Benzene

BENZENE, Benzolum, the primary hydrocarbon of the aromatic series, C₆H₆. Discovered by Faraday (1825); Mitscherlich (1833) obtained benzene by the dry distillation of benzoic acid with lime, named it Benzinum, and determined its formula as C₆H₆; it was named benzene by Liebig. The constitutional formula for benzene was provided by Kekulé (1865), which constituted an epoch in organic chemistry. It was first synthesized by Berthelot (1866) from acetylene. Benzene is contained in illuminating gas, in the light oil of coal tar, in Burmese petroleum, and in certain other types of petroleum. Benzene is a colorless, mobile, slightly aromatic liquid; it boils at 80.5°, solidifies at about 0° in the form of large rhombic leaflets that melt at +5.48°; specific gravity at 15° is 0.8841; it is almost insoluble in water, miscible with methyl and ethyl alcohols, ether, acetone, and oils; it dissolves small amounts of sulfur and phosphorus, and is a good solvent for bromine, iodine, fats, resins, rubber, essential oils, certain alkaloids, etc. Chemically pure benzene is obtained by the dry distillation of benzoic acid with calcium hydrate; benzene is obtained, mainly, during the dry distillation of coal at gas and coking plants. Benzene is purified by distillation in column apparatuses, then by freezing; to remove thiophene (C₄H₄S), it is treated with H₂SO₄; the presence of thiophene in benzene is detected by a blue coloration from H₂SO₄ with a small amount of isatin. Benzene is detected in liquids or in the air by treatment with concentrated HNO₃; the nitrobenzene formed in this process has a sharp odor of bitter almonds. Among the derivatives of benzene, those of medical significance are: 1) phenol C₆H₅OH, or crystalline carbolic acid, and 2) nitrobenzene, or oil of mirbane, C₆H₅NO₂—a poisonous, cheap product with the odor of bitter almonds, used to add scent to soap, sweets, liqueurs, and fruit drinks. Benzene was prescribed in doses of 0.5, 1.0 to 1.5, 3 to 4 times a day for intestinal parasites (its effect on maternal trichinae is doubtful), and for chronic vomiting and digestive disorders. Doses of 25–30 g of benzene have a poisonous, sometimes fatal, effect; inhalation of benzene vapors is also dangerous. Benzene, being a good solvent for paraffin (at 20° it dissolves 8% of paraffin with a boiling point of 57–58°), is used in microtechnique as an intermediate medium during embedding. It is a good solvent for Canada balsam and other resins; due to its high refractive index (n_D = 1.501), benzene provides strong clearing of preparations. In the processing of nerve fibers, benzene is used to dissolve myelin.

N.

Kornilov. Benzene as an industrial poison. Benzene is one of the most serious occupational hazards. While yielding to gasoline (see) in the number of cases of occupational poisoning, it significantly surpasses it in its toxicity and the severity of the changes it causes. Chemically pure benzene (boiling point 80–82°) is rarely used in industry. Various grades of unrefined benzene are more commonly used, containing only 50–85% benzene, but with a significant amount of impurities that have a higher boiling point (toluene, xylene, paraffin, thiophene, carbon disulfide, ethylene, etc.). In connection with this, the toxicity of various types of "crude benzene" may be unequal. The danger of benzene poisoning exists wherever it is encountered: during its extraction (distillation of coal tar and at coke-benzene plants); in industries where benzene is a starting product or an essential component—in the production of aniline and other aromatic substances, especially coal-tar dyes; in the manufacture of explosives; in the preparation of all kinds of perfumes and various pharmaceutical preparations. Benzene is used for dissolving or extracting substances that are difficult or completely insoluble in water: iodine, phosphorus, fats (from bones, meat-and-fish residues, coconuts), various alkaloids (from seeds and other parts of plants), caoutchouc and rubber (in the manufacture of "rubber glue"), various resins, glues, varnishes, and coloring compositions (in particular, in the aviation industry); for impregnation in the manufacture of oilcloth, linoleum, and waterproof fabrics; in the processes of stain removal, and chemical cleaning of clothing and fabrics. Benzene is used as a fuel (mixing with gasoline, alcohol, illuminating gas, water gas for autogenous welding, etc.). Often, various benzene-containing and highly poisonous compositions are sold under the most whimsical patented names; sometimes benzene is confused with gasoline (in French, the same term—benzene—is often used). Benzene is absorbed into the blood regardless of the route of entry into the body. The penetration of benzene through the skin plays an insignificant role, although benzene, by dissolving the superficial skin fat, can be absorbed even in the absence of damage. Most often, poisonings occur from the inhalation of benzene vapors (according to Lehmann, 80–85% of benzene vapors are absorbed by inhalation from the air in 1/2 hour). Benzene is eliminated from the body quite slowly, mainly with exhaled air (a characteristic smell of benzene from the mouth for several days after poisoning) and with urine, in the form of paired compounds of benzene oxidation products—phenol, pyrocatechin, and hydroquinone with sulfuric acid. A case of detecting benzene in the tissues of corpses of persons who died from poisoning by it has been described. Occupational benzene poisonings can be acute and chronic (sometimes subacute). Acute poisonings often take the form of an accident: during the cleaning of various vessels, tanks, and receivers from benzene, during the accidental spilling of significant quantities of benzene, during the rupture of pipelines, during the unexpected cessation of ventilation, etc. Acute poisonings can differ in intensity, causing changes in the body of the victims—from very insignificant and quickly passing to a "lightning-fast" lethal outcome. Death occurs upon inhalation of significant quantities of benzene within a few minutes (up to an hour), probably due to paralysis of the respiratory center. Profuse sweating appears immediately, followed by severe dizziness, sometimes hallucinations, and coma. In other cases of acute poisoning, symptoms of nervous system excitation appear first—headaches, ringing in the ears, general excitement resembling intoxication, hallucinations, delirium, nausea, vomiting, coughing, loss of sensitivity, paresis, coma, death. In milder cases, the matter is limited to the stage of excitation, along with malaise (nausea, dizziness, vomiting, etc.); a special sensation of euphoria appears, which causes the victim to lose proper orientation in what is happening and not notice the danger, which can sometimes become the cause of further poisoning. Phenomena from the circulatory system, as well as the blood, recede into the background during acute poisoning; initially, pallor is noted, then dilation of the vessels of the face and visible mucous membranes, rapid and weak pulse, lowering of blood pressure, and leukopenia. The prognosis is difficult to make immediately. Even mild cases can lead to severe complications and heal very slowly. In chronic and subacute poisonings, phenomena from the hematopoietic organs and the cardiovascular system come to the fore, but the nervous system also experiences a number of disorders. And here, poisonings provide a huge range in terms of intensity. The point of view of Lehmann (K. B. Lehmann), who believed that the severe occupational benzene poisonings described several decades ago (Santesson in 1897, Lenoire and Claude) could not occur under the conditions of modern technology, has been refuted by life itself. In recent years, a number of very severe, often fatal, cases have been described as a result of subacute and chronic poisoning by benzene vapors. Teleky and Weiner collected from literary sources a casuistry of 31 cases of chronic benzene poisoning that ended in death and added to them a number of severe cases from their personal practice. In 1925, Lowy described an interesting case of the death of a worker from an automobile tire factory who, in addition to a number of other symptoms characteristic of benzene poisoning, had necrosis (periostitis gangraenosa et osteomyelitis) of the lower jaw. Chronic poisoning, both in severe and mild cases, produces changes in the blood, and, depending on the strength of the intoxication and the resistance of the body, these changes are more or less clearly expressed in an aplastic-pernicious character. Hemoglobin drops to 70–25%, the number of erythrocytes decreases to 1 million and even to 600,000 (without serious morphological changes); Paul, Friedlander, and Mac Cord found basophilic stippling and polychromasia of erythrocytes in a number of workers handling benzene in the absence of poisoning, as well as in individual cases of mild chronic poisoning. Therefore, they tentatively consider basophilic stippling an early symptom of the effect of benzene on the body, especially since their experiments on rabbits and guinea pigs confirmed this connection. Also, the number of blood platelets decreases sharply, sometimes reaching zero; the color index turns out to be sometimes higher, sometimes lower than unity. Leukopenia is especially characteristic (benzene is used, as is known, for the treatment of leukemia). After a short period of leukocytosis, as an indicator of bone marrow irritation, a decrease in leukocytes begins, in individual cases to 1,000 and even less. The American "Safety Council" commission for the study of occupational benzene poisoning believes that a drop in the number of leukocytes below 5,600, even in the absence of other clinical phenomena, indicates the onset of benzene poisoning. As for the leukocyte formula, different authors obtained different pictures. According to Brücken, lymphocytosis, mononucleosis, a decrease in segmented cells, erythrocytes—normal; according to Flaudin and Roberti, mononucleosis reached 94%, and eosinopenia 1%; according to Chamboket—eosinopenia; according to Heim, Agasse-Lafon, and Feil—mononucleosis and eosinopenia; according to Teleky and Weiner—lymphocytosis. Experiments and pathological-anatomical autopsies of the poisoned (Selling, Rubner, Baldridge and Hausmann, Brandino, Bruni) have firmly established that benzene acts electively on the hematopoietic system, causing fatty degeneration and aplasia of the bone marrow of flat and tubular bones. Only with very small doses can one assume an effect only on erythrocytes (see also Gasoline). Aplasia of the bone marrow, causing thrombocytopenia, contributes to the appearance of sharp bleeding and small hemorrhages. Therefore, in chronic benzene poisoning, in milder degrees, nosebleeds, bleeding from the gums, increased menstruation, and uterine bleeding are noted; in more severe, sometimes fatal cases, along with symptoms of severe anemia (pallor), dizziness, headaches, general weakness, fatigue, and often a significant decrease in temperature appear. Numerous subcutaneous hemorrhages are noted—from pinpoint to diffuse patchy ones, scurvy-like changes in the gums and oral mucosa, and bleeding from internal organs (intestinal, gastric, renal). This whole state can be characterized as a hemorrhagic diathesis (Freyfeld). Finally, as with acute poisonings, the nervous system is also affected. In addition to various subjective sensations, retrobulbar neuritis of the optic nerve and polyneuritis sometimes appear. Sometimes the effect of benzene on the skin (sensation of dryness, redness, swelling, eczema) and mucous membranes (conjunctivitis, blepharitis, and even keratitis), irritation of the nasal mucosa and upper respiratory tract is observed. It is highly probable that this local effect of benzene depends on impurities in it. Benzene is determined in the air by absorption with activated charcoal, etc. Permissible hygienic standards for benzene content in the air have not been firmly established; according to Lehmann, benzene is 4 times, and according to Kohn-Abrest—10 times more poisonous than gasoline.

Cases of poisoning have been described with a benzene content in the air of 2-3 : 100,000 (by volume). An American commission (1926) established that 1 : 10,000 already produces definite changes in the organism. Based on these data and considering the particular danger of chronic benzene poisoning, it is more correct to set this standard at 1 : 50,000, which would correspond to approximately 0.06 g per 1 cubic meter. The State Institute for Labor Protection (Moscow) in 1928 proposed a maximum concentration of benzene in the air of industrial establishments of 0.05-0.1 mg per 1 liter. According to Navrotsky, at the Donetsk soda plant, from 0.1 to 0.787 g of benzene per 1 cubic meter of air was detected, and symptoms of chronic poisoning were observed in all workers. Since the effect of benzene and gasoline on the nervous system is quite similar and since they are encountered in more or less similar production conditions, for the question of a general explanation of the mechanism of action of benzene and preventive measures, see Gasoline. It is only necessary to add that habituation to benzene is usually not observed. According to experiments on animals and individual observations, an increase in sensitivity to further poisoning is more likely to be observed. Adolescents and women are particularly susceptible to poisoning. According to labor protection legislation in the USSR, women and adolescents under 18 years of age are not allowed to perform this work. Since benzene is significantly more toxic than gasoline, the latter should be used wherever possible. Likewise, according to recent studies, homologs of benzene - toluene and xylene - are less volatile and less toxic, as a result of which it should be recommended to expand their use at the expense of benzene.

S. Kaplun.

Detection of benzene in forensic cases and occupational poisonings. In fatal poisonings, it is rarely possible to detect benzene in the viscera. The viscera are subjected to steam distillation (see Poisons). The end of the condenser tube is lowered into a receiver with carbon tetrachloride. Upon completion of distillation, the carbon tetrachloride is separated, dried with calcium chloride, and repeatedly shaken with a solution (20%) of dry ammonium nitrate in concentrated sulfuric acid (specific gravity 1.84), and the acid mixture, together with the carbon tetrachloride, is poured into water, shaken, and the carbon tetrachloride is separated. The latter is evaporated, the residue is dissolved in acetone, and 4-5 drops of a 5% sodium hydroxide solution are added: a blue-violet coloration appears. To detect benzene in the air, a certain volume of the latter is drawn with the help of an aspirator through 2-3 absorption flasks (see Industrial Poisons) with a 20% solution of dry ammonium nitrate in concentrated sulfuric acid (specific gravity 1.84). The liquid is poured into water, extracted with ether, the extract is evaporated, the residue is dissolved in acetone, proceeding further as described above. For quantitative determination, the obtained color of the acetone solution is compared with the color of standard solutions taken in the same volume, prepared from m-dinitrobenzene (melting point 90°), under exactly the same conditions as the test solution (amount of alkali, observation time, etc.). A. Stepanov.

BENZENE RING. To explain the peculiar properties of benzene, its homologs, and derivatives, which constitute a special class of organic chemistry (see Aromatic compounds), a whole series of theories has been proposed. In benzene, its carbon atoms are mutually linked in the form of a six-membered ring—the benzene ring, the diameter of which, with the help of X-ray measurements (Debye), was found to be equal to 12.4 * 10^-8 cm, and the 6 C atoms of which are apparently located in one plane. The first formula of benzene, often used as a scheme even at the present time, was proposed by the German chemist Kekulé in 1865. This formula consists of 6 groups (-CH-), arranged in the form of a hexagon (formula I). In view of the fact that the Kekulé formula assumes the presence of three double bonds in benzene, and the properties of benzene do not correspond to the properties of compounds with double bonds, some additional assumptions were introduced. One of these was the hypothesis of partial valencies by Thiele, according to which the second bonds of the C atoms in benzene mutually saturate, forming a closed system; these bonds (formula II, dashed lines) are in "conjugation"—mutual conjugation. With the development of the doctrine of the nature of chemical forces, mainly in connection with the theory of Werner (see Coordination theory), ideas about the structure of benzene underwent some further changes. According to Werner, the forces of chemical affinity of C do not represent separate, independently acting forces (affinity units), but are a partial expression of one force—the general reserve of affinity inherent in the C atom. Thus, the value of each given valence is not predetermined, but depends on the state of saturation of the carbon atom, i.e., on the number of affinity units spent on saturation with other atoms or groups. Such representations can be expressed by formula III, where arc-shaped bonds schematically depict the presence of internal cyclic saturation. Recently, in connection with the doctrine of atomic structure, new electronic formulas for the structure of benzene and other aromatic compounds have been proposed, which, however, have not received wide distribution in organic chemistry and are a more or less successful attempt to explain the properties of benzene as a result of the action of electrostatic forces. S. Medvedev.