1,3-Dimethylbutylamine
The hydrochloride and citrate salts of DMBA has been identified as unapproved ingredients in some over-the-counter dietary supplements, in which it is used in an apparent attempt to circumvent bans on methylhexanamine. The U.S. Food and Drug Administration (FDA) considers any dietary supplement containing DMBA to be "adulterated". Despite the FDA's opposition, DMBA continues to be sold in the US.


1,3-Dimethylbutylamine
There are no known human safety studies on DMBA and its health effects are entirely unknown.


1,3-Dinitrobenzene
1,3-Dinitrobenzene is an organic compound with the formula C6H4(NO2)2. It is one of three isomers of dinitrobenzene. The compound is a yellow  solid that is soluble in organic solvents.


1,3-Dinitrobenzene, Preparation
1,3-Dinitrobenzene is accessible by nitration of nitrobenzene. The reaction proceeds under acid catalysis using sulfuric acid. The directing effect of the nitro group of nitrobenzene leads to 93% of the product resulting from nitration at the meta-position. The ortho- and para-products occur in only 6% and 1%, respectively.


1,3-Dinitrobenzene, Reactions
Reduction of 1,3-dinitrobenzene with sodium sulfide in aqueous solution leads to 3-nitroaniline. Further reduction with iron and hydrochloric acid (HCl) gives m-phenylenediamine.


1,3-Dioxane
1,3-Dioxane or m-dioxane is a chemical compound with the molecular formula C4H8O2. It is a saturated six-membered heterocycle with two oxygen atoms in place of carbon atoms at the 1- and 3- positions. The corresponding five-membered rings are known as 1,3-dioxolanes.


1,3-Dioxane
Like 1,3-dioxolanes, 1,3-dioxanes are acetals which can be used as protecting groups for carbonyl compounds. They are prepared from the reaction between carbonyl compounds (formaldehyde for the parent 1,3-dioxane) and 1,3-propanediol in the presence of Brönsted or Lewis acid catalysts.


1,3-Dioxetane
1,3-Dioxetane (1,3-dioxacyclobutane) is a heterocyclic organic compound with formula C2O2H4, whose backbone is a four-member ring of alternating oxygen and carbon atoms. It can be viewed as a dimer of formaldehyde (COH2).


1,3-Dioxetane
Derivatives of 1,3-dioxetane are rarely encountered as intermediates in the literature. Usually, they are prepared via [2+2] cycloadditions of two carbonyl compounds. Molecular orbital theory calculations suggest that they should be more stable than the 1,2-isomers, which are more intensively studied.


1,3-Dioxetanedione
The chemical compound 1,3-dioxetanedione, or 1,3-dioxacyclobutane-2,4-dione is a hypothetical oxide of carbon with formula C2O4. It can be considered a cyclic dimer of carbon dioxide (CO2) or as a double ketone of 1,3-dioxetane (1,3-dioxacyclobutane).


1,3-Dioxetanedione
Theoretical calculations indicate that the compound would be extremely unstable at room temperature (half-life of less than 1.1 μs); but may be stable at −196 °C.


1,3-Diphenylisobenzofuran
1,3-Diphenylisobenzofuran is a highly reactive diene that can scavenge unstable and short-lived dienophiles in a Diels-Alder reaction. It is furthermore used as a standard reagent for the determination of singlet oxygen, even in biological systems. Cycloadditions with 1,3-diphenylisobenzofuran and subsequent oxygen cleavage provide access to a variety of polyaromatics.


1,3-Diphenylisobenzofuran, Preparation
The first synthesis of 1,3-diphenylisobenzofuran was reported in 1905 by A. Guyot and J. Catel. Phenylmagnesium bromide was reacted with 3-phenylphthalide (the latter accessible from the methyl ester of 3-hydroxyphthalide with phenylboronic acid in 95% yield) to a lactol, which gives with mineral acids upon elimination of water 1,3-diphenylisobenzofuran with 87% yield.


1,3-Diphenylisobenzofuran, Preparation
The patent literature describes the preparation of 1,3-diphenylisobenzofuran by [4+2]cycloaddition of 1,3-butadiene and dibenzoylethylene (1,4-diphenyl-2-butene-1,4-dione, accessible from fumaryl chloride and benzene in the presence of aluminum chloride.). Dibenzoylethylene is predominantly present in the trans configuration but it can be converted into the needed cis configuration by simple heating.


1,3-Diphenylisobenzofuran, Preparation
The 4,5-dibenzoylcyclohexene formed previously is cyclized with acetic anhydride to the dihydroisobenzofuran. By bromine addition and hydrogen bromide elimination, 1,2-dibenzoylbenzene is formed and recyclized with zinc acetic acid to the final product 1,3-diphenylisobenzofuran. A publication from 1940 describes high yields for the individual stages of the extensive reaction sequence.


1,3-Diphenylisobenzofuran, Preparation
The (much cheaper) phthaloyl chloride gives also access to 1,2-dibenzoylbenzene via Friedel-Crafts acylation with benzene, which is reduced to 1,3-diphenylisobenzofuran in 78% yield using potassium borohydride.


1,3-Diphenylisobenzofuran, Preparation
The synthesis of 1,3-diarylisobenzofurans from 2-acylbenzaldehydes and boronic acids is less cumbersome and gives better yields,


1,3-Diphenylisobenzofuran, Preparation
just like the synthesis from salicylaldehydes via phenacylhydrazones, which undergo oxidation with lead(IV) acetate to give ortho-diketones, followed by the reaction with an aryl Grignard reagent.


1,3-Diphenylisobenzofuran, Properties
1,3-Diphenylisobenzofuran is a yellow, light- and air-sensitive, crystalline solid that is soluble in many organic solvents with a maximum absorption around 420 nm (in solution), which generates intense fluorescence. Fluorescence measurements can be performed  in DMF and DMSO because of the stability of 1,3-DPBF in those solvents. In chloroform and carbon tetrachloride the dissolved 1,3-diphenylisobenzofuran is rapidly photolyzed by attack of CHCl2 and CCl3 radicals, even in the absence of oxygen. [ 24 ]


1,3-Diphenylisobenzofuran, Properties
With ethanol, 1,3-diphenylisobenzofuran forms an orange-yellow, fluorescent solution. On  irradiation, it forms a colorless photodimer (upon with exclusion of oxygen), upon discolouration of the solution.


1,3-Diphenylisobenzofuran, Properties
The compound's refractive index is 1,6700 at 25 °C and 589 nm.


1,3-Diphenylisobenzofuran, Use, Reagent for determination of singlet oxygen
In the presence of methylene blue irradiated with red laser light, 1,3-diphenylisobenzofuran reacts with intermediate singlet oxygen 1O2, forming an unstable peroxide that decomposes into (colorless) 1,2-dibenzoylbenzene. The detection of singlet oxygen by 1,3-diphenylisobenzofuran is based on this reaction, even in biological systems. For biological systems, water-soluble derivatives of 1,3-diphenylisobenzofuran were developed. The singlet oxygen generation of Photosensitizers were monitored by photolysis of 1,3-diphenylisobenzofuran (DPBF).


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
Isobenzofurans like 1,3-diphenylisobenzofuran are among the most reactive Diels-Alder dienes known to date, and are useful for scavenging short-lived and unstable olefins and alkynes. The group led by Georg Wittig made important contributions to this topic.


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
With the unstable cyclohexyne, 1,3-diphenylisobenzofuran reacts to a tricyclic compound that gives a 9,10-diphenylcyclohexenonaphthalene after hydrogenation and hydrogen abstraction.


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
1,3-Diphenylisobenzofuran gives similarly with benzyne (dehydrobenzene) an oxygen-bridged anthracene (in 85% yield), which can be reduced with zinc to 9,10-diphenylanthracene (88% yield).


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
Cyclopropenone (which is unstable above its melting point of -29 °C) reacts quantitatively at room temperature with 1,3-diphenylisobenzofuran to form a Diels-Alder adduct, which is exclusively an exo isomer.


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
Dimethyl acetylenedicarboxylate reacts with 1,3-diphenylisobenzofuran as dienophile in 84% yield to yield the corresponding adduct.


1,3-Diphenylisobenzofuran, Use, Dienophile in Diels-Alder reactions
1,3-Diphenylisobenzofuran reacts also with heterocyclic dienophiles such as 3-sulfolene to the corresponding Diels-Alder adduct.


1,3-Diphenylisobenzofuran, Use, Molecular building block for polyaromatics
Polyaromatic hydrocarbons (PAHs) are of interest as precursors to graphite but also raise concern as ingredients of pollution. They have persistence and carcinogenicity. 1,3-diphenylisobenzofuran reacts quantitatively with acenaphthylene when heated to 160 °C to give 7,12-diphenylbenzo[k]fluoranthene.


1,3-Diphenylisobenzofuran, Use, Molecular building block for polyaromatics
The twice occurring Diels-Alder reaction of 1,3-diphenylisobenzofuran with p-benzoquinone yields almost quantitatively a product that can be reacted further with p-toluenesulfonic acid to give a pentacene derivative in 49% yield.


1,3-Diphenyltriazene
1,3-Diphenyltriazene is the organic compound with the formula PhN=N-N(H)Ph (Ph = C6H5). It is a prototypical triazene, i.e. a compound with the functional group RN=N-NR2. It is a pale yellow solid, prepared by the reaction of phenyldiazonium salts with aniline. It is a planar molecule. The N-N distances are 1.287 and 1.337 Å.


1,3-Diphenylurea
1,3-Diphenylurea is a phenylurea-type compound with the formula (PhNH)2CO (Ph = C6H5). It is a colorless solid that is prepared by transamidation of urea with aniline.


1,3-Diphenylurea
DPU is a cytokinin, a type of plant hormone that induces flower development. It occurs in coconut milk. The cytokinin effect of DPU is relatively low, but other more potent phenylurea-type cytokinins have been reported.


1,3-Dipolar cycloaddition
The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition (this term is often used to specifically describe the 1,3-dipolar cycloaddition between an organic azide and an alkyne to generate 1,2,3-triazole). 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. The dipolarophile is typically an alkene or alkyne, but can be other pi systems. When the dipolarophile is an alkyne, aromatic rings are generally produced.


1,3-Dipolar cycloaddition, Mechanistic overview
Originally two proposed mechanisms describe the 1,3-dipolar cycloaddition: first, the concerted pericyclic cycloaddition mechanism, proposed by Rolf Huisgen; and second, the stepwise mechanism involving a diradical intermediate, proposed by Firestone. After much debate, the former proposal is now generally accepted—the 1,3-dipole reacts with the dipolarophile in a concerted, often asynchronous, and symmetry-allowed π4s + π2s fashion through a thermal six-electron Huckel aromatic transition state. However, a few examples exist of a stepwise mechanism for the catalyst-free 1,3-dipolar cycloaddition reactions of thiocarbonyl ylides, and nitrile oxides


1,3-Dipolar cycloaddition, Mechanistic overview, Pericyclic mechanism
Huisgen investigated a series of cycloadditions between the 1,3-dipolar diazo compounds and various dipolarophilic alkenes. The following observations support the concerted pericyclic mechanism, and refute the stepwise diradical or the stepwise polar pathway.


1,3-Dipolar cycloaddition, Mechanistic overview, 1,3-Dipole
A 1,3-dipole is an organic molecule that can be represented as either an allyl-type or a propargyl/allenyl-type zwitterionic octet/sextet structures. Both types of 1,3-dipoles share four electrons in the π-system over three atoms. The allyl-type is bent whereas the propargyl/allenyl-type is linear in geometry. 1,3-Dipoles containing higher-row elements such as sulfur or phosphorus are also known, but are utilized less routinely.


1,3-Dipolar cycloaddition, Mechanistic overview, 1,3-Dipole
Resonance structures can be drawn to delocalize both negative and positive charges onto any terminus of a 1,3-dipole (see the scheme below). A more accurate method to describe the electronic distribution on a 1,3-dipole is to assign the major resonance contributor based on experimental or theoretical data, such as dipole moment measurements or computations. For example, diazomethane bears the largest negative character at the terminal nitrogen atom, while hydrazoic acid bears the largest negative character at the internal nitrogen atom.


1,3-Dipolar cycloaddition, Mechanistic overview, 1,3-Dipole
Consequently, this ambivalence means that the ends of a 1,3-dipole can be treated as both nucleophilic and electrophilic at the same time. The extent of nucleophilicity and electrophilicity at each end can be evaluated using the frontier molecular orbitals, which can be obtained computationally. In general, the atom that carries the largest orbital coefficient in the HOMO acts as the nucleophile, whereas that in the LUMO acts as the electrophile. The most nucleophilic atom is usually, but not always, the most electron-rich atom. In 1,3-dipolar cycloadditions, identity of the dipole-dipolarophile pair determines whether the HOMO or the LUMO character of the 1,3-dipole will dominate (see discussion on frontier molecular orbitals below).


1,3-Dipolar cycloaddition, Mechanistic overview, Dipolarophile
The most commonly used dipolarophiles are alkenes and alkynes. Heteroatom-containing dipolarophiles such as carbonyls and imines can also undergo 1,3-dipolar cycloaddition. Other examples of dipolarophiles include fullerenes and nanotubes, which can undergo 1,3-dipolar cycloaddition with azomethine ylide in the Prato reaction.


1,3-Dipolar cycloaddition, Mechanistic overview, Solvent effects
1,3-dipolar cycloadditions experience very little solvent effect because both the reactants and the transition states are generally non-polar. For example, the rate of reaction between phenyl diazomethane and ethyl acrylate or norbornene (see scheme below) changes only slightly upon varying solvents from cyclohexane to methanol.


1,3-Dipolar cycloaddition, Mechanistic overview, Solvent effects
Lack of solvent effects in 1,3-dipolar cycloaddition is clearly demonstrated in the reaction between enamines and dimethyl diazomalonate (see scheme below). The polar reaction, N-cyclopentenyl pyrrolidine nucleophilic addition to the diazo compound, proceeds 1,500 times faster in polar DMSO than in non-polar decalin. On the other hand, a close analog of this reaction, N-cyclohexenyl pyrrolidine 1,3-dipolar cycloaddition to dimethyl diazomalonate, is sped up only 41-fold in DMSO relative to decalin.


1,3-Dipolar cycloaddition, Frontier molecular orbital theory
1,3-Dipolar cycloadditions are pericyclic reactions, which obey the Dewar-Zimmerman rules and the Woodward–Hoffmann rules. In the Dewar-Zimmerman treatment, the reaction proceeds through a 5-center, zero-node, 6-electron Huckel transition state for this particular molecular orbital diagram. However, each orbital can be randomly assigned a sign to arrive at the same result. In the Woodward–Hoffmann treatment, frontier molecular orbitals (FMO) of the 1,3-dipole and the dipolarophile overlap in the symmetry-allowed π4s + π2s manner. Such orbital overlap can be achieved in three ways: type I, II and III. The dominant pathway is the one which possesses the smallest HOMO-LUMO energy gap.


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Type I
The dipole has a high-lying HOMO which overlaps with LUMO of the dipolarophile. A dipole of this class is referred to as a HOMO-controlled dipole or a nucleophilic dipole, which includes azomethine ylide, carbonyl ylide, nitrile ylide, azomethine imine, carbonyl imine and diazoalkane. These dipoles add to electrophilic alkenes readily. Electron-withdrawing groups (EWG) on the dipolarophile would accelerate the reaction by lowering the LUMO, while electron-donating groups (EDG) would decelerate the reaction by raising the HOMO. For example, the reactivity scale of diazomethane against a series of dipolarophiles is shown in the scheme below. Diazomethane reacts with the electron-poor ethyl acrylate more than a million times faster than the electron rich butyl vinyl ether.


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Type I
This type resembles the normal-electron-demand Diels-Alder reaction, in which the diene HOMO combines with the dienophile LUMO.


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Type II
HOMO of the dipole can pair with LUMO of the dipolarophile; alternatively, HOMO of the dipolarophile can pair with LUMO of the dipole. This two-way interaction arises because the energy gap in either direction is similar. A dipole of this class is referred to as a HOMO-LUMO-controlled dipole or an ambiphilic dipole, which includes nitrile imide, nitrone, carbonyl oxide, nitrile oxide, and azide. Any substituent on the dipolarophile would accelerate the reaction by lowering the energy gap between the two interacting orbitals; i.e., an EWG would lower the LUMO while an EDG would raise the HOMO. For example, azides react with various electron-rich and electron-poor dipolarophile with similar reactivities (see reactivity scale below).


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Type III
The dipole has a low-lying LUMO which overlaps with HOMO of the dipolarophile (indicated by red dashed lines in the diagram). A dipole of this class is referred to as a LUMO-controlled dipole or an electrophilic dipole, which includes nitrous oxide and ozone. EWGs on the dipolarophile decelerate the reaction, while EDGs accelerate the reaction. For example, ozone reacts with the electron-rich 2-methylpropene about 100,000 times faster than the electron-poor tetrachloroethene (see reactivity scale below).


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Type III
This type resembles the inverse electron-demand Diels-Alder reaction, in which the diene LUMO combines with the dienophile HOMO.


1,3-Dipolar cycloaddition, Frontier molecular orbital theory, Reactivity
Concerted processes such as the 1,3-cycloaddition require a highly ordered transition state (high negative entropy of activation) and only moderate enthalpy requirements. Using competition reaction experiments, relative rates of addition for different cycloaddition reactions have been found to offer general findings on factors in reactivity.


1,3-Dipolar cycloaddition, Stereospecificity
1,3-dipolar cycloadditions usually result in retention of configuration with respect to both the 1,3-dipole and the dipolarophile. Such high degree of stereospecificity is a strong support for the concerted over the stepwise reaction mechanisms. As mentioned before, many examples show that the reactions were stepwise, thus, presenting partial or no stereospecificity.


1,3-Dipolar cycloaddition, Stereospecificity, With respect to dipolarophile
cis-Substituents on the dipolarophilic alkene end up cis, and trans-substituents end up trans in the resulting five-membered cyclic compound (see scheme below).


1,3-Dipolar cycloaddition, Stereospecificity, With respect to dipole
Generally, the stereochemistry of the dipole is not of major concern because only few dipoles could form stereogenic centers, and resonance structures allow bond rotation which scrambles the stereochemistry. However, the study of azomethine ylides has verified that cycloaddition is also stereospecific with respect to the dipole component. Diastereopure azomethine ylides are generated by electrocyclic ring opening of aziridines, and then rapidly trapped with strong dipolarophiles before bond rotation can take place (see scheme below). If weaker dipolarophiles are used, bonds in the dipole have the chance to rotate, resulting in impaired cycloaddition stereospecificity.


1,3-Dipolar cycloaddition, Stereospecificity, With respect to dipole
These results altogether confirm that 1,3-dipolar cycloaddition is stereospecific, giving retention of both the 1,3-dipole and the dipolarophile.


1,3-Dipolar cycloaddition, Diastereoselectivity
When two or more stereocenters are generated during the reaction, diastereomeric transition states and products can be obtained. In the Diels-Alder cycloaddition, the endo diastereoselectivity due to secondary orbital interactions is usually observed. In 1,3-dipolar cycloadditions, however, two forces influence the diastereoselectivity: the attractive π-interaction (resembling secondary orbital interactions in the Diels-Alder cycloaddition) and the repulsive steric interaction. Unfortunately, these two forces often cancel each other, causing poor diastereoselection in 1,3-dipolar cycloaddition.


1,3-Dipolar cycloaddition, Diastereoselectivity
Examples of substrate-controlled diastereoselective 1,3-dipolar cycloadditions are shown below. First is the reaction between benzonitrile N-benzylide and methyl acrylate. In the transition state, the phenyl and the methyl ester groups stack to give the cis-substitution as the exclusive final pyrroline product. This favorable π-interaction offsets the steric repulsion between the phenyl and the methyl ester groups. Second is the reaction between nitrone and dihydrofuran. The exo-selectivity is achieved to minimize steric repulsion. Last is the intramolecular azomethine ylide reaction with alkene. The diastereoselectivity is controlled by the formation of a less strained cis-fused ring system.


1,3-Dipolar cycloaddition, Diastereoselectivity, Directed 1,3-dipolar cycloaddition
Trajectory of the cycloaddition can be controlled to achieve a diastereoselective reaction. For example, metals can chelate to the dipolarophile and the incoming dipole and direct the cycloaddition selectively on one face. The example below shows addition of nitrile oxide to an enantiomerically pure allyl alcohol in the presence of a magnesium ion. The most stable conformation of the alkene places the hydroxyl group above the plane of the alkene. The magnesium then chelates to the hydroxyl group and the oxygen atom of nitrile oxide. The cycloaddition thus comes from the top face selectively.


1,3-Dipolar cycloaddition, Diastereoselectivity, Directed 1,3-dipolar cycloaddition
Such diastereodirection has been applied in the synthesis of epothilones.


1,3-Dipolar cycloaddition, Regioselectivity
For asymmetric dipole-dipolarophile pairs, two regioisomeric products are possible. Both electronic/stereoelectronic and steric factors contribute to the regioselectivity of 1,3-dipolar cycloadditions.


1,3-Dipolar cycloaddition, Regioselectivity, Electronic/stereoelectronic effect
The dominant electronic interaction is the combination between the largest HOMO and the largest LUMO. Therefore, regioselectivity is governed by the atoms that bear the largest orbital HOMO and LUMO coefficients.


1,3-Dipolar cycloaddition, Regioselectivity, Electronic/stereoelectronic effect
For example, consider the cycloaddition of diazomethane to three dipolarophiles: methyl acrylate, styrene or methyl cinnamate. The carbon of diazomethane bears the largest HOMO, while the end olefinic carbons of methyl acrylate and styrene bear the largest LUMO. Hence, cycloaddition gives the substitution at the C-3 position regioselectively. For methyl cinnamate, the two substituents (Ph v.s. COOMe) compete at withdrawing electrons from the alkene. The carboxyl is the better electron-withdrawing group, causing the β-carbon to be most electrophilic. Thus, cycloaddition yields the carboxyl group on C-3 and the phenyl group on C-4 regioselectively.


1,3-Dipolar cycloaddition, Regioselectivity, Steric effect
Steric effects can either cooperate or compete with the aforementioned electronic effects. Sometimes steric effects completely outweighs the electronic preference, giving the opposite regioisomer exclusively.


1,3-Dipolar cycloaddition, Regioselectivity, Steric effect
For example, diazomethane generally adds to methyl acrylate to give 3-carboxyl pyrazoline. However, by putting more steric demands into the system, we start to observe the isomeric 4-carboxyl pyrazolines. The ratio of these two regioisomers depends on the steric demands. At the extreme, increasing the size from hydrogen to t-butyl shifts the regioselectivity from 100% 3-carboxyl to 100% 4-carboxyl substitution.


1,3-Dipolar cycloaddition, Synthetic applications
1,3-dipolar cycloadditions are important ways toward the synthesis of many important 5-membered heterocycles such as triazoles, furans, isoxazoles, pyrrolidines, and others. Additionally, some cycloadducts can be cleaved to reveal the linear skeleton, providing another route toward the synthesis of aliphatic compounds. These reactions are tremendously useful also because they are stereospecific, diastereoselective and regioselective. Several examples are provided below.


1,3-Dipolar cycloaddition, Synthetic applications, Nitrile oxides
1,3-dipolar cycloaddition with nitrile oxides is a widely used masked-aldol reaction. Cycloaddition between a nitrile oxide and an alkene yields the cyclic isoxazoline product, whereas the reaction with an alkyne yields the isoxazole. Both isoxazolines and isoxazoles can be cleaved by hydrogenation to reveal aldol-type β-hydroxycarbonyl or Claisen-type β-dicarbonyl products, respectively.


1,3-Dipolar cycloaddition, Synthetic applications, Nitrile oxides
Nitrile oxide-alkyne cycloaddition followed by hydrogenation was utilized in the synthesis of Miyakolide as illustrated in the figure below.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides
1,3-dipolar cycloaddition reactions have emerged as powerful tools in the synthesis of complex cyclic scaffolds and molecules for medicinal, biological, and mechanistic studies. Among them, [3+2] cycloaddition reactions involving carbonyl ylides have extensively been employed to generate oxygen-containing five-membered cyclic molecules.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
Ylides are regarded as positively charged heteroatoms connected to negatively charged carbon atoms, which include ylides of sulfonium, thiocarbonyl, oxonium, nitrogen, and carbonyl. Several methods exist for generating carbonyl ylides, which are necessary intermediates for generating oxygen-containing five-membered ring structures, for [3+2] cycloaddition reactions.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
One of the earliest examples of carbonyl ylide synthesis involves photocatalysis. Photolysis of diazotetrakis(trifluoromethyl)cyclopentadiene* (DTTC) in the presence of tetramethylurea can generate the carbonyl ylide by an intermolecular nucleophilic attack and subsequent aromatization of the DTTC moiety. This was isolated and characterized by X-ray crystallography due to the stability imparted by aromaticity, electron withdrawing trifluoromethyl groups, and the electron donating dimethylamine groups. Stable carbonyl ylide dipoles can then be used in [3+2] cycloaddition reactions with dipolarophiles.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
Another early example of carbonyl ylide synthesis by photocatalysis was reported by Olah et al. Dideuteriodiazomethane was photolysed in the presence of formaldehyde to generate the dideuterioformaldehyde carbonyl ylide.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
Carbonyl ylides can be synthesized by acid catalysis of hydroxy-3-pyrones in the absence of a metal catalyst. An initial tautomerization occurs, followed by elimination of the leaving group to aromatize the pyrone ring and to generate the carbonyl ylide. A cycloaddition reaction with a dipolarophile lastly forms the oxacycle. This approach is less widely employed due to its limited utility and requirement for pyrone skeletons.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
5-hydroxy-4-pyrones can also be used to synthesize carbonyl ylides by an intramolecular hydrogen transfer. After hydrogen transfer, the carbonyl ylide can then react with dipolarophiles to form oxygen-containing rings.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
Dihalocarbenes have also been employed to generate carbonyl ylides, exploiting the electron withdrawing nature of dihalocarbenes. Both phenyl(trichloromethyl)mercury and phenyl(tribromomethyl)mercury are sources dichlorocarbenes and dibromocarbenes, respectively. The carbonyl ylide can be generated upon reaction of the dihalocarbenes with ketones or aldehydes. However, the synthesis of α-halocarbonyl ylides can also undesirably lead to the loss of carbon monoxide and the generation of the deoxygenation product.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Preparation of carbonyl ylides for 1,3-dipolar cycloaddition reactions
A universal approach for generating carbonyl ylides involves metal catalysis of α-diazocarbonyl compounds, generally in the presence of dicopper or dirhodium catalysts. After release of nitrogen gas and conversion to the metallocarbene, an intermolecular reaction with a carbonyl group can generate the carbonyl ylide. Subsequent cycloaddition reaction with an alkene or alkyne dipolarophile can afford oxygen-containing five-membered rings. Popular catalysts that give modest yields towards synthesizing oxacycles include Rh2(OAc)4 and Cu(acac)2.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The universality and extensive use of 1,3-dipolar cycloaddition reactions mediated by metal catalysis of diazocarbonyl molecules, for synthesizing oxygen-containing five-membered rings, has spurred significant interest into its mechanism. Several groups have investigated the mechanism to expand the scope of synthetic molecules with respect to regio- and stereo-selectivity. However, due to the high turn over frequencies of these reactions, the intermediates and mechanism remains elusive. The generally accepted mechanism, developed by characterization of stable ruthenium-carbenoid complexes and rhodium metallocarbenes, involves an initial formation of a metal-carbenoid complex from the diazo compound. Elimination of nitrogen gas then affords a metallocarbene. An intramolecular nucleophilic attack by the carbonyl oxygen regenerates the metal catalyst and forms the carbonyl ylide. The carbonyl ylide can then react with an alkene or alkyne, such as dimethyl acetylenedicarboxylate (DMAD) to generate the oxacycle.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
However, it is uncertain whether the metallocarbene intermediate generates the carbonyl ylide. In some cases, metallocarbenes can also react directly with dipolarophiles. In these cases, the metallocarbene, such as the dirhodium(II)tetracarboxylate carbene, is stabilized through hyperconjugative metal enolate-type interactions. Subsequent 1,3-dipolar cycloaddition reaction occurs through a transient metal-complexed carbonyl ylide. Therefore, a persistent metallocarbene can influence the stereoselectivity and regioselectivity of the 1,3-dipolar cycloaddition reaction based on the stereochemistry and size of the metal ligands.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The mechanism of the 1,3-dipolar cycloaddition reaction between the carbonyl ylide dipole and alkynyl or alkenyl dipolarophiles has been extensively investigated with respect to regioselectivity and stereoselectivity. As symmetric dipolarophiles have one orientation for cycloaddition, only one regioisomer, but multiple stereoisomers can be obtained. On the contrary, unsymmetric dipolarophiles can have multiple regioisomers and stereoisomers. These regioisomers and stereoisomers may be predicted based on frontier molecular orbital (FMO) theory, steric interactions, and stereoelectronic interactions.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
Regioselectivity of 1,3-dipolar cycloaddition reactions between carbonyl ylide dipoles and alkynyl or alkenyl dipolarophiles is essential for generating molecules with defined regiochemistry. FMO theory and analysis of the HOMO-LUMO energy gaps between the dipole and dipolarophile can rationalize and predict the regioselectivity of experimental outcomes. The HOMOs and LUMOs can belong to either the dipole or dipolarophile, for which HOMOdipole-LUMOdipolarophile or HOMOdipolarophile-LUMOdipole interactions can exist. Overlap of the orbitals with the largest coefficients can ultimately rationalize and predict results.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The archetypal regioselectivity of the 1,3-dipolar cycloaddition reaction mediated by carbonyl ylide dipoles has been examined by Padwa and coworkers. Using a Rh2(OAc)4 catalyst in benzene, diazodione underwent a 1,3-dipolar cycloaddition reaction with methyl propiolate and methyl propargyl ether. The reaction with methyl propiolate affords two regioisomers with the major resulting from the HOMOdipole-LUMOdipolarophile interaction, which has the largest coefficients on the carbon proximal to the carbonyl group of the carbonyl ylide and on the methyl propiolate terminal alkyne carbon. The reaction with methyl propargyl ether affords one regioisomer resulting from the HOMOdipolarophile-LUMOdipole interaction, which has largest coefficients on the carbon distal to the carbonyl group of the carbonyl ylide and on the methyl propargyl ether terminal alkyne carbon.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
Regioselectivities of 1,3-dipolar cycloaddition reactions mediated by metal catalysis of diazocarbonyl compounds may also be influenced by the metal through formation of stable metallocarbenes. Stabilization of the metallocarbene, via metal enolate-type interactions, will prevent the formation of carbonyl ylides, resulting in a direct reaction between the metallocarbene dipole and an alkynyl or alkenyl dipolarophile (see image of The dirhodium(II)tetracarboxylate metallocarbene stabilized by πC-Rh→πC=O hyperconjugation.). In this situation, the metal ligands will influence the regioselectivity and stereoselectivity of the 1,3-dipolar cycloaddition reaction.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The stereoselectivity of 1,3-dipolar cycloaddition reactions between carbonyl ylide dipoles and alkenyl dipolarophiles has also been closely examined. For alkynyl dipolarophiles, stereoselectivity is not an issue as relatively planar sp2 carbons are formed, while regioselectivity must be considered (see image of the Products of the 1,3-Dipolar Cycloaddition Reaction Between Carbonyl Ylide Dipoles and Alkenyl or Alkynyl Dipolarophiles). However, for alkenyl dipolarophiles, both regioselectivity and stereoselectivity must be considered as sp3 carbons are generated in the product species.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
1,3-dipolar cycloaddition reactions between carbonyl ylide dipoles and alkenyl dipolarophiles can generate diastereomeric products. The exo product is characterized with dipolarophile substituents being cis to the ether bridge of the oxacycle. The endo product is characterized with the dipolarophile substituents being trans to the ether bridge of the oxacycle. Both products can be generated through pericyclic transitions states involving concerted synchronous or concerted asynchronous processes.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
One early example conferred stereoselectivity in terms of endo and exo products with metal catalysts and Lewis acids. Reactions with just the metal catalyst Rh2(OAc)4 prefer the exo product while reactions with the additional Lewis acid Yb(OTf)3 prefer the endo product. The endo selectivity observed for Lewis acid cycloaddition reactions is attributed to the optimized orbital overlap of the carbonyl π systems between the dipolarophile coordinated by Yb(Otf)3 (LUMO) and the dipole (HOMO). After many investigations, two primary approaches for influencing the stereoselectivity of carbonyl ylide cycloadditions have been developed that exploit the chirality of metal catalysts and Lewis acids.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The first approach employs chiral metal catalysts to modulate the endo and exo stereoselectivity. The chiral catalysts, in particular Rh2[(S)-DOSP]4 and Rh2[(S)-BPTV]4 can induce modest asymmetric induction and was used to synthesize the antifungal agent pseudolaric acid A. This is a result of the chiral metal catalyst remaining associated with the carbonyl ylide during the cycloaddition, which confers facial selectivity. However, the exact mechanisms are not yet fully understood.


1,3-Dipolar cycloaddition, Synthetic applications, Carbonyl ylides, Mechanism of the 1,3-dipolar cycloaddition reaction mediated by metal catalysis of diazocarbonyl compounds
The second approach employs a chiral Lewis acid catalyst to induce facial stereoselectivity after the generation of the carbonyl ylide using an achiral metal catalyst. The chiral Lewis acid catalyst is believed to coordinate to the dipolarophile, which lowers the LUMO of the dipolarophile while also leading to enantioselectivity.


1,3-Dipolar cycloaddition, Synthetic applications, Azomethine ylides
1,3-Dipolar cycloaddition between an azomethine ylide and an alkene furnishes an azacyclic structure, such as pyrrolidine. This strategy has been applied to the synthesis of spirotryprostatin A.


1,3-Dipolar cycloaddition, Synthetic applications, Ozone
Ozonolysis is a very important organic reaction. Alkenes and alkynes can be cleaved by ozonolysis to give aldehyde, ketone or carboxylic acid products.


1,3-Dipolar cycloaddition, Biological applications
The 1,3-dipolar cycloaddition between organic azides and terminal alkynes (i.e., the Huisgen cycloaddition) has been widely utilized for bioconjugation.


1,3-Dipolar cycloaddition, Biological applications, Copper catalysis
The Huisgen reaction generally does not proceed readily under mild conditions. Meldal et al. and Sharpless et al. independently developed a copper(I)-catalyzed version of the Huisgen reaction, CuAAC (for Copper-catalyzed Azide-Alkyne Cycloaddition), which proceeds very readily in mild, including physiological, conditions (neutral pH, room temperature and water solution). This reaction is also bioorthogonal: azides and alkynes are both generally absent from biological systems and therefore these functionalities can be chemoselectively reacted even in the cellular context. They also do not react with other functional groups found in nature, so they do not perturb biological systems. The reaction is so versatile that it is termed the "Click" chemistry. Although copper(I) is toxic, many protective ligands have been developed to both reduce cytotoxicity and improve rate of CuAAC, allowing it to be used in in vivo studies.


1,3-Dipolar cycloaddition, Biological applications, Copper catalysis
For example, Bertozzi et al. reported the metabolic incorporation of azide-functionalized saccharides into the glycan of the cell membrane, and subsequent labeling with fluorophore-alkyne conjugate. The now fluorescently labeled cell membrane can be imaged under the microscope.


1,3-Dipolar cycloaddition, Biological applications, Strain-promoted cycloaddition
To avoid toxicity of copper(I), Bertozzi et al. developed the strain-promoted azide-alkyne cycloaddition (SPAAC) between organic azide and strained cyclooctyne. The angle distortion of the cyclooctyne helps to speed up the reaction by both reducing the activation strain and enhancing the interactions, thereby enabling it to be used in physiological conditions without the need for the catalyst.


1,3-Dipolar cycloaddition, Biological applications, Strain-promoted cycloaddition
For instance, Ting et al. introduced an azido functionality onto specific proteins on the cell surface using a ligase enzyme. The azide-tagged protein is then labeled with cyclooctyne-fluorophore conjugate to yield a fluorescently labeled protein.


1,3-Dithietane
1,3-Dithietane is a dithietane. It is a colorless, crystalline, unpleasant-smelling solid. It was first prepared in 1976 by the reaction of bis(chloromethyl) sulfoxide with sodium sulfide to give  1,3-dithietane 1-oxide, followed by THF-borane reduction.


1,3-Dithietane
Examples of compounds bearing this functional group include the antibiotic Cefotetan and the pesticide Fosthietan.


1,3-Dithiole
In organosulfur chemistry, 1,3-dithioles are a class of heterocycles based on the parent compound 1,3-dithiacyclopentene (also known as 1,3-dithiole). The ligand dmit2- is a 1,3-dithiole. Heating solutions of Na2dmit gives the isomeric disulfide, a 1,2-dithiole.


1,3-Indandione
1,3-Indandione (sometimes simply indanedione) is an organic compound with the molecular formula C9H6O2. Chemically, it is a β-diketone on an indane framework. In standard conditions it is referred to in different sources as either a colorless or yellowish, green, or (most commonly) yellow solid.


1,3-Indandione, Structural properties
In the solid state, 1,3-indandione occurs as a diketone; in water, it is partially (~2%) enolized. The enolate anion exhibits significant delocalization, and the highest electron density is on the second carbon. This explains many of chemical properties of the compound.


1,3-Indandione, Preparation
1,3-Indandione can be prepared by decarboxylation of the sodium salt of 2-ethoxycarbonyl-1,3-indandione, which itself is obtained by Claisen condensation of ethyl acetate and dimethyl phthalate.


1,3-Indandione, Chemical properties
The carbon at the C-2 position is alpha to both carbonyls, and thus can act as a nucleophile. It undergoes self-aldol condensation quite easily, resulting in bindone.


1,3-Indandione, Chemical properties
One or both carbonyl groups can be reduced to alcohol groups or methylene groups, depending on the method used.


1,3-Propane sultone
1,3-Propane sultone is the organosulfur compound with the formula (CH2)3SO3. It is a cyclic sulfonate ester, a class of compounds called sultones. It is a readily melting colorless solid.


1,3-Propane sultone, Synthesis
It may be prepared by the acid catalyzed reaction of allyl alcohol and sodium bisulfite.


1,3-Propane sultone, Reactions
1,3-propane sultone is an activated ester and is susceptible to nucleophilic attack. It hydrolyzes to the hydroxysulfonic acid.


1,3-Propane sultone, Reactions
It has been used in the synthesis of specialist surfactants, such as CHAPS detergent.


1,3-Propane sultone, Safety
Typical of activated esters, 1,3-propane sultone is an alkylating agent. 1,3-Propane sultone is toxic, carcinogenic, mutagenic, and teratogenic.


1,3-Propanediol
1,3-Propanediol is the organic compound with the formula CH2(CH2OH)2. This 3-carbon diol is a colorless viscous liquid that is miscible with water.


1,3-Propanediol, Products
It is mainly used as a building block in the production of polymers such as polytrimethylene terephthalate.


1,3-Propanediol, Products
1,3-Propanediol can be formulated into a variety of industrial products including composites, adhesives, laminates, coatings, moldings, aliphatic polyesters, copolyesters. It is also a common solvent. It is used as an antifreeze and as a component in wood paint.


1,3-Propanediol, Production
1,3-Propanediol is mainly produced by the hydration of acrolein. An alternative route involves the hydroformylation of ethylene oxide to form 3-hydroxypropionaldehyde. The aldehyde is subsequently hydrogenated to give 1,3-propanediol. Biotechnological routes are also known.


1,3-Propanediol, Safety
1,3-Propanediol does not appear to pose a significant hazard via inhalation of either the vapor or a vapor/aerosol mixture.


1,3-Propanedisulfonic acid
1,3-Propanedisulfonic acid is a sulfonic acid containing two sulfonate units. Its salts are called eprodisates and have been evaluated as a protector of renal function in AA amyloidosis.


1,3-Thiazepine
1,3-Thiazepine is a thiazepine, which is a seven-membered heterocyclic chemical compound containing nitrogen and sulfur.


1,3-Thiazepine
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1,3-alpha-L-fucosidase
In enzymology, a 1,3-alpha-L-fucosidase (EC ) is an enzyme that catalyzes the chemical reaction of cleaving the 1,3-linkages between alpha-L-fucose and N-acetylglucosamine residues in glycoproteins.


1,3-alpha-L-fucosidase
This enzyme belongs to the family of hydrolases, specifically those glycosidases that hydrolyse O- and S-glycosyl compounds. The systematic name of this enzyme class is 3-alpha-L-fucosyl-N-acetylglucosaminyl-glycoprotein fucohydrolase. This enzyme is also called almond emulsin fucosidase I. This enzyme participates in the degradation of glycan structures.


1,3-beta-D-glucan phosphorylase
In enzymology, a 1,3-beta-D-glucan phosphorylase (EC ) is an enzyme that catalyzes the chemical reaction


1,3-beta-D-glucan phosphorylase
Thus, the two substrates of this enzyme are (1,3-beta-D-glucosyl)n and phosphate, whereas its two products are (1,3-beta-D-glucosyl)n-1 and alpha-D-glucose 1-phosphate.


1,3-beta-D-glucan phosphorylase
This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. The systematic name of this enzyme class is 1,3-beta-D-glucan:phosphate alpha-D-glucosyltransferase. Other names in common use include laminarin phosphoryltransferase, 1,3-beta-D-glucan:orthophosphate glucosyltransferase, and laminarin phosphoryltransferase.


1,3-beta-galactosyl-N-acetylhexosamine phosphorylase
In enzymology, a 1,3-beta-galactosyl-N-acetylhexosamine phosphorylase (EC ) is an enzyme that catalyzes the chemical reaction


1,3-beta-galactosyl-N-acetylhexosamine phosphorylase
Thus, the two substrates of this enzyme are beta-D-galactopyranosyl-(1->3)-N-acetyl-D-glucosamine and phosphate, whereas its two products are alpha-D-galactopyranose 1-phosphate and N-acetyl-D-glucosamine.


1,3-beta-galactosyl-N-acetylhexosamine phosphorylase
This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. The systematic name of this enzyme class is beta-D-galactopyranosyl-(1->3)-N-acetyl-D-hexosamine:phosphate galactosyltransferase.


1,3-beta-oligoglucan phosphorylase
In enzymology, a 1,3-beta-oligoglucan phosphorylase (EC ) is an enzyme that catalyzes the chemical reaction


1,3-beta-oligoglucan phosphorylase
Thus, the two substrates of this enzyme are (1,3-beta-D-glucosyl)n and phosphate, whereas its two products are (1,3-beta-D-glucosyl)n-1 and alpha-D-glucose 1-phosphate.


1,3-beta-oligoglucan phosphorylase
This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. The systematic name of this enzyme class is 1,3-beta-D-oligoglucan:phosphate alpha-D-glucosyltransferase. Other names in common use include beta-1,3-oligoglucan:orthophosphate glucosyltransferase II, and beta-1,3-oligoglucan phosphorylase.


1,3-dipole
In organic chemistry, a 1,3-dipolar compound or 1,3-dipole is a dipolar compound with delocalized electrons and a separation of charge over three atoms. They are reactants in 1,3-dipolar cycloadditions.


1,3-dipole
In fact, the dipole has at least one resonance structure with positive and negative charges having a 1,3 relationship which can generally be denoted as a+−b−c−{\displaystyle {\ce {a^+ - b - c-}}} where a may be a carbon, oxygen or nitrogen, b may be nitrogen or oxygen and c may be a carbon, oxygen or nitrogen.


1,3-propanediol dehydrogenase
In enzymology, a 1,3-propanediol dehydrogenase (EC ) is an enzyme that catalyzes the chemical reaction


1,3-propanediol dehydrogenase
Thus, the two substrates of this enzyme are propane-1,3-diol and NAD+, whereas its 3 products are 3-hydroxypropanal, NADH, and H+.


1,3-propanediol dehydrogenase
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is propane-1,3-diol:NAD+ 1-oxidoreductase. Other names in common use include 3-hydroxypropionaldehyde reductase, 1,3-PD:NAD+ oxidoreductase, 1,3-propanediol:NAD+ oxidoreductase, and 1,3-propanediol dehydrogenase. This enzyme participates in ether lipid metabolism as a step in glycerolipid biosynthesis.


1,4,2-Dithiazole
1,4,2-Dithiazole is a heterocyclic compound consisting of an unsaturated five-membered ring containing two carbon atoms, one nitrogen atom, and two sulfur atoms. 1,4,2-Dithiazole compounds may be formed by the reaction of nitrile sulfide (formed by the thermolysis of oxathiazolone) with various reactive species; for instance thiocarbonyls via a 1,3-dipolar cycloaddition reaction. These compounds may be protonated by strong acids to give synthetically useful aromatic cations.


1,4,6-Androstatriene-3,17-dione
1,4,6-Androstatriene-3,17-dione (ATD) is a potent irreversible aromatase inhibitor that inhibits estrogen biosynthesis by permanently binding and inactivating aromatase in adipose and peripheral tissue. It is used to control estrogen synthesis.


1,4,6-Androstatriene-3,17-dione
ATD was present in some over-the-counter bodybuilding supplements until 2009, as well as Topical ATD solutions that work transdermally. The product was developed and commercialized in the dietary supplement market place by industry journeyman Bruce Kneller, who holds a United States Patent for use of the compound and related compounds (#7,939,517) and Gaspari Nutrition. ATD has many names in sports supplements including: 1,4,6 etiollochan-dione, 3, 17-keto-etiochol-triene, androst-1,4,6-triene-3,17-dione and many others. These all refer to CAS# 633-35-2.


1,4,6-Androstatriene-3,17-dione
ATD may cause a positive test for the anabolic steroid Boldenone, of which it is a possible metabolite and production contaminant. ATD is also prohibited in amateur and professional sports which forbids aromatase inhibitors.


1,4,7-Triazacyclononane
1,4,7-Triazacyclononane, known as "TACN" which is pronounced "tack-en," is an aza-crown ether with the formula (C2H4NH)3. TACN is derived, formally speaking, from cyclononane by replacing three equidistant CH2 groups with NH groups. TACN is one of the oligomers derived from aziridine, C2H4NH. Other members of the series include piperazine, C4H8(NH)2, and the cyclic tetramer 1,4,7,10-tetraazacyclododecane.


1,4,7-Triazacyclononane, Synthesis
The ligand is prepared from diethylene triamine as follows by macrocyclization using ethyleneglycol ditosylate.


1,4,7-Triazacyclononane, Coordination chemistry
TACN is a popular tridentate ligand. It is threefold symmetric and binds to one face of an octahedron of metalloids and transition metals. The (TACN)M unit is kinetically inert, allowing further synthetic transformations on the other coordination sites. A bulky analogue of TACN, is the N,N',N"-trimethylated analogue trimethyltriazacyclononane.


1,4,7-Trimethyl-1,4,7-triazacyclononane
1,4,7-Trimethyl-1,4,7-triazacyclononane is the aza-crown ether with the formula (CH2CH2NCH3)3. This colorless liquid is the N-methylated derivative of triazacyclononane (TACN), a face-capping tridentate ligand that is popular in coordination chemistry.


1,4,7-Trimethyl-1,4,7-triazacyclononane
Although TACN is known for forming 2:1 "sandwich" complexes with many metal ions, corresponding 2:1 complexes of Me3TACN are only known for Ag+, Na+, and K+. This effect is mainly due to the greater bulk of Me3TACN, which requires ions with a larger ionic radius to accommodate two ligands.


1,4,7-Trimethyl-1,4,7-triazacyclononane
Several related derivatives have been prepared with diverse substituents on nitrogen.


1,4,7-Trithiacyclononane
1,4,7-Trithiacyclononane, also called 9-ane-S3, is the heterocyclic compound with the formula (CH2CH2S)3. This cyclic thioether is most often encountered as a tridentate ligand in coordination chemistry.


1,4,7-Trithiacyclononane
9-ane-S3 forms complexes with many metal ions, including those considered hard, such as copper(II) and iron(II). Most of its complexes have the formula [M(9-ane-S3)2]2+ and are octahedral. The point group of [M(9-ane-S3)2]2+ is S6.


1,4,7-Trithiacyclononane, Synthesis
This compound was first reported in 1977, and the current synthesis entails the assembly within the coordination sphere of a metal ion followed by decomplexation:


1,4,7-Trithiacyclononane, Related ligands
1,4,7-Trithiacyclononane is one of several thia crown ethers, analogues of crown ethers with S in place of O. They exhibit affinities for transition metals. Another thia crown ligan are the tetradentate 14-ane-S4 and the hexadentate 18-ane-S6.


1,4-Benzodioxine
1,4-Benzodioxine, in chemistry, especially organic chemistry, is an aromatic ring.


1,4-Benzoquinone
1,4-Benzoquinone, commonly known as para-quinone, is a chemical compound with the formula C6H4O2. In a pure state, it forms bright-yellow crystals with a characteristic irritating odor, resembling that of chlorine, bleach, and hot plastic or formaldehyde. This six-membered ring compound is the oxidized derivative of 1,4-hydroquinone. The molecule is multifunctional: it exhibits properties of a ketone, being able to form oximes; an oxidant, forming the dihydroxy derivative; and an alkene, undergoing addition reactions, especially those typical for α,β-unsaturated ketones. 1,4-Benzoquinone is sensitive toward both strong mineral acids and alkali, which cause condensation and decomposition of the compound.


1,4-Benzoquinone, Preparation
1,4-Benzoquinone is prepared industrially by oxidation of hydroquinone, which can be obtained by several routes. One route involves oxidation of diisopropylbenzene and the Hock rearrangement. The net reaction can be represented as follows:


1,4-Benzoquinone, Preparation
The reaction proceeds via the bis(hydroperoxide) and the hydroquinone. Acetone is a coproduct.


1,4-Benzoquinone, Preparation
Another major process involves the direct hydroxylation of phenol by acidic hydrogen peroxide:C6H5OH  +  H2O2   →   C6H4(OH)2  +  H2OBoth hydroquinone and catechol are produced. Subsequent oxidation of the hydroquinone gives the quinone.


1,4-Benzoquinone, Preparation
Quinone was originally prepared industrially by oxidation of aniline, for example by manganese dioxide. This method is mainly practiced in PRC where environmental regulations are more relaxed.


1,4-Benzoquinone, Preparation
Oxidation of hydroquinone is facile. One such method makes use of hydrogen peroxide as the oxidizer and iodine or an iodine salt as a catalyst for the oxidation occurring in a polar solvent; e.g. isopropyl alcohol.


1,4-Benzoquinone, Preparation
When heated to near its melting point, 1,4-benzoquinone sublimes, even at atmospheric pressure, allowing for an effective purification. Impure samples are often dark-colored due to the presence of quinhydrone, a dark green 1:1 charge-transfer complex of quinone with hydroquinone.


1,4-Benzoquinone, Structure and redox
Benzoquinone is a planar molecule with localized, alternating C=C, C=O, and C–C bonds. Reduction gives the semiquinone anion C6H4O2−}, which adopts a more delocalized structure. Further reduction coupled to protonation gives the hydroquinone, wherein the C6 ring is fully delocalized.


1,4-Benzoquinone, Reactions and applications
Quinone is mainly used as a precursor to hydroquinone, which is used in photography and rubber manufacture as a reducing agent and antioxidant. Benzoquinonium is a skeletal muscle relaxant, ganglion blocking agent that is made from benzoquinone.


1,4-Benzoquinone, Reactions and applications, Organic synthesis
It is used as a hydrogen acceptor and oxidant in organic synthesis. 1,4-Benzoquinone serves as a dehydrogenation reagent. It is also used as a dienophile in Diels Alder reactions.


1,4-Benzoquinone, Reactions and applications, Organic synthesis
Benzoquinone reacts with acetic anhydride and sulfuric acid to give the triacetate of hydroxyquinol. This reaction is called the Thiele reaction or Thiele–Winter reaction after Johannes Thiele, who first described it in 1898, and after Ernst Winter, who further described its reaction mechanism in 1900. An application is found in this step of the total synthesis of Metachromin A:


1,4-Benzoquinone, Reactions and applications, Organic synthesis
Benzoquinone is also used to suppress double-bond migration during olefin metathesis reactions.


1,4-Benzoquinone, Reactions and applications, Organic synthesis
An acidic potassium iodide solution reduces a solution of benzoquinone to hydroquinone, which can be reoxidized back to the quinone with a solution of silver nitrate.


1,4-Benzoquinone, Reactions and applications, Organic synthesis
Due to its ability to function as an oxidizer, 1,4-benzoquinone can be found in methods using the Wacker-Tsuji oxidation, wherein a palladium salt catalyzes the conversion of an alkene to a ketone. This reaction is typically carried out using pressurized oxygen as the oxidizer, but benzoquinone can sometimes preferred. It is also used as a reagent in some variants on Wacker oxidations.


1,4-Benzoquinone, Reactions and applications, Organic synthesis
1,4-Benzoquinone is used in the synthesis of Bromadol and related analogs.


1,4-Benzoquinone, Related 1,4-benzoquinones
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a stronger oxidant and dehydrogenation agent than 1,4-benzoquinone. Chloranil 1,4-C6Cl4O2 is another potent oxidant and dehydrogenation agent. Monochloro-p-benzoquinone is yet another but milder oxidant.


1,4-Benzoquinone, Metabolism
1,4-Benzoquinone is a toxic metabolite found in human blood and can be used to track exposure to benzene or mixtures containing benzene and benzene compounds, such as petrol. The compound can interfere with cellular respiration, and kidney damage has been found in animals receiving severe exposure. It is excreted in its original form and also as variations of its own metabolite, hydroquinone.


1,4-Benzoquinone, Safety
1,4-Benzoquinone is able to stain skin dark brown, cause erythema (redness, rashes on skin) and lead on to localized tissue necrosis. It is particularly irritating to the eyes and respiratory system. Its ability to sublime at commonly encountered temperatures allows for a greater airborne exposure risk than might be expected for a room-temperature solid. IARC has found insufficient evidence to comment on the compound's carcinogenicity, but has noted that it can easily pass into the bloodstream and that it showed activity in depressing bone marrow production in mice and can inhibit protease enzymes involved in cellular apoptosis.


1,4-Bis(diphenylphosphino)butane
1,4-Bis(diphenylphosphino)butane (dppb) is an organophosphorus compound with the formula (Ph2PCH2CH2)2. It is less commonly used in coordination chemistry than other diphosphine ligands such as dppe. It is a white solid that is soluble in organic solvents.


1,4-Bis(diphenylphosphino)butane, Coordination complexes
Nickel complexes in which the ligand is bidentate or monodentate are known. Palladium complexes containing dppb are used in a variety of catalytic reactions. The ligand's natural bite angle is 94° in its bidentate coordination mode.


1,4-Butane sultone
1,4-butane sultone is a six-membered δ-sultone and the cyclic ester of 4-hydroxybutanesulfonic acid. As a sulfo-alkylating agent, 1,4-butanesultone is used to introduce the sulfobutyl group (–(CH2)4–SO3−) into hydrophobic compounds possessing nucleophilic functional groups, for example hydroxy groups (as in the case of β-cyclodextrin) or amino groups (as in the case of polymethine dyes). In such, the sulfobutyl group is present as neutral sodium salt and considerably increases the water solubility of the derivatives.


1,4-Butane sultone, Preparation
A lab scale synthesis of 1,4-butanesultone starts from 4,4'-dichlorodibutyl ether (accessible from tetrahydrofuran treated with phosphorus oxychloride and concentrated sulfuric acid), which reacts with sodium sulfite forming the corresponding 4,4'-butanedisulfonic disodium salt. By passing it through an acidic ion exchanger, the disodium salt is converted into the disulphonic acid which forms two molecules of 1,4-butanesultone at elevated temperature and reduced pressure under elimination of water. The yields obtained range from 72 to 80%.


1,4-Butane sultone, Preparation
Starting from 4-chlorobutan-1-ol (from tetrahydrofuran and hydrogen chloride in 54 to 57% yield), the sodium salt of 4-hydroxybutan-1-sulfonic acid is obtained with sodium sulfite. This salt is converted with strong acids (such as hydrochloric acid) into the very hygroscopic 4-hydroxybutanesulfonic acid and cyclized to 1,4-butanesultone under elimination of water.


1,4-Butane sultone, Preparation
The cyclization of 4-hydroxybutanesulfonic acid in aqueous solution proceeds particularly efficiently when heated with high-boiling, water-immiscible solvents (for example 1,2-dichlorobenzene or diethylbenzene, both boiling at about 180 °C) in which 1,4-butane-sultone dissolves and is thereby protected from hydrolysis in the aqueous medium. 1,4-butanesultone is obtained in yields of up to 99% upon reflux within one hour.


1,4-Butane sultone, Preparation
The vacuum distillation of the sodium salt of 4-hydroxybutanesulfonic acid leads in the presence of concentrated sulfuric acid directly to 1,4-butanesultone. The sodium salt of 4-chlorobutane-1-sulfonic acid, which is obtained from 1,4-dichlorobutane with sodium sulfite, can also be cyclized to 1,4-butanesultone by heating to 180-250 °C.


1,4-Butane sultone, Preparation
The free-radical initiated sulfochlorination of 1-chlorobutane leads to a mixture of positionally isomeric sulfochlorides and chlorination products and is therefore not suitable for the direct preparation of 1,4-butanesultone.


1,4-Butane sultone, Properties
1,4-butanesultone is a viscous, clear, colorless and odorless liquid which reacts in boiling water (to 4-hydroxybutanesulfonic acid) and alcohols (to 4-alkoxybutanesulfonic acid) and dissolves in many organic solvents. At temperatures below the melting point, the compound crystallizes giving "large, magnificent plates". [ 3] Compared to the homologous γ-sultone 1,3-propanesultone, 1,4-butanesultone is significantly less reactive as alkylating agent, but classified as mutagenic and carcinogenic.


1,4-Butane sultone, Applications, Sulfobetaines
1,4-butanesultone reacts smoothly with nucleophiles such as ammonia to form the corresponding zwitterionic, usually very water-soluble sulfobutylbetaines.


1,4-Butane sultone, Applications, Sulfobetaines
Sulfobetaines with longer alkyl chains (CnH2n+1 mit n > 10) show interesting properties as surface-active compounds (surfactants, detergents) with antimicrobial properties.


1,4-Butane sultone, Applications, Sulfobetaines
In the reaction of  N-N-butylimidazole with 1,4-Butansultone in Toluene in a 98% yield is formed 1-butylimidazolium-3-(n-butylsulfonate)


1,4-Butane sultone, Applications, Sulfobetaines
1-Butylimidazolium-3-(n-butylsulfonate) catalyses as a component of multifunctional catalysts the reaction of platform chemicals from biomass (for example levulinic acid or itaconic acid) into the corresponding lactones, diols or cyclic ethers.


1,4-Butane sultone, Applications, Sulfobetaines
Aminoalkylphosphonic acids (such as aminomethane diphosphonic acid, accessible from phosphorus trichloride, formamide and phosphonic acid) form with 1,4-butanesultone N-(sulfobutyl)aminomethane diphosphonic acids:


1,4-Butane sultone, Applications, Sulfobetaines
N-(sulfobutyl)aminomethane diphosphonic acid is characterized by very high water solubility (< 1000 g·l−1) and a strong capability as complexing agent and water softener.


1,4-Butane sultone, Applications, Sulfobetaines
Sulfobutylation of cyanine dyes leads to readily water-soluble compounds which react with proteins like antibodies and can be used as pH-sensitive fluorescence markers.


1,4-Butane sultone, Applications, Ionic liquids
The ionic liquid 4-triethylammonium butane-1-sulfonic acid hydrogensulfate (TEBSA HSO4) is formed by the reaction of 1,4-butanesultone with triethylamine in acetonitrile to the zwitterion (85% yield) and subsequent reaction with concentrated sulfuric acid.


1,4-Butane sultone, Applications, Ionic liquids
4-triethylammonium butane-1-sulfonic acid hydrogensulfate can replace conventional mineral acids as effective and easily recyclable acid catalyst in solvent-free reactions.


1,4-Butane sultone, Applications, Ionic liquids
The ring opening of 1,4-butanesultone with organic chloride salts yields ionic liquids of the 4-chlorobutylsulfonate type in quantitative yield.


1,4-Butane sultone, Applications, Ionic liquids
The chlorine atom in the 4-chlorobutylsulfonate anion can be substituted by heating with inorganic (e.g. potassium fluoride) or organic salts (e.g. sodium acetate) by the respective anion.


1,4-Butane sultone, Applications, Sulfobutylated β-cyclodextrin
Already in 1949 the reaction of 1,4-butanesultone with the water-insoluble polysaccharide cellulose in sodium hydroxide solution was reported, which leads to a water-soluble product. Derived from this the derivatization of β-cyclodextrin to sulfobutyl ether-beta-cyclodextrin (SBECD) is by now an important application of 1,4-butanesultone. Sulfobutyl ether-beta-cyclodextrin is a water-soluble inclusion compound for the solubilization and stabilization of sparsely water-soluble and chemically instable components. β-Cyclodextrin can be reacted with 1,4-butanesultone in sodium hydroxide solution at 70 °C to the sulfobutyl ether in yields of up to 80% and a degree of substitution of 6.68.


1,4-Butane sultone, Applications, Sulfobutylated β-cyclodextrin
Thereby, the water solubility of the β-cyclodextrin increases from 18.5 g · l-1 to more than 900 g · l-1 at 25 °C. Sulfobutyl ether-beta-cyclodextrin also finds a wide range of applications as an inert vehicle for drug delivery (the drugs transport and release).


1,4-Butanediol
1,4-Butanediol, colloquially known as BD, is a primary alcohol, and an organic compound, with the formula HOCH2CH2CH2CH2OH. It is a colorless viscous liquid. It is one of four stable isomers of butanediol.


1,4-Butanediol, Synthesis
Tellurium oxide-containing catalysts are used for the oxidation of butane:


1,4-Butanediol, Synthesis
In another industrial synthesis, acetylene reacts with two equivalents of formaldehyde to form 1,4-butynediol. Hydrogenation of 1,4-butynediol gives 1,4-butanediol. It is also manufactured on an industrial scale from maleic anhydride in the Davy process, which is first converted to the methyl maleate ester, then hydrogenated. Other routes are from butadiene, allyl acetate and succinic acid.


1,4-Butanediol, Synthesis
A biological route to BD has been commercialized that uses a genetically modified organism. The biosynthesis proceeds via 4-hydroxybutyrate.


1,4-Butanediol, Industrial use
1,4-Butanediol is used industrially as a solvent and in the manufacture of some types of plastics, elastic fibers and polyurethanes. In organic chemistry, 1,4-butanediol is used for the synthesis of γ-butyrolactone (GBL). In the presence of phosphoric acid and high temperature, it dehydrates to the important solvent tetrahydrofuran. At about 200 °C in the presence of soluble ruthenium catalysts, the diol undergoes dehydrogenation to form butyrolactone.


1,4-Butanediol, Industrial use
World production of 1,4-butanediol was claimed to be about one million metric tons per year and market price is about US$2,000 (€1,600) per ton (2005). In 2013, worldwide production was claimed to be billions of lbs (consistent with approximately one million metric tons).


1,4-Butanediol, Industrial use
Almost half of it is dehydrated to tetrahydrofuran to make fibers such as Spandex. The largest producer is BASF.


1,4-Butanediol, Use as a recreational drug
1,4-Butanediol is also used as a recreational drug known by some users as "One Comma Four", "Liquid Fantasy", "One Four Bee" or "One Four B-D-O". It exerts effects similar to γ-hydroxybutyrate (GHB), which is a metabolic product of 1,4-butanediol.


1,4-Butanediol, Use as a recreational drug, Pharmacokinetics
1,4-Butanediol is converted into GHB by the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, and differing levels of these enzymes may account for differences in effects and side effects between users. While co-administration of ethanol and GHB already poses serious risks, co-administration of ethanol with 1,4-butanediol will interact considerably and has many other potential risks. This is because the same enzymes that are responsible for metabolizing alcohol also metabolize 1,4-butanediol so there is a strong chance of a dangerous drug interaction. Emergency room patients who overdose on both ethanol and 1,4-butanediol often present with symptoms of alcohol intoxication initially and as the ethanol is metabolized the 1,4-butanediol is then able to better compete for the enzyme and a second period of intoxication ensues as the 1,4-butanediol is converted into GHB.


1,4-Butanediol, Use as a recreational drug, Pharmacodynamics
1,4-Butanediol seems to have two types of pharmacological actions. The major psychoactive effects of 1,4-butanediol are because it is metabolized into GHB; however there is a study suggesting that 1,4-butanediol may have potential alcohol-like pharmacological effects on its own. The study arrived at this conclusion based on the finding that 1,4-butanediol co-administered with ethanol led to potentiation of some of the behavioral effects of ethanol. However, potentiation of ethanol's effects may simply be caused by competition for the alcohol dehydrogenase and aldehyde dehydrogenase enzymes with co-administered 1,4-butanediol. The shared metabolic rate-limiting steps thus leads to slowed metabolism and clearance for both compounds including ethanol's known toxic metabolite acetaldehyde.


1,4-Butanediol, Use as a recreational drug, Pharmacodynamics
Another study found no effect following intracerebroventricular injection in rats of 1,4-butanediol. This contradicts the hypothesis of 1,4-butanediol having inherent alcohol-like pharmacological effects.


1,4-Butanediol, Use as a recreational drug, Pharmacodynamics
Like GHB, 1,4-butanediol is only safe in small amounts. Adverse effects in higher doses include nausea, vomiting, dizziness, sedation, vertigo, and potentially death if ingested in large amounts. Anxiolytic effects are diminished and side effects increased when used in combination with alcohol.


1,4-Butanediol, Use as a recreational drug, Legality
While 1,4-butanediol is not currently scheduled federally in the United States, a number of states have classified 1,4-butanediol as a controlled substance. Individuals have been prosecuted for 1,4-butanediol  under the Federal Analog Act as substantially similar to GHB. A federal case in New York in 2002 ruled that 1,4-butanediol could not be considered an analog of GHB under federal law, but that decision was later overturned by the Second Circuit.


1,4-Butanediol, Use as a recreational drug, Legality
However, a jury in Federal District Court in Chicago found that 1,4-butanediol was not be an analog of GHB under federal law, and the Seventh Circuit Court of Appeals upheld that verdict. In the United Kingdom, 1,4-butanediol was scheduled in December 2009 (along with another GHB precursor, gamma-butyrolactone) as a Class C controlled substance. In Germany, the drug is not explicitly illegal, but might also be treated as illegal if used as a drug. It is controlled as a Schedule VI precursor in Canada.


1,4-Butanediol, Use as a recreational drug, 2007 contamination of Bindeez toy
A toy called "Bindeez" ("Aqua Dots" in North America) was recalled by the distributor in November 2007 because of the presence of 1,4-butanediol. The toy consists of small beads that stick to each other by sprinkling water. 1,4-Butanediol was detected by GC-MS. The production plant seems to have intended to cut costs by replacing less toxic 1,5-pentanediol with 1,4-butanediol. ChemNet China listed the price of 1,4-butanediol at between about US$1,350–2,800 per metric ton, while the price for 1,5-pentanediol is about US$9,700 per metric ton.


1,4-Butanediol, Use as a recreational drug, 2021 poisoning at Darmstadt Technical University
In August 2021, several people fell severely ill after consuming drinks at building L2.01 at the Lichtwiese Campus of Darmstadt Technical University, Germany. Seven showed severe symptoms, two were transported to a hospital in Frankfurt, and a 30 year old person was, for a time, in a critical state. 1,4-butanediol had been detected in milk packages, as well as in water filters. At the location, detectives also found bromophenols and dicyclohexylamine.


1,4-Butynediol
1,4-Butynediol is an organic compound that is an alkyne and a diol. It is a colourless, hygroscopic solid that is soluble in water and polar organic solvents. It is a commercially significant compound in its own right and as a precursor to other products.


1,4-Butynediol, Synthesis
1,4-Butynediol can be produced in the Reppe synthesis, where formaldehyde and acetylene are the reactants:


1,4-Butynediol, Synthesis
Several patented production methods use copper bismuth catalysts coated on an inert material. The normal temperature range for the reaction is 90 °C up to 150 °C, depending on the pressure used for the reaction which can range from 1 to 20 bar.


1,4-Butynediol, Applications
1,4-Butynediol is a precursor to 1,4-butanediol and 2-butene-1,4-diol by hydrogenation. It is also used in the manufacture of certain herbicides, textile additives, corrosion inhibitors, plasticizers, synthetic resins, and polyurethanes. It is the major raw material used in the synthesis of vitamin B6. It is also used for brightening, preserving, and inhibiting nickel plating.


1,4-Butynediol, Applications
It reacts with a mixture of chlorine and hydrochloric acid to give mucochloric acid, HO2CC(Cl)=C(Cl)CHO (see mucobromic acid).


1,4-Butynediol, Safety
1,4-Butynediol is corrosive and irritates the skin, eyes, and respiratory tract.


1,4-Cycloheptadiene
1,4-Cycloheptadiene is a highly flammable cycloalkene that occurs as a colorless clear liquid.


1,4-Cyclohexanedione
1,4-Cyclohexanedione is an organic compound with the formula (CH2)4(CO)2. This white solid is one of the three isomeric cyclohexanediones. This particular diketone is used as a building block in the synthesis of more complex molecules.


1,4-Cyclohexanedione, Preparation
1,4-Cyclohexanedione is prepared in two steps from diesters of succinic acid. Specifically under basic conditions, the diethyl ester condenses to give the cyclohexenediol derivative diethylsuccinoylsuccinate. This intermediate can be hydrolysed and decarboxylated to afford the desired dione.


1,4-Diamino-2,3-dihydroanthraquinone
1,4-Diamino-2,3-dihydroanthraquinone is an anthraquinone dye used with Disperse Red 9 in colored smoke to introduce a violet color. It is also used in dyes and marine flares.


1,4-Diazacycloheptane
1,4-Diazacycloheptane is an organic compound with the formula (CH2)5(NH)2. This cyclic diamine is a colorless oily liquid that is soluble in polar solvents. It is studied as a chelating ligand. The N-H centers can be replaced with many other groups.


1,4-Diazepine
1,4-Diazepine is a diazepine. It is a core element in the structure of benzodiazepines and thienodiazepines.


1,4-Diazepine
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1,4-Dibromobenzene
1,4-Dibromobenzene (p-dibromobenzene) is an organic compound that is solid at room temperature. This compound has two bromine atoms (bromo substituents) off the central benzene ring. It has a strong smell similar to that of the lighter chlorine analogue. It can be used as a precursor to the dye 6,6-Dibromoindigo.


1,4-Dichloro-2-nitrobenzene
1,4-Dichloro-2-nitrobenzene is an organic compound with the formula C6H3Cl2NO2. One of several isomers of dichloronitrobenzene, it is a yellow solid that is insoluble in water. It is produced by nitration of 1,4-dichlorobenzene. It is a precursor to many derivatives of commercial interest. Hydrogenation gives 1,4-dichloroaniline. Nucleophiles displace the chloride adjacent to the nitro group: ammonia gives the aniline derivative, aqueous base gives the phenol derivative, and methoxide gives the anisole derivative. These compounds are respectively 4-chloro-2-nitroaniline, 4-chloro-2-nitrophenol, and 4-chloro-2-nitroanisole.


1,4-Dichlorobenzene
1,4-Dichlorobenzene (1,4-DCB, p-DCB, or para-dichlorobenzene, sometimes abbreviated as PDCB or para) is an organic compound with the formula C6H4Cl2. This colorless solid has a strong odor. The molecule consists of a benzene ring with two chlorine atoms (replacing hydrogen atoms) on opposing sites of the ring.


1,4-Dichlorobenzene
It is used as a disinfectant, pesticide, and deodorant, most familiarly in mothballs in which it is a replacement for the more traditional naphthalene because of naphthalene's greater flammability (though both chemicals have the same NFPA 704 rating). It is also used as a precursor in the production of the chemically and thermally resistant polymer poly(p-phenylene sulfide).


1,4-Dichlorobenzene, Production
p-DCB is produced by chlorination of benzene using ferric chloride as a catalyst:


1,4-Dichlorobenzene, Production
The chief impurity is the 1,2 isomer. The compound can be purified by fractional crystallization, taking advantage of its relatively high melting point of 53.5 °C; the isomeric dichlorobenzenes and chlorobenzene melt well below room temperature.


1,4-Dichlorobenzene, Uses, Disinfectant, deodorant, and pesticide
p-DCB is used to control moths, molds, and mildew. It also finds use as a disinfectant in waste containers and restrooms and is the characteristic smell associated with urinal cakes. Its usefulness for these applications arises from p-DCB's low solubility in water and its relatively high volatility: it sublimes readily near room temperature.


1,4-Dichlorobenzene, Uses, Precursor to other chemicals
Nitration gives 1,4-dichloronitrobenzene, a precursor to commercial dyes and pigments. The chloride sites on p-DCB can be substituted with hydroxylamine and sulfide groups. In a growing application, p-DCB is the precursor to the high performance polymer poly(p-phenylene sulfide):


1,4-Dichlorobenzene, Environmental and health effects
p-DCB is poorly soluble in water and is not easily broken down by soil organisms. Like many hydrocarbons, p-DCB is lipophilic and will accumulate in fatty tissues if consumed by a person or animal.


1,4-Dichlorobenzene, Environmental and health effects
The United States Department of Health and Human Services (DHHS) and the International Agency for Research on Cancer (IARC) have determined that p-DCB may reasonably be anticipated to be a carcinogen. This has been indicated by animal studies, although a full-scale human study has not been done.


1,4-Dichlorobenzene, Environmental and health effects
The United States Environmental Protection Agency (EPA) has set a target maximum contaminant level of 75 micrograms of p-DCB per liter of drinking water (75 μg/L), but publishes no information on the cancer risk. p-DCB is also an EPA-registered pesticide. The United States Occupational Safety and Health Administration (OSHA) has set a maximum level of 75 parts of p-DCB per million parts air in the workplace (75 ppm) for an 8-hour day, 40-hour workweek.


1,4-Dichlorobenzene, Environmental and health effects
Under California's Proposition 65, p-DCB is listed as "known to the State to cause cancer". A mechanism for the carcinogenic effects of mothballs and some types of air fresheners containing p-DCB has been identified in roundworms.


1,4-Dichlorobut-2-ene
1,4-Dichlorobut-2-ene is a chlorinated butene. It is an intermediate in the industrial production of chloroprene, and the main impurity in technical grade chloroprene. The (E)-isomer is also one of the starting materials for Birman's total synthesis of the poriferic natural product sceptrin.


1,4-Dichlorobut-2-ene, Production of chloroprene
Chloroprene is a monomer for the production of synthetic rubbers such as Neoprene. It is produced from butadiene in a three-step process. The first step is the liquid- or vapour-phase chlorination of butadiene to a mixture of 3,4-dichlorobut-1-ene and 1,4-dichlorobut-2-ene (both isomers). In the second step, the mixture of 1,4-dichlorobut-2-ene and 3,4-dichlorobut-1-ene is isomerized to pure 3,4-dichlorobut-1-ene by heating to temperatures of 60–120 °C in the presence of a catalyst. Finally, dehydrochlorination (elimination of hydrogen chloride) of 3,4-dichlorobut-1-ene with dilute sodium hydroxide solution in the presence of polymerization inhibitors gives crude chloroprene.


1,4-Dicyanobenzene
1,4-Dicyanobenzene is an organic compound with the formula C6H4(CN)2. Two other isomers exist, phthalonitrile and isophthalonitrile. All three isomers are produced commercially by ammoxidation of the corresponding xylene isomers. 1,4-Dicyanobenzene is a colorless or white solid with low solubility in water. Hydrogenation of isophthalonitrile affords p-xylylenediamine.


1,4-Dihydropyridine
1,4-Dihydropyridine (DHP) is an organic compound with the formula CH2(CH=CH)2NH. The parent compound is uncommon, but derivatives of 1,4-dihydropyridine are important commercially and biologically. The pervasive cofactors NADH and NADPH are derivatives of 1,4-dihydropyridine. 1,4-Dihydropyridine-based drugs are L-type calcium channel blockers, used in the treatment of hypertension. 1,2-Dihydropyridines are also known.


1,4-Dihydropyridine, Properties and reactions
A recurring feature of 1,4-dihydropyridines is the presence of substituents at the 2- and 6-positions. Dihydropyridines are enamines, which otherwise tend to tautomerize or hydrolyze.


1,4-Dihydropyridine, Properties and reactions
The dominant reaction of dihydropyridines is their ease of oxidation. In the case of dihydropyridines with hydrogen as the substituent on nitrogen, oxidation yields pyridines:


1,4-Dihydropyridine, Properties and reactions
The naturally-occurring dihydropyridines NADH and NADPH contain N-alkyl groups. Therefore, their oxidation does not yield pyridine, but N-alkylpyridinium cations:


1,4-Dihydroxyanthraquinone
1,4-Dihydroxyanthraquinone, also called quinizarin or Solvent Orange 86, is an organic compound derived from anthroquinone. Quinizarin is an orange or red-brown crystalline powder. It is formally derived from anthraquinone by replacement of two hydrogen atoms by hydroxyl (OH) groups. It is one of ten dihydroxyanthraquinone isomers and occurs in small amounts (as a glycoside) in the root of the madder plant, Rubia tinctorum.


1,4-Dihydroxyanthraquinone, Production
Quinizarin is produced by the reaction of phthalic anhydride and 4-chlorophenol followed by hydrolysis of the chloride:


1,4-Dihydroxyanthraquinone, Production
It can also be prepared less efficiently from phthalic anhydride and hydroquinone.


1,4-Dihydroxyanthraquinone, Uses
Quinizarin is an inexpensive dye that is used to colour gasoline and some heating oils. It is used as an intermediate for the synthesis of indanthrene- and alizarin-derived dyes. The OH groups can be replaced by chloride. Chlorination and bromination afford other dyes. Amination (replacement of one OH by ArNH) with aniline derivatives followed by sulfonation affords other dyes such as Acid Violet 43. It is also used to form lake pigments with calcium, barium, and lead.


1,4-Dimethoxybenzene
1,4-Dimethoxybenzene is an organic compound with the formula C6H4(OCH3)2. It is one of three isomers of dimethoxybenzene. It is a white solid with an intensely sweet floral odor. It is produced by several plant species.


1,4-Dimethoxybenzene, Occurrence
It occurs naturally in willow (Salix), tea, hyacinth, zucchini (Cucurbita pepo). It appears to attract bees as it has a powerful response in their antenna. In a study in mice, Iranian scientists identified 1,4-dimethoxybenzene as the major psychoactive chemical in musk willow (Salix aegyptiaca) by its ability to cause somnolescence and depressed activity.


1,4-Dimethoxybenzene, Preparation
It is produced by the methylation of hydroquinone using dimethylsulfate and an alkali.


1,4-Dimethoxybenzene, Uses
It is an intermediate in synthesis of organic compounds, including pharmaceuticals such as methoxamine and butaxamine.


1,4-Dimethoxybenzene, Uses, Niche uses
It can be used as a developer in black and white film, and as a base in synthesizing catecholamines and phenethylamines.


1,4-Dimethylnaphthalene
1,4-Dimethylnaphthalene (1,4DMN) is a plant growth regulator that occurs naturally in potato tubers, preventing them from sprouting. Synthetic forms such as 1-4SIGHT are applied to potatoes during storage.


1,4-Dimethylnaphthalene
Although discovered in the 1970s, it was not used commercially in the USA until 1996 and in Europe until the 2010s.


1,4-Dinitrobenzene
1,4-Dinitrobenzene is an organic compound with the formula C6H4(NO2)2. It is one of three isomers of dinitrobenzene. The 1,4-isomer is most symmetrical. The compound is a yellow solid that is soluble in organic solvents. It is prepared from 4-nitroaniline by diazotization followed by treatment with sodium nitrite in the presence of a copper catalyst.


1,4-Dioxane
1,4-Dioxane (/daɪˈɒkseɪn/) is a heterocyclic organic compound, classified as an ether. It is a colorless liquid with a faint sweet odor similar to that of diethyl ether. The compound is often called simply dioxane because the other dioxane isomers (1,2- and 1,3-) are rarely encountered.


1,4-Dioxane
Dioxane is used as a solvent for a variety of practical applications as well as in the laboratory, and also as a stabilizer for the transport of chlorinated hydrocarbons in aluminum containers.


1,4-Dioxane, Synthesis
Dioxane is produced by the acid-catalysed dehydration of diethylene glycol, which in turn is obtained from the hydrolysis of ethylene oxide.


1,4-Dioxane, Synthesis
In 1985, the global production capacity for dioxane was between 11,000 and 14,000 tons. In 1990, the total U.S. production volume of dioxane was between 5,250 and 9,150 tons.


1,4-Dioxane, Structure
The dioxane molecule is centrosymmetric, meaning that it adopts a chair conformation, typical of relatives of cyclohexane. However, the molecule is conformationally flexible, and the boat conformation is easily adopted, e.g. in the chelation of metal cations. Dioxane resembles a smaller crown ether with only two ethyleneoxyl units.


1,4-Dioxane, Uses, Trichloroethane transport
In the 1980s, most of the dioxane produced was used as a stabilizer for 1,1,1-trichloroethane for storage and transport in aluminium containers. Normally aluminium is protected by a passivating oxide layer, but when these layers are disturbed, the metallic aluminium reacts with trichloroethane to give aluminium trichloride, which in turn catalyses the dehydrohalogenation of the remaining trichloroethane to vinylidene chloride and hydrogen chloride. Dioxane "poisons" this catalysis reaction by forming an adduct with aluminum trichloride.


1,4-Dioxane, Uses, As a solvent
Dioxane is used in a variety of applications as a versatile aprotic solvent, e. g. for inks, adhesives, and cellulose esters. It is substituted for tetrahydrofuran (THF) in some processes, because of its lower toxicity and higher boiling point (101 °C, versus 66 °C for THF).


1,4-Dioxane, Uses, As a solvent
While diethyl ether is rather insoluble in water, dioxane is miscible and in fact is hygroscopic. At standard pressure, the mixture of water and dioxane in the ratio 17.9:82.1 by mass is a positive azeotrope that boils at 87.6 C.


1,4-Dioxane, Uses, As a solvent
The oxygen atoms are Lewis-basic, and so dioxane is able to solvate many inorganic compounds and serves as a chelating diether ligand. It  forms 1:1 adducts with a variety of Lewis acid such as I2, phenols, alcohols, and bis(hexafloroacetylacetonato)copper(II). It is classified as a hard base and its base parameters in the ECW model are EB =1.86 and CB = 1.29. It reacts with Grignard reagents to precipitate the magnesium dihalide. In this way, dioxane is used to drive the Schlenk equilibrium. Dimethylmagnesium is prepared in this manner:


1,4-Dioxane, Uses, Spectroscopy
Dioxane is used as an internal standard for nuclear magnetic resonance spectroscopy in deuterium oxide.


1,4-Dioxane, Toxicology, Safety
Dioxane has an LD50 of 5170 mg/kg in rats. It is irritating to the eyes and respiratory tract. Exposure may cause damage to the central nervous system, liver and kidneys. In a 1978 mortality study conducted on workers exposed to 1,4-dioxane, the observed number deaths from cancer was not significantly different from the expected number. Dioxane is classified by the National Toxicology Program as "reasonably anticipated to be a human carcinogen". It is also classified by the IARC as a Group 2B carcinogen: possibly carcinogenic to humans because it is a known carcinogen in other animals.


1,4-Dioxane, Toxicology, Safety
The United States Environmental Protection Agency classifies dioxane as a probable human carcinogen (having observed an increased incidence of cancer in controlled animal studies, but not in epidemiological studies of workers using the compound), and a known irritant (with a no-observed-adverse-effects level of 400 milligrams per cubic meter) at concentrations significantly higher than those found in commercial products. Under California Proposition 65, dioxane is classified in the U.S. State of California to cause cancer. Animal studies in rats suggest that the greatest health risk is associated with inhalation of vapors in the pure form. The State of New York has adopted a first-in-the-nation drinking water standard for 1,4-Dioxane and set the maximum contaminant level of 1 part per billion.


1,4-Dioxane, Toxicology, Safety
It also has low toxicity to aquatic life and can be biodegraded via a number of pathways. The problems are exacerbated since dioxane is highly soluble in water, does not readily bind to soils, and readily leaches to groundwater. It is also resistant to naturally occurring biodegradation processes. Due to these properties, a dioxane plume can be larger (and further downgradient) than the associated solvent plume.


1,4-Dioxane, Toxicology, Explosion hazard
Like some other ethers, dioxane combines with atmospheric oxygen upon prolonged exposure to air to form potentially explosive peroxides. Distillation of these mixtures is dangerous. Storage under metallic sodium could limit the risk of explosion.


1,4-Dioxane, Toxicology, Environment
Dioxane has affected groundwater supplies in several areas. Dioxane at the level of 1 μg/L (~1 ppb) has been detected in many locations in the US. In the U.S. state of New Hampshire, it had been found at 67 sites in 2010, ranging in concentration from 2 ppb to over 11,000 ppb. Thirty of these sites are solid waste landfills, most of which have been closed for years.


1,4-Dioxane, Toxicology, Cosmetics
As a byproduct of the ethoxylation process, a route to some ingredients found in cleansing and moisturizing products, dioxane can contaminate cosmetics and personal care products such as deodorants, perfumes, shampoos, toothpastes and mouthwashes. The ethoxylation process makes the cleansing agents, such as sodium laureth sulfate and ammonium laureth sulfate, less abrasive and offers enhanced foaming characteristics. 1,4-Dioxane is found in small amounts in some cosmetics, a yet unregulated substance used in cosmetics in both China and the U.S. Research has found the chemical in ethoxylated raw ingredients and in off-the-shelf cosmetic products. The Environmental Working Group (EWG) found that 97% of hair relaxers, 57% of baby soaps and 22 percent of all products in Skin Deep, their database for cosmetic products, are contaminated with 1,4-dioxane.


1,4-Dioxane, Toxicology, Cosmetics
Since 1979 the U.S. Food and Drug Administration (FDA) have conducted tests on cosmetic raw materials and finished products for the levels of 1,4-dioxane. 1,4-Dioxane was present in ethoxylated raw ingredients at levels up to 1410 ppm (~0.14%wt), and at levels up to 279 ppm (~0.03%wt) in off the shelf cosmetic products. Levels of 1,4-dioxane exceeding 85 ppm (~0.01%wt) in children's shampoos indicate that close monitoring of raw materials and finished products is warranted. While the FDA encourages manufacturers to remove 1,4-dioxane, it is not required by federal law.


1,4-Dioxane, Toxicology, Cosmetics
On December 9, 2019, New York passed a bill to ban the sale of cosmetics with more than 10 ppm of 1,4-dioxane as of the end of 2022. The law will also prevent the sale of household cleaning and personal care products containing more than 2 ppm of 1,4-dioxane at the end of 2022.


1,4-Dioxene
1,4-Dioxene is an organic compound with the formula (C2H4)(C2H2)O2. The compound is derived from dioxane by dehydrogenation. It is a colourless liquid.


1,4-Dioxin
1,4-Dioxin (also referred as dioxin or p-dioxin) is a heterocyclic, organic, non-aromatic compound with the chemical formula C4H4O2. There is an isomeric form of 1,4-dioxin, 1,2-dioxin (or o-dioxin). 1,2-Dioxin is very unstable due to its peroxide-like characteristics.


1,4-Dioxin
The term “dioxin” is most commonly used for a family of derivatives of dioxin, known as polychlorinated dibenzodioxins (PCDDs).


1,4-Dioxin, Preparation
1,4-Dioxin can be prepared by cycloaddition, namely by the Diels–Alder reaction of furan and maleic anhydride. The adduct formed has a carbon-carbon double bond, which is converted to an epoxide. The epoxide then undergoes a retro-Diels–Alder reaction, forming 1,4-dioxin and regenerating maleic anhydride.


1,4-Dioxin, Derivatives
The word “dioxin” can refer in a general way to compounds which have a dioxin core skeletal structure with substituent molecular groups attached to it. For example, dibenzo-1,4-dioxin is a compound whose structure consists of two benzo- groups fused onto a 1,4-dioxin ring.


1,4-Dioxin, Derivatives, Polychlorinated dibenzodioxins
Because of their extreme importance as environmental pollutants, current scientific literature uses the name dioxins commonly for simplification to denote the chlorinated derivatives of dibenzo-1,4-dioxin, more precisely the polychlorinated dibenzodioxins (PCDDs), among which 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a tetrachlorinated derivative, is the best known. The polychlorinated dibenzodioxins, which can also be classified in the family of halogenated organic compounds, have been shown to bioaccumulate in humans and wildlife due to their lipophilic properties, and are known teratogens, mutagens, and carcinogens.


1,4-Dioxin, Derivatives, Polychlorinated dibenzodioxins
PCDDs are formed through combustion, chlorine bleaching and manufacturing processes. The combination of heat and chlorine creates dioxin. Since chlorine is often a part of the Earth's environment, natural ecological activity such as volcanic activity and forest fires can lead to the formation of PCDDs. Nevertheless, PCDDs are mostly produced by human activity.


1,4-Dioxin, Derivatives, Polychlorinated dibenzodioxins
Famous PCDD exposure cases include Agent Orange sprayed over vegetation by the British military in Malaya during the Malayan Emergency and the U.S. military in Vietnam during the Vietnam War, the Seveso disaster, and the poisoning of Viktor Yushchenko.


1,4-Dioxin, Derivatives, Polychlorinated dibenzodioxins
Polychlorinated dibenzofurans are a related class compounds to PCDDs which are often included within the general term “dioxins”.


1,4-Naphthoquinone
1,4-Naphthoquinone or para-naphthoquinone is an quinone derived from naphthalene. It forms volatile yellow triclinic crystals and has a sharp odor similar to benzoquinone. It  is almost insoluble in cold water, slightly soluble in petroleum ether, and more soluble in polar organic solvents. In alkaline solutions it produces a reddish-brown color. Vitamin K is a derivative of 1,4-naphthoquinone. It is a planar molecule with one aromatic ring fused to a quinone subunit. It is an isomer of 1,2-naphthoquinone.


1,4-Naphthoquinone, Preparation
The industrial synthesis involves aerobic oxidation of naphthalene over a vanadium oxide catalyst:


1,4-Naphthoquinone, Preparation
In the laboratory, naphthoquinone can be produced by the oxidation of a variety of naphthalene compounds. An inexpensive route involves oxidation of naphthalene with chromium trioxide.


1,4-Naphthoquinone, Reactions
1,4-Naphthoquinone acts as strong dienophile in Diels-Alder reaction. Its adduct with 1,3-butadiene can be prepared by two methods: 1) long (45 days) exposure of naphthoquinone in neat liquid butadiene taken in huge excess at room temperature in a thick-wall glass tube or 2) fast catalyzed cycloaddition at low temperature in the presence of 1 equivalent of tin(IV) chloride:


1,4-Naphthoquinone, Uses
1,4-Naphthoquinone is mainly used as a precursor to anthraquinone by reaction with butadiene followed by oxidation. Nitration gives 5-nitro-1,4-naphthalenedione, precursor to an aminoanthroquinone that is used as a dye precursor.


1,4-Naphthoquinone, Derivatives
Naphthoquinone forms the central chemical structure of many natural compounds, most notably the K vitamins. 2-Methyl-1,4-naphthoquinone, called menadione, is a more effective coagulant than vitamin K.