[CONTRIBUTION FROM THE (>HEMICdL
LABORATORIES O F STAXFORD
UNIVRRSITY]
T H E ACTIOS OF BASES ON ORGXXIC HALOGEP; COMPOUNDS. V. T H E ACTION OF POTASSIUM AMIDE OK SOME AROMATIC HALIDES (1) F. W. BERGSTROW
AND
C. H. HORNISG
Received December 16, 1945
Earlier work (2, 3, 4) from these laboratories has s h o m that the alkali metal amides react with aryl halides in liquid ammonia to give aromatic amines. It has recently been found ( 5 ) that solutions of the alkali amides in liquid ammonia react mith 4-bromo- and 4-iodo-dibenzofuran to give 3-aminodibenzofuran, although the expected (not rearranged) products are obtained from 2-bromo- and 2-iodo-dibenzofuran. m-Anisidine is formed from o-chloro- or o-iodo-anisole, and 3-aininodiphenyl ether may be prepared from 2-iododiphenyl ether. Urner and Bergstrom (4) found that 2-naphthylamine is the chief product of the action of potassium amide on both the cy- and the p-naphthyl halides, with the exception of a-fluoronaphthalene. Meharg and Allen, Jr. (6) many years ago hydrolyzed 0- and p-chlorotoluenes with aqueous sodium hydroxide at temperatures above 300", and in each case found m-cresol in addition to the expected isomer. In continuation of this work, it was found that the 0-, m-,and p-tolyl halides, with the exception of the fluoride, react readily with a liquid ammonia solution of potassium amide to give mixtures which contain some of the amine corresponding to the halide used. p-Chlorophenetole and potassium amide react to give a p-phenetidine which probably contains an isomer. 9-Phenanthrylamine is formed from 9-bromophenanthrene and potassium amide. 2-Chloroquinoline is converted rapidly to a tar, by reaction with a strong base such as potassium amide, but it is not,appreciably attacked by the ammonia-insoluble calcium amide a t -33". 2-Bromopyridine, 3-bromopyridine, 6-chloroquinoline, 4-bromoisoquinoline, and p -chloronitrobenzene react vigorously with potassium amide without the formation of definite products. Because of its very low solubility in liquid ammonia, sodium p-bromobenzenesulfonate is not appreciably attacked by the alkali amides at room temperatures. Secondary amine fractions of low basicity were obtained in working up the products of the action of potassium amide on 0- and m-chlorotoluene, o-iodotoluene, p-bromotoluene, and p-chlorophenetole, but they were unquestionably mixtures. It is evident that potassium amide "catalyzes" the reaction of a tolyl halide with the potassium salt of a toluidine to form ditolylamines (or isomers), in the same manner that the alkali amides catalyze the reaction between an alkali anilide and the phenyl halides t o give diphenylamine, triphenylamine, and p-aminobiphenyl (3). h attempt to prepare pure di- or tri-ptolylamines by adding potassium amide to a solution of potassium p-toluide and p-bromotoluene in liquid ammonia resulted in forming a mixture, from which 1 Deceased,
Mar. 29, 1946. 334
POTASSIUM AMIDE W I T H AROMATIC HALIDES
335
was separated a solid, melting a t 145", and isomeric with the tri-p-tolylamine of Wieland (7) (m.p. 117'). The reaction between potassium amide and 1.5-2 molar proportions of a tolyl halide gives somewhat more than the quantity of potassium halide calculated from the equation, C7HTX 2KNH2 --+ C;H7NHK KX NH3 indicating a further reaction of the type,
+ C7HvSHK + C7H7X
+
+
KV'H
+
+
* ', (C7H7)zNK KX NHs A tolylquinaldine of unknoan orientation is obtained in 11% yield by the action of potassium amide on quinaldylpotassium and p-chlorotoluene in liquid ammonia. In view of the rearrangements observed by Meharg and Allen, by Gilman, and by workers in these laboratories, itj is suggested that similar rearrangements may occur in the Ullmah-Goldberg (8) syntheses of di- and tri-arylamines by heating an aryl halide other than a phenyl halide with primary or secondary arylamines in the presence of potassium carbonate or other alkali and metallic copper. The preparation of a primary arylamine is generally best carried out by adding the phenyl halide-alone, or dissolved in ether or ligroin-to a well stirred solution of the alkali amide in liquid ammonia. The reverse addition of the amide to the halide may decrease tar formation, but it often increases the amount of the secondary amine fraction, and complicates the separation of the products. Operation at -78" appears to increase the yield of toluidine from p-chlorotoluene. but the speed of the reaction is noticeably slower. The solubility of sodium amide in liquid ammonia at -33" is of the order of one grsm per liter, while potassium amide is very readily soluble. Furthermore, the conductance of a solution of sodium amide is much less than that of a solution of potassium amide of the same concentration (9), indicating the possible presence of complex ions in the former (10). Accordingly, an otherwise too vigorous reaction may be somewhat moderated and controlled by the use of sodium amide. By means of competition reactions (3),the relative ease of removal of halogen from the m-tolyl halides has been found to be the following: m-C7H7CI, 1.0; m-C7H7Br, 13.4; m-C7H7I, 5.2. If the reactivity of CsHsCl = 1.0, these figures become, respectively, 0.6, 8.2, and 3.4. The methyl group accordingly slightly decreases the rate of removal of the halogen from a tolyl halide, but it should be pointed out that the results are of qualitative significance only because the mechanism of replacement of the halogen may not be identical in the three cases. The order of decreasing reactivity, Br > I > C1, is the same as observed with the phenyl halides (3).
EXPERIMENTAL
Method 1 . Potassium amide solution, made in vessel 1 of Fig. 1 of a previous article (2), was slowly forced over with stirring into a solution of the aryl halide in vessel 2. A small amount of ammonia was condensed in vessel 1, and the residual potassium amide washed over into the other vessel. Halides of low solubility in liquid ammonia a t -33'
336
F. W. BERGSTROM AKD C. H. HORNING
were generally dissolved in a mixture of ether and liquid ammonia. A t the end of a period of time that varied from about half an hour to four or five hours, C.P. ammonium nitrate equivalent to the alkali metal used in forming the amide was added t o destroy reactive potassium salts. Since no nitrogen or hydrogen was formed in the first few experiments with the tolyl halides, subsequent gas collection was omitted. The residue left after evaporating the ammonia was treated with water to dissolve inorganic salts, and then extracted several times with benzene to remove amines. The extracts were distilled from a small flask with a sealed-on fractionating column, first a t atmospheric pressure to remove solvent, unchanged aryl halide, and primary aromatic amine, and then in vacuo to obtain the secondary amine fraction. No attempts were made to separate tertiary amines from the residual tar. The primary amines were often extracted from the benzene solution with dilute hydrochloric acid. The aqueous solution of the benzene-insoluble material was occasionally analyzed for halide ion. Method 9. Two three-necked round-bottomed flasks were so arranged that potassium amide, prepared in one of them, could be transferred by ammonia pressure to the other, which contaihed the aryl halide (11, 12). Method 3. A 1000-cc. three-necked round-bottomed flask was fitted with a mechanical stirrer and with a separatory funnel containing the aryl halide or its solution in ether or in ligroin. A liquid ammonia solution of potassium amide was prepared in the flask (vhich was about half filled with solvent) by adding ferric oxide (0.05 g . ) to a solution of metallic potassium. The aryl halide was slowly introduced with good stirring, and the reaction was stopped at the desired time by adding ammonium chloride or ammonium nitrate equivalent to the potassium. The working up of the reaction products is described under method 1. TABLE I
THEACTIONO F K?JHz
MOLES
POTAsSIlJM .4MIDE ON A R Y L HALIDES
ARYL HALIDE MOLES
ETHOD
LEACTION TIME
HRS.
ARNH~ MOLES
%
-(1) 0.26 (2) .10 (3) .313 (4) ,205 (5) .10 (6) .215 (7) .307 (8) .151 (9) .128 (10) 0.26 (11) .25 (12) .25 (13) .319 (14) .306 (15) .243 (16) .201 (17) .020 (18) NaNHz 0.33
1
o - C ~ H ~ C I0.080 , o-CrH7C1, ,080 o-C~H~C~ .150 , O-CrHtI, .151 m-C7H7C1, .OS0 m-C7H7C1, .SO0 m-CrH7C1, ,150 V Z - C ~ H ~ C.158 I, p-CiH7C1, .OS0 p-C?H?Cl, .16 p-C?H?Cl, .12 p-C?H,Cl, .10 p - C ? H ~ c l , ,151) p-C7H7Brl .151 p-CsHsOC1, .115 p-CsHgOC1, .150 9-ClaHgBr, .010
3 2 3 3 2 2 1 2 3 3 3 3 3 2 3
p-C7HrC1,
3
.11
S
5 5 1.5 1 5 1 4.5 1 0.5 5 5 6 (-78’ 1.5 1.5 0.5 2.2 5
2
22 39 39 18 22 29 7. 26 33 24 44 52 29 32 .048 .0475 41 .0262 23 .OS8 88
0.018 .023 .0580 .028 .012 .029 .011 .020 .026 ,033 ,053 .052 .043
.024
22
AR~NH MOLES
0.022 .010
.014 .013
.011 .018 .os1 .018
-
NOTES
POTASSIUM AMIDE WITH AROMATIC HALIDES
337
Notes to Table I (a) The yield of primary amine was calculated on the basis of the proper limiting factor KX N H I . I n experiments designated by in the equation, ArX 2 K N H z -+ArSHK note (h). a small amount of aryl halide was recovered; the yields are here calculated on the basis of the halide actually consumed. The higher-boiling fractions have been designated as "ArJH" for comparative purposes only, without implication as to complete identity with this formula. (15) Products from the o-tolyl halides. I n this and the following, all melting points are uncorrected. .411 organic halides were white label preparations of the Eastman Kodak Co., refractionated before use. Thc f-action boiling at about 195-205' (760 mm.) was heated with acetic anhydride and glacial acetic acid to form an acetyl derivative which melted a t 108-109" after crystallizations from dilute alcohol, and at the same temperature when mixed with authentic acetoo-toluide (run no. l ) . The m.p. of the acetyl derivative from run 4 is 108.7-109.8"; several Crystallizations were required to attain this purity, suggesting that the original material (n: 1.56136) was a mixture. In run 3, a somewhat viscous liquid fraction boiling at 198-210' (46 mm.) (n: 1.6097) ITas readily converted to a solid hydrochloride by passing dry hydrochloric acid gas through its solution in absolute ether (yield, 0.42 g. from 1.1 g. of liquid. The melting point was about 14r3-165°, indicating a mixture). It is partly decomposed by heating near its melting poinl , and it is easily hydrolyzed by water. (c) Products from the m-tolyl halides. The tolylamine fractions boiled (760 mm.) at 190-207' (no. 6, table I ) ; 195-215" (no. 7 ) ; and a t 190-210' (no. 8). The tolylamine from run 8 had n f 1.5689, as compared with n: 1.5686 for m-toluidine and n: 1.5688 for o-toluidine. The acsetyl derivatives of the above fractions were uncrystallizable oils, and were accordingly mixtures. The benzoyl derivative of the tolylamine fraction from run 8 melted at 136.5139" after many crystallizations; Benz-o-toluidine melts a t 146", benz-m-toluide at 125".and benz-p-toluide a t 158" (13,14,15). The toluidine from run 5, when refractionated, boiled at 203-204" and gave an acetyl derivative melting a t 64-65', in agreement with the literature (16). The oily ditolylamine fraction from run no. 7 boiled a t 195-205" (24 mm.) and that from run 8 a t 184-210" (26 mm.). Concentrated aqueous hydrochloric acid slomTly converts this material to a pasty hydrochloride, which is readily hydrolyzed to the original oil. The m.p. of the hydrochloride, washed with hot benzene and dried, was 201-229", indicating a mixture. S o solid benzoyl derivative could be made. (d) Products from the p-tolyl halides. I n many of the reported runs, as well as in several that are not listed, the tolylamine fraction boiling about 195-205" a t 760 mm. was converted to an acetyl derivative, m.p. 152-153" alone or when mixed with authentic aceto-p-toluide. However, the benzoyl derivative of the tolylamine fraction in run 14 could not be obtained in a purcl condition (m.p. 110-128' after several crystallizations). The tolylamine from run 13 had nf 1.5663, indicating contamination with a n isomer, since p-toluidine has n:.' 1.5532. The oily ditolylamine fraction in expt. 13 boiled a t 198-215" at 24 mm.; n',"'61.6210. An easily hydrolyzed hydrochloride was precipitated from dried ethereal solution by dry hydrochloric acid gas. The fraction from run 14 boiledat 198-212"at 24.5 mm.; 1.6197. (e) Products from p-chlorophenetole. I n an unreported run, a fraction boiling at 253259" (760 mm.) gave an acetyl derivative, m.p. 136", in agreement with the literature (17). The acetyl derivatives from runs 15 and 16 could not be purified to this melting point, though a benzoyl derivative melting at 170-171" was readily obtained [benz-pphenetidide melts at 173" (IS)]. A hydrochloride, prepared by the action of concentrated hydrochloric acid on the base, melted at 233-231", in agreement with the literature (19). The lower-boiling fraction of these runs appears therefore t o be chiefly p-phenetidine.
+
+
+
338
F. W. BERGSTROM AKD C, H. HORNING
Viscous liquid secondary amine fractions of low basicity were obtained a t 250-290' (27 mm.; run 16) and a t 250-260' (24 mm.; run 15). These are undoubtedly mixtures, since di-p-phenetylamine is probably a solid. (f) The flask containing the potassium amide was cooled approximately to -%' by a bath of solid carbon dioxide in alcohol. A duplicate of this experiment with a shorter time of reaction (2 hrs.) gave a 32% yield of toluidine. (g) The benzene solution of the reaction product was evaporated to give crude 9-aminophenanthrene, m.p. 127-129'. The m.p. after several crystallizations from absolute alcohol was 136-137.5' [literature, 135-136" (20)l. The oxalate, prepared in alcohol and crystallized from the same solvent, melted a t 215' in agreement with the value of Schmidt and Strobe1 (21). (h) The tolyl halide not consumed in the reaction was recovered; yields m-ere calculated on the basis of the tolyl halide actually used. (i) The p-toluidine was obtained as a solid a t room temperatures. Catalytic tolylation of p-toluidine. I n accordance with method 2, the potassium amide, prepared from 4.05 g. of potassium, was siphoned over into500 cc. of a solution of potassium p-toluidine [made by adding 11.5 g. of p-toluidine to the potassium amide from 4.11 g. of potassium (1000-cc. flask)] and 18.0 g. of p-bromotoluene, with good stirring. The reaction was stopped a t the end of 1.5 hours by adding 10 g. of ammonium chloride. -4fter evaporation of the ammonia, water was introduced to dissolve inorganic salts, and the oil remaining extracted several time6 with benzene. All material (benzene, p-bromotoluene, p-toluidine) boiling under 215" at 760 mm. was discarded. A weakly basic secondary amine fraction distilled a t 198-215' (24 mm.) (4.6 g.; n; 1.6213); it was, as expected, somewhat larger than would have been obtained by the action of the potassium amide upon p-bromotoluene alone (cf. run 14). No definite compounds were isolated from this material. .A fraction boiling a t 245-275" (24 mm.) partly solidified in the receiver (4.6 8.); when crystallized several times from alcohol, i t melted a t 144-154" (the yield of purified material was small). 9 n a l . Calc'd for CHHUN:C, 87.76; H, 7.37; N, 4.88. Found: C, 87.77; H , 6.89; 3,5.00. This is accordingly tritolylamine or an isomer; tri-p-tolylamine melts a t 117". according t o Wieland (7). Material approximating this m.p. (m.p. 110-111") was obtained from the filtrate of the analyzed precipitate, but was thought to be a solid solution. I-Tolylquinaldine. Quinaldine (0.09 mole) was added to the potassium amide from 0.10 atom of potassium dissolved in 200 cc. of liquid ammonia (method 2) ; after the formation of the red quinaldylpotassium, 0.09 mole OF p-chlorotoluene was introduced, followed by 0.025 mole of potassium amide in 70 cc. of liquid ammonia contained in the second flask. After two hours, a n excess of ammonium chloride was added, the solvent evaporated and the residue extracted with benzene. The benzene was extracted with dil. hydrochloric acid and excess alkali added to precipitate the organic bases, which were in turn extracted with benzene. Distillation of this extract gave a fraction boiling at 250-263' (52 mm.), which formed 4.4 g. (11%) of a picrate, m.p. 167-167.5", after several crystallizations from methyl isobutyl ketone (picrate of a tolylquinaldine) . Anal. Calc'd for ClaHlsNaO,: C, 59.74; H, 3.92; N, 12.12. Found: C, 59.96; H, 3.74; N , 12.30. Competition reactions. The method has been described in a previous article (3). Potassium amide, prepared in about 50 cc. of liquid ammonia from oxide-free potassium (22) and an iron wire catalyst, was siphoned over into a stirred solution of a mixture of two aryl halides in 50 cc. of ether and 50 cc. of liquid ammonia. Calculations are essentially as already given (3), and the reactivities have been corrected for the change in concentration of one halide with respect to the other during the reaction. m-Chlorotoluene and m-bromotoluene. Potassium amide, 0.0229 mole; m-chlorotoluene, 0.0421 mole; m-bromotoluene, 0.0418 mole. VC't. of silver halide, 0.2315 g. from one-tenth
POTASSIUM AMIDE WITH AROXQTIC HALIDES
330
aliquot. Moles silver halide from 0.1 aliquot, 0.001256. Calculated average mol. wt. of the silver halide, 184.3. Mole per cent, AgBr, 92.1; mole per cent ,4gC1,7.9. Ratio, Br/Cl, 11.6; corrected ratio, 13.4. m-Chlorotoluene and m-aodotoluene. Potassium amide, 0.0218 mole; m-chlorotoluene, 0.0450 mole; m-iodotoluene, 0.0451 mole. Wt. silver halide (0.1 aliquot), 0.2595 g. Moles of silver halide, 0.001178 in 0.1 aliquot. Average mol. m t . of the silver halide, 220.0. Mole per cent AgI, 83.8; mole per cent AgCl, 16.2!. Ratio I/Cl, 5.2; corrected ratio, 6.5. M-Bromotoluene and m-iodotoluene. Potassium amide, 0.151 mole; m-bromotoluene, 0.0311 mole; m-iodotoluene, 0.0311 mole. WL. of silver halide inO.1 aliquot, 0.1670 g. Moles of silver halide, 0.00827. Average mol. at. silver halide, 202.0. Mole per cent AgBr, 69.8; mole per cent AgI, 30.2. Ratio, Br/I, 2.3; corrected ratio, 2.4. Chlorobenzene and m-bromotoluene. Potassium amide, 0.0254 mole; chlorobenzene, 0.0500 mole; m-bromotoluene, 0.0503 mole. Wt. of silver halide in 0.1 aliquot, 0.2551 g. Moles of halide, 0.001398. Ave. mol. wt. of silver halide, 182.5. Mole per cent AgBr, 88.0; mole per cent AgCl, 12.0. Ratio, Br/C1,7.3, or 8.2, when corrected. The same qualitative order of reactivity was found for the o- and p-tolyl halides, that is to say, the bromides were in all cases the most reactive, and the chlorides the least. Yields of polassaum halide in the reactaon between potassium amzde and a n excess of a tolyl halide. Potassium amide, prepared from potassium metal in weighed capsules (22) was added to an excess (generally 1.5-2 moles per atom of potassium) of a tolyl halide dissolved in liquid ammonia, in accordance with method 1. After evaporation of the ammonia, the residue was taken up in water and extracted with benzene to remove amines. The aqueous solution was then analyzed for halide ion in the usual manner, taking a tenth aliquot of a 1000 cc. solution. The figures below, each referring to a separate determination, represent the per cent of the halide ion, as determined by analysis and calculated in accordance with the equation, CTH~T; KYHz + C;H,XHz KX. p-C:HiCl: 57.0, 56.7, 53.9, 56.6. o-CiHjC1: 56.6, 55.9, 57.0. tn-C;HiCl: 57.0, 53.1, 58.1. p-C;HiBr: 61.4, 54.0, 54.0. o-C;H,Br: 58.0, 54.5. tn-CiHrBr: 49.4, 53.1, 52.6. p-C7HiI: 61.1, 58.4. o - C j H j I : 57.0, 55.5. R L - C ~ H60.2, ~ I : 61.2.
+
+
SUMMARY
1. The tolyl halides react with a solution of potassium amide in liquid ammonia to give in every case a mixture of toluidines, which contains some of the expected (not rearranged) isomer. p-Phenetidine, mixed possibly with an isomer, is prepared by the action of potassium amide on p-chlorophenetole, and 9-aminophenanthrene is similarly obtained from 9-bromophenanthrene. 2. Liquid secondary amine fractions of low basicity were isolated from the products of the reaction of potassium amide with the tolyl halides, or with pchlorophenetole. In all cases, these mere mixtures of u n k n o m composition. 3. The formation of these secondary amines is doubtless due to an activation of the halogen in the tolyl halides or in p-chlorophenetole by the potassium amide, in the manner previously described for the phenyl halides (3). This activation has been demonstrated in the reaction between p-bromotoluene and potassium p-toluidine, and in the reaction betreen p-chlorotoluene and quin-
340
F. W. BERGSTROM AND C. H. HORSIXG
aldylpotassium; in the former case, an isomer of tritolylamine, m.p. 145", was obtained ; in the latter case, a tolylquinaldine of unknown orientation. STANFORD UNIVERSITY, CALIP. REFERESCES (1) (2) (3) (4) (5) (6) (7) (8)
HORSING, Thesis, Stanford University. BERGSTROM, WRIGHT,CHAXDLER, AND GILKEY,J. Org. Chem., 1, 170 (1936). WRIGHTA N D BERGSTROM, J . Org. Chem., 1, 179 (1936). URNERAND BERGSTROM, J. Am. Chem. Sac., 67, 2108 (1945). GILMAN.4ND -&VAKIAN, J. A m . Chem. soc., 67, 349 (1945). MEHARGAND ALLEN,JR.,J. A m . Chem. Sac., 64, 2920 (1932). WIELAND,Ber., 40, 4279 (1907). GOLDBERG, Ber., 39, 169 (1906); 40, 4541 (1907). GOLDBERG AND SIMEROVSKY, Ber., 40, 2448 (190i). ULLMAN, Ber., 29, 1880 (1896). ULLMAN AND SPOlri.4GEL,
Bw.,38, 2211 (1905).
(9) FRANKLIN A N D KRAUS, A m . Chem. J.,23, 292 (1900); FRANKLIN, 2. physik. Chem., 69, (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22)
290 (1909). C j . Fuoss A N D KRAUS, J. Am. Chem. Sac., 6 6 , 2387 (1933); 57, 1 (1935). URNERAND BERGSTROM, J. Am. Chem. SOC.,67, 2108 (1945). SEIBERT AA-D BERGSTROM, J . Org. Chem., 10, 544 (1945). JACOBSOS AND HUBER, Ber., 41, 663 (1908). JUST, Ber., 19, 983 (1886). WALLACH,Ann., 214, 217 (1882). BEILSTEINA N D KUHLBERG, Ann., 166, 83 (1870). PAWLEWSKI, Ber., 35, 111 (1902). BISCHOFF, Ber., 31, 3246 (1898). LIEBERMAA-N AA-D KOSTAXECKI, Ber., 17, 884 (1884); BISCHOFF, Ber., 22, 1782 (1889). SCHMIDT AA-D STROEBEL, Ber., 34, 1464 (1901). SCHMIDT AND STROEBEL, Bw., 36, 2515 (1903). KRAUSA N D CHIC,J. Am. Chem. soc., 44, 2001 (1922).
