Occupational exposure to polycyclic aromatic amines (PAA) has
occurred historically in the rubber, textile, and dye industries.
Some sources of nonoccupational exposure to PAAs include
inhalation of tobacco smoke, emissions from heated cooking oil
and diesel engine exhaust, and dermal exposure to hair dyes.
During the 1870s, the first aromatic amine dyes were
manufactured in Germany (dyes of natural origin were used
prior to the synthesis of dyes). In 1895, a physician by the name
Rehn reported a cluster of patients who had developed bladder
cancer. He observed that all of the affected workers were
employed at a site in Germany that manufactured fuschsin dye.
The workers had all been exposed to large amounts of intermediate
arylamines. The United States first started manufacturing
dyes in the early 1900s when trade between the
United States and Germany was halted during the First World
War. DuPont was the first company to begin manufacturing
synthetic dyes in the United States, and shortly thereafter
(1930s) the physicians employed by DuPont also started
reporting an increased incidence of workers who had developed
bladder cancer. During 1947, a physician by the name of
Mengellsdorf who was employed by DuPont reported that
100% of the workers who handled the chemical betanaphthylamine
had developed bladder cancer. By the 1950s,
Chinese dye manufacturers reported the development of
bladder cancer in workers who handled benzidine. Evidence of
the development of bladder cancer associated with the manufacture
of dyes continued to mount, and during the 1970s dye
manufacturing was discontinued in the United States and was
taken over by developing nations. During the early 1970s, the
US Occupational Safety and Health Administration (OSHA)
began regulating aromatic amines that had been associated
with the development of bladder cancers. During the 1980s,
DuPont reported retrospectively that 316 of their dye
manufacturing workers had developed bladder cancer prior to
the discontinuation of dye manufacturing in the United States.
During the 1990s, the first reports of bladder cancer in the
Chinese dye manufacturing industry became public.
Hair dye products manufactured prior to the mid-1970s
contained chemicals that were shown to produce cancer in rodents. Some of these chemical included aromatic amines.
The manufacturers of hair coloring products began reformulating
their products to remove these potentially carcinogenic
compounds from their products beginning in the mid-1970s. It
is not clear if some of the ingredients in contemporary hair
products can cause an increased risk of cancer. The US National
Cancer Institute reported that there may be an increased risk of
developing non-Hodgkin’s lymphoma in people who used hair
dyes prior to the 1980s; however, the data are limited and often
inconsistent.
WHITE TO SLIGHTLY BROWN CRYSTALLINE POWDER
PAAs are used in the rubber, textile, and dye industries. They are
used as intermediates in the manufacture of plastics, drugs, and
carbamate pesticides. The aromatic amines 2-aminofluorene
and N-acetyl aminofluorene were being developed during the
1930s for use as pesticides; however, they were found to be
carcinogenic in laboratory animals. They were never marketed
as pesticides.
2-Aminofluorene is sensitive to prolonged exposure to air. Insoluble in water.
2-AMINO FLUORENE forms salts with acids and can react with oxidizing materials.
ACUTE/CHRONIC HAZARDS: When heated to decomposition 2-Aminofluorene emits toxic fumes.
Flash point data for 2-Aminofluorene are not available, but 2-Aminofluorene is probably combustible.
Suspected carcinogen
with experimental carcinogenic,
neoplastigenic, and tumorigenic data. Poison
by intraperitoneal route. Mutation data
reported. When heated to decomposition it
emits toxic fumes of NOx. See also AMINES.
The general method for the synthesis of 2-aminofluorene from 2-nitrofluorene was as follows: in a 25 mL round-bottomed flask, nitroaromatics (1 mmol), SS-Pd (2 mol% Pd), and sodium borohydride (3 mmol) were added sequentially. At 0 °C and under stirring conditions, 3 mL of MeOH:H2O (3:7, v/v) was slowly added to the mixture via syringe. after 10 min, the reaction system was warmed up to 50 °C to continue the reaction. The reaction process was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was extracted with ethyl acetate and the organic phase was dried over anhydrous Na2SO4. After the solvent was removed by evaporation under reduced pressure, the crude product was purified by column chromatography on silica gel (60-120 mesh) to afford the target product 2-aminofluorene.
PAAs may be transported as vapor or adsorbed onto particulates.
Due to low water solubility, PAAs are not transported in
water but adsorb onto soil and sediments. Leaching is negligible.
Bioaccumulation is not considered a concern.
Wash the amine well with H2O and recrystallise it from Et2O or 50% aqueous EtOH (25g with 400mL), and dry it in a vacuum. Store it in the dark. [Bavin Org Synth Coll Vol V 30 1973, Beilstein 12 H 1331, 12 IV 337.]
N-hydroxy metabolites within the gastrointestinal tract transform
fluoren-2-amine into a mutagen or carcinogen. A number
of PAAs are potent bladder carcinogens. As noted previously,
sequential hydroxylation and glucuronidation lead to urinary
excretion, with metabolites in the urinary bladder. While glucuronidation
enhances excretion via the urine, a glucuronidase
in the bladder hydrolyzes the glucuronide and under acidic
conditions N-hydroxylarylamines are formed. Subsequent conversion of the amine leads to an aryl nitrenium ion, which
can initiate tumor formation. Sulfate esters can degrade to
electrophilic nitronium ion–carbonium ion, which can form
adducts with macromolecules.
[1] Analytical Chemistry, 1988, vol. 60, # 3, p. 194 - 199
[2] Tetrahedron Letters, 2012, vol. 53, # 36, p. 4858 - 4861
[3] Chemical Communications, 2013, vol. 49, # 86, p. 10088 - 10090
[4] ChemSusChem, 2017, vol. 10, # 15, p. 3035 - 3039
[5] Applied Organometallic Chemistry, 2018, vol. 32, # 1,
