H5)3) is derived, in terms of its name (but not its synthesis) from orthoformic acid (HC(OH)3) and ethanol.
Esters can also be derived from an inorganic acid and an alcohol. Thus, the nomenclature extends to inorganic oxo acids and their corresponding esters: phosphoric acid and phosphate esters/organophosphates, sulfuric acid and sulfate esters/organosulfates, nitric acid and nitrate, and boric acid and borates. For example, triphenyl phosphate is the ester derived from phosphoric acid and phenol. Organic carbonates are derived from carbonic acid; for example, ethylene carbonate is derived from carbonic acid and ethylene glycol.
So far an alcohol and inorganic acid are linked via oxygen atoms. The definition of inorganic acid ester that feature inorganic chemical elements links between alcohols and the inorganic acid – the phosphorus atom linking to three alkoxy functional groups in organophosphate – can be extended to the same elements in various combinations of covalent bonds between carbons and the central inorganic atom and carbon–oxygen bonds to central inorganic atoms. For example, phosphorus features three carbon–oxygen–phosphorus bonds and one phosphorus–oxygen double bond in organophosphates, three carbon–oxygen–phosphorus bonds and no phosphorus–oxygen double bonds in phosphite esters or organophosphites, two carbon–oxygen–phosphorus bonds, no phosphorus–oxygen double bonds but one phosphorus–carbon bond in phosphonites, one carbon–oxygen–phosphorus bonds, no phosphorus–oxygen double bonds but two phosphorus–carbon bonds in phosphinites.
As oxygen is a group 16 chemical element, sulfur atoms can replace some oxygen atoms in carbon–oxygen–central inorganic atom covalent bonds of an ester. As a result, thiosulfinates and thiosulfonates, with a central inorganic sulfur atom, demonstrate clearly the assortment of sulfur esters, that also includes sulfates, sulfites, sulfonates, sulfinates, sulfenates esters.
Esters contain a carbonyl center, which gives rise to 120 ° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. The pKa of the alpha-hydrogens on esters is around 25.
Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.
Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.
Esters are generally identified by gas chromatography, taking advantage of their volatility. IR spectra for esters feature an intense sharp band in the range 1730–1750 cm−1 assigned to νC=O. This peak changes depending on the functional groups attached to the carbonyl. For example, a benzene ring or double bond in conjugation with the carbonyl will bring the wavenumber down about 30 cm−1.
Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Several billion kilograms of polyesters are produced industrially annually, important products being polyethylene terephthalate, acrylate esters, and cellulose acetate.
Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials, and often have a characteristic pleasant, fruity odor. This leads to their extensive use in the fragrance and flavor industry. Ester bonds are also found in many polymers.
The equilibrium constant for such reactions is about 5 for typical esters, e.g., ethyl acetate. The reaction is slow in the absence of a catalyst. Sulfuric acid is a typical catalyst for this reaction. Many other acids are also used such as polymeric sulfonic acids. Since esterification is highly reversible, the yield of the ester can be improved using Le Chatelier's principle:
Reagents are known that drive the dehydration of mixtures of alcohols and carboxylic acids. One example is the Steglich esterification, which is a method of forming esters under mild conditions. The method is popular in peptide synthesis, where the substrates are sensitive to harsh conditions like high heat. DCC (dicyclohexylcarbodiimide) is used to activate the carboxylic acid to further reaction. 4-Dimethylaminopyridine (DMAP) is used as an acyl-transfer catalyst.
Another method for the dehydration of mixtures of alcohols and carboxylic acids is the Mitsunobu reaction:
Carboxylic acids can be esterified using diazomethane:
Using this diazomethane, mixtures of carboxylic acids can be converted to their methyl esters in near quantitative yields, e.g., for analysis by gas chromatography. The method is useful in specialized organic synthetic operations but is considered too hazardous and expensive for large-scale applications.
Carboxylic acids are esterified by treatment with epoxides, giving β-hydroxyesters:
The reactions are irreversible simplifying work-up. Since acyl chlorides and acid anhydrides also react with water, anhydrous conditions are preferred. The analogous acylations of amines to give amides are less sensitive because amines are stronger nucleophiles and react more rapidly than does water. This method is employed only for laboratory-scale procedures, as it is expensive.
Although not widely employed for esterifications, salts of carboxylate anions can be alkylating agent with alkyl halides to give esters. In the case that an alkyl chloride is used, an iodide salt can catalyze the reaction (Finkelstein reaction). The carboxylate salt is often generated in situ. In difficult cases, the silver carboxylate may be used, since the silver ion coordinates to the halide aiding its departure and improving the reaction rate. This reaction can suffer from anion availability problems and, therefore, can benefit from the addition of phase transfer catalysts or highly polar aprotic solvents such as DMF.
Transesterification, which involves changing one ester into another one, is widely practiced:
Like the hydrolysation, transesterification is catalysed by acids and bases. The reaction is widely used for degrading triglycerides, e.g. in the production of fatty acid esters and alcohols. Poly(ethylene terephthalate) is produced by the transesterification of dimethyl terephthalate and ethylene glycol:
Direct routes to this same ester are not possible because vinyl alcohol is unstable.
Carboxylic acids also add across alkynes to give the same products.
Esters react with nucleophiles at the carbonyl carbon. The carbonyl is weakly electrophilic but is attacked by strong nucleophiles (amines, alkoxides, hydride sources, organolithium compounds, etc.). The C–H bonds adjacent to the carbonyl are weakly acidic but undergo deprotonation with strong bases. This process is the one that usually initiates condensation reactions. The carbonyl oxygen in esters is weakly basic, less so than the carbonyl oxygen in amides due to resonance donation of an electron pair from nitrogen in amides, but forms adducts.
Esterification is a reversible reaction. Esters undergo hydrolysis under acid and basic conditions. Under acidic conditions, the reaction is the reverse reaction of the Fischer esterification. Under basic conditions, hydroxide acts as a nucleophile, while an alkoxide is the leaving group. This reaction, saponification, is the basis of soap making.
This reaction is not usually reversible. Hydrazines and hydroxylamine can be used in place of amines. Esters can be converted to isocyanates through intermediate hydroxamic acids in the Lossen rearrangement.
Sources of carbon nucleophiles, e.g., Grignard reagents and organolithium compounds, add readily to the carbonyl.
Compared to ketones and aldehydes, esters are relatively resistant to reduction. The introduction of catalytic hydrogenation in the early part of the 20th century was a breakthrough; esters of fatty acids are hydrogenated to fatty alcohols.
A typical catalyst is copper chromite. Prior to the development of catalytic hydrogenation, esters were reduced on a large scale using the Bouveault–Blanc reduction. This method, which is largely obsolete, uses sodium in the presence of proton sources.
Especially for fine chemical syntheses, lithium aluminium hydride is used to reduce esters to two primary alcohols. The related reagent sodium borohydride is slow in this reaction. DIBAH reduces esters to aldehydes.
Direct reduction to give the corresponding ether is difficult as the intermediate hemiacetal tends to decompose to give an alcohol and an aldehyde (which is rapidly reduced to give a second alcohol). The reaction can be achieved using triethylsilane with a variety of Lewis acids.
As for aldehydes, the hydrogen atoms on the carbon adjacent ("α to") the carboxyl group in esters are sufficiently acidic to undergo deprotonation, which in turn leads to a variety of useful reactions. Deprotonation requires relatively strong bases, such as alkoxides. Deprotonation gives a nucleophilic enolate, which can further react, e.g., the Claisen condensation and its intramolecular equivalent, the Dieckmann condensation. This conversion is exploited in the malonic ester synthesis, wherein the diester of malonic acid reacts with an electrophile (e.g., alkyl halide), and is subsequently decarboxylated. Another variation is the Fráter–Seebach alkylation.
As a class, esters serve as protecting groups for carboxylic acids. Protecting a carboxylic acid is useful in peptide synthesis, to prevent self-reactions of the bifunctional amino acids. Methyl and ethyl esters are commonly available for many amino acids; the t-butyl ester tends to be more expensive. However, t-butyl esters are particularly useful because, under strongly acidic conditions, the t-butyl esters undergo elimination to give the carboxylic acid and isobutylene, simplifying work-up.
Many esters have distinctive fruit-like odors, and many occur naturally in the essential oils of plants. This has also led to their commonplace use in artificial flavorings and fragrances when those odors aim to be mimicked.
|Ester name||Formula||Odor or occurrence|
|Benzyl acetate||pear, strawberry, jasmine|
|Butyl acetate||apple, honey|
|Butyl propanoate||pear drops|
|Ethyl acetate||nail polish remover, model paint, model airplane glue|
|Ethyl benzoate||sweet, wintergreen, fruity, medicinal, cherry, grape|
|Ethyl butyrate||banana, pineapple, strawberry|
|Ethyl hexanoate||pineapple, waxy-green banana|
|Ethyl formate||lemon, rum, strawberry|
|Ethyl heptanoate||apricot, cherry, grape, raspberry|
|Ethyl lactate||butter, cream|
|Isobutyl acetate||cherry, raspberry, strawberry|
|Isoamyl acetate||pear, banana (flavoring in Pear drops)|
|Linalyl acetate||lavender, sage|
|Linalyl formate||apple, peach|
|Methyl anthranilate||grape, jasmine|
|Methyl benzoate||fruity, ylang ylang, feijoa|
|Methyl butyrate (methyl butanoate)||pineapple, apple, strawberry|
|Methyl pentanoate (methyl valerate)||flowery|
|Methyl salicylate (oil of wintergreen)||Modern root beer, wintergreen, Germolene and Ralgex ointments (UK)|
|Amyl acetate (pentyl acetate)||apple, banana|
|Pentyl butyrate (amyl butyrate)||apricot, pear, pineapple|
|Pentyl hexanoate (amyl caproate)||apple, pineapple|
|Pentyl pentanoate (amyl valerate)||apple|
|Propyl hexanoate||blackberry, pineapple, cheese, wine|
b. Ester oder sauerstoffsäure Aetherarten.
Ethers du troisième genre.
Viele mineralische und organische Sauerstoffsäuren treten mit einer Alkohol-Art unter Ausscheidung von Wasser zu neutralen flüchtigen ätherischen Verbindungen zusammen, welche man als gepaarte Verbindungen von Alkohol und Säuren-Wasser oder, nach der Radicaltheorie, als Salze betrachten kann, in welchen eine Säure mit einem Aether verbunden ist.
b. Ester or oxy-acid ethers.
Ethers of the third type.
Many mineral and organic acids containing oxygen combine with an alcohol upon elimination of water to [form] neutral, volatile ether compounds, which one can view as coupled compounds of alcohol and acid-water, or, according to the theory of radicals, as salts in which an acid is bonded with an ether.
Agnuside is a chemical compound found in Vitex agnus-castus. Agnuside is the ester of aucubin and p-hydroxybenzoic acid.Androgen ester
An androgen or anabolic steroid ester is an ester of an androgen/anabolic steroid (AAS) such as the natural testosterone or dihydrotestosterone (DHT) or the synthetic nandrolone (19-nortestosterone). Esterification renders AAS into metabolism-resistant prohormones of themselves, improving oral bioavailability, increasing lipophilicity, and extending the elimination half-life (which necessitates less frequent administration). In addition, with intramuscular injection, AAS esters are absorbed more slowly into the body, further improving the elimination half-life. Aside from differences in pharmacokinetics (e.g., duration), these esters essentially have the same effects as the parent drugs. They are used in androgen replacement therapy (ART), among other indications. Examples of androgen esters include testosterone esters such as testosterone cypionate, testosterone enanthate, testosterone propionate, and testosterone undecanoate and nandrolone esters such as nandrolone decanoate and nandrolone phenylpropionate.Anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia - in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which cause a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.
A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside anesthesiology, but others are used commonly in various fields of healthcare. Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects. Adverse effects, however, may also be increased. Anesthetics are distinct from analgesics, which block only sensation of painful stimuli.Benzocaine
Benzocaine, sold under the brand name Orajel among others, is an ester local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is also combined with antipyrine to form A/B otic drops to relieve ear pain and remove earwax. It is not recommended in children younger than two years old.Bile salt-dependent lipase
Bile salt-dependent lipase (or BSDL), also known as carboxyl ester lipase (or CEL) is an enzyme produced by the adult pancreas and aids in the digestion of fats. Bile salt-stimulated lipase (or BSSL) is an equivalent enzyme found within breast milk. BSDL has been found in the pancreatic secretions of all species in which it has been looked for. BSSL, originally discovered in the milk of humans and various other primates, has since been found in the milk of many animals including dogs, cats, rats, and rabbits.Carbamate
A carbamate is an organic compound derived from carbamic acid (NH2COOH). A carbamate group, carbamate ester (e.g., ethyl carbamate), and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.Creatine
Creatine ( or is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. This species exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups. Creatine also acts as a buffer.Dinalbuphine sebacate
Dinalbuphine sebacate (DNS), also known as nalbuphine sebacate or as sebacoyl dinalbuphine ester (SDE) and sold under the brand name Naldebain, is an opioid analgesic which is used as a 7-day long-acting injection in the treatment of moderate to severe postoperative pain. It was developed by Lumosa Therapeutics and was approved in Taiwan in the spring of 2017; development is ongoing in the United States. The compound is a diester of nalbuphine (Nubain) joined via a sebacic acid linker, and acts as a long-lasting prodrug of nalbuphine via slow hydrolysis. It was developed to extend the duration of action of nalbuphine, which has a short duration and requires frequent injections. Whereas nalbuphine must be injected every 4 to 6 hours, a single injection of DNS lasts for up to 7 to 10 days. Nalbuphine, and hence DNS, acts as a mixed agonist/antagonist opioid modulator, or more specifically as a moderate-efficacy partial agonist or antagonist of the μ-opioid receptor and as a high-efficacy partial agonist of the κ-opioid receptor.Ester Dean
Esther Renay Dean, known professionally as Ester Dean, (born April 15, 1986) is an American singer, songwriter, record producer, and actress. Dean has also written songs for many artists, with numerous Top 10 hits, including No. 1 hits for Rihanna and Katy Perry, earning the name “The Song Factory”.
In 2011, Dean contributed to the soundtrack for the animated film, Rio by Blue Sky Studios.
At the 54th Annual Grammy Awards, Dean was nominated for Album of the Year as a producer on Rihanna's album Loud.
In 2012, she voiced two of the characters in the fourth film in the Ice Age franchise, Ice Age: Continental Drift, and also wrote a song for the movie, entitled "We Are (Family)". Dean made her acting debut in the film Pitch Perfect (2012) as Cynthia-Rose Adams, a role she reprised for the sequels, Pitch Perfect 2 (2015) and Pitch Perfect 3 (2017).Ester Peony
Alexandra Crețu, known professionally as Ester Peony, is a Romanian-Canadian singer and songwriter. She will represent Romania in the Eurovision Song Contest 2019 with the song "On a Sunday", after winning Selecția Națională 2019. She was born in Bucharest, Romania but was raised in Montreal, Quebec in Canada, until returning to Romania for studying music.Her scene name, Ester, comes from the Babylonian goddess of love, beauty, sex, desire, fertility, war, justice, and political power Ishtar. In Old Persian it means "star".Esther is also the heroine of the book in the Bible that bears her name. It is a Syro-Arabian modification of the Persian word satarah, which means a star.
Esther appears in the Bible as a "woman of deep piety, faith, courage, patriotism, and caution, combined with resolution; a dutiful daughter to her adopted father, docile and obedient to his counsels, and anxious to share the king's favour with him for the good of the Jewish people. She was a Jewess named Hadas'sah (the myrtle), but her uncle Mordecai changed her name into Esther.Ethyl acetate
Ethyl acetate (systematically ethyl ethanoate, commonly abbreviated EtOAc, ETAC or EA) is the organic compound with the formula CH3–COO–CH2–CH3, simplified to C4H8O2. This colorless liquid has a characteristic sweet smell (similar to pear drops) and is used in glues, nail polish removers, decaffeinating tea and coffee. Ethyl acetate is the ester of ethanol and acetic acid; it is manufactured on a large scale for use as a solvent. The combined annual production in 1985 of Japan, North America, and Europe was about 400,000 tonnes. In 2004, an estimated 1.3 million tonnes were produced worldwide.Functional group
In organic chemistry, functional groups are specific substituents or moieties within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction(s) regardless of the size of the molecule it is a part of. This allows for systematic prediction of chemical reactions and behavior of chemical compounds and design of chemical syntheses. Furthermore, the reactivity of a functional group can be modified by other functional groups nearby. In organic synthesis, functional group interconversion is one of the basic types of transformations.
Functional groups are groups of one or more atoms of distinctive chemical properties no matter what they are attached to. The atoms of functional groups are linked to each other and to the rest of the molecule by covalent bonds. For repeating units of polymers, functional groups attach to their nonpolar core of carbon atoms and thus add chemical character to carbon chains. Functional groups can also be charged, e.g. in carboxylate salts (–COO−), which turns the molecule into a polyatomic ion or a complex ion. Functional groups binding to a central atom in a coordination complex are called ligands. Complexation and solvation are also caused by specific interactions of functional groups. In the common rule of thumb "like dissolves like", it is the shared or mutually well-interacting functional groups which give rise to solubility. For example, sugar dissolves in water because both share the hydroxyl functional group (–OH) and hydroxyls interact strongly with each other. Plus, when functional groups are more electronegative than atoms they attach to, the functional groups will become polar, and the otherwise nonpolar molecules containing these functional groups become polar and so become soluble in some aqueous environment.
Combining the names of functional groups with the names of the parent alkanes generates what is termed a systematic nomenclature for naming organic compounds. In traditional nomenclature, the first carbon atom after the carbon that attaches to the functional group is called the alpha carbon; the second, beta carbon, the third, gamma carbon, etc. If there is another functional group at a carbon, it may be named with the Greek letter, e.g., the gamma-amine in gamma-aminobutyric acid is on the third carbon of the carbon chain attached to the carboxylic acid group. IUPAC conventions call for numeric labeling of the position, e.g. 4-aminobutanoic acid. In traditional names various qualifiers are used to label isomers, for example, isopropanol (IUPAC name: propan-2-ol) is an isomer of n-propanol (propan-1-ol).List of androgen esters
This is a list of androgen esters, including esters (as well as ethers) of natural androgens like testosterone and dihydrotestosterone (DHT) and synthetic anabolic–androgenic steroids (AAS) like nandrolone (19-nortestosterone).List of corticosteroid esters
This is a list of corticosteroid esters, including esters of steroidal glucocorticoids and mineralocorticoids.List of estrogen esters
This is a list of estrogen esters, or ester prodrugs of estrogens. It includes esters, as well as ethers, of steroidal estrogens like estradiol, estrone, and estriol and of nonsteroidal estrogens like the stilbestrols diethylstilbestrol and hexestrol.List of progestogen esters
This is a list of progestogen esters, or esters of progestogens.Unlike the case of testosterone and estradiol, progesterone cannot be esterified as it lacks hydroxyl groups, so all progestogen esters, with the exception of esters of 17α-hydroxyprogesterone like hydroxyprogesterone caproate, are esters of progestins (synthetic progestogens) and are non-bioidentical. In addition, whereas all androgen and estrogen esters are prodrugs of the parent compound, only some and not all progestogen esters act as prodrugs. Esters of 17α-hydroxyprogesterone and 19-norprogesterone derivatives like hydroxyprogesterone caproate, medroxyprogesterone acetate, and nomegestrol acetate are active themselves and are not prodrugs, whereas esters of 19-nortestosterone derivatives like norethisterone acetate and norethisterone enanthate are not active themselves and are prodrugs.Methyl acetate
Methyl acetate, also known as MeOAc, acetic acid methyl ester or methyl ethanoate, is a carboxylate ester with the formula CH3COOCH3. It is a flammable liquid with a characteristically pleasant smell reminiscent of some glues and nail polish removers. Methyl acetate is occasionally used as a solvent, being weakly polar and lipophilic, but its close relative ethyl acetate is a more common solvent being less toxic and less soluble in water. Methyl acetate has a solubility of 25% in water at room temperature. At elevated temperature its solubility in water is much higher. Methyl acetate is not stable in the presence of strong aqueous bases or aqueous acids. Methyl acetate is not considered as a VOC.Organophosphate
Organophosphates (also known as phosphate esters) are a class of organophosphorus compounds with the general structure O=P(OR)3. They can be considered as esters of phosphoric acid. Like most functional groups organophosphates occur in a diverse range of forms, with important examples including key biomolecules such as DNA, RNA and ATP, as well as many insecticides, herbicides, and nerve agents.THC-O-phosphate
THC-O-phosphate is a water-soluble organophosphate ester derivative of THC, which functions as a metabolic prodrug for THC itself. It was invented in 1978 in an attempt to get around the poor water solubility of THC and make it easier to inject for the purposes of animal research into its pharmacology and mechanism of action. The main disadvantage of THC phosphate ester is the slow rate of hydrolysis of the ester link, resulting in delayed onset of action and lower potency than the parent drug. Pharmacologically, it parallels the action of psilocybin as a metabolic prodrug for psilocin.
THC phosphate ester is made by reacting THC with phosphoryl chloride using pyridine as a solvent, following by quenching with water to produce THC phosphate ester. In the original research the less active but more stable isomer Δ8THC was used, but the same reaction scheme could be used to make the phosphate ester of the more active isomer Δ9THC.