Isothiocyanate is the chemical group –N

Nitrogen

Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...

=C

Carbon

Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...

=S

Sulfur

Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

, formed by substituting sulfur

Sulfur

Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...

 for oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 in the isocyanate

Isocyanate

Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...

 group. Many natural isothiocyanates from plants are produced by enzymatic conversion of metabolites called glucosinolate

Glucosinolate

The glucosinolates are a class of organic compounds that contain sulfur and nitrogen and are derived from glucose and an amino acid. They occur as secondary metabolites of almost all plants of the order Brassicales , but also in the genus Drypetes .-Chemistry:Glucosinolates are water-soluble...

s. These natural isothiocyanates, such as allyl isothiocyanate

Allyl isothiocyanate

Allyl isothiocyanate is the organosulfur compound with the formula CH2CHCH2NCS. This colorless oil is responsible for the pungent taste of mustard, horseradish, and wasabi. This pungency and the lachrymatory effect of AITC is mediated through the TRPA1 and TRPV1 ion channels...

, are also known as mustard oil

Mustard oil

The term mustard oil is used for three different oils that are made from mustard seeds:*A fatty vegetable oil resulting from pressing the seeds,...

s. An artificial isothiocyanate, phenyl isothiocyanate, is used for amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 sequencing in the Edman degradation

Edman degradation

Edman degradation, developed by Pehr Edman, is a method of sequencing amino acids in a peptide. In this method, the amino-terminal residue is labeled and cleaved from the peptide without disrupting the peptide bonds between other amino acid residues....

.

Synthesis

General method for synthesis of isothiocyanates by reacting primary amine (e.g. aniline

Aniline

Aniline, phenylamine or aminobenzene is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is the prototypical aromatic amine. Being a precursor to many industrial chemicals, its main use is in the manufacture of precursors to polyurethane...

) with carbon disulphide in aqueous ammonia

Ammonia

Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

 resulting in precipitation of ammonium dithiocarbamate derivative, which then treated with lead nitrate to yield corresponding isothiocyanate derivative.
Another method relies on a tosyl chloride mediated decomposition of a dithiocarbamate salts that are generated in first step.
Isothiocyanates may also be accessed via the thermally-induced fragmentation reactions of 1,4,2-oxathiazoles.
This synthetic methodology has been appplied to a polymer-supported synthesis of isothiocyanates.

Reactions

In general, isothiocyanates act as electrophile

Electrophile

In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...

s with the carbon atom as the electrophilic center.

Biological activity

Isothiocyanates, such as phenethyl isothiocyanate (PEITC) and sulforaphane

Sulforaphane

Sulforaphane is an organosulfur compound that exhibits anticancer, antidiabetic, and antimicrobial properties in experimental models. It is obtained from cruciferous vegetables such as broccoli, Brussels sprouts or cabbages. The enzyme myrosinase transforms glucoraphanin, a glucosinolate, into...

, have been shown to inhibit carcinogenesis and tumorigenesis and as such are useful chemopreventive agents against the development and proliferation of cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s. They work on a variety of levels, the most notable one being the inhibition of carcinogenesis through inhibition of cytochrome P450 enzymes, which oxidize compounds such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons (PAHs) into more polar epoxy-diols, which can then cause mutation and induce cancer development. Phenethyl isothiocyanate (PEITC) has been shown to induce apoptosis

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 in certain cancer cell lines, and, in some cases, is even able to induce apoptosis in cells that are resistant to some currently used chemotherapeutic drugs, for example, in drug-resistant leukemia cells that produce the powerful apoptosis inhibitor protein Bcl-2

Bcl-2

Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...

. Furthermore, isothiocyanates have been the basis of a drug in development that replaces the sulfur bonds with selenium, with far stronger potency against melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

. Certain isothiocyanates have also been shown to bind to the mutated p53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

 proteins found in many types of tumors, causing an increase in the rate of cell death.

In foods

Vegetable foods with characteristic flavors due to isothiocyanates include wasabi

Wasabi

, also known as Japanese horseradish, is a member of the Brassicaceae family, which includes cabbages, horseradish, and mustard. Its root is used as a condiment and has an extremely strong flavor. Its hotness is more akin to that of a hot mustard rather than the capsaicin in a chili pepper,...

, horseradish

Horseradish

Horseradish is a perennial plant of the Brassicaceae family, which also includes mustard, wasabi, broccoli, and cabbages. The plant is probably native to south eastern Europe and the Arab World , but is popular around the world today...

, mustard

Mustard (condiment)

Mustard is a condiment made from the seeds of a mustard plant...

, radish

Radish

The radish is an edible root vegetable of the Brassicaceae family that was domesticated in Europe, in pre-Roman times. They are grown and consumed throughout the world. Radishes have numerous varieties, varying in size, color and duration of required cultivation time...

, Brussels sprout

Brussels sprout

The Brussels sprout is a cultivar of wild cabbage grown for its edible buds. The leafy green vegetables are typically 2.5–4 cm in diameter and look like miniature cabbages. The sprout is Brassica oleracea, in the "gemmifera" group of the family Brassicaceae...

s, watercress

Watercress

Watercresses are fast-growing, aquatic or semi-aquatic, perennial plants native from Europe to central Asia, and one of the oldest known leaf vegetables consumed by human beings...

, nasturtiums and caper

Caper

Capparis spinosa, the caper bush, is a perennial winter-deciduous species that bears rounded, fleshy leaves and large white to pinkish-white flowers. A caper is also the pickled bud of this plant...

s. These various species generate different isothiocyanates in different proportions, and so have different, but recognisably related, flavors. All these species are members of the Brassicales

Brassicales

The Brassicales are an order of flowering plants, belonging to the eurosids II group of dicotyledons under the APG II system. One character common to many members of the order is the production of glucosinolate compounds...

, an order which is characterised by the production of glucosinolate

Glucosinolate

The glucosinolates are a class of organic compounds that contain sulfur and nitrogen and are derived from glucose and an amino acid. They occur as secondary metabolites of almost all plants of the order Brassicales , but also in the genus Drypetes .-Chemistry:Glucosinolates are water-soluble...

s, and of the enzyme myrosinase

Myrosinase

Myrosinase is a family of enzymes involved in plant defense against herbivores. Their structure has been elucidated and is available.-Myrosinase activity:...

, which acts on glucosinolates resulting in the creation of isothiocyanates.