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1-AZAFULVENE

1-Azafulvene is a five-membered aromatic heterocycle containing one nitrogen atom, serving as a fundamental building block in medicinal chemistry, materials science, and natural product synthesis.
1-Azafulvene's diverse applications include the synthesis of pharmaceuticals, agrochemicals, dyes, and conductive polymers such as poly1-Azafulvene, which is used in sensors, batteries, and antistatic coatings.
1-Azafulvene’s unique electronic structure and reactivity make it a critical intermediate in both biological systems—like heme and chlorophyll—and in the design of advanced materials and industrial chemicals.

CAS number: 109-97-7
EC number: 203-724-7
Molecular Formula: C4H5N
Molecular Weight: 67.09

Synonyms: PYRROLE, 1H-Pyrrole, 109-97-7, Divinylenimine, Imidole, Pyrrol, Monopyrrole, Divinyleneimine, 1-Aza-2,4-cyclopentadiene, FEMA No. 3386, NSC 62777, CCRIS 2933, HSDB 119, CHEBI:19203, EINECS 203-724-7, UNII-86S1ZD6L2C, NSC-62777, 86S1ZD6L2C, DTXSID5021910, AI3-18817, DTXCID201910, Pyrrole1539, CHEBI:35556, 203-724-7, Azole, 30604-81-0, Pyrrole-15N, (1H-Pyrrole)x, PYROLLE, MFCD00005216, 26120-22-9, Pyrroles, C4H5N, Pyrrhol, Pyrole, beta-pyrrole, a pyrrole, pyrrole-, Pyrrole, Reagent, Polypyrrole (undoped, extent of labeling: ~20 wt. % loading, composite with carbon black), 1-H-pyrrole, 1-aza-cyclopentadiene, PYRROLE [FHFI], PYRROLE [HSDB], PYRROLE [FCC], 1H-PYRROLE [MI], Epitope ID:136031, WLN: T5MJ, Pyrrole, analytical standard, CHEMBL16225, Pyrrole, reagent grade, 98%, QSPL 001, FEMA 3386, Pyrrole, >=98%, FCC, FG, NSC62777, NSC72470, STR00296, Tox21_303910, BBL011520, NSC-72470, STL146636, AKOS000120094, FP14738, NCGC00357161-01, BP-21154, CAS-109-97-7, 1H-Pyrrole; Azole; Divinylenimine; Imidole, DB-003771, NS00014390, P0574, EN300-20590, C19907, H27771, A802120, InChI=1/C4H5N/c1-2-4-5-3-1/h1-5, Q242627, F2190-0643, Z104479036, 107760-17-8

1-Azafulvene is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula C4H4NH.
1-Azafulvene is a colorless volatile liquid that darkens readily upon exposure to air.

Substituted derivatives are also called 1-Azafulvenes, e.g., N-methyl1-Azafulvene, C4H4NCH3.
Porphobilinogen, a trisubstituted 1-Azafulvene, is the biosynthetic precursor to many natural products such as heme.

1-Azafulvenes are components of more complex macrocycles, including the porphyrinogens and products derived therefrom, including porphyrins of heme, the chlorins, bacteriochlorins, and chlorophylls.

1-Azafulvene is a heterocyclic aromatic compound that forms a liquid at room temperature.
Due to its basic structure, 1-Azafulvene is used in the synthesis of a wide variety of chemicals, from pharmaceuticals and agrochemicals to dyes and spices.

1-Azafulvene is a five-membered aromatic heterocycle containing one nitrogen atom.
1-Azafulvene is a fundamental building block in medicinal chemistry, materials science, and natural product synthesis due to its planar structure, conjugated π-system, and ability to participate in hydrogen bonding via its N–H group.

Classic synthetic routes like the Knorr, Paal–Knorr, and Hantzsch methods remain widely used, while modern approaches, such as multicomponent reactions (MCRs), enable efficient access to functionalized derivatives.
1-Azafulvene's bioactivity stems from its electronic properties, which allow interactions with enzymes and receptors, making it a key scaffold in drug discovery (e.g., thrombin inhibitors and antiviral agents).

1-Azafulvene plays a major role in synthesis of drugs, spices, agrochemicals, dyes, photographic chemicals and perfumes.
1-Azafulvene plays an important role in the electropolymerisation of macroporous conducting polymer films.

1-Azafulvene acts as a catalyst for polymerization process; as a standard substance in chromatographic analysis; as corrosion inhibitors and preservatives and as solvents for resins and terpenes.
1-Azafulvene is utilized to study the hydrogen-bond mediated coupling of 1,2,3-triazole to 1-Azafulvene and in the preparation of 1-(4-Chloro-benzoyl)-1-Azafulvene by reacting with 4-Chloro-benzoyl chloride.
In Ciamician-Dennstedt rearrangement, 1-Azafulvene is used to prepare 3-chloropyridine by reacting with dichlorocarbene.

1-Azafulvene, any of a class of organic compounds of the heterocyclic series characterized by a ring structure composed of four carbon atoms and one nitrogen atom.
The simplest member of the 1-Azafulvene family is 1-Azafulvene itself, a compound with molecular formula C4H5N.

The 1-Azafulvene ring system is present in the amino acids proline and hydroxyproline; and in coloured natural products, such as chlorophyll, heme (a part of hemoglobin), and the bile pigments.
1-Azafulvene compounds also are found among the alkaloids, a large class of alkaline organic nitrogen compounds produced by plants.

In heme and chlorophyll, four 1-Azafulvene rings are joined in a larger ring system known as porphyrin.
The bile pigments are formed by decomposition of the porphyrin ring and contain a chain of four 1-Azafulvene rings.

1-Azafulvene is an important five membered aromatic heterocyclic compound p g ossessing a nitrogen atom as hetero atom.
1-Azafulvene plays an important role in the chemistry of living organisms.

1-Azafulvene has three pairs of delocalized π electrons.
Two of the pairs are shown as bonds and third pair is shown as a non bonding electron on the nitrogen atom.

These non bonding electrons are in a sp2 hybrid orbital perpendicular to the p-orbitals.
Since 1-Azafulvene is cyclic planer molecule, with three pairs of delocalized π electrons, fulfill the criteria for aromaticity.

1-Azafulvene is a heterocyclic compound that functions as a ligand in coordination chemistry, forming complexes with various metal ions.
1-Azafulvene acts as a π-electron donor, participating in coordination bonds with metal centers to stabilize the resulting complexes.

1-Azafulvene′s mode of action involves the formation of coordination complexes through the lone pair of electrons on the nitrogen atom, allowing it to act as a chelating agent.
This enables 1-Azafulvene to play a role in the synthesis of metalloporphyrins and related compounds, contributing to the development of novel materials and catalysts.

Heterocyclic compound of 1-Azafulvene:
1-Azafulvene is a five-membered heterocyclic compound which contains one nitrogen atom, it is colorless liquid at room temperature, naturally presents in coal tar and bone oil, turns black color quickly in the air, it has significant irritant odor.
The relative density is 0.9691, the boiling point is 130~131℃, freezing point is-24℃.

1-Azafulvene is almost insoluble in water and dilute alkali solution, soluble in alcohol, ether, benzene and mineral acid solution.
1-Azafulvene is very stable for alkali, it easily polymerizes into dark red resin trimer in the presence of small amount of inorganic acid, when it is stored, it exposes to light or air will cause resinification.

1-Azafulvene vapor meets loose pieces which moistened with hydrochloric acid can show red, this is called loose piece reaction (pine flakes reaction; pine splint test), 1-Azafulvene can be used to identify 1-Azafulvene.
5 atoms on the 1-Azafulvene ring are sp2 hybrid, they are in the same plane, one pair not shared electrons of the nitrogen atom occupy the p-orbital, four carbon atoms and p-orbital are parallel and overlapping, forming 5 atoms, 6 π electrons closed conjugated system, it has aromatic character, prone to electrophilic substitution reactions.

Thus, alkalinity of nitrogen atom in 1-Azafulvene is small (pKb13.6); On the contrary, combination of hydrogen on the nitrogen atom is weak acid.
In addition, 1-Azafulvene ring with benzene and other aromatic compounds are same, it can conduct nitration, sulfonation, diazo coupling reaction, Friedel-Crafts type acylation.

This reaction can get 2-substituted compound.
Nitrogen atom of 1-Azafulvene molecule is sp2 hybridized, unshared electron pair occupys p-orbitals, p-orbitals with parallel 4 sp2 hybridized carbon atoms overlap to form a six-electron conjugated system, 1-Azafulvene has aromatic character, electrophilic substitution reactions can occur.

Unshared electron pairs of 1-Azafulvene nitrogen atoms involve in the conjugated ring system, and binding capacity with H + is very weak, it is not showing alkaline.
Since the electron density on the nitrogen atom is relatively lower, the hydrogen atom attached to the nitrogen atom can leave in the form of positive ions, thus 1-Azafulvene has faintly acid.

Ionization constant Ka = 10-15, 1-Azafulvene can react with solid potassium hydroxide to form a salt.
Many 1-Azafulvene derivatives are important drugs and have strong physiologically active substances, such as chlorophyll, heme.
1-Azafulvene is basic structural unit of heme, chlorophyll, bile pigments, some amino acids, several alkaloids and some enzymes, these compounds have strong physiological activity and drugs functional.

Vitamin B12, glycopyrrolate, kainic acid (drive roundworm medicine), clindamycin (antibiotic) drugs contain hydrogenated 1-Azafulvene ring structure.
Since 1979, 1-Azafulvene found that flexible conductive polymer film can be obtained by electrochemical oxidation of 1-Azafulvene, the conductivity is 104S/m, and it had good stability.

Market Overview of 1-Azafulvene:
The global 1-Azafulvene market is experiencing steady and promising growth, primarily fueled by its wide-ranging applications in pharmaceuticals, agrochemicals, and the development of advanced materials.
1-Azafulvene, a heterocyclic aromatic organic compound, plays a crucial role as a chemical intermediate in the synthesis of numerous high-value products, particularly in drug development.

As of 2024, the global 1-Azafulvene market is valued at approximately USD 234 million and is projected to reach around USD 350 million by 2033, reflecting a compound annual growth rate (CAGR) of 4.5% between 2026 and 2033.
The pharmaceutical industry remains the largest consumer segment, accounting for nearly 40% of total 1-Azafulvene demand due to its critical role in the synthesis of several active pharmaceutical ingredients (APIs).

In agrochemicals, 1-Azafulvene derivatives are utilized in the production of effective herbicides and insecticides.
Additionally, 1-Azafulvene's use in the electronics sector—especially in the manufacturing of conductive polymers and organic semiconductors—is steadily increasing.

Regionally, Asia-Pacific dominates both production and consumption, supported by extensive chemical manufacturing infrastructure and growing industrialization.
Meanwhile, North America and Europe also hold significant shares, owing to their mature pharmaceutical and specialty chemical sectors.

Market trends suggest a growing interest in sustainable and bio-based synthesis methods, reflecting environmental concerns and regulatory pressure.
Furthermore, derivative products such as N-methyl 1-Azafulvene and tetrahydro 1-Azafulvene are gaining traction due to their specialized industrial uses and relatively higher market value.
Overall, the 1-Azafulvene market is set to benefit from technological advancements, increasing end-user demand, and innovations in green chemistry approaches.

Uses of 1-Azafulvene:
1-Azafulvene plays a major role in synthesis of drugs, spices, agrochemicals, dyes, photographic chemicals and perfumes.
1-Azafulvene plays an important role in the electropolymerisation of macroporous conducting polymer films.

1-Azafulvene is a highly versatile organic compound used across several key industries due to its unique chemical structure and reactivity.
In the pharmaceutical sector, 1-Azafulvene serves as a crucial building block in the synthesis of a wide range of therapeutic agents, including anti-inflammatory, anticancer, antiviral, and cardiovascular drugs.

1-Azafulvene's structure is also integral to natural biological molecules such as heme and chlorophyll, making it essential for designing biomimetic compounds.
In agriculture, 1-Azafulvene derivatives are employed in the formulation of herbicides, insecticides, and fungicides, offering effective crop protection solutions.

The electronics industry makes extensive use of poly1-Azafulvene—a conductive polymer derived from 1-Azafulvene—which is valued for 1-Azafulvene's electrical conductivity, flexibility, and stability.
Applications include antistatic coatings, sensors, batteries, and supercapacitors.

Additionally, 1-Azafulvene is used in the production of high-performance dyes and pigments, particularly those that require strong light absorption and vivid coloration.
1-Azafulvene's role in these sectors continues to expand as innovation drives the demand for multifunctional and sustainable chemical intermediates.

Commercial Uses:
Poly1-Azafulvene is of some commercial value.
N-Methyl1-Azafulvene is a precursor to N-methyl1-Azafulvenecarboxylic acid, a building-block in pharmaceutical chemistry.

1-Azafulvenes are also found in several drugs, including atorvastatin, ketorolac, and sunitinib.
1-Azafulvenes are used as lightfast red, scarlet, and carmine pigments.

Industrial uses:
1-Azafulvene is a five-member nitrogen heterocyclic ring that contains two carbon-carbon double bond configurations which gives the solvent a pronounced aromatic character.
1-Azafulvene is an intermediate in the synthesis of a variety of commercial chemical derivatives.

1-Azafulvene has only limited solubility in water but are miscible with many organic solvents.
1-Azafulvene when freshly distilled is a colorless liquid, but the solvent can rapidly acquire a brown coloration due to air oxidation.

Prolonged standing in the air will promote slow polymerization of the 1-Azafulvene to give a dark brown polymer.
1-Azafulvene has a viscosity of 1.31 centipoise and a medium surface tension value of 37.1 dynes/cm.

1-Azafulvene is used as a chemical intermediate in the preparation of electrically conducting poly1-Azafulvene by means of an electrochemical polymerization process.
1-Azafulvene has few other industrial uses.

1-Azafulvene is used to a limited extent as a solvent for polymeric esters, but its primary value lies in its function as a chemical intermediate.
1-Azafulvene is used in the synthesis of non-heterocyclic compounds and its derivatives have been used in the manufacture of dyes, herbicides, perfumes, and as cross-linking agents for curing resins.
Derivatives of 1-Azafulvene are utilized in pharmaceutical applications, particularly as anti-inflammation drugs and drugs with central nervous system activity, including antihypertensive effects and as antimicrobial agents, such as fungicides and bactericides.

Polymers of 1-Azafulvene have been used in the preparation of photoconductive materials.
The main utility of poly(1-Azafulvene) has been for the modification of electrode surfaces, although numerous other applications can be envisioned.

Applications of 1-Azafulvene:
1-Azafulvene plays a major role in synthesis of drugs, spices, agrochemicals, dyes, photographic chemicals and perfumes.
1-Azafulvene plays an important role in the electropolymerisation of macroporous conducting polymer films.

Properties of 1-Azafulvene:
1-Azafulvene has very low basicity compared to amines and other aromatic compounds like pyridine where the ring nitrogen is not bonded to a hydrogen atom.
This decreased basicity is attributed to the delocalization of the lone pair of electrons of the nitrogen atom in the aromatic ring.

1-Azafulvene is a very weak base with a pKaH of about -4.
Protonation results in loss of aromaticity and is therefore unfavorable.

Chemical Properties:
1-Azafulvene is colorless to yellowish liquid, long-term storage in the process is easy to expose the action of light and the polymerize to turn brown.
1-Azafulvene has warm sweet fruity of nuts and esters.

1-Azafulvene's boiling point is 130 ℃ (decomposition), a flash point is 39 ℃, a melting point is-24 ℃.
1-Azafulvene is soluble in alcohol, ether, benzene, acid and most of the non-volatile oil, insoluble in water and dilute alkali.

Six π-electrons are distributed over the five ring atoms of 1-Azafulvene.
Delocalization of these electrons stabilizes the ring and the lone pair of electrons on the nitrogen atom, which is responsible for the usual basicity of nitrogen compounds, is involved in the electron cloud, and is not available for sharing.

Hence, 1-Azafulvene is an extremely weak base and the pyrrolic nitrogen is not readily susceptible to electrophilic enzymic attack.
There is a high electron density, however, at all positions of the ring, which causes 1-Azafulvene to be reactive toward electrophilic substitution.
In general, electrophilic substitution reactions on the neutral molecule occur preferentially at the C-2 or C-5 positions.

Physical properties:
1-Azafulvene is a colorless to brown liquid that has a sweet, warm-ethereal smell, similar to chloroform.
1-Azafulvene dissolves in ethanol, ether, benzene, dilute acids, and most non-volatile oils but does not dissolve in water or dilute alkalis.
When stored for extended periods, 1-Azafulvene tends to aggregate and become brown due to the influence of light.

Biosynthesis of 1-Azafulvene:
The biosynthesis of 1-Azafulvene rings begins with aminolevulinic acid (ALA), which is synthesized from glycine and succinyl-CoA.
ALA dehydratase catalyzes the condensation of two ALA molecules via a Knorr-type ring synthesis to form porphobilinogen (PBG).
This later reacts to form, for example, the macrocycles heme and chlorophyll.

Proline is biosynthetically derived from the amino acid L-glutamate.
Glutamate-5-semialdehyde is first formed by glutamate 5-kinase (ATP-dependent) and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH).
This can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase (using NADH or NADPH), or turned into ornithine by ornithine aminotransferase, followed by cyclisation by ornithine cyclodeaminase to form proline.

Proline can be used as precursor of aromatic 1-Azafulvenes in secondary natural products, as in prodigiosins.
The biosynthesis of Prodigiosin involves the convergent coupling of three 1-Azafulvene type rings from L-proline, L-serine, L-methionine, pyruvate, and 2-octenal.

Ring A is synthesized from L-proline through the nonribosomal peptide synthase (NRPS) pathway, wherein the pyrrolidine ring of proline is oxidized twice through FAD+ to yield 1-Azafulvene ring A.

Ring A is then expanded via the polyketide synthase pathway to incorporate L-serine into ring B.
Ring A fragment is transferred from the peptidyl carrier protein (PCP) to the Acyl Carrier Protein (ACP) by a KS domain, followed by transfer to malonyl-ACP via decarboxylative Claisen condensation.

This fragment is then able to react with the masked carbanion formed from the PLP mediated decarboxylation of L-serine, which cyclizes in a dehydration reaction to yield the second 1-Azafulvene ring.
This intermediate is then modified by methylation (which incorporates a methyl group from L-methionine onto the alcohol at the 6 position) and oxidation of the primary alcohol to the aldehyde to yield the core A–B ring structures.

Reactions and Reactivity of 1-Azafulvene:
Due to its aromatic character, 1-Azafulvene is difficult to hydrogenate, does not easily react as a diene in Diels–Alder reactions, and does not undergo usual olefin reactions.
1-Azafulvene's reactivity is similar to that of benzene and aniline, in that it is easy to alkylate and acylate.

Under acidic conditions, 1-Azafulvenes oxidize easily to poly1-Azafulvene and thus many electrophilic reagents that are used in benzene chemistry are not applicable to 1-Azafulvenes.
In contrast, substituted 1-Azafulvenes (including protected 1-Azafulvenes) have been used in a broad range of transformations.

Reaction of 1-Azafulvene with electrophiles:
1-Azafulvenes generally react with electrophiles at the α position (C2 or C5), due to the highest degree of stability of the protonated intermediate.

1-Azafulvenes react easily with nitrating (e.g. HNO3/Ac2O), sulfonating (Py·SO3), and halogenating (e.g. NCS, NBS, Br2, SO2Cl2, and KI/H2O2) agents.
Halogenation generally provides polyhalogenated 1-Azafulvenes, but monohalogenation can be performed.

As is typical for electrophilic additions to 1-Azafulvenes, halogenation generally occurs at the 2-position, but can also occur at the 3-position by silation of the nitrogen.
This is a useful method for further functionalization of the generally less reactive 3-position.

Acylation:
Acylation generally occurs at the 2-position, through the use of various methods.
Acylation with acid anhydrides and acid chlorides can occur with or without a catalyst.

2-Acyl1-Azafulvenes are also obtained from reaction with nitriles, by the Houben–Hoesch reaction.
1-Azafulvene aldehydes can be formed by a Vilsmeier–Haack reaction.

Reaction of deprotonated 1-Azafulvene:
The NH proton in 1-Azafulvenes is moderately acidic with a pKa of 17.5.
1-Azafulvene can be deprotonated with strong bases such as butyllithium and sodium hydride.

The resulting alkali pyrrolide is nucleophilic.
Treating this conjugate base with an electrophile such as iodomethane gives N-methyl1-Azafulvene.

N-Metalated 1-Azafulvene can react with electrophiles at the N or C positions, depending on the coordinating metal.
More ionic nitrogen–metal bonds (such as with lithium, sodium, and potassium) and more solvating solvents lead to N-alkylation.

Nitrophilic metals, such as MgX, lead to alkylation at C (mainly C2), due to a higher degree of coordination to the nitrogen atom.
In the cases of N-substituted 1-Azafulvenes, metalation of the carbons is more facile.
Alkyl groups can be introduced as electrophiles, or by cross-coupling reactions.

Substitution at C3 can be achieved through the use of N-substituted 3-bromo1-Azafulvene, which can be synthesized by bromination of N-silyl1-Azafulvene with NBS.

Reductions:
1-Azafulvenes can undergo reductions to pyrrolidines and to pyrrolines.
For example, Birch reduction of 1-Azafulvene esters and amides produced pyrrolines, with the regioselectivity depending on the position of the electron-withdrawing group.

Cyclization reactions:
1-Azafulvenes with N-substitution can undergo cycloaddition reactions such as [4+2]-, [2+2]-, and [2+1]-cyclizations.
Diels-Alder cyclizations can occur with the 1-Azafulvene acting as a diene, especially in the presence of an electron-withdrawing group on the nitrogen.
Vinyl1-Azafulvenes can also act as dienes.

1-Azafulvenes can react with carbenes, such as dichlorocarbene, in a [2+1]-cycloaddition.
With dichlorocarbene, a dichlorocyclopropane intermediate is formed, which breaks down to form 3-chloropyridine (the Ciamician–Dennstedt rearrangement).

Isolation of 1-Azafulvene:
1-Azafulvene occurs in coal tar and bone oil.
1-Azafulvene can be isolated from bone oil by washing the oil be dilute alkali to remove acidic impurities and then with acid to remove basic impurities.

The crude oil is distilled.
1-Azafulvene is collected in the fraction at 100 to 150 0C.

1-Azafulvene may further be purified by fusing with Potassium hydroxide where upon solid potassio1-Azafulvene potassio1-Azafulvene is formed.
Which on steam distillation distillation gives pure 1-Azafulvene 1-Azafulvene.

Properties, Structure, Bonding
1-Azafulvene is a colorless volatile liquid that darkens readily upon exposure to air, and is usually purified by distillation immediately before use.
1-Azafulvene has a nutty odor.

1-Azafulvene is a 5-membered aromatic heterocycle, like furan and thiophene.
Unlike furan and thiophene, 1-Azafulvene has a dipole in which the positive end lies on the side of the heteroatom, with a dipole moment of 1.58 D.

In CDCl3, 1-Azafulvene has chemical shifts at 6.68 (H2, H5) and 6.22 (H3, H4).
1-Azafulvene is an extremely weak base for an amine, with a conjugate acid pKa of −3.8.

The most thermodynamically stable pyrrolium cation (C4H6N+) is formed by protonation at the 2 position.
Substitution of 1-Azafulvene with alkyl substituents provides a more basic molecule—for example, tetramethyl1-Azafulvene has a conjugate acid pKa of +3.7.

1-Azafulvene is also weakly acidic at the N–H position, with a pKa of 16.5.
As a hydrogen bonding Lewis acid 1-Azafulvene is classified as a hard acid and the ECW model lists its acid parameters as EA = 1.38 and CA = 0.68.

1-Azafulvene has aromatic character because the lone pairs of electrons on the nitrogen atom is partially delocalized into the ring, creating a 4n + 2 aromatic system (see Hückel's rule).
In terms of its aromaticity, 1-Azafulvene's is modest relative to benzene but comparable to related heterocycles thiophene and furan.

The resonance energies of benzene, 1-Azafulvene, thiophene, and furan are, respectively, 152, 88, 121, and 67 kJ/mol (36, 21, 29, and 16 kcal/mol).
The molecule is flat.

Occurrence of 1-Azafulvene:
The 1-Azafulvene ring is the basic unit of the porphyrin system which occurs, for example, in chlorophyll and in hemoglobin.
Other 1-Azafulvene-based natural products include pigments such as bilirubin and biliverdin, which are degradative products from porphyrins.

1-Azafulvene has been found in surface waters and in filtrates from cultures of the blue-green algae, Anabaenaflos aquae.
The presence of 1-Azafulvene and other organic nitrogen compounds in natural waters is of environmental concern because they may exert significant chlorine demand.

1-Azafulvene is also a precursor to trihalomethane formation.
At ambient temperature, 1-Azafulvene can be volatilized from shale oil wastewaters.

Concentrations of approximately 3 g/m3 have been measured indoors in air at an oil shale wastewater facility.
1-Azafulvene has been identified in tobacco smoke, although not in tobacco itself; in cigarette smoke; in cigar butt aroma and in Cannabis smoke condensate.

1-Azafulvene was found to be naturally occurring in foods; in fact, it is on the Food and Drug Administration GRAS list, with an average usage level of 3 p.p.m. in flavoring formulations.
1-Azafulvene is a volatile constituent of roasted coffee, roasted peanuts, and fried chicken.

1-Azafulvene has also been identified in beef aroma and is a constituent of cocoa aroma.
1-Azafulvene should be noted that all the foods listed have undergone some degree of thermal treatment; 1-Azafulvene was not present in the fresh, raw foods.

In model system studies, 1-Azafulvene was among the resulting compounds when hydroxyproline and glucose were heated under nitrogen at temperatures ranging from 120° to 200°C.
Large amounts of 1-Azafulvene were found, as well, when casein and collagen were pyrolyzed and when proline underwent high temperature pyrolysis.

Occurrence in Nature of 1-Azafulvene:
1-Azafulvene itself is not naturally occurring, but many of its derivatives are found in a variety of cofactors and natural products.
Common naturally produced molecules containing 1-Azafulvenes include vitamin B12, bile pigments like bilirubin and biliverdin, and the porphyrins of heme, chlorophyll, chlorins, bacteriochlorins, and porphyrinogens.

Other 1-Azafulvene-containing secondary metabolites include PQQ, makaluvamine M, ryanodine, rhazinilam, lamellarin, prodigiosin, myrmicarin, and sceptrin.
The syntheses of 1-Azafulvene-containing haemin, synthesized by Hans Fischer was recognized by the Nobel Prize.

1-Azafulvene is a constituent of tobacco smoke and may contribute to its toxic effects.

Production Methods of 1-Azafulvene:
1-Azafulvene originally was prepared industrially by fractional distillation of coal tar, bone oil or other protein material, and purified through formation of its potassium derivative.
Later 1-Azafulvene was produced by heating ammonium mucate with glycerol or mineral oil.

1-Azafulvene is now manufactured by addition of ammonia to either acetylene or butadiene.
Good yields of 1-Azafulvene also may be obtained from the reaction of ammonia with the corresponding heterocyclic compound (furan) in a vapor-phase process at 480° to 500°C, using alumina as a catalyst or by catalytic reaction of furan with ammonia over a molybdenum or vanadium oxide catalyst at 350-400°C.

1-Azafulvene may be made (1) by reaction of succinimide with zinc and acetic acid, or with hydrogen in the presence of finely divided platinum heated, (2) by reaction of ammonium saccharate or mucate COONH4·(CHOH)4·COONH4 with glycerol at 200 °C by loss of carbon dioxide, ammonia, and water.
When 1-Azafulvene is treated with potassium (but not with sodium) or boiled with solid potassium hydroxide, potassium 1-Azafulvene C4H4NK is formed, which is the starting point for N-derivatives of 1-Azafulvene, since reaction of the potassium with halogen of organic compound and with carbon dioxide, readily occurs.

Synthesis of 1-Azafulvene:
1-Azafulvene is prepared industrially by treatment of furan with ammonia in the presence of solid acid catalysts, like SiO2 and Al2O3.
1-Azafulvene can also be formed by catalytic dehydrogenation of pyrrolidine.

Several syntheses of the 1-Azafulvene ring have been described.
Three routes dominate, but many other methods exist.

Many methods exist for the organic synthesis of 1-Azafulvene and its derivatives.
Classic named reactions are the Knorr 1-Azafulvene synthesis, the Hantzch 1-Azafulvene synthesis and the Paal-Knorr synthesis.

The starting materials in the Piloty-Robinson 1-Azafulvene synthesis are 2 equivalents of an aldehyde and hydrazine.
The product is a 1-Azafulvene with specific substituents in the 3 and 4 positions.
The aldehyde reacts with the diamine to an intermediate di-imine (R-C=N-N=C-R) which with added hydrochloric acid, gives ring-closure and loss of ammonia to the 1-Azafulvene.

In one modification propionaldehyde is reacted first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation:
In the second step a sigmatropic reaction takes place between two intermediates.

Hantzsch 1-Azafulvene synthesis:
The Hantzsch 1-Azafulvene synthesis is the reaction of β-ketoesters (1) with ammonia (or primary amines) and α-haloketones (2) to give substituted 1-Azafulvenes (3).

Knorr 1-Azafulvene synthesis:
The Knorr 1-Azafulvene synthesis involves the reaction of an α-amino ketone or an α-amino-β-ketoester with an activated methylene compound.
The method involves the reaction of an α-aminoketone (1) and a compound containing a methylene group α to (bonded to the next carbon to) a carbonyl group (2).

Paal–Knorr 1-Azafulvene synthesis:
In the Paal–Knorr 1-Azafulvene synthesis, a 1,4-dicarbonyl compound reacts with ammonia or a primary amine to form a substituted 1-Azafulvene.

Other methods:
Van Leusen reaction 1-Azafulvenes are produced by reaction of tosylmethyl isocyanide (TosMIC) with an enone in the presence of base, in a Michael addition.
A 5-endo cyclization then forms the 5-membered ring, which reacts to eliminate the tosyl group.
The last step is tautomerization to the 1-Azafulvene.

By the Barton–Zard synthesis, an isocyanoacetate reacts with a nitroalkene in a 1,4-addition, followed by 5-endo-dig cyclization, elimination of the nitro group, and tautomerization.

The starting materials in the Piloty–Robinson 1-Azafulvene synthesis, named for Gertrude and Robert Robinson and Oskar Piloty, are two equivalents of an aldehyde and hydrazine.
The product is a 1-Azafulvene with substituents at the 3 and 4 positions.

The aldehyde reacts with the diamine to an intermediate di-imine (R−C=N−N=C−R).
In the second step, a [3,3]-sigmatropic rearrangement takes place between.

Addition of hydrochloric acid leads to ring closure and loss of ammonia to form the 1-Azafulvene.
The mechanism was developed by the Robinsons.

In one modification, propionaldehyde is treated first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation.

1-Azafulvenes bearing multiple substituents have been obtained from the reaction of münchnones and alkynes.
The reaction mechanism involves 1,3-dipolar cycloaddition followed by loss of carbon dioxide by a retro-Diels–Alder process.
Similar reactions can be performed using azalactones.

1-Azafulvenes can also be prepared by silver-catalyzed cyclization of alkynes with isonitriles, where R2 is an electron-withdrawing group, and R1 is an alkane, aryl group, or ester.
Examples of disubstituted alkynes have also been seen to form the desired 1-Azafulvene in considerable yield.

The reaction is proposed to proceed via a silver acetylide intermediate.
This method is analogous to the azide–alkyne click chemistry used to form azoles.

One synthetic route to 1-Azafulvene involves the decarboxylation of ammonium mucate, the ammonium salt of mucic acid.
The salt is typically heated in a distillation setup with glycerol as a solvent.

The Trofimov reaction allows for the synthesis of 2,3-disubstituted 1-Azafulvenes from ketoximes and acetylene in basic medium.

Reactivity of 1-Azafulvene:
Both NH and CH protons in 1-Azafulvenes are moderately acidic and can be deprotonated with strong bases such as butyllithium and the metal hydrides.
The resulting "pyrrolides" are nucleophilic.

Trapping of the conjugate base with an electrophile (e.g. an alkyl or acyl halide) reveals which sites were deprotonated based on which ring positions actually react as nucleophiles.
1-Azafulvene distribution of such a reaction can often be complex and depends on the base used (especially the counterion, such as lithium from butyllithium or sodium from sodium hydride), existing substitution of the 1-Azafulvene, and the electrophile.

1-Azafulvene undergoes electrophilic aromatic substitution predominantly at the 2 and 5 positions, though the substitution product at positions 3 and 4 is obtained in low yields.
Two such reactions that are especially significant for producing functionalized 1-Azafulvenes are the Mannich reaction and the Vilsmeier-Haack reaction (depicted below), both of which are compatible with a variety of 1-Azafulvene substrates.
Reaction of 1-Azafulvenes with formaldehyde form porphyrins.

1-Azafulvene compounds can also participate in cycloaddition (Diels-Alder) reactions under certain conditions, such as Lewis acid catalysis, heating, or high pressure.

History of 1-Azafulvene:
1-Azafulvene was first detected by F. F. Runge in 1834, as a constituent of coal tar.
In 1857, 1-Azafulvene was isolated from the pyrolysate of bone.
1-Azafulvene's name comes from the Greek pyrrhos (πυρρός, "reddish, fiery"), from the reaction used to detect it—the red color that it imparts to wood when moistened with hydrochloric acid.

Analogs and derivatives of 1-Azafulvene:

Structural analogs of 1-Azafulvene include:
Pyrroline, a partially saturated analog with one double bond
Pyrrolidine, the saturated hydrogenated analog
Derivatives of 1-Azafulvene include indole, a derivative with a fused benzene ring.

Handling and Storage of 1-Azafulvene:

Handling:
Handle in a well-ventilated area away from ignition sources.
Use explosion-proof equipment.

Avoid breathing vapors or contact with skin and eyes.
Only trained personnel should handle.

Storage:
Store in tightly sealed containers in a cool, dry, and well-ventilated place.
Keep away from heat, sparks, open flames, and incompatible substances like oxidizing agents and acids.
1-Azafulvene can polymerize spontaneously in the presence of air and light—store under inert gas (e.g., nitrogen or argon) and protect from light.

Stability and Reactivity of 1-Azafulvene:

Stability:
1-Azafulvene is stable under inert conditions (absence of air/light).
However, 1-Azafulvene can oxidize and polymerize spontaneously when exposed to air, especially at elevated temperatures.

Incompatible materials:
Strong oxidizers, acids, and light/air exposure.

Hazardous decomposition products:
When decomposed by heat or fire, 1-Azafulvene may produce toxic gases like nitrogen oxides (NOₓ) and carbon monoxide (CO).

First Aid Measures of 1-Azafulvene:

Inhalation:
Move person to fresh air.
If breathing is difficult, administer oxygen.
Seek medical attention.

Skin Contact:
Immediately wash with plenty of soap and water for at least 15 minutes.
Remove contaminated clothing.

Eye Contact:
Rinse thoroughly with plenty of water for at least 15 minutes, lifting upper and lower eyelids.
Seek medical attention immediately.

Ingestion:
Do NOT induce vomiting.
Rinse mouth and give water if the person is conscious.
Get immediate medical help.

Fire Fighting Measures of 1-Azafulvene:

Suitable Extinguishing Media:
Use carbon dioxide (CO₂), dry chemical powder, or alcohol-resistant foam.

Special Hazards:
1-Azafulvene vapors may form explosive mixtures with air.

Protective Equipment:
Firefighters should wear self-contained breathing apparatus (SCBA) and full protective gear.
Cool exposed containers with water spray to prevent explosion.

Accidental Release Measures of 1-Azafulvene:

Personal Precautions:
Evacuate area.
Wear appropriate PPE (gloves, goggles, lab coat, respirator if needed).

Environmental Precautions:
Prevent entry into sewers, waterways, or soil.

Clean-Up Procedures:
Absorb with inert material (e.g., vermiculite or sand), place in chemical waste container.
Ventilate area thoroughly and wash spill site.

Exposure Controls / Personal Protective Equipment of 1-Azafulvene:

Engineering Controls:
Use chemical fume hoods and proper ventilation systems.

Eye/Face Protection:
Safety goggles or face shield with side protection.

Skin Protection:
Nitrile gloves and protective clothing.

Respiratory Protection:
If ventilation is insufficient, use an approved organic vapor respirator.

Hygiene Measures:
Wash hands thoroughly after handling.
Do not eat, drink, or smoke near the chemical.

Identifiers of 1-Azafulvene:
CAS Number: 109-97-7
Beilstein Reference: 1159
ChEBI: CHEBI:19203
ChEMBL: ChEMBL16225
ChemSpider: 7736
ECHA InfoCard: 100.003.387
EC Number: 203-724-7
Gmelin Reference: 1705
PubChem CID: 8027
RTECS number: UX9275000
UNII: 86S1ZD6L2C
UN number: 1992, 1993
CompTox Dashboard (EPA): DTXSID5021910
InChI: InChI=1S/C4H5N/c1-2-4-5-3-1/h1-5H
Key: KAESVJOAVNADME-UHFFFAOYSA-N
InChI=1/C4H5N/c1-2-4-5-3-1/h1-5H
SMILES:
N1C=CC=C1
[nH]1cccc1

CAS number: 109-97-7
EC number: 203-724-7
Hill Formula: C₄H₅N
Molar Mass: 67.09 g/mol
HS Code: 2933 99 99

CAS No: 109-97-7
Chemical Name: 1-Azafulvene
CBNumber: CB3852794
Molecular Formula: C4H5N Lewis structure
Molecular Weight: 67.09

Properties of 1-Azafulvene:
Chemical formula: C4H5N
Molar mass: 67.091 g·mol−1
Appearance: colorless volatile liquid
Density: 0.967 g cm−3
Melting point: −23 °C (−9 °F; 250 K)
Boiling point: 129 to 131 °C (264 to 268 °F; 402 to 404 K)
Vapor pressure: 7 mmHg at 23 °C
Acidity (pKa): 17.5 (for the N−H proton)
Basicity (pKb): 13.6 (pKa 0.4 for C.A.)
Magnetic susceptibility (χ): −47.6×10−6 cm3 mol−1
Viscosity: 0.001225 Pa s

Boiling point: 129 - 131 °C
Density: 0.966 g/cm3
Explosion limit: 3.10 - 14.8 %(V)
Flash point: 36 °C
Ignition temperature: 550 °C
Melting Point: -23 °C
pH value: >6 (10 g/l, H₂O, 20 °C)
Vapor pressure: 8.7 hPa (20 °C)
Solubility: 60 g/l

Melting point: -23 °C (lit.)
Boiling point: 131 °C (lit.)
Density: 0.967 g/mL at 25 °C (lit.)
vapor density: 2.31 (vs air)
vapor pressure: 8.7 hPa (20 °C)
FEMA: 3386 | 1-Azafulvene
refractive index: n20/D 1.508(lit.)
Flash point: 92 °F
storage temp.: Store at +2°C to +8°C.
solubility: 60g/l
pka: 15(at 25℃)
form: Liquid
color: Clear almost colorless to brownish
PH: >6 (10g/l, H2O, 20℃)
Odor: at 0.10 % in propylene glycol. sweet warm nutty ethereal
Odor Type: nutty
biological source: synthetic
explosive limit: 3.10-14.8%(V)
Water Solubility: 60 g/L (20 ºC)
Sensitive: Air & Light Sensitive
JECFA Number: 1314
Merck: 14,8014
BRN: 1159
Dielectric constant: 7.5（17℃）
Stability: Stable. Incompatible with strong acids, strong oxidizing agents. Combustible.
InChIKey: KAESVJOAVNADME-UHFFFAOYSA-N
LogP: 0.85
Surface tension: 36.6mN/m at 20°C

Molecular Weight: 67.09 g/mol
XLogP3: 0.7
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 0
Rotatable Bond Count: 0
Exact Mass: 67.042199164 Da
Monoisotopic Mass: 67.042199164 Da
Topological Polar Surface Area: 15.8 Å²
Heavy Atom Count: 5
Complexity: 22.8
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Specifications of 1-Azafulvene:
Assay (GC, area%): ≥ 97.0 % (a/a)
Density (d 20 °C/ 4 °C): 0.967 - 0.971
Identity (IR): passes test

Thermochemistry of 1-Azafulvene:
Heat capacity (C): 1.903 J K−1 mol−1
Std enthalpy of formation (ΔfH⦵298): 108.2 kJ mol−1 (gas)
Std enthalpy of combustion (ΔcH⦵298): 2242 kJ mol−1

Related compounds of 1-Azafulvene:
Phosphole
arsole
bismole
stibole

Names of 1-Azafulvene:

Preferred IUPAC name:
1H-1-Azafulvene

Other names:
Azole
Imidole