108-91-8

Cyclohexylamine(108-91-8) appears as a clear colorless to yellow liquid with an odor of ammonia. Flash point 90 °F. Irritates the eyes and respiratory system. Skin contact may cause burns. Less dense than water. Vapors heavier than air. Toxic oxides of nitrogen produced during combustion.

CYCLOHEXYLAMINE(108-91-8) neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

Highly flammable. Sensitive to air and light. Soluble in water.

This is classified as very toxic--probable oral lethal dose is 50-500 mg/kg or between 1 teaspoon and 1 ounce for a 70 kg (150 lb.) person. It is considered a nerve poison. This is a weak methemoglobin-forming substance.

CHA is used in making dyes, chemi- cals, dry cleaning chemicals; insecticides, plasticizers, rub- ber chemicals; and as a chemical intermediate in the production of cyclamate sweeteners. Used in water treat- ment and as a boiler feedwater additive. It is also used in rubber production to retard degradation.

When heated to decomposition, CYCLOHEXYLAMINE emits highly toxic fumes. Vapor may travel a considerable distance to source of ignition and flash back. Toxic oxides of nitrogen are produced during combustion. Nitric acid; reacts vigorously with oxiding materials. Stable, avoid physical damage, storage with oxidizing material.

If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, includ- ing resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medi- cal attention. If victim is conscious, administer water or milk. Do not induce vomiting. Medical observation is recommended for 24 to 48 hours after breathing overexpo- sure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy.

UN2357 Cyclohexylamine, Hazard class: 8; Labels: 8-Corrosive material, 3-Flammable liquid.

May form explosive mixture with air. Cyclohexylamine is a strong base: it reacts violently with acid. Contact with strong oxidizers may cause fire and explosion hazard. Incompatible with organic anhydrides; isocyanates, vinyl acetate; acrylates, substituted allyls; alkylene oxides; epichlorohydrin, ketones, aldehydes, alco- hols, glycols, phenols, cresols, caprolactum solution; lead. Corrosive to copper alloys, zinc, or galvanized steel.

Cyclohexylamine is a colorless to yellow liquid (amines, primary aromatic). It has an unpleasant fishyodor. Molecular weight=99.20; Specific gravity=0.87;Boiling point=134.4℃; Freezing/Melting point 52 -17.7℃; Vapor pressure=11 mmHg at 20℃; Flashpoint=31℃; Autoignition temperature=293℃. Explosivelimits: LEL=1.5%; UEL=9.4%. Hazard Identification(based on NFPA-704 M Rating System): Health 3,Flammability 3, Reactivity 0. Soluble in water.

Cyclohexylamine is a colorless to yellow liquid (amines, primary aromatic). It has an unpleasant fishy odor.

Incineration; incinerator equipped with a scrubber or thermal unit to reduce nitrogen oxides emissions.

Cyclohexylamine is used in the manufactureof a number of products, including plasticizers, drycleaning soaps, insecticides, andemulsifying agents. It is also used as a cor rosion inhibitor and in organic synthesis.

In organic synthesis, manufacture of insecticides, plasticizers, corrosion inhibitors, rubber chemicals, dyestuffs, emulsifying agents, dry-cleaning soaps, acid gas absorbents.

ChEBI: Cyclohexylamine is a primary aliphatic amine consisting of cyclohexane carrying an amino substituent. It has a role as a human xenobiotic metabolite and a mouse metabolite. It is a conjugate base of a cyclohexylammonium.

Cyclohexylamine is produced by the reaction of ammonia and cyclohexanol at elevated temperature and pressure in the presence of a silica-alumina catalyst (SRI 1985). It is also prepared by a similar process of catalytic hydrogenation of aniline at elevated temperature and pressure. Fractionation of the product of this reaction yields CHA, aniline, and a high-boiling residue containing n-phenylcyclohexylamine and dicyclohexylamine (Carswell and Morrill 1937). In 1982, U.S. production was 4.54 metric tons and 739.3 metric tons were imported into the U.S. (SRI 1985).

Cyclohexylamine reacts with chlorine to form N,N-dichlorocyclohexylamine. N-Cyclohexylidenecyclohexylamine reacts with chloramine to give 1-cyclohexyl-3,3-pentamethylenediaziridine, which can be hydrolyzed to give cyclohexylhydrazine [46]. Cyclohexylamine and formaldehyde together react with peracetic acid to give 2-cyclohexyloxaziridine. In addition to using alkyl halides, alkyl sulfates, or alkyl phosphates, cyclohexylamine can be alkylated with an alcohol in the presence of a catalyst, such as aluminum oxide, copper, nickel, cobalt, or platinum, or by the Leuckart – Wallach method.

Flammable

The primary use of cyclohexylamine is as a corrosion inhibitor in boiler water treatment and in oil field applications (HSDB 1989). It is also a chemical intermediate for rubber processing chemicals, dyes (acid blue 62, former use), cyclamate artificial sweeteners and herbicides and a processing agent for nylon fiber production (SRI 1985). Windholz et al (1983) reports its use in the manufacture of insecticides, plasticizers, emulsifying agents, dry-cleaning soaps, and acid gas absorbents.

Prepared by catalytic hydrogenation of aniline at elevated temp and pressures. Fractionation of crude reaction product yields cyclohexylamine, unchanged aniline, and high-boiling residue containing n-phenylcyclohexylamine (cyclohexylaniline) and dicyclohexylamine.

According to the International Agency for Research of Cancer (IARC) working group, there is no evidence that cyclohexylamine is teratogenic or carcinogenic.
Price et al. reported the development of bladder tumors in Charles River rats fed cyclohexylamine sulfate for 2 years at doses of 0, 0.15, 1.5, and 15 mg/kg/day, 25 male and 25 female per dosage group. During the first year, there was only a slight depression of weight gain in the males of the high-dose group; no other signs of toxicity were observed. At the end of 2 years (104 weeks) 13–16 animals were still alive in the 0.15- and 1.5- mg/kg groups, and eight males and nine females in the 15- mg/kg group. An invasive transitional-cell carcinoma of the bladder was observed in one of eight male survivors of the high-dose group. The author noted that spontaneous bladder tumors were very rare in the strain of rats used. No other relevant findings were noted. Gaunt used the same dosages for a 2 year diet feeding study in Wistar rats. They observed no evidence of carcinogenicity, slight anemia, failure to produce normally concentrated urine, and an increase in the number of animals with foamy macrophages in the pulmonary alveoli at the highest dosage level. Decreased food intake caused the lessened body weight gain and organ weights as compared to the controls. Animals that received 2000 or 6000 ppm showed testicular atrophy or tubules with few spermatids. The no-untoward-effect level in both of these studies was 600 ppm, equivalent to an intake of about 30 mg/kg/day.

Cyclamate is metabolized to cyclohexylamine by the gut flora in the rat (Renwick and Williams 1969; Bickel et al 1974; Tesoriero and Roxon 1975) and is excreted in the urine after cyclamate ingestion by rats, rabbits, dogs, monkeys, and humans (Asahina et al 1971; Coulston et al 1977; Kojima and Ichibagase 1968; Leahy et al 1967; Oser et al 1968). There is individual variation in the ability to biotransform cyclamate to cyclohexylamine, probably due to the presence or absence of the necessary bacteria. Bacteria exposed to cyclamate seem to acquire the ability to convert cyclamate. Those individuals that do produce cyclohexylamine have been categorized by researchers as convertors. Rhesus monkeys fed cyclamate for eight years converted 0.5% of the dose to cyclohexylamine which in turn was metabolized to cyclohexanone and cyclohexanol to the extent of 1-2% (Coulston et al 1977).
Generally, cyclohexylamine is readily absorbed and rapidly excreted from the body. After administration to rats, cyclohexylamine appears in body tissues with the highest concentrations in the lungs, spleen, liver, adrenals, heart, gastrointes- tinal tract and kidneys (Estep and Wiegand 1967 as reported by Bopp et al 1986).
After oral administration (0.2 g/kg) to rabbits, cyclohexylamine gave rise to unchanged cyclohexylamine and 7V-hydroxycyclohexylamine in the urine (Elliott et al 1968). When [¹⁴C]-labelled cyclohexylamine was administered, 68% of the radioactivity was recovered in the urine after 60 h. A small amount (0.5%) was eliminated in the breath and 45% of the administered dose was shown to be excreted in the urine as unconjugated cyclohexylamine, 0.2% as JV-hydroxycyclohexylamine in conjugated form, and 2.5% as cyclohexanone oxime. The authors postulated the latter metabolite to be an artifact formed from the glucuronide of TV-hydroxy cyclohexylamine during the hydrolysis procedure.
In contrast to rabbits, man, as well as rats and guinea pigs, excrete 90% or more of a dose of [¹⁴C]-labelled cyclohexylamine unchanged in the urine (Renwick and Williams 1972). Small amounts of radioactivity were found in the feces, 1% or less in man, rat and rabbit, and 4-7% in the guinea pig. Only 4-5% of the dose was metabolized in 24 h in the rat and guinea pig and 1-2% in man. The metabolites identified indicated that in rats, the metabolism of cyclohexylamine was mainly through hydroxylation of the cyclohexane ring, in man by deamination and in guinea pigs and rabbits by ring hydroxylation and deamination. The metabolites to cyclohexylamine were excreted in both free and conjugated forms.
When cyclohexylamine was administered orally to healthy adult humans at doses of 2.5, 5, and 10 mg/kg body weight, 86-95% of the dose was excreted in the urine in 48 h as unchanged cyclohexylamine (Eichelbaum et al 1974). Dose dependency was shown by the plasma half-lives which ranged from 3.5 to 4.8 h. A study by Roberts and Renwick (1985) showed other species and strain differences in metabolism of cyclohexylamine. After administration of [¹⁴C]- cyclohexylamine (35-500 mg/kg) to male mice and rats, 80% of the dose was excreted in the urine 24 h after dosing. In Wistar rats, 14-19% of the ¹⁴C was present as 3- and 4-aminocyclohexanols, while in the DA strain rat, aminocyclohexanols accounted for only 1-2% of the activity, and in mouse, <1%. Dose or route of administration did not significantly affect metabolism.
When [¹⁴C]-cyclohexylamine hydrochloride was administered to pregnant rhesus monkeys by infusion into the antecubital vein, maternal and fetal levels of radioactivity were virtually identical over a period of 6 h (Pitkin et al 1969) indicating that cyclohexylamine freely crosses the hemochorial placenta.
Rabbit liver microsomes have been shown to deaminate cyclohexylamine to cyclohexanone in the presence of NADPH and molecular oxygen (Kurebayashi et al 1979). The hexanone was then reduced to the alcohol (approximately 75% of the deaminated product). Carbon monoxide, SKF 525A, metyrapone, potassium cyanide and mercuric chloride inhibited the deamination. These results suggest that the deamination is catalyzed by a microsomal cytochrome P-450 monooxygenase system.

Cyclohexylamine can be stored and shipped in iron tanks. Nonferrous metals, particularly copper-containing materials, are attacked and are therefore unsuitable. The amine discolors on contact with air and therefore must be kept under nitrogen.

Dry the amine with CaCl2 or LiAlH4, then distil it from BaO, KOH or Na, under N2. Also purify it by conversion to the hydrochloride (which is crystallised several times from water), then liberation of the amine with alkali and fractional distillation under N2. The hydrochloride has m 205-207o (dioxane/EtOH). [Lycan et al. Org Synth Coll Vol II 319 1943, Beilstein 12 III 10, 12 IV 8.]