Isomers ortho

Phenol may be nitrated with dilute nitric acid to 3deld a mixture of o- and nitrophenols the 3deld of p-nitrophenol is increased if a mixture of sodium nitiute and dilute sulphuric acid is employed. Upon steam distilling the mixture, the ortho isomer passes over in a substantially pure form the para isomer remains in the distillation flask, and can be readily isolated by extraction with hot 2 per cent, hydrochloric acid. The preparation of m-nitrophenol from wt-nitroaniline by means of the diazo reaction is described in Section IV,70. 

Reagent Temp. X ortho Isomers (%) meta % para Ref. 

When the ortho para directing bromine is introduced first the major product is p bro moacetophenone (along with some of its ortho isomer from which it is separated by distillation)... 

Orthoferrites Ortho isomer Orthometallation Orthomumetal Orthonol... 

Triaryl phosphates are produced from the corresponding phenols (usually mixtures) by reaction with phosphoms oxychloride, usually in the presence of a catalyst (94—96). They are subsequently distilled and usually washed with aqueous bases to the desired level of purity. Tricresyl phosphate was originally made from petroleum-derived or coal-tar-derived cresyflc acids, ie, cresols, variously admixed with phenol and xylenols. Discovery of the toxicity of the ortho-cresyl isomers led manufacturers to select cresols having very Httle ortho-isomer. 

Economic Aspects. U.S. production of chloronitrobenzenes in 1993 was 54,431 metric tons per year of which 19,099 metric tons were the ortho isomer and 35,332 metric tons the para isomer. The meta isomer is not isolated in U.S. production. The bulk, fob prices of o- and / -chloronitrobenzene were 1.72/kg and 2.01/kg, respectively. Chloronitrobenzenes are manufactured by Du Pont and Monsanto Co. 

Health nd Safety Factors. The mononitrochlorobenzenes are toxic substances which may be absorbed through the skin and lungs giving rise to methemoglobin. Their toxicity is about the same as or greater than that of nitrobenzene. The para isomer is less toxic than the ortho isomer, and the maximum allowable concentration that has been adopted for -nitrochlorobenzene is 1 mg/m (0.1 ppm) (6). The mononitrochlorobenzenes are moderate fire hazards when exposed to heat or flame. They ate classified by the ICC as Class-B poisons. The same handling precautions should be used for these compounds as are used for nitrobenzene. 

Economic Aspects. Annual 1993 U.S. production of the mononitrotoluenes is 26,000 metric tons, with about 16,120 metric tons of the ortho isomer, 780 metric tons of the meta isomer, and 9,100 metric tons of the para isomer. The prices of (9-, m-., and -nitrotoluene in bulk fob are 1.15/kg, 2.54/kg, and 3.64/kg, respectively. The mononitrotoluenes are manufactured by Du Pont and First Chemical Corp. 

In the reaction of arulinium sulfate [542-16-5] with fuming sulfuric acid, the major products are m- and -aminoben2enesulfonic acid with less than 2% of the ortho isomer. With excess concentrated sulfuric acid (96.8—99.9%) at 60—100°C, the sulfate salt gives mainly the ortho and para isomers of the sulfonic acid (42). 

The -phenylenediamines are special and are used in many appHcations where the other isomers are ineffective. They are unique because they are more readily oxidi2ed than the meta or ortho isomers, as seen by the ioni2ation potentials Hsted in Table 2. The enhanced reactivity of -phenylenediamine is due to the high degree of resonance stabili2ation of its radical cation. 

Early Synthesis. Reported by Kolbe in 1859, the synthetic route for preparing the acid was by treating phenol with carbon dioxide in the presence of metallic sodium (6). During this early period, the only practical route for large quantities of sahcyhc acid was the saponification of methyl sahcylate obtained from the leaves of wintergreen or the bark of sweet bitch. The first suitable commercial synthetic process was introduced by Kolbe 15 years later in 1874 and is the route most commonly used in the 1990s. In this process, dry sodium phenate reacts with carbon dioxide under pressure at elevated (180—200°C) temperature (7). There were limitations, however not only was the reaction reversible, but the best possible yield of sahcyhc acid was 50%. An improvement by Schmitt was the control of temperature, and the separation of the reaction into two parts. At lower (120—140°C) temperatures and under pressures of 500—700 kPa (5—7 atm), the absorption of carbon dioxide forms the intermediate phenyl carbonate almost quantitatively (8,9). The sodium phenyl carbonate rearranges predominately to the ortho-isomer. sodium sahcylate (eq. 8). 

Ethyltoluene is manufactured by aluminum chloride-cataly2ed alkylation similar to that used for ethylbenzene production. All three isomers are formed. A typical analysis of the reactor effluent is shown in Table 9. After the unconverted toluene and light by-products are removed, the mixture of ethyltoluene isomers and polyethyltoluenes is fractionated to recover the meta and para isomers (bp 161.3 and 162.0°C, respectively) as the overhead product, which typically contains 0.2% or less ortho isomer (bp 165.1°C). This isomer separation is difficult but essential because (9-ethyltoluene undergoes ring closure to form indan and indene in the subsequent dehydrogenation process. These compounds are even more difficult to remove from vinyltoluene, and their presence in the monomer results in inferior polymers. The o-ethyltoluene and polyethyltoluenes are recovered and recycled to the reactor for isomerization and transalkylation to produce more ethyltoluenes. Fina uses a zeoHte-catalyzed vapor-phase alkylation process to produce ethyltoluenes. 

Toluenesulfonyl Chloride. Toluene reacts with chlorosulfonic acid to yield both ortho- and j )i7n7-toluenesulfonyl chlorides, of which Monsanto is the only producer. The ortho isomer is converted to saccharin. 

Diazophenols, ie, o-hydroxyaryldiazonium salts, couple to 1-naphthol in weaMy basic solution primarily in the para position, but as the hydroxyl ion concentration is increased, formation of the ortho isomer is favored and is frequentiy the sole product. Pyridine and pyridine derivatives, urea, and acetate, etc, used as buffers can also catalyze azo coupling reactions (28). l-amino-2-naphthol-4-sulfonic acid [116-63-2] (1,2,4-acid) and 1-naphthol yield the important Eriochrome Black A [3564-14-5] (18a, R = H) (Cl Mordant Black 3 Cl 14640) which is reportedly (20) a mixture of ortho and para isomers. 

Continuous chlorination of benzene at 30—50°C in the presence of a Lewis acid typically yields 85% monochlorobenzene. Temperatures in the range of 150—190°C favor production of the dichlorobenzene products. The para isomer is produced in a ratio of 2—3 to 1 of the ortho isomer. Other methods of aromatic ring chlorination include use of a mixture of hydrogen chloride and air in the presence of a copper—salt catalyst, or sulfuryl chloride in the presence of aluminum chloride at ambient temperatures. Free-radical chlorination of toluene successively yields benzyl chloride, benzal chloride, and benzotrichloride. Related chlorination agents include sulfuryl chloride, tert-huty hypochlorite, and /V-ch1orosuccinimide which yield benzyl chloride under the influence of light, heat, or radical initiators. 

Chlorotoluene [106-43-4] (l-chloto-4-methylbenzene, PCT) and y -chlorotoluene [108-41-8] (l-chloto-3-methylbenzene, MCT) ate mobile, colorless Hquids with solvent properties similar to those of the ortho isomer. 

Compound ortho Isomers formed (%) meta para 2,4... 

Several flaoraza reagents shown in Tables 3a and 3b (B, C, E, F, J, and K) are reactive enough to fluorinate an aromatic ring (Table 1). The ortho isomer predominates in the o/mlp mixture Reagent K has been used to prepare fluorinated derivatives of tyrosine and estradiol [77 (equation 35) (Table 1, entry 10)... 

Like the chloronitrobenzenes, a chloroquinoline reacts faster with sodium p-tolylsulfide when the chloro group is para to the aza-group than when it is orthoy the factor involved being about 10. However, a strikingly different behavior is noted in the much lower BS-/ BO- ratio which is 2.5 for 4-chloroquinoline ( para isomer) and 0.24 for 2-chloroquinoline ( ortho isomer). For p-chloronitro-benzene this ratio is 38, and for 2,4-dinitrochlorobenzene it is 1950. Thus far there is no case in which the reaction of a chloronitrobenzene derivative with sodium methoxide is faster than that with sodium phenylsulfide. 

In many cases, however, the ortho isomer is the predominant product, and it is the meta para ratio which is close to the statistical value, in reactions both on benzenoid compounds and on pyri-dine. " There has been no satisfactory explanation of this feature of the reaction. One theory, which lacks verification, is that the radical first forms a complex with the aromatic compound at the position of greatest electron density that this is invariably cither the substituent or the position ortho to the substituent, depending on whether the substituent is electron-attracting or -releasing and that when the preliminary complex collapses to the tr-complex, the new bond is most likely to be formed at the ortho position.For heterocyclic compounds such as pyridine it is possible that the phenyl radical complexes with the nitrogen atom and that a simple electronic reorganization forms the tj-complex at the 2-position. 

The product is analyzed by vapor phase chromatography using a 6-ft., f-in. O.D. copper tube, packed with 5% Bentone-34 (Wilkins Instrument Co.) and 0.5% XF-1150 (General Electric Silicone Products) on Diatoport-S (80-100 mesh) (F and M Co.) flow rate of helium 60 ml./min., oven temperature 85°. This column separates m-cymene (retention time 12 minutes) from />-cymene (retention time 10 minutes) but does not resolve the ortho isomer. The purity of the distilled w-cymene is above 98%. 

The mass spectra of all three isomers are different. The ortho isomer loses 17 Daltons (OH, small peak) from its intense molecular ion. The m- and p-isomers lose 16 Daltons from their molecular ions and can be distinguished by comparing the relative abundances of the m/z 65 fragment ion versus their molecular ions. The m/z 65 ion is the most abundant ion in the mass spectrum of the m-isomer (see Figure 22.2), while the molecular ion at m/z 138 is the most abundant ion in the mass spectrum of the p-isomer. 

Meta-Nitrobenzoate. A solid, mp 102—3° prepd the same way as the ortho isomer using m-nitrobenzoyl chioride, yield 71% (Ref 3). Impact sensy with a 2kg wt, no explns at 175cm... 

In general the para isomer is the main product but about 5 % ortho isomer was detected6 when the solvent was aqueous acetic acid. All the evidence suggests that the rearrangement is intermolecular involving the reversible formation of free chlorine and the anilide, reaction (2), followed by C-chlorination of the anilide, reaction (3)... 

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