重氮化反应 氨基变羟基 m-METHOXYBENZALDEHYDE

Organic Syntheses, Coll. Vol. 3, p.185 (1955); Vol. 24, p.22 (1944).o-CHLOROBROMOBENZENE[Benzene, 1-bromo-2-chloro-]Submitted by Jonathan L. HartwellChecked by H. R. Snyder and Zeno Wicks, Jr..1. ProcedureA mixture of 127.5 g. (1 mole) of a good commercial grade of o-chloroaniline and 300 ml. (2.5 moles) of 48% hydrobromic acid(Note 1) in a 2-l. flask set in an ice bath is cooled to 0° by the addition of ice. A solution of 70 g. (1 mole) of sodium nitrite in 125 ml. of water is added rapidly, with stirring, the temperature being kept below 10° by the addition of small pieces of ice. When only about 5 ml. of the sodium nitrite solution remains, further additions are made cautiously until an excess of nitrous acid remains after the last addition (Note 2).In the meantime, a mixture of 79 g. (0.55 mole) of cuprous bromide(Note 3) and 80 ml. (0.6 mole) of 48% hydrobromic acid(Note 1) is heated to boiling in a 5-l. round-bottomed three-necked flask, equipped with a condenser set for distillation and provided with a 2-l. receiving flask, a steam inlet tube closed by a screw clamp, and a separatory funnel. About one-fourth of the diazonium solution is transferred to the separatory funnel, without filtration, and immediately run into the cuprous bromide-hydrobromic acid solution, which is kept boiling over a free flame, at such a rate that boiling is continuous. When the separatory funnel is nearly empty a further portion of the cold diazonium solution is transferred to it without interrupting the addition. All the diazonium solution is added in this way over a period of about 30 minutes, during which time much of the product steam-distils. When the addition is complete, the stopcock in the separatory funnel is closed, the screw clamp in the steam line is opened, and a vigorous current of steam is passed through the mixture until no more organic material distils. About 1–1.5 l. of distillate is collected.The heavy organic layer is separated from the distillate and washed with 10-ml. portions of concentrated sulfuric acid until the acid becomes only slightly colored during the washings; four washings usually suffice. The oil is then washed with one 100-ml. portion of water, two 50-ml. portions of 5% aqueous sodium hydroxide, and finally with one 100-ml. portion of water. The product is dried over about 3 g. of calcium chloride and distilled from a 250-ml. distilling flask. The yield of pure, colorless o-chlorobromobenzene, boiling at 199–201°/742 mm., is 170–183 g. (89–95%) (Note 4) and (Note 5).2. Notes1. When 40% hydrobromic acid is used in both the diazotization and Sandmeyer reaction the yield is only about 75%.2. Free nitrous acid causes an immediate blue color at the point of contact with starch-iodide test paper.A delayed color or a color around the periphery of the wetted area is of no significance. At all timesthere must be an excess of mineral acid (blue color on Congo paper).3. The submitter used commercial cuprous bromide. The checkers prepared cuprous bromide by dissolving 600 g. (2.4 moles) of commercial copper sulfate crystals and 350 g. (3.4 moles) of sodium bromide in 2 l. of warm water; the solution was stirred while 151 g. (1.2 moles) of solid sodium sulfite was added over a period of 10 minutes. Occasionally a little more sodium sulfite was required to discharge the blue color. The mixture was cooled, and the solid collected on an 8-in. Büchner funnel, washed once with water, pressed nearly dry, and then dried in the air overnight. The yield of cuprous bromide was 320 g. (93%).4. Runs 3 times this size give proportional yields.5. The checkers have prepared the following bromides by the same procedure: m-chlorobromobenzene(b.p. 191–194°) from m-chloroaniline in 91–94% yields; m-dibromobenzene (b.p. 215–217°) from m-bromoaniline in 80–87% yields; and o-bromoanisole (b.p. 114–116°/29 mm.) from o-anisidine in 88–93% yields. In the preparation of o-bromoanisole the washing with sulfuric acid was omitted.3. Discussiono-Chlorobromobenzene has been prepared by the diazotization of o-bromoaniline followed by replacement of the diazonium group by chlorine;1 by the elimination of the amino group from 3-chloro-4-bromoaniline;2 by the chlorination of bromobenzene in the presence of thallous chloride,3aluminum chloride,4 or ferric chloride;4 by the bromination of chlorobenzene without a catalyst5 or in the presence of aluminum,4iron,4ferric bromide,4 or aluminum-mercury couple;6 by the diazotization of o-chloroaniline followed by replacement of the diazonium group with bromine;4,7 from o-chlorophenylmercuric chloride by the action of bromine;8 and by treatment of silver o-chlorobenzoate with bromine.9This preparation is referenced from:z Org. Syn. Coll. Vol. 3, 200z Org. Syn. Coll. Vol. 6, 36References and Notes1.Dobbie and Marsden, J. Chem. Soc., 73, 254 (1898).2.Wheeler and Valentine, Am. Chem. J., 22, 266 (1899).3.Thomas, Compt. rend., 144, 33 (1907).4.Vander Linden, Rec. trav. chim., 30, 305 (1911).5.Van Loon and Wibaut, Rec. trav. chim., 56, 815 (1937).6.Sen and Bhargava, J. Indian Chem. Soc., 25, 277 (1948).7.Narbutt, Ber, 52, 1028 (1919).8.Hanke, J. Am. Chem. Soc., 45, 1321 (1923).9.Dauben and Tilles, J. Am. Chem. Soc., 72, 3185 (1950).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)cuprous bromide-hydrobromic acidcalcium chloride (10043-52-4)sulfuric acid(7664-93-9)sodium sulfite (7757-83-7)sodium hydroxide (1310-73-2)iron (7439-89-6) HYDROBROMIC ACID (10035-10-6) bromine (7726-95-6)sodium bromide (7647-15-6)copper sulfate (7758-98-7)sodium nitrite (7632-00-0)nitrous acid (7782-77-6)aluminum (7429-90-5)chlorobenzene (108-90-7)aluminum chloride (3495-54-3)chlorine (7782-50-5)bromobenzene (108-86-1)cuprous bromide (7787-70-4)ferric chloride (7705-08-0)Benzene, 1-bromo-2-chloro-,o-Chlorobromobenzene (694-80-4) 3-chloro-4-bromoaniline (21402-26-6)thallous chlorideferric bromide (10031-26-2)aluminum-mercurym-chloroaniline (108-42-9)o-chloroaniline (95-51-2)o-bromoaniline (615-36-1)m-bromoaniline(591-19-5)o-bromoanisole (578-57-4)m-chlorobromobenzene (108-37-2)m-dibromobenzene (108-36-1)o-anisidine (90-04-0)o-chlorophenylmercuric chloridesilver o-chlorobenzoate Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 2, p.580 (1943); Vol. 12, p.76 (1932).THIOSALICYLIC ACID[Benzoic acid, o -mercapto-]Submitted by C. F. H. Allen and D. D. MacKay.Checked by Roger Adams and A. E. Knauf. 1. ProcedureCaution! Recently it was reported to us that workers, following the procedure in Coll. Vol. II, pg 580 (diazotization of anthranilic acid and its reaction with sodium disulfide) but substituting 2,3-dimethylaniline for anthranilic acid, experienced a serious explosion upon addition of the diazonium salt solution to the disulfide solution. We urge that extreme caution should always be exercised in the handling of diazonium salts even when they are in solution.In a 4-l. beaker, 290 cc. of water is heated to boiling, and 260 g. (1.1 moles) of crystallized sodium sulfide (Na 2S·9H 2O) and 34 g. of powdered sulfur are dissolved by heating and stirring. A solution of 40 g. of sodium hydroxide in 100 cc. of water is then added and the mixture cooled, first in cold water, and finally by a freezing mixture of ice and salt.In a 2-l. beaker, set in a freezing mixture and provided with a stirrer and a thermometer for reading temperatures to 0°, are placed 500 cc. of water, 137 g. (1 mole) of anthranilic acid , and 200 cc. of concentrated hydrochloric acid ; the stirrer is started and the mixture cooled to about 6°. Meanwhile 69 g. (1 mole) of sodium nitrite is dissolved in 280 cc. of hot water and the solution cooled in ice; portions are then placed in a separatory funnel of convenient size, supported in such a way that the lower end of the stem extends beneath the surface of the anthranilic acid solution. When the temperature has fallen to 5°, the nitrite solution is run in; about 500 g. of cracked ice is added at such a rate as to keep the temperature below 5°. This takes about ten minutes (Note 1). A drop of the solution should give an immediate blue color with starch-iodide paper.The stirrer and thermometer are now transferred to the alkaline sulfide solution, the temperature of which must be below 5°. The diazo solution is added over a period of twenty to thirty minutes along with 950 g. of ice to prevent the temperature from rising above 5°. When addition is complete, the waterbath is removed and the mixture allowed to warm up to room temperature; after two hours the evolution of nitrogen ceases (Note 2). About 180 cc. of concentrated hydrochloric acid is added until the solution is acid to Congo red paper, and the precipitate of dithiosalicylic acid is filtered and washed with water.To remove the excess sulfur, the precipitate is dissolved by boiling with a solution of 60 g. of anhydrous sodium carbonate (soda ash) in 2 l. of water, and the mixture is filtered while hot. It is divided into five equal parts (Note 3), and the dithiosalicylic acid is reprecipitated as before with concentrated hydrochloric acid. The solid is filtered, the cake being sucked as dry as possible.The moist cake is mixed with 27 g. of zinc dust and 300 cc. of glacial acetic acid in a 1-l. round-bottomed flask, and the mixture is refluxed vigorously for about four hours (Note 4). When the reduction is complete, the mixture is cooled and filtered with suction. The filter cake is washed once with water and then transferred to a 1-l. beaker. The cake is suspended in 200 cc. of water, and the suspension is heated to boiling. The hot solution is made strongly alkaline by the addition of about 40 cc. of 33 per cent aqueous sodium hydroxide solution. The alkaline solution is boiled for about twenty minutes to ensure complete extraction of the product from the filter cake, filtered from the insoluble material (Note 5), and the thiosalicylic acid is then precipitated by the addition of sufficient concentrated hydrochloric acid to make the solution acid to Congo red paper. The product is filtered with suction, washed once with water, and dried in an oven at 100–110°. The yield of a product which melts at 162–163° is 110–130 g. (71–84 per cent of the theoretical amount based on the anthranilic acid).This product is sufficiently pure for most purposes (Note 6).For recrystallization 5 g. of this material is dissolved in 20 cc. of hot 95 per cent alcohol, and 40 cc. of water is added. The solution is boiled with a little decolorizing carbon, filtered hot, and then allowed to cool. The product crystallizes in yellow flakes. The yield of recrystallized material is 4.7 g.; the melting point of the material is 163–164°.2. Notes1. This method is much more rapid than when external cooling alone is used (Org. Syn. Coll. Vol. I, 1941, 374). The total volume of the solution is not important since the insoluble dithiosalicylic acid is readily filtered.2. Foaming sometimes becomes very during the evolution of nitrogen. The addition of a few cubic centimeters of ether from time to time helps to keep this foaming under control.3. The dithiosalicylic acid may be precipitated all at once if desired and the entire amount reduced in one operation. If this is done, the reduction must be carried out in a 5-l. flask fitted with a good stirrer. The mixture needs to be refluxed about ten hours over a ring burner. In the laboratory, this is much less convenient than it is to divide the material and reduce in smaller amounts. The yield is not materially lowered by making the reduction in one portion.4. The reduction does not always run smoothly. If the zinc lumps and becomes inactive more must be added. To determine whether reduction is complete, a sample is removed, cooled, and filtered. The precipitate is boiled with strong sodium hydroxide solution, filtered, and then acidified with hydrochloric acid. If the reduction is complete, the precipitated material will melt at 164° or lower. If the reduction is not complete, the precipitated material will melt above 164°. If the reduction is not complete, the refluxing of the main portion must be continued (and perhaps more zinc must be added) until a test portion shows that the reaction is complete.In determining the melting point of the material, the capillary tube containing the test sample should be inserted in a bath previously heated to 163–164°.5. When the reduction is carried out in five portions, one extraction with sodium hydroxide is usually sufficient for each portion. If the reduction is carried out in one operation, several extractions are usually required. When the material is to be extracted more than once, it is best to boil the residue from the first alkaline treatment with hydrochloric acid, filter, and then treat again with the alkali.6. Thiosalicylic acid is used for the preparation of oxythionaphthene and many thioindigoid dyes.3. DiscussionOf the several methods described for the production of thiosalicylic acid, only the following are of preparative interest: heating o-halogenated benzoic acids with an alkaline hydrosulfide at 150–200° in the presence of copper or copper salts,1, 2 or with sodium sulfide at 200°;3 and reduction of dithiosalicylic acid with glucose,4 or metals5, 2 in alkaline solution. The dithiosalicylic acid is prepared by treating diazotized anthranilic acid with sodium disulfide in alkaline solution.5This preparation is referenced from:z Org. Syn. Coll. Vol. 3, 809References and Notes1.(a) Cassella and Company, Ger. pat. 189,200 [C. A. 2, 607 (1908)]; (b) Cain, "IntermediateProducts for Dyes," p. 151.2.Chem. Age 21, Dyestuffs Suppl. p. 11 (1929).3.Cassella and Company, Ger. pat. 193,290 [C. A. 2, 1514 (1908)]; Ref. 1(b).4.Claasz, Ber. 45, 2427 (1912).5.Kalle and Company, Ger. pat. 204,450 [C. A. 3, 1695 (1909)]; Ref. 1(b).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)sodium sulfide (Na2S·9H2O)dithiosalicylic acid sodium carbonate (soda ash) copper or copper saltso-halogenated benzoic acidsalcohol (64-17-5) hydrochloric acid (7647-01-0) acetic acid (64-19-7)ether (60-29-7) sodium hydroxide (1310-73-2) nitrogen (7727-37-9) sodium nitrite(7632-00-0)sulfur (7704-34-9)decolorizing carbon (7782-42-5)zinc (7440-66-6)sodium sulfide (1313-82-2)sodium disulfideAnthranilic Acid (118-92-3)glucose (492-62-6)hydrosulfideThiosalicylic acid,Benzoic acid, o-mercapto- (147-93-3)oxythionaphtheneCopyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

重氮化反应1，历史回顾：1858 年，Peter Griess首次发现了芳香重氮化合物。

1884 年，德国化学家T.Sandmeyer在用乙炔铜和苯胺的重氮盐（PhN2Cl）合成苯乙炔时，得到的主产物却是氯苯，经过仔细研究，发现原来是由于反应中产生的CuCl催化使重氮基被氯取代。

随后，Sandmeyer发现用CuBr和CuCN也能得到相应的溴苯和苯甲腈，因此我们把这一类反应称为Sandmeyer反应。

1890 年，L.Gatterman发现直接用铜粉和盐酸或氢溴酸也能从苯胺得到相应的氯苯或溴苯，这种类型的反应称为Gatterman反应。

1927 年，同样是德国的化学家G.Balz和G.Schiemann发现直接加热苯胺的硼氟酸重氮盐能得到氟苯，这就是Balz-Schiemann反应。

1935 年，F.B.Dains和 F.Eberly用KI去处理重氮盐，成功合成了碘代苯。

随后重氮化羟基取代和重氮化去胺反应也相继被发现，加上偶氮反应，形成了比较完善的芳香重氮化合物反应体系。

2，定义：是指一级胺与亚硝酸在低温下作用生成重氮盐(dizaonium salt)的反应(diazotization)。

脂肪族伯胺与亚硝酸反应，可以订量释放出来氮气，这是测量脂肪伯胺非常好的方法，可以形成碳正离子，副反应比较多，在合成上很少使用。

芳香族伯胺和亚硝酸作用生成的重氮盐，由于氮正离子与苯环的共轭，稳定性大大提高，这样一个中间体，在酸性介质中，在0-5oC可以稳定存在。

一旦遇到光照和加热，会马上分解。

所以这样的一个重氮盐在合成中要现制现用。

3，反应机理：芳胺的重氮化反应需经2步，首先是亲电试剂进攻芳胺氮原子生成不稳定的中间产物，然后不稳定中间产物迅速分解，整个反应受第一步控制。

无机酸不同，参与重氮化反应的亲电试剂也不同。

稀硫酸中参与反应的是N2O3（一为不稳定结构ONONO,一为稳定结构ONNO2），盐酸中参与反应的是亚硝酰氯NOCl；在浓硫酸中则是亚硝基正离子N+O。

重氮化反应氨基变羟基m-METHOXYBENZALDEHYDE Organic Syntheses, Coll. Vol. 3, p.564 (1955); Vol. 29, p.63 (1949).m-METHOXYBENZALDEHYDE[Benzaldehyde, m-methoxy-]Submitted by Roland N. Icke, C. Ernst Redemann, Burnett B. Wisegarver, and Gordon A. Alles.Checked by H. R. Snyder and Frank X. Werber.1. ProcedureA. m-Hydroxybenzaldehyde. In a 2-l. three-necked flask, equipped with a mechanical stirrer, a thermometer, and a 250-ml. dropping funnel, 575 ml. of 6 N sulfuric acid is cooled to 0° by means of a salt-ice bath. The acid is stirred and maintained at 0° or below while 167 g. (1 mole) of m-aminobenzaldehyde dimethylacetal(p. 59) is added dropwise. The solution becomes deep orange or red. When the addition of the amino compound is complete, a solution of 71 g. (1 mole) of 97% sodium nitrite in about 175 ml. of water is introduced slowly while the temperature of the acid solution is maintained at 5°. Stirring at 5° is continued for 1 hour to complete the reaction.In each of two 4-l. beakers are placed 450 ml. of water and 50 ml. of concentrated sulfuric acid, and the solutions are heated to boiling with large burners. The cold diazonium solution is divided into two approximately equal portions which are placed in 500-ml. separatory funnels suspended above the beakers containing the boiling acid. The two portions of the diazonium solution are run dropwise into the strongly heated acid at such a rate that boiling continues. The solutions are boiled for 5 minutes after the additions are complete. They are then allowed to cool to room temperature and are finally stored overnight in a refrigerator. The crude product separates as a dark oil which crystallizes (Note 1) and becomes lighter in color upon standing. It is collected on a Büchner funnel and used in part B without purification (Note 2).Methyl sulfate is quite toxic. Caution! The methylation should be carried out in a good hood.B. m-Methoxybenzaldehyde. The crude m-hydroxybenzaldehyde is dissolved in about 550 ml. of 2 N sodium hydroxide in a 2-l. three-necked flask equipped with a mechanical stirrer, a thermometer, and a 125-ml. dropping funnel. The dark-colored solution is stirred while 126 g. (95 ml., 1 mole) of methyl sulfate(Note 3) is added dropwise and the temperature is maintained at 40–45°. When the addition is complete the mixture is stirred for 5 minutes. A 275-ml. portion of 2 N sodium hydroxide(Note 4) is added in one lot, and then 63 g. (47.5 ml.) of methyl sulfate is added as before, except that the temperature is allowed to rise to 50°. Stirring at 50° is continued for 30 minutes, the mixture is cooled, and the organic layer is extracted withether(Note 5). The ether solution is dried over anhydrous sodium sulfate for 8 hours, then filtered and concentrated by distillation. The residue is distilled under reducedpressure. The yield of m-methoxybenzaldehyde, a pale yellow liquid boiling at 88–90° /3 mm., is 86–98 g. (63–72%) (Note 6).2. Notes1. Seeding the mixture helps to initiate crystallization.2. If m-hydroxybenzaldehyde is desired, the crude product may be purified as described elsewhere (p. 453).3. A good technical grade of methyl sulfate was used.4. The optimum amount of sodium hydroxide solution apparently varies according to the amount of acid remaining in the crude, wet hydroxybenzaldehyde employed in the methylation. The checkers found it advisable to increase the amount added at this point to 345 ml. It is wise to test the reaction mixture with litmus paper occasionally during the final heating period and to add alkali as necessary to keep the solution from becoming acid.5. If the methylation is not complete, some m-hydroxybenzaldehyde will remain dissolved in the aqueous phase. This may be recovered by acidifying the alkaline solution and collecting any crystalline solid which separates.6. As with other aromatic aldehydes, m-methoxybenzaldehyde is susceptible to air oxidation and should be stored in a bottle which will just hold the product, so that air space above the liquid is minimized.3. Discussionm-Methoxybenzaldehyde has been prepared by the reduction of m-methoxybenzoic acid,1 by the reaction of diazotized m-aminobenzaldehyde with methanol,2 by an acid hydrolysis of the phenylhydrazone which was obtained by oxidation of the hydrazine analog,3 and by the methylation of m-hydroxybenzaldehyde, with methyl iodide,4,5,6,7 and with methyl sulfate.2,7,8,9References and Notes1.Asano and Huziwara, J. Pharm. Soc. Japan, 50, 141 (1939).2.Noelting, Ann. chim., (8) 19, 541 (1910).3.Grammaticakis, Compt. rend., 210, 303 (1940).4.Tiemann and Ludwig, Ber., 15, 2043 (1882).5.Pschorr and Jaeckel, Ber., 33, 1826 (1900).6.Staudinger and Kon, Ann., 384, 90 (1911).7.Sp?th, Monatsh., 34, 1998 (1913).8.Posner, J. prakt. Chem., (2) 82, 431 (1910).9.Livshits, Bazilevskaya, Bainova, Dobrovinskaya, and Preobrazhenskii, J. Gen. Chem. U.S.S.R.,17, 1671 (1947) [C. A., 42, 2606 (1948)].AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)phenylhydrazonesulfuric acid (7664-93-9)methanol (67-56-1)ether(60-29-7)sodium hydroxide (1310-73-2)sodium sulfate (7757-82-6)sodium nitrite (7632-00-0)hydroxybenzaldehyde (90-02-8)Methyl iodide (74-88-4)methyl sulfate (75-93-4)m-Hydroxybenzaldehyde (100-83-4)m-aminobenzaldehyde (1709-44-0)m-Aminobenzaldehyde dimethylacetal (53663-37-9)m-Methoxybenzaldehyde,Benzaldehyde, m-methoxy- (591-31-1)m-methoxybenzoic acid (586-38-9) Copyright ? 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

重氮化反应氨基变硝基1,4-DINITRONAPHTHALENEOrganic Syntheses, Coll. Vol. 3, p.341 (1955); Vol. 28, p.52 (1948).1,4-DINITRONAPHTHALENE[Naphthalene, 1,4-dinitro-]Submitted by H. H. Hodgson, A. P. Mahadevan, and E. R. Ward.Checked by C. C. Price and Sing-Tuh Voong.1. ProcedureTen grams (0.14 mole) of powdered sodium nitrite is dissolved in 50 ml. of concentrated sulfuric acid (sp. gr. 1.84) contained in a 1-l. beaker placed in an ice bath. A solution of 10 g. of 4-nitro-1-naphthylamine (0.053 mole) (p. 664) in 100 ml. of glacial acetic acid is prepared by heating, and the well-stirred solution is cooled below 20°. Some crystals separate. The resulting thin slurry is dropped slowly into the cold solution of nitrosylsulfuric acid with mechanical stirring. Throughout the addition, and for 30 minutes thereafter, the temperature is kept below 20°. Seven hundred milliliters of dry ether is added slowly with stirring, and the temperature of the mixtur e is kept at 0° for 1 hour. At the end of this period, the precipitation (aided byscratching) of the crystalline 4-nitronaphthalene-1-diazonium sulfate is complete (Note 1). This precipitate is collected, washed with ether and then with 95% ethanol until all the acid is removed, and finally dissolved in 100 ml. of iced water.A saturated aqueous solution containing 50 g. of crystalline copper sulfate is treated with a similar solution of 50 g. of crystallized sodium sulfite. The greenish brown precipitate is collected, washed with water (Note 2), and then stirred into a solution of 100 g. (1.45 moles) of sodium nitrite in 400 ml. of water contained in a 2-l. beaker provided with an efficient mechanical stirrer.The cold aqueous solution of the diazonium salt is then added slowly to the decomposition mixture. Considerable frothing occurs, and 4–5 ml. of ether is added from time to time to break the foam. After stirring for 1 hour (Note 3), the mixture is filtered and the crude dark brown precipitate of the 1,4-dinitronaphthalene is washed several times with water, then with 2% aqueous sodium hydroxide, and again with water. The precipitate is dried and extracted three times with boiling 95% ethanol (450 ml. in all). The extract is concentrated to 75 ml.; most of the 1,4-dinitronaphthalene separates and is collected. Additional amounts can be obtained by further concentration. The resulting product melts at 130–132° and weighs 6.0–7.0 g. (52–60%). The product can be purified either by steam distillation (Note 4) or by recrystallization from aqueous ethanol. Pale yellow needles melting at 134° are obtained (Note 5) and (Note 6).2. Notes1. This precipitate is sometimes sticky. It can be made granular by treating it with a small amount of 95% ethanol (after the removal of the supernatant liquid). Alternatively, it maysuffice to keep the ethereal diazotized solution cold and scratch the sides of the beaker with a glass rod.2. The cupro-cupri sulfite of this variety is more efficient as a decomposition reagent than the red-violet precipitate obtained by treating a hot solution of copper sulfate with a solution of ammonium sulfite saturated with sulfur dioxide and subsequently heating the mixture for 10 minutes at 90°.3. The decomposition appears to be immediate, and at the end of 1 hour most of the inorganic material has passed into solution.4. Steam distillation of 1,4-dinitronaphthalene is very slow. However, the cupro-cupri sulfite method1 isa general one for the replacement of the diazonium group by the nitro group, and steam distillation is preferable whenever the product is readily volatile.5. The solution is decolorized with charcoal in the course of the recrystallization. The checkers obtained5 g. (43%) of golden needles after three recrystallizations.6. 1,2-Dinitronaphthalene may be obtained similarly from 2-nitro-1-naphthylamine, or less satisfactorily from 1-nitro-2-naphthylamine; 1,6- and 2,6-dinitronaphthalenes can be prepared from the 5-nitro- and 6-nitro-2-naphthylamines, respectively, by a modification of the process. Since the solubility of these amines in glacial acetic acid is slight, it is preferable to prepare the diazonium sulfate as follows: Ten grams of the amine is dissolved in 50 ml. of sulfuric acid (sp. gr. 1.84), and the solution is mixed with one of 10 g. of sodium nitrite in 50 ml. of sulfuric acid (sp. gr. 1.84). This mixture is stirred into 200 ml. of glacial acetic acid. The temperature is maintained below 20° throughout these operations. After 30 minutes, the diazonium sulfate isprecipitated at 0° by the addition of 200–500 ml. of ether as previously described.3. Discussion1,4-Dinitronaphthalene has been prepared previously from diazotized 4-nitro-1-naphthylamine by a modified Sandmeyer procedure,2,3 from 5,8-dinitrotetralin by dehydrogenation,4 by the deamination of 1,4-dinitro-2-naphthylamine,5 and by the decomposition of 4-nitro-1-naphthalenediazonium cobaltinitrite.6 The method described above has been published.1References and Notes1.Hodgson, Mahadevan, and Ward, J. Chem. Soc., 1947, 1392.2.Vesely and Dvorak, Bull. soc. chim. France, 33, 319 (1923).3.Contardi and Mor, Rend. ist. lombardo sci., 57, 646 (1924)[C. A., 19, 827 (1925)].4.Chudozilov, Collection Czechoslov. Chem. Commun., 1, 302 (1929) [C. A., 23, 4212 (1929)].5.Hodgson and Hathway, J. Chem. Soc., 1945, 453.6.Hodgson and Ward, J. Chem. Soc., 1947, 127.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)diazonium sulfatecupro-cupri sulfite1,6- and 2,6-dinitronaphthalenes5-nitro-and 6-nitro-2-naphthylamines4-nitro-1-naphthalenediazonium cobaltinitriteethanol (64-17-5)sulfuric acid (7664-93-9)acetic acid (64-19-7)ether (60-29-7)sodium sulfite (7757-83-7)sodium hydroxide (1310-73-2)sulfur dioxide (7446-09-5)copper sulfate (7758-98-7)sodium nitrite (7632-00-0)charcoal (7782-42-5)nitrosylsulfuric acid (7782-78-7)1,4-Dinitronaphthalene,Naphthalene, 1,4-dinitro- (6921-26-2)4-nitro-1-naphthylamine (776-34-1)4-nitronaphthalene-1-diazonium sulfateammonium sulfite (10196-04-0)1,2-Dinitronaphthalene2-nitro-1-naphthylamine (607-23-8)1-nitro-2-naphthylamine5,8-dinitrotetralin1,4-dinitro-2-naphthylamine Copyright ? 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 4, p.727 (1963); Vol. 31, p.80 (1951).1-(p-NITROPHENYL)-1,3-BUTADIENE[1,3-Butadiene, 1-(p-nitrophenyl)-]Submitted by Gus A. Ropp and Eugene C. Coyner1.Checked by Arthur C. Cope and David J. Marshall.1. ProcedureA. 1-(p-Nitrophenyl)-4-chloro-2-butene. p-Nitroaniline hydrochloride is prepared by heating 138 g.(1.0 mole) of p-nitroaniline(Note 1) with 240 ml. of concentrated hydrochloric acid and 100 ml. of water on a steam bath for 15 minutes with occasional stirring. The mixture is cooled in an ice-salt bath and stirred rapidly in order to precipitate the hydrochloride as fine crystals. Cracked ice (100 g.) is added, and a solution of 70 g. of sodium nitrite is added dropwise with rapid mechanical stirring during a 1-hour period while the temperature of the reaction mixture is held between −4° and +4.5° by cooling with the ice-salt bath. The mixture is stirred for an additional period of 20 minutes and then is filtered through a chilled funnel into an ice-cooled filter flask. The filtrate is kept below 4° (Note 2) and is added through a dropping funnel during 90 minutes to a cold, vigorously stirred mixture composed of 1 l. of acetone, a solution of 80 g. of sodium acetate trihydrate in 100 ml. of water, a solution of 30 g. of cupric chloride in 50 ml. of water, and 130 ml. of liquid butadiene(Note 3). The reaction mixture is kept at −3° to +2° by means of an ice-salt bath while the diazonium salt solution is added. After the addition is completed the cooling bath is removed and the mixture is stirred for 16 hours. One liter of ether is added, and after several minutes' stirring the ethereal layer is separated, washed with four 1-l. portions of water, and dried over 20 g. of anhydrous magnesium sulfate. The solvent is removed by distillation at 15 mm. by heating on a steam bath, leaving a dark brown oily residue (187–199 g.) of crude 1-(p-nitrophenyl)-4-chloro-2-butene(Note 4).B. 1-(p-Nitrophenyl)-1,3-butadiene. The crude 1-(p-nitrophenyl)-4-chloro-2-butene obtained in Part A is dissolved in a mixture of 500 ml. of ligroin, b.p. 90–100°, and 500 ml. of benzene; 5 g. of decolorizing carbon is added, and the mixture is heated under reflux for 2 hours. After filtration to separate the decolorizing carbon the solvents are removed by distillation from a steam bath under reduced pressure, and the residual clear oil is dissolved in 400 ml. of methanol. A solution of 112 g. of potassium hydroxide in 600 ml. of methanol is added from a dropping funnel during 30 minutes while the mixture is stirred mechanically and kept at 15–30° by cooling with a bath of cold water. After being stirred for an additional period of 5 minutes the mixture, which contains some precipitated product, ispoured into 1.2 l. of cold water. The crude product is collected on a filter, washed well with cold water, and air-dried. It is dissolved in 700 ml. of hot ligroin, b.p. 90–100°, and the solution is treated with 5 g. of decolorizing carbon, and filtered. On cooling, 1-(p-nitrophenyl)-1,3-butadiene separates as a yellow crystalline solid which is collected on a filter and dried in a desiccator. The yield of pure product, m.p. 77–79° (Note 5), is 100–108 g. (57–62% based on p-nitroaniline).2. Notes1. Either a pure grade of p-nitroaniline obtained from the Eastman Kodak Company or a technical grade purified by one recrystallization from ethanol was used, m.p. 147.5–148°.2. The filtrate is kept in an ice-salt bath and transferred to the dropping funnel in small amounts in order to keep the temperature below 4°.3. Butadiene from a commercial cylinder is passed through an 8-mm. glass tube leading to the bottom ofa graduated cylinder cooled with Dry Ice and acetone, where it condenses and is measured as a liquid.4. The submitters report that small samples of the crude product can be distilled in order to obtain pure 1-(p-nitrophenyl)-4-chloro-2-butene, b.p. 160–165°/1 mm.5. Two recrystallizations from ligroin raise the melting point of the 1-(p-nitrophenyl)-1,3-butadiene to a constant value of 78.6–79.4°. The product can be kept for several weeks in a dark bottle at room temperature without evidence of decomposition.3. Discussion1-(p-Nitrophenyl)-1,3-butadiene has been prepared only by the method described,2 which is an example of the Meerwein reaction (addition of diazonium salts to a carbon-carbon double bond with the elimination of nitrogen).3This preparation is referenced from:z Org. Syn. Coll. Vol. 6, 21References and Notes1.University of Tennessee, Knoxville, Tennessee.2.Coyner and Ropp, J. Am. Chem. Soc., 70, 2283 (1948); Dombrovskii, Doklady Akad. NaukS.S.S.R., 111, 827 (1956) [C. A., 51, 9507 (1957)].3.Müller, Angew. Chem., 61, 179 (1949).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)ligroinethanol (64-17-5)hydrochloric acid (7647-01-0)Benzene (71-43-2)methanol(67-56-1)ether (60-29-7)nitrogen (7727-37-9)sodium nitrite (7632-00-0)acetone (67-64-1)decolorizing carbon (7782-42-5)potassium hydroxide (1310-58-3)cupric chloride (7758-89-6)magnesium sulfate (7487-88-9)butadiene (106-99-0)sodium acetate trihydrate (6131-90-4)1-(p-Nitrophenyl)-1,3-butadiene,1,3-Butadiene, 1-(p-nitrophenyl)- (20264-89-5)p-nitroaniline (100-01-6)p-nitroaniline hydrochloride (15873-51-5)1-(p-Nitrophenyl)-4-chloro-2-butene (98011-65-5) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 1, p.135 (1941); Vol. 9, p.22 (1929).o-BROMOTOLUENE[Toluene, o-bromo-]Submitted by L. A. BigelowChecked by C. S. Marvel and S. V. Puntambeker.1. ProcedureA solution of 162 g. (1.5 moles) of commercial o-toluidine in 880 cc. (6 moles) of 40 per cent commercial hydrobromic acid(Note 1) in a 3-l. flask is cooled to 10° and diazotized with 116 g. (1.7 moles) of coarsely powdered commercial sodium nitrite, added about 10 g. at a time. After each addition the flask is stoppered and shaken until all the red fumes are absorbed. The temperature must be kept below 10°. When diazotization is complete, 5 g. of copper powder(Note 2) is added, the flask is attached to a reflux condenser and heated very cautiously. As soon as the first sign of reaction is observed, the flask is cooled with ice. Nitrogen is evolved vigorously. When the reaction subsides, the mixture is heated one-half hour on the steam bath.Then 1 l. of water is added and the mixture is distilled with steam until about 1.5 l. has passed over. The distillate is made alkaline with about 10 g. of powdered sodium hydroxide and the lower red layer of crude o-bromotoluene separated (Note 3). This weighs about 140 g. It is washed with concentrated sulfuric acid, which removes almost all the color, and then twice with water. It is dried over a little calcium chloride, filtered and distilled twice from a modified Claisen flask (p. 130). The yield of pure product boiling at 178–181° is 110–120 g. (43–47 per cent of the theoretical amount).2. Notes1. If 48 per cent (constant boiling) hydrobromic acid is used the diazotization is very difficult to control. The reaction becomes very vigorous and forces out the stopper.2. Either reduced copper or fine copper filings may be used.3. This gives as good results as when the o-bromotoluene is extracted from the alkaline mixture with ether.3. Discussiono-Bromotoluene can be prepared by the bromination of toluene;1 by the bromination of potassium p-toluenesulfonate and subsequent hydrolysis;2 and by the diazotization of o-toluidine under different conditions.3References and Notes1.Jannasch and Hübner, Ann. 170, 117 (1873); Varma and Narayan, Quart. J. Indian Chem. Soc. 4,283 (1927) [Chem. Zentr. I, 489 (1928)].ler, J. Chem. Soc. 61, 1027 (1892).3.Wroblevsky, Ann. 168, 171 (1873); Körner, Gazz. chim. ital. 4, 305 (1874); Jackson, Am. Chem.J. 1, 100 (1879); Feitler, Z. physik. Chem. 4, 72 (1889); Neogi and Mitra, J. Chem. Soc. 1332 (1928).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)calcium chloride (10043-52-4)sulfuric acid (7664-93-9)ether (60-29-7)sodium hydroxide (1310-73-2)HYDROBROMIC ACID (10035-10-6)nitrogen (7727-37-9)sodium nitrite (7632-00-0)copper,copper powder,copper filings (7440-50-8)toluene (108-88-3)o-Bromotoluene,Toluene, o-bromo- (95-46-5)o-toluidine (95-53-4)potassium p-toluenesulfonateCopyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 3, p.809 (1955); Vol. 27, p.81 (1947).m-THIOCRESOL[m-Toluenethiol; m-tolyl mercaptan]Submitted by D. S. Tarbell and D. K. Fukushima.Checked by C. F. H. Allen and John R. Byers, Jr..1. ProcedureAll the steps in this preparation, including sealing the product in bottles or ampoules, should be carried out under a good hood. Care should be exercised to avoid contact with m-thiocresol or its solutions since it is a skin irritant.In a 1-l. flask, equipped with a mechanical stirrer and thermometer for reading low temperatures, and immersed in an ice bath, are placed 150 ml. of concentrated hydrochloric acid (sp. gr. 1.18) and 150 g. of crushed ice. The stirrer is started, and 80 g. (0.75 mole) of m-toluidine (b.p. 92–93°/15 mm.) is slowly added. The mixture is cooled to 0°, and a cold solution of 55 g. (0.8 mole) of sodium nitrite in 125 ml. of water is slowly added, the temperature being kept below 4°.In a 2-l. flask equipped with a thermometer, dropping funnel, and stirrer is placed a solution of 140 g. of potassium ethyl xanthate(Note 1) in 180 ml. of water. This mixture is warmed to 40–45° and kept in that range during the slow addition of the cold diazonium solution (Note 2); about 2 hours is required (Note 3). After an additional 30 minutes at this temperature to ensure complete decomposition of the intermediate compound, the red, oily m-tolyl ethyl xanthate is separated and the aqueous layer is extracted twice, using 100-ml. portions of ether. The combined oil and extracts are washed once with 100 ml. of 10% sodium hydroxide solution (Note 4) and then with several portions of water until the washings are neutral to litmus. The ether solution is dried over 25 g. of anhydrous calcium chloride, and the ether is removed by distillation. The crude residual m-tolyl ethyl xanthate is dissolved in 500 ml. of 95% ethanol, the solution brought to boiling, and the source of heat removed. To this hot solution is added slowly 175 g. of potassium hydroxide pellets so that the solution keeps boiling, and the mixture is refluxed until a sample is completely soluble in water (about 8 hours). Approximately 400 ml. of ethanol is then removed by distillation on a steam bath, and the residue is taken up in the minimum of water (about 500 ml.). The aqueous solution is extracted with three 100-ml. portions of ether, the extract being discarded. The aqueous solution is now made strongly acid to Congo red paper, using 6 N sulfuric acid(Note 5) (625–650 ml.). The acidified solution is placed in a 3-l. flask, 2 g. of zinc dust is added, and the m-thiocresol is distilled with steam. The lower layer of the m-thiocresol is separated; the aqueous layer is extracted with three 100-ml. portions of ether, the extracts being added to the oil. Afterdrying with 50 g. of Drierite, the ether is removed by distillation, and the oily residue is distilled under reduced pressure. The yield of colorless m -thiocresol , b.p. 90–93°/25 mm., is 59–69 g. (63–75%) (Note 6) and (Note 7). It is best preserved in sealed glass bottles because of its disagreeable odor.2. Notes1. Eastman Kodak Company technical potassium ethyl xanthate was used.2. The diazonium solution is left in the ice bath, and only 10- to 15-ml. portions are placed in the dropping funnel at one time.3. Many diazonium solutions have been reported to react explosively with solutions of metallic polysulfides even at low temperatures.1,2 A violent reaction with xanthates is mentioned only in one report.3 Neither the authors nor the checkers observed any unusual reactivity during this preparation or with the procedure given for dithiosalicylic acid.4 On a large scale (100 moles of m -toluidine ) flashes of light have been occasionally observed (private communication, L. J. Roll).4. This wash serves to remove any m -cresol present.5. This acidification liberates carbon oxysulfide, which has a very disagreeable odor.6. The refractive index is n D 1.568–1.571.7. Other boiling points are 195°/760 mm.; 120°/100 mm.; 107°/50 mm.3. DiscussionThe only practical laboratory procedure for preparing m -thiocresol is by the alkaline hydrolysis of m -tolyl ethyl xanthate , obtained from m -toluenediazonium chloride and potassium ethyl xanthate .3,5 The procedure described is essentially that of Bourgeois.5This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 1050References and Notes1.Nawiasky, Ebersole, and Werner, Chem. Eng. News , 23, 1247 (1945). 2.Hodgson, Chemistry & Industry , 1945, 362. 3.Leuckart, J. prakt. Chem., [2] 41, 189 (1890). 4.Org. Syntheses Coll. Vol. 2, 580 (1943). 5.Bourgeois, Rec. trav. chim., 18, 447 (1899).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)carbon oxysulfideDrieriteethanol (64-17-5)calcium chloride (10043-52-4)sulfuric acid (7664-93-9)25hydrochloric acid (7647-01-0)ether (60-29-7)sodium hydroxide (1310-73-2)sodium nitrite (7632-00-0)potassium hydroxide (1310-58-3)zinc (7440-66-6)potassium ethyl xanthate (140-89-6)m-Thiocresol,m-Toluenethiol,m-tolyl mercaptan (108-40-7)m-toluidine (108-44-1)m-tolyl ethyl xanthatem-cresol (108-39-4)m-toluenediazonium chloride Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 2, p.130 (1943); Vol. 13, p.28 (1933).m -CHLOROBENZALDEHYDE[Benzaldehyde, m -chloro-]Submitted by Johannes S. Buck and Walter S. Ide.Checked by John R. Johnson and Paul W. Vittum.1. ProcedureA solution of 450 g. (2 moles) of stannous chloride crystals (Note 1) in 600 cc. of concentrated hydrochloric acid is placed in a 3-l. beaker provided with an efficient mechanical stirrer and cooled in an ice bath. When the temperature of the solution has fallen to +5°, 100 g. (0.66 mole) of m -nitrobenzaldehyde (Note 2) is added in one portion. The temperature rises slowly at first, reaching 25–30° in about five minutes, then rises very rapidly to about 100°. Stirring must be vigorous or the reaction mixture may be forced out of the beaker (Note 3). During the reaction the nitrobenzaldehyde dissolves, and an almost clear, red solution is obtained. The solution is cooled in an ice-salt mixture until the temperature has fallen to about +2°. During the cooling, orange-red crystals separate and a pasty suspension results.A 250-cc. separatory funnel is fixed so that its stem extends below the surface of the pasty suspension. A solution of 46 g. (0.67 mole) of sodium nitrite in 150 cc. of water is placed in the funnel and is slowly added to the well-stirred mixture until it shows a positive starch-iodide test for nitrous acid . The temperature of the mixture is maintained between 0° and +5° (Note 4) throughout the addition of the nitrite solution, which requires about ninety minutes. Usually, all but 5–8 cc. of the nitrite solution must be added before a positive test for nitrous acid appears.During the latter part of the diazotization of the aminobenzaldehyde , a hot solution of cuprous chloride is prepared. In a 5-l. round-bottomed flask, 189 g. (0.75 mole) of powdered copper sulfate crystals and 161 g. of sodium chloride are dissolved in 600 cc. of hot water, and to this solution is added a solution of 41 g. (0.22 mole) of sodium metabisulfite (Na 2S 2O 5)and 27 g. (0.67 mole) of sodiumhydroxide in 300 cc. of water. The final temperature of the resulting cuprous chloride solution should be about 75°.The diazonium solution is added to the hot cuprous chloride solution while the latter is shaken by hand but is not cooled. After the solutions are thoroughly mixed, 840 cc. of concentrated hydrochloric acid is added and the mixture is allowed to stand overnight. The reaction mixture is steam-distilled to separate the m-chlorobenzaldehyde, which is collected practically completely in the first 1.5 l. of distillate. The m-chlorobenzaldehyde is removed from the aqueous distillate by extraction with two 150-cc. portions of ether, and the ethereal solution is dried with 10–15 g. of anhydrous calcium chloride. After being decanted from the drying agent, the ether is distilled, and the residual liquid is distilled under diminished pressure. The m-chlorobenzaldehyde boils at 84–86°/8 mm., 107–109°/26 mm. (Note 5). The yield is 70–74 g. (75–79 per cent of the theoretical amount) (Note 6).2. Notes1. A chemically pure grade of stannous chloride crystals (SnCl2·2H2O) was used. Lower yields wereobtained when technical stannous chloride was used.2. A practical grade of m-nitrobenzaldehyde was used; m.p. 52–55°.3. During the vigorous reaction it is advisable to keep the cooling bath and the reaction mixture well stirred. Less satisfactory yields were obtained when the reaction was moderated by adding the nitrobenzaldehyde in several portions.4. At temperatures below 0° the speed of diazotization is markedly decreased. Above +5° some decomposition of the diazonium salt takes place.5. Since m-chlorobenzaldehyde is oxidized easily by atmospheric oxygen, it should be stored in a tightly corked or sealed container.6. According to the submitters m-bromobenzaldehyde can be prepared by the same general procedure using, in place of cuprous chloride, a solution of cuprous bromide prepared from 189 g. of copper sulfate, 91 g. of sodium bromide, 41 g. of sodium metabisulfite, and 27 g. of sodium hydroxide. Instead of 840 cc. of concentrated hydrochloric acid, 200 cc. of 48 per cent hydrobromic acid is added after the diazonium solution has been mixed with the cuprous bromide. The m-bromobenzaldehyde boils at 93–98°/8 mm. The yield is 80 g. or 65 per cent of the theoretical amount.It is reported, however, that m-bromobenzaldehyde prepared in this way may contain as much as 20 per cent of m-chlorobenzaldehyde. This contamination can be avoided by using stannous bromide as the reducing agent.A solution of stannous bromide is prepared by heating 119 g. (1 gram atom) of mossy tin with 705 g. (4 moles) of 46 per cent hydrobromic acid for two hours on a steam bath, with mechanical stirring. The solution is cooled to 40°, and 50 g. (0.33 mole) of m-nitrobenzaldehyde is added in one portion, with continued stirring. The temperature rises from the heat of reaction and finally reaches about 105°. After heating for one-half hour longer on a steam bath, the reaction mixture is cooled to 0° and the aminobenzaldehyde diazotized by the gradual addition of 23 g. (0.33 mole) of sodium nitrite in 75 cc. of water. The diazonium solution is poured into a hot suspension of cuprous bromide, 100 cc. of 46 per cent hydrobromic acid is added, with stirring, and the mixture is allowed to stand overnight. The mixture is steam-distilled and the m-bromobenzaldehyde isolated by ether extraction and vacuum distillation; b.p. 90–92°/4 mm. The yield is 41 g. (67 per cent of the theoretical amount). (F. T. Tyson, private communication.)3. Discussionm-Chlorobenzaldehyde has been prepared by the chlorination of benzaldehyde1 and by the oxidation of m-chlorobenzyl alcohol2 and of m-chlorotoluene.3 It is most conveniently prepared from m-nitrobenzaldehyde through m-aminobenzaldehyde and the diazonium reaction.4 The procedure given above is essentially that described in the patent literature.4This preparation is referenced from:z Org. Syn. Coll. Vol. 2, 583z Org. Syn. Coll. Vol. 3, 453References and Notes1.Müller, Ger. pat. 30,329; 33,064 [Frdl. 1, 143, 146 (1877–87)].2.Mettler, Ber. 38, 2812 (1905).w and Perkin, J. Chem. Soc. 93, 1636 (1908).4.Meister, Lucius, and Brüning, Ger. pat. 31,842 [Frdl. 1, 144 (1877–87)]; Erdmann andSchwechten, Ann. 260, 59 (1890); Eichengrün and Einhorn, ibid. 262, 135 (1891).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)sodium metabisulfitecalcium chloride (10043-52-4)hydrochloric acid (7647-01-0)ether (60-29-7)sodium hydroxide (1310-73-2)sodium chloride (7647-14-5)HYDROBROMIC ACID (10035-10-6)sodium bromide (7647-15-6)oxygen (7782-44-7)copper sulfate (7758-98-7)sodium nitrite (7632-00-0)nitrous acid (7782-77-6)tin (7440-31-5)stannous chloridebenzaldehyde (100-52-7)cuprous bromide (7787-70-4)cuprous chloride (7758-89-6)nitrobenzaldehyde(552-89-6)aminobenzaldehyde (529-23-7)stannous bromide (10031-24-0)m-Bromobenzaldehyde (3132-99-8)m-Chlorobenzaldehyde,Benzaldehyde, m-chloro- (587-04-2)m-Nitrobenzaldehyde (99-61-6)m-chlorobenzyl alcohol (873-63-2)m-chlorotoluene (108-41-8)m-aminobenzaldehyde (1709-44-0) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

重氮化和重氮盐的反应综述一、重氮化芳香族伯胺和亚硝酸作用生成重氮盐的反应标为重氮化，芳伯胺常称重氮组分，亚硝酸为重氮化剂，因为亚硝酸不稳定，通常使用亚硝酸钠和盐酸或硫酸使反应时生成的亚硝酸立即与芳伯胺反应，避免亚硝酸的分解，重氮化反应后生成重氮盐。

重氮化反应可用反应式表示为：Ar-NH2 + 2HX + NaNO2--—Ar-N2X + NaX + 2H20重氮化反应进行时要考虑下列三个因素：1、酸的用量从反应式可知酸的理论用量为2mol，在反应中无机酸的作用是，首先使芳胺溶解，其次与亚硝酸钠生成亚硝酸，最后生成重氮盐。

重氮盐一般是容易分解的，只有在过量的酸液中才比较稳定，所以重氮化时实际上用酸量过量很多，常达3mol，反应完毕时介质应呈强酸性(pH值为3)，对刚果红试纸呈蓝色．重氮过程中经常检查介质的pH 值是十分必要的。

反应时若酸用量不足，生成的重氮盐容易和未反应的芳胺偶合，生成重氮氨基化合物：Ar-N2Cl + ArNH2——Ar-N＝N—NHAr + HCl这是一种自我偶合反应，是不可逆的，一旦重氮氨基物生成，即使补加酸液也无法使重氮氨基物转变为重氮盐，因此使重氮盐的质量变坏，产率降低。

在酸量不足的情况下，重氮盐容易分解，温度越高，分解越快。

2、亚硝酸的用量重氮化反应进行时自始至终必须保持亚硝酸稍过量，否则也会引起自我偶合反应。

重氮化反应速度是由加入亚硝酸钠溶液加速度来控制的，必须保持一定的加料速度，过慢则来不及作用的芳胺会和重氮盐作用生成自我偶合反应。

亚硝酸钠溶液常配成30％的浓度使用．因为在这种浓度下即使在－15℃也不会结冰。

反应时检定亚硝酸过量的方法是用碘化钾淀粉试纸试验，一滴过量亚硝酸液的存在可使碘化钾淀粉试纸变蓝色。

由于空气在酸性条件下也可位碘化钾淀粉试纸氧化变色，所以试验的时间以0.5-2s内显色为准。

亚硝酸过量对下一步偶合反应不利，所以过量的亚硝酸常加入尿素或氨基磺酸以消耗过量亚硝酸。

Organic Syntheses, Coll. Vol. 2, p.351 (1943); Vol. 19, p.55 (1939).IODOBENZENE[Benzene, iodo-]Submitted by H. J. Lucas and E. R. Kennedy.Checked by John R. Johnson and P. L. Barrick.1. ProcedureIn a 3- or 5-gallon stoneware crock are placed 950 cc. (1130 g., 11.7 moles) of concentrated hydrochloric acid (sp. gr. 1.19), 950 cc. of water, 200 g. (196 cc., 2.15 moles) of aniline, and 2 kg. of ice (Note 1). The mixture is agitated by a mechanical stirrer, and, as soon as the temperature drops below 5°, a chilled solution of 156 g. (2.26 moles) of sodium nitrite in a measured volume (700–1000 cc.) of water is introduced fairly rapidly from a separatory funnel, the stem of which projects below the surface of the reaction mixture. The addition should not be fast enough to cause the temperature to rise to 10° or to cause evolution of oxides of nitrogen. The last 5 per cent of the nitrite solution is added more slowly, and the reaction mixture is tested with starch-iodide paper at intervals until an excess of nitrous acid is indicated.Stirring is continued for ten minutes, and if necessary the solution is filtered rapidly through a loose cotton plug in a large funnel. An aqueous solution of 358 g. (2.16 moles) of potassium iodide is added and the reaction mixture allowed to stand overnight. The mixture is transferred to a large flask (or two smaller flasks) and heated on a steam bath, using an air-cooled reflux condenser, until no more gas is evolved, then allowed to cool and stand undisturbed until the heavy organic layer has settled thoroughly.A large part of the upper aqueous layer is siphoned off, and discarded (Note 2). The residual aqueous and organic layers are made alkaline by the cautious addition of strong sodium hydroxide solution (100–125 g. of solid technical sodium hydroxide is usually required) and steam-distilled at once. The last one-third of the steam distillate is collected separately and combined with the aqueous layer separated from the earlier portions of the distillate. This mixture is acidified with 5–10 cc. of concentrated sulfuric acid and steam-distilled again. The iodobenzene from this operation is combined with the main portion and dried with 10–15 g. of calcium chloride(Note 3) and (Note 4). Distillation under reduced pressure gives 327–335 g. (74–76 per cent of the theoretical amount) of iodobenzene, b.p. 77–78°/20 mm. or 63–64°/8 mm. (Note 5).2. Notes1. If more ice is used a portion remains unmelted after the diazotization is completed.2. If a good separation has been made not more than 1–2 g. of iodobenzene is lost with the upper layer.3. An appreciable amount of iodobenzene is retained by the solid calcium chloride. By treating the spent drying agent with water 8–12 g. of iodobenzene can be recovered.4. The crude iodobenzene weighs 350–355 g. (80 per cent of the theoretical amount) and is pure enough for many purposes without redistillation.5. If the distillation is carried too far, the distillate will be colored.3. DiscussionThe preparation of iodobenzene by iodination of benzene, with iodine and nitric acid, and a survey of preparative methods have been given in an earlier volume.1 The present procedure, based upon the method of Gattermann,2 gives a purer product.This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 660z Org. Syn. Coll. Vol. 5, 665References and Notes. Syn. Coll. Vol. I, 1941, 323.2.Gattermann-Wieland, "Laboratory Methods of Organic Chemistry," p. 283. Translated from thetwenty-fourth German edition by W. McCartney, The Macmillan Company, New York, 1937.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)oxides of nitrogencalcium chloride (10043-52-4)sulfuric acid (7664-93-9)hydrochloric acid (7647-01-0)Benzene (71-43-2)aniline (62-53-3)sodium hydroxide (1310-73-2)nitric acid (7697-37-2)potassium iodide (7681-11-0)sodium nitrite (7632-00-0)nitrous acid (7782-77-6)iodine (7553-56-2)Iodobenzene,Benzene, iodo-(591-50-4)Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 2, p.580 (1943); Vol. 12, p.76 (1932).THIOSALICYLIC ACID[Benzoic acid, o -mercapto-]Submitted by C. F. H. Allen and D. D. MacKay.Checked by Roger Adams and A. E. Knauf. 1. ProcedureCaution! Recently it was reported to us that workers, following the procedure in Coll. Vol. II, pg 580 (diazotization of anthranilic acid and its reaction with sodium disulfide) but substituting 2,3-dimethylaniline for anthranilic acid, experienced a serious explosion upon addition of the diazonium salt solution to the disulfide solution. We urge that extreme caution should always be exercised in the handling of diazonium salts even when they are in solution.In a 4-l. beaker, 290 cc. of water is heated to boiling, and 260 g. (1.1 moles) of crystallized sodium sulfide (Na 2S·9H 2O) and 34 g. of powdered sulfur are dissolved by heating and stirring. A solution of 40 g. of sodium hydroxide in 100 cc. of water is then added and the mixture cooled, first in cold water, and finally by a freezing mixture of ice and salt.In a 2-l. beaker, set in a freezing mixture and provided with a stirrer and a thermometer for reading temperatures to 0°, are placed 500 cc. of water, 137 g. (1 mole) of anthranilic acid , and 200 cc. of concentrated hydrochloric acid ; the stirrer is started and the mixture cooled to about 6°. Meanwhile 69 g. (1 mole) of sodium nitrite is dissolved in 280 cc. of hot water and the solution cooled in ice; portions are then placed in a separatory funnel of convenient size, supported in such a way that the lower end of the stem extends beneath the surface of the anthranilic acid solution. When the temperature has fallen to 5°, the nitrite solution is run in; about 500 g. of cracked ice is added at such a rate as to keep the temperature below 5°. This takes about ten minutes (Note 1). A drop of the solution should give an immediate blue color with starch-iodide paper.The stirrer and thermometer are now transferred to the alkaline sulfide solution, the temperature of which must be below 5°. The diazo solution is added over a period of twenty to thirty minutes along with 950 g. of ice to prevent the temperature from rising above 5°. When addition is complete, the waterbath is removed and the mixture allowed to warm up to room temperature; after two hours the evolution of nitrogen ceases (Note 2). About 180 cc. of concentrated hydrochloric acid is added until the solution is acid to Congo red paper, and the precipitate of dithiosalicylic acid is filtered and washed with water.To remove the excess sulfur, the precipitate is dissolved by boiling with a solution of 60 g. of anhydrous sodium carbonate (soda ash) in 2 l. of water, and the mixture is filtered while hot. It is divided into five equal parts (Note 3), and the dithiosalicylic acid is reprecipitated as before with concentrated hydrochloric acid. The solid is filtered, the cake being sucked as dry as possible.The moist cake is mixed with 27 g. of zinc dust and 300 cc. of glacial acetic acid in a 1-l. round-bottomed flask, and the mixture is refluxed vigorously for about four hours (Note 4). When the reduction is complete, the mixture is cooled and filtered with suction. The filter cake is washed once with water and then transferred to a 1-l. beaker. The cake is suspended in 200 cc. of water, and the suspension is heated to boiling. The hot solution is made strongly alkaline by the addition of about 40 cc. of 33 per cent aqueous sodium hydroxide solution. The alkaline solution is boiled for about twenty minutes to ensure complete extraction of the product from the filter cake, filtered from the insoluble material (Note 5), and the thiosalicylic acid is then precipitated by the addition of sufficient concentrated hydrochloric acid to make the solution acid to Congo red paper. The product is filtered with suction, washed once with water, and dried in an oven at 100–110°. The yield of a product which melts at 162–163° is 110–130 g. (71–84 per cent of the theoretical amount based on the anthranilic acid).This product is sufficiently pure for most purposes (Note 6).For recrystallization 5 g. of this material is dissolved in 20 cc. of hot 95 per cent alcohol, and 40 cc. of water is added. The solution is boiled with a little decolorizing carbon, filtered hot, and then allowed to cool. The product crystallizes in yellow flakes. The yield of recrystallized material is 4.7 g.; the melting point of the material is 163–164°.2. Notes1. This method is much more rapid than when external cooling alone is used (Org. Syn. Coll. Vol. I, 1941, 374). The total volume of the solution is not important since the insoluble dithiosalicylic acid is readily filtered.2. Foaming sometimes becomes very during the evolution of nitrogen. The addition of a few cubic centimeters of ether from time to time helps to keep this foaming under control.3. The dithiosalicylic acid may be precipitated all at once if desired and the entire amount reduced in one operation. If this is done, the reduction must be carried out in a 5-l. flask fitted with a good stirrer. The mixture needs to be refluxed about ten hours over a ring burner. In the laboratory, this is much less convenient than it is to divide the material and reduce in smaller amounts. The yield is not materially lowered by making the reduction in one portion.4. The reduction does not always run smoothly. If the zinc lumps and becomes inactive more must be added. To determine whether reduction is complete, a sample is removed, cooled, and filtered. The precipitate is boiled with strong sodium hydroxide solution, filtered, and then acidified with hydrochloric acid. If the reduction is complete, the precipitated material will melt at 164° or lower. If the reduction is not complete, the precipitated material will melt above 164°. If the reduction is not complete, the refluxing of the main portion must be continued (and perhaps more zinc must be added) until a test portion shows that the reaction is complete.In determining the melting point of the material, the capillary tube containing the test sample should be inserted in a bath previously heated to 163–164°.5. When the reduction is carried out in five portions, one extraction with sodium hydroxide is usually sufficient for each portion. If the reduction is carried out in one operation, several extractions are usually required. When the material is to be extracted more than once, it is best to boil the residue from the first alkaline treatment with hydrochloric acid, filter, and then treat again with the alkali.6. Thiosalicylic acid is used for the preparation of oxythionaphthene and many thioindigoid dyes.3. DiscussionOf the several methods described for the production of thiosalicylic acid, only the following are of preparative interest: heating o-halogenated benzoic acids with an alkaline hydrosulfide at 150–200° in the presence of copper or copper salts,1, 2 or with sodium sulfide at 200°;3 and reduction of dithiosalicylic acid with glucose,4 or metals5, 2 in alkaline solution. The dithiosalicylic acid is prepared by treating diazotized anthranilic acid with sodium disulfide in alkaline solution.5This preparation is referenced from:z Org. Syn. Coll. Vol. 3, 809References and Notes1.(a) Cassella and Company, Ger. pat. 189,200 [C. A. 2, 607 (1908)]; (b) Cain, "IntermediateProducts for Dyes," p. 151.2.Chem. Age 21, Dyestuffs Suppl. p. 11 (1929).3.Cassella and Company, Ger. pat. 193,290 [C. A. 2, 1514 (1908)]; Ref. 1(b).4.Claasz, Ber. 45, 2427 (1912).5.Kalle and Company, Ger. pat. 204,450 [C. A. 3, 1695 (1909)]; Ref. 1(b).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)sodium sulfide (Na2S·9H2O)dithiosalicylic acid sodium carbonate (soda ash) copper or copper saltso-halogenated benzoic acidsalcohol (64-17-5) hydrochloric acid (7647-01-0) acetic acid (64-19-7)ether (60-29-7) sodium hydroxide (1310-73-2) nitrogen (7727-37-9) sodium nitrite(7632-00-0)sulfur (7704-34-9)decolorizing carbon (7782-42-5)zinc (7440-66-6)sodium sulfide (1313-82-2)sodium disulfideAnthranilic Acid (118-92-3)glucose (492-62-6)hydrosulfideThiosalicylic acid,Benzoic acid, o-mercapto- (147-93-3)oxythionaphtheneCopyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

重氮化反应氨基变醛基2-BROMO-4-METHYLBENZALDEHYDEOrganic Syntheses, Coll. Vol. 5, p.139 (1973); Vol. 46, p.13 (1966).2-BROMO-4-METHYLBENZALDEHYDE[p-Tolualdehyde, 2-bromo-]Submitted by S. D. Jolad and S. Rajagopalan1.Checked by A. G. Szabo and Peter Yates.1. ProcedureA. Formaldoxime. A mixture of 11.5 g. (0.38 mole) of paraformaldehyde and 26.3 g. (0.38 mole) of hydroxylamine hydrochloride in 170 ml. of water is heated until a clear solution is obtained. Then there is added 51 g. (0.38 mole) of hydrated sodium acetate, and the mixture is boiled gently under reflux for15 minutes to give a 10% solution of formaldoxime.B. 2-Bromo-4-methylbenzenediazonium chloride. A mixture of 46.0 g. (0.25 mole) of 2-bromo-4-methylaniline2 and 50 ml. of water is placed in a 1-l. three-necked flask equipped with an efficient stirrer, a dropping funnel, and a thermometer. The stirrer is started, and 57 ml. of concentrated hydrochloric acid is added slowly. The mixture is cooled to room temperature, 100 g. of ice is added, and the temperature of the mixture is maintained at ?5° to +5° by means of an ice-salt bath. To the stirred mixture there is added, dropwise, a solution of 17.5 g. (0.25 mole) of sodium nitrite in 25 ml. of water. After completion of the addition, the stirring is continued for a period of 15 minutes. The stirred solution of the diazonium salt is made neutral to Congo red by the addition of a solution of hydrated sodium acetate (22 g.) in water (35 ml.) (Note 1).C. 2-Bromo-4-methylbenzaldehyde. A 3-l. three-necked flask is equipped with an efficient stirrer, a dropping funnel (Note 2), and a thermometer. The aqueous 10% formaldoxime prepared in step A is placed in the flask, and to it are added 6.5 g. (0.026 mole) of hydrated cupric sulfate, 1.0 g. (0.0079 mole) of sodium sulfite, and a solution of 160 g. of hydrated sodium acetate in 180 ml. of water. The solution is maintained at 10–15° by means of a cold-water bath and stirred vigorously. The neutral diazonium salt solution prepared in step B is slowly introduced below the surface of the formaldoxime solution (Note 3) and (Note 4). After the addition of the diazonium salt solution is complete, the stirring is continued for an additional hour and then the mixture is treated with 230 ml. of concentratedhydrochloric acid. The stirrer and the dropping funnel are replaced by stoppers, and the mixture is gently heated under reflux for 2 hours. The flask is set up for steam distillation, and the reaction product is steam-distilled. The distillate is saturated with sodium chloride, extracted with three 150-ml. portions of ether, and the ethereal extracts are washed successively with three 20-ml. portions of a saturated sodium chloride solution, three 20-ml. portions of an aqueous 10% sodium bicarbonate solution, and again with three 20-ml. portions of a saturated sodium chloride solution.The ether is distilled and to the residue there is added, with cooling, 90 ml. of an aqueous 40% sodium metabisulfite solution, previously heated to 60°. The mixture is shaken for 1 hour and allowed to stand overnight. The solid addition product is filtered, washed twice with ether, and then suspended in 200 ml. of water in a 500-ml. flask, and 40 ml. of concentrated sulfuric acid is slowly added with cooling. The mixture is gently boiled under reflux for 2 hours, cooled, and extracted with three 100-ml. portions of ether. The ethereal extract is washed with three 15-ml. portions of a saturated sodium chloride solution and dried over anhydrous sodium sulfate. The ether is evaporated, and the product is distilled under reduced pressure. 2-Bromo-4-methylbenzaldehyde distills at 114–115° (5 mm.) as a colorless oil, yield 17.5–22.5 g. (35–45%), which crystallizes in the receiver, m.p. 30–31°.2. Notes1. Exact neutralization of the diazonium salt solution is necessary in order to minimize coupling.2. The stem of the dropping funnel should extend a little below the surface of the solution in the three-necked flask.3. Addition of the diazonium salt solution sometimes results in the formation of a pasty mass which prevents further stirring; the mixture is then allowed to stand for a further period of 1 hour.4. The checkers found it preferable to transfer the diazonium salt solution by siphoning under slight nitrogen pressure.3. DiscussionThe preparation of this aldehyde is based on the reaction due to Beech3 for the conversion of an aromatic amine to the corresponding aldehyde and has been described earlier by Jolad and Rajagopal.44. Merits of the PreparationThis method of preparation of a halobenzaldehyde is of wide application and has been used for the preparation of the following substituted benzaldehydes: 2-bromo-5-methyl-,4 2,3-dichloro- and 2,4-dichloro-,5 2-chloro-4-methyl-,6 2-methyl-4-bromo- and 3-methyl-4-bromo-,7 2-methyl-5-chloro- and 2-methyl-5-bromo-,8p-iodo-, p-fluoro-, 2-iodo-4-methyl-, and 6-iodo-3-methyl-.9References and Notes1.Department of Chemistry, Karnatak University, Dharwar, S. India.2.J. R. Johnson and L. T. Sandborn, Org. Syntheses, Coll. Vol. 1, 111 (1951).3.W. F. Beech, J. Chem. Soc., 1297 (1954).4.S. D. Jolad and S. Rajagopal, J. Sci. Ind. Res. (India), 21B, 359 (1961) [C. A., 56, 1381 (1962)].5.N. Gudi, S. Hiremath, V. Badiger, and S. Rajagopal, Arch. Pharm., 295, 16 (1962).6.S. D. Jolad and S. Rajagopal, Naturwiss., 48, 645 (1961).7.S. S. Vernekar, S. D. Jolad, and S. Rajagopal, Monatsh., 93, 271 (1962).8.S. D. Jolad and S. Rajagopal, Chimia, 16, 196 (1962).9.S. D. Jolad and S. Rajagopal, unpublished results.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)sodium metabisulfitesulfuric acid (7664-93-9)hydrochloric acid (7647-01-0)ether (60-29-7)sodium acetate (127-09-3)sodium sulfite (7757-83-7)sodium bicarbonate (144-55-8)sodium chloride (7647-14-5)sodium sulfate (7757-82-6)nitrogen (7727-37-9)cupric sulfate (7758-98-7)sodium nitrite (7632-00-0)2-bromo-4-methylaniline (583-68-6)Hydroxylamine hydrochloride (5470-11-1)formaldoxime (75-17-2)2-Bromo-4-methylbenzaldehyde,p-Tolualdehyde, 2-bromo- (824-54-4)2-Bromo-4-methylbenzenediazonium chlorideparaformaldehyde (30525-89-4) Copyright ? 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 5, p.829 (1973); Vol. 46, p.85 (1966).2-NITROCARBAZOLE[Carbazole, 2-nitro]Submitted by G. David Mendenhall and Peter A. S. Smith1.Checked by Howard A. Harris and Kenneth B. Wiberg.1. ProcedureA. o-Aminobiphenyl. A Parr bottle is charged with 60 g. (0.30 mole) of o-nitrobiphenyl(Note 1), 3 g. of 5% palladium-on-carbon catalyst (Note 2), and 200 ml. of 95% ethanol. The mixture is shaken with hydrogen under 25–50 p.s.i. until the gas is no longer absorbed (about 70 minutes), the catalyst is filtered from the hot solution and washed with 20 ml. of ethanol, and the filtrates are poured in a thin stream into 1 l. of ice water contained in a 2-l. Erlenmeyer flask (Note 3). After standing for 20 minutes the white solid is filtered with suction, pressed to remove excess water, and allowed to dry in air. The yield of essentially pure o-aminobiphenyl is 48–51 g. (94–100%), m.p. 43–45.5°.B. o-Amino-p'-nitrobiphenyl. Concentrated sulfuric acid (400 ml.) is placed in a 1-l. round-bottomed flask fitted with a mechanical stirrer and a thermometer. Stirring is begun, and 45.0 g. (0.27 mole) ofpowdered o-aminobiphenyl is added all at once through a powder funnel. When the amine has dissolved, the flask is placed in an ice-salt bath and its contents cooled to a temperature between 0° and −5°. A mixture of 30 ml. of concentrated sulfuric acid and 11.0 ml. of fuming nitric acid (density 1.5) is then added dropwise from a separatory funnel while the temperature is kept below 0°. The addition requires about an hour, and stirring is continued 45 minutes longer. The liquid is poured onto 1.5 kg. of ice in a 4-l. beaker and treated carefully until neutral with a solution of 580 g. (14.5 moles) of sodium hydroxide in 1.5 l. of water cooled to room temperature. The resultant hot suspension of product is allowed to cool nearly to room temperature, filtered with suction, and the orange solid is washed with 500 ml. of water. The crude material is pressed free of excess water and recrystallized from 850–1000 ml. of 95% ethanol(Note 4), giving 32–42 g. (56–74%) of orange needles, m.p. 156–158.5°.C. o-Azido-p'-nitrobiphenyl. Water (100 ml.) is placed in a 1-l. round-bottomed flask equipped with a thermometer and an efficient mechanical stirrer. With stirring, 30 ml. of concentrated sulfuric acid is added, followed by 32.1 g. (0.15 mole) of recrystallized o-amino-p'-nitrobiphenyl. When all the amine has been converted to the white sulfate, 50 ml. more of water is added and the suspension is cooled to 0–5° in an ice-salt bath. A solution of 11 g. (0.16 mole) of sodium nitrite in 30 ml. of water is added dropwise over a period of 15 minutes (Note 5), and the mixture is stirred for 45 minutes longer. A thick precipitate of the sparingly soluble diazonium salt may have separated from the initially clear solution by this time. With strong stirring, a solution of 12 g. (0.17 mole) of sodium azide in 40 ml. of water is run in (Note 6), and stirring is continued for 40 minutes longer. The thick white solid is filtered with suction and washed with 200 ml. of water. After pressing free of excess water, the material is allowed to dry in air in a dark place. The yield of gray-white azide is 35.5–36 g. (99–100%), m.p. 91.5–92.5° (Note7).D. 2-Nitrocarbazole. In a 2-l. round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a short air condenser are placed 35.5 g. (0.15 mole) of powdered o-azido-p'-nitrobiphenyl and 1 l. of o-dichlorobenzene(Note 8). The stirred mixture is heated above 170° for 1 hour by means of a heating mantle, allowed to cool to room temperature, and chilled in a refrigerator (5°) for several hours. The crude product is filtered with suction, washed with 40 ml. of light petroleum, and sucked dry on the filter. There results 26–28 g. of yellow-brown crystals, m.p. 171.5–174°. The filtrate is distilled under aspirator pressure to a volume of 150–200 ml. and chilled as before, to yield an additional 2–3 g., m.p. 171–174°. The total yield is 28–30 g. (89–96%). The combined crops are dissolved in 400–450 ml. of boiling 95% ethanol with 3–4 g. of Norit® to remove impurities and filtered through a preheated Büchner funnel. The filtrate on cooling deposits bright yellow needles of product, which are filtered after standing at 5° for several hours. This crop weighs 23–25 g., m.p. 174–175.5°. Concentration of the mother liquor to a small volume (50–70 ml.) and chilling gives a second crop of lesser purity, 1–2 g., m.p. 172–175°. The total yield of recrystallized material is 24–26.5 g. (77–85%), and the overall yield from o-nitrobiphenyl is 40–63%.2. Notes1. An Eastman Kodak technical grade of o-nitrobiphenyl was used by the submitters. This is no longer available, and the checkers used the material supplied by K and K Laboratories. Both o-amino- and o-nitrobiphenyl are available from the Aldrich Chemical Company.2. The Baker Co. catalyst was used.3. This carcinogen is more easily handled in a flask than in a beaker. Contact with the skin obviously should be avoided.4. Recrystallization is best accomplished by adding the compound to boiling ethanol and filtering. Prolonged heating should be avoided, as the substance gradually decomposes in hot solvent.5. The sodium nitrite solution must be added carefully in order to avoid loss of material due to vigorous foaming.6. This operation should be carried out in a hood to avoid the unpleasant effects of exposure to hydrogen azide vapors.7. The compound may be recrystallized from a large volume of ethanol, but no increase in yield was noted using recrystallized material in the next step.8. Eastman Kodak o-dichlorobenzene of 95% purity was used. Olefin-free kerosene or decalin may be substituted for the solvent, keeping the reaction temperature between 170°and 190°.3. Discussiono-Aminobiphenyl has been prepared by the reduction of the corresponding nitro compound with zinc and acetic acid,2zinc and hydrochloric acid,3iron and hydrochloric acid,4sodium bisulfite under pressure,5 or hydrazine and palladium;6 by the Hofmann reaction on o-phenylbenzamide;7 and by pyrolysis of diazoaminobenzene.8,9o-Amino-p'-nitrobiphenyl has been made by the nitration of o-aminobiphenyl with ethyl nitrate;10 by hydrolysis of the corresponding acetamide derivative;11,12 and by partial reduction of o, p'-dinitrobiphenyl with sodium bisulfite under pressure.52-Nitrocarbazole has been prepared by the dehydrogenation of 2-nitro-1,2,3,4-tetrahydrocarbazole with chloranil,13 by the deamination of 2-nitro-3-aminocarbazole,14 and by the thermal decomposition of o-azido-p'-nitrobiphenyl.15 The procedure given here is a slight modification of the last-mentioned method.4. Merits of the PreparationThe decomposition of o-azidobiphenyls is a convenient and general synthesis for a variety of carbazoles in good yield,15 especially those not available through direct substitution of carbazole itself. Many of the required intermediates can be prepared from o-aminobiphenyl by substitution reactions. The method is also applicable to the preparation of analogs of the carbazole system in which a heterocyclic ring replaces a benzene ring, to the preparation of indoles, and to certain analogous aliphatic systems.References and Notes1.Department of Chemistry, University of Michigan, Ann Arbor, Michigan.2.H. Hübner, Ann.209, 339 (1881).3. F. Fichter and A. Sulzberger, Ber.37, 878 (1904).4.T. Maki and K. Obayashi, J. Chem. Soc. Japan, Ind. Chem. Sect., 55, 108 (1952).5. C. Finzi and G. Leandri, Ann. Chim. (Rome), 40, 334 (1950).6.P. M. G. Bavin, Can. J. Chem., 36, 238 (1958).7.M. Chaix and F. de Rochebouët, Bull. Soc. Chim. France, [5] 2, 273 (1935).8. F. Heusler, Ann., 260, 227 (1890).9.J. A. Aeschlimann, N. D. Lees, N. P. McCleland, and G. N. Nicklin, J. Chem. Soc., 127, 66(1925).10. C. Finzi and V. Bellavito, Gazz. Chim. Ital., 64, 335 (1934).11.H. A. Scarborough and W. A. Waters, J. Chem. Soc., 89, (1927).12.S. Sako, Bull. Chem. Soc. Japan, 10, 585 (1935).13. B. M. Barclay and N. Campbell, J. Chem. Soc., 530 (1945).14.G. Anderson and N. Campbell, J. Chem. Soc., 2904 (1950).15.P. A. S. Smith and B. B. Brown, J. Am. Chem. Soc., 73, 2435 (1951); P. A. S. Smith and J. H.Hall, J. Am. Chem. Soc., 84, 480 (1962); P. A. S. Smith, in W. Lvowski, "Nitrenes," Wiley-Interscience, New York, 1970, Chapter 4.AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)palladium-on-carbonlight petroleumo-amino- and o-nitrobiphenylchloranilo-azidobiphenylsethanol (64-17-5)sulfuric acid (7664-93-9) hydrochloric acid (7647-01-0) acetic acid (64-19-7)Benzene (71-43-2)hydrogen (1333-74-0) sodium hydroxide (1310-73-2) iron (7439-89-6)nitric acid (7697-37-2) sodium nitrite (7632-00-0) sodium bisulfite (7631-90-5)zinc (7440-66-6)palladium (7440-05-3)hydrazine (302-01-2) sodium azide (26628-22-8)carbazole (86-74-8) Diazoaminobenzene (136-35-6) ethyl nitrate (625-58-1)decalin (91-17-8)hydrogen azideo-Aminobiphenyl (90-41-5)2-Nitrocarbazole,Carbazole, 2-nitro (14191-22-1)2-nitro-1,2,3,4-tetrahydrocarbazole2-nitro-3-aminocarbazoleo-dichlorobenzene (95-50-1)o, p'-dinitrobiphenylo-nitrobiphenyl (86-00-0)o-phenylbenzamideo-Azido-p'-nitrobiphenyl (14191-25-4)o-Amino-p'-nitrobiphenyl (6272-52-2) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。