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Vol. 13, No. 6
ORIGINAL PAPERS The Alkylation of Aromatic Amines by Heating with Aliphatic alcohol^^,*^ By Arthur J. Hill and John J. Donleavy DEPARTMENT OB CHEMISTRY, YALE USIVFRSITY, NEW HAVES, COSNSCTICUT
It was shown in a recent publication4 t h a t t h e formation of diethylaniline, C ~ H ~ N ( C Z Hby ~ )tZh e, interaction of aniline hydrochloride and ethyl alcohol could be promoted t o a considerable degree by certain catalysts, among which the two following combinations were found t o be the most active: Sodium bromide Calcium chloride Cupric chloride
Sodium bromidr Copper powder
has recently been investigated b y Reilly and Hickinbottom,I with particular regard t o t h e factors affecting nucleus substitution. They have shown t h a t t h e product, obtained b y heating this salt with butyl alcohol a t 200 O is,2 quantitatively speaking, a mixture of the secondary and tertiary bases, whereas a t 240Oto 260 O the product3 is chiefly $-n-butylaminobenzene (I). NH,.HCI
T h e present investigation is a n extension of this problem t o the toluidine series, and comprises two distinct phases, namely, 1-The action of ethyl alcohol upon the hydrochlorides of m-, and p-toluidine. 2-The action of n-butyl alcohol upon the hydrochlorides of aniline, and 0-, m-, and p-toluidine.
CaHoOH
n
NH.CaHo.HC1
v
NHP.HCI
-- rlv CaH ------f
9
0-,
The catalysts which were found efficient i n t h e alkylation of aniline hydrochloride with ethyl alcohol have likewise promoted alkylation in this new series of experiments. Furthermore, t h e experimental results have a n important bearing, on t h e one hand, as regards t h e comparative activity of ethyl and butyl alcohol, and on t h e other, respecting t h e spatial influence of nuclear substituents on t h e ease of alkylating aromatic
amines. As pointed out i n t h e previous p ~ b l i c a t i o nthe , ~ nat u r e of the product resulting from t h e alkylation of a n aromatic amine with alcohol is conditioned, in particular, b y two factors, namely, the temperature of t h e reaction, and t h e presence of certain catalysts. Influenced by these factors, t h e reaction may proceed i n one of two directions, as represented by Equations 1 and 2. NHzHCl
A
NHCzHs A
NHzHCl
A
With regard t o t h e effect of temperature, it appears t h a t there is a favorable one at, or below which, nitrogen alkylation predominates, a n d above which nucleus substitution is facilitated. This temperature is highest with methyl alcohol a n d is apparently lowered i n proportion t o the complexity of t h e alcohol molecule. T h e action of butyl alcohol upon aniline hydrochloride 1 Received February 26, 1921. The previous papers of this series, with 2 “Researches on Amines, IX.” 12 (1920), 636, have been published the exception of VII, THISJOURNAL, in the Journal of the American Chemical Society. 8 This paper is constructed from a dissertation presented by John J. Donleavy t o the Faculty of the Graduate School of Yale University, 1920, in candidacy for the Degree of Doctor ol Philosophy. (A. J. H.) 4 “Researches on Amines, VII.” 6 Lor. cit.
Somewhat similar results were also obtained with $-toluidine hydrochloride4 a n d butyl alcohol. Reilly and Hickinbottom6 have subjected the factors underlying t h e intramolecular rearrangement of @-abutylaminobenzene t o a very thorough investigation, a n d conclude t h a t this rearrangement of alkylarylamines is conditioned b y t h e presence of substances which are capable of uniting with amino groups. For example, HC1, ZnC12, CoC12, and CdC12 greatly facilit a t e this reaction, while compounds such as CaSOI, NaC1, CaC12, a n d Si02 are substantially inactive. Cupric chloride is stated t o be slightly active. N-butylaniline may be heated for several hours a t 240’ t o 260 without suffering rearrangement, whereas t h e introduction of t h e above-mentioned catalysts will promote intramolecular rearrangement t o t h e extent of 50 per cent or more, in 7 t o 8 hrs. I n t h e light of these observations i t is important t o note t h a t our most efficient catalytic mixture for tertiary amine formation is composed of CaC12, NaBr, and CuCL, t h e first two of which are inactive with respect t o producing nucleus substitution, and t h e last named, active t o a small degree only. Further, in the interaction of aniline hydrochloride a n d ethyl alcohol we observed6 t h a t ZnClz functioned much less favorably as a catalyst of nitrogen alkylation t h a n CaCL. Our results are therefore decidedly in accord with those of Reilly a n d Hickinbottom. T h e latter have further contributed data bearing on the comparative tendency for rearrangement of methyl- and n-butylaniline, i n which it seems evident t h a t t h e latter is far more prone t o undergo this reaction t h a n t h e former, i n t h e presence of t h e catalysts previously referred to. T h e object of our investigation has been primarily t o study t h e factors productive of t h e maximum yield of the tertiary bases i n t h e action of ethyl a n d n-butyl J . Chem. Soc., 117 (1920), 103. Ibid., 113 (1918). 102. Ibid , 113 (1918), 976. Ibtd., 113 (19181, 976. 6 Ibzd., 117 (1920), 103; Chem. News, 119 (1919),161. 6 LOC. C i l .
1
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alcohols upon t h e hydrochlorides of aniline and t h e isomeric toluidines. This problem has therefore involved an investigation of t h e conditions promoting a maximum transformation of A t o C, with a minimum production of B on t h e one hand, and D on t h e other.
(A)
(6)
(C)
(13)
We have observed t h a t three factors have a predominant influence on t h e formation of t h e tertiary base, C, namely, t h e concentration of t h e alcohol, t h e nature of t h e catalyst, and t h e temperature of t h e reaction. It has hitherto been common practice1 t o utilize two or three moles of alcohol in the interaction of amine hydrochlorides with alcohols for t h e production of tertiary bases. The utilization of a large excess of alcohol, ten molecular proportions, greatly decreases secondary amine formation, B. With regard t o the use of catalysts, we have found t h a t t h e combined influence of calcium chloride, sodium bromide, and cupric chloride, together with the hydrogen chloride of the salt, facilitates t h e transformation of A t o C. However, these same catalysts, particularly t h e last named, above a temperature which is apparently definite for each alcohol-amine mixture, initiate also the above-described nitrogen t o carbon rearrangements. This critical temperature we have found t o be 175' t o 180" in all of t h e alkylations herein described, t h e extent of tertiary amine formation, however, being considerably less in every case where butyl alcohol was used, as compared with ethyl alcohol. This is shown in the following table: Aniline Per cent
Ethyl alcohol.. Butyl alcohol..
.. .. ....
95 75
$-Toluidine Per cent
91.6 77.4
nz-Toluidine Per cent
90.25 79.8
o-Toluidine Per cent
76 48.5
I n other words, t h e temperature at which nitrogen t o carbon rearrangement sets in with butyl alcohol is apparently lower t h a n t h a t of ethyl alcohol, and although tertiary amine formation might hypothetically be increased a t temperatures higher t h a n 180°, t h e possible result is nullified by t h e initiation of t h e reaction typified b y t h e transformation of C t o D. The interaction of alcohols and t h e derivatives of aniline presents a more complicated problem t h a n is involved with t h e prototype of t h e series. I n t h e latter case, t h e entering group need only be considered, whereas, when derivatives of aniline, such as t h e isomeric toluidines, are employed, the orientation of t h e methyl groups in t h e benzene nucleus markedly affects the reactivity of t h e amine in question. T h a t ortho substituents inhibit t h e reactivity of adjacent nucleus groups has long been recognized. We should therefore expect t h e alkylation of a-toluidine hydrochloride to present certain anomalies, as compared with the reactivit,y of t h e meta and para derivatives. This has been found t o be remarkably t h e case in the present investigation. While t h e p - and m-toluidines could be ethylated or butylated t o substantially t h e same 1 THISJOURNAL, i a (igzo), me.
505
degree, t h e extent of tertiary amine formation was 14 t o 16 per cent less in the case of o-toluidine and ethyl alcohol, and as much as 29 t o 31 per cent less when butyl alcohol was used as t h e alkylating agent. This is by no means t h e first observation concerning t h e steric influence' of ortho substituents upon t h e alkylation of amines. However, so far as t h e writers have been able t o ascertain, t h e present observation on the steric influence of ortho substituents upon t h e reaction between aliphatic alcohols and t h e salts of aryl amines is t h e first of this nature t o be recorded. Quite recently, ReillyZ investigated the action of n-butylchloride upon o-toluidine, and was able t o obtain only mono-butyl-0-toluidine. I n an effort t o prepare the tertiary amine he digested mono-n-butylo-toluidine with a n excess of n-butylchloride for 10 days. Even under these conditions he was unable t o obtain t h e tertiary base. EXPERIMENTAL
The alkylations described below were all carried out in an iron autoclave of 1.7 liters' capacity. The latter was equipped with the usual pressure gage and thermometer well, and protected from corrosion by means of a glass inset. The location of the thermometer well was such t h a t t h e temperatures recorded were those of t h e vapor phase. The autoclave was heated in a bath of cottonseed oil. Thk method of isolating the alkylation products in each experiment was as follows: The unchanged alcohol was first removed by distillation under diminished pressure. By this means very economical recovery could be made of the large excess of alcohol required t o effect complete alkylation. The residue was then made strongly alkaline with sodium hydroxide, and t h e liberated bases distilled with steam. The amines were separated from the aqueous distillate by ether extraction and dried over anhydrous sodium sulfate. I n the case of t h e butyltoluidines, however, t h e amines were not steam-distilled but extracted directly from the alkaline solution ,with ether, by reason of t h e fact t h a t t h e aromatic butyl amines steam-distil a t a much slower rate than the corresponding ethyl derivatives. After removal of the ether, the oils were fractionally distilled a t atmospheric pressure, t h e distillates being collected at 2" intervals. The extent of tertiary amine formation in each experiment was determined by an estimation of t h e acetylizable material in t h e reaction product (see previous paper for details), a n d . t h e result calculated in terms of the mgno-alkylated amine. SYNTHESIS O F THE ISOMERIC DIETHYLTOLUIDINES
Romburgh3 prepared diethyl-o- and -?-toluidine by t h e interaction of ethyl alcohol and the corresponding primary bases in t h e presence of hydrochloric acid. I n order t o effect alkylation he heated his reaction mixtures a t 200' t o 220' for 48 hrs. Since t h e primary purpose of his investigation was t h e study of the ni1 Ber., 6 (1872), 707; 8 (1875), 61; 18 (1885),1824; 33 (1899),1401; 33 (1900),345,33 (1900). 1967; J . prakl. Chem., 65 (1902), 252;A n n . , 346 (19061,128. 2 J . Chem. Soc., 113 (1918).974. a Rec. lrav. chim. S 11884).392.
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tration of these bases, he apparently devoted but little attention t o their synthesis. This brief reference- is t h e only record in the literature concerning the action of ethyl alcohol upon the hydrochlorides of 0 - and p-toluidine. However, t h e preparation of diethyl-oand -$-toluidine from the primary amine hydrobromides or hydriodides and ethyl alcohol is recorded by Stade1,l who states t h a t yields of 90 per cent or better are obtained a t 150" and 125") respectively. Monoas well as diethyl-o- and -$-toluidines have also been prepared by alkylation of t h e primary bases with alkyl halides.2 So far as the writers are aware, there is no available information concerning the action of ethyl alcohol upon m-toluidine hydrochloride. Beilsteins refers t o t h e work of Stade14 for t h e preparation of diethylm-toluidine, but t h e latter appears t o have prepared only t h e ortho and para derivatives. Further, t h e patent which covers Stadel's alkylation procedure does not designate t h e preparation of diethyl-m-toluidine, although t h e ortho and para derivatives are specifically mentioned. Weinburgs accurately determined the boiling point of t h e mono- and diethylated toluidines, including diethyl-m-toluidine, but did not state how the bases were prepared. I n fact, t h e only direct information respecting the preparation of this tertiary base is t o be found in a paper by Goldschmidt and Keller; who, giving no details, merely mention t h e fact t h a t they prepared this compound by Stadel's general method. The writers have now carefully studied the factors affecting tertiary amine formation in t h e interaction of ethyl alcohol and t h e isomeric toluidines. The results of these experiments are embodied in Tables I, 11, and 111.
DIETHYL-p-TOLUIDINE
Vol. 13, No. 6
TABLB I-DI~THYL-9-TO~UIDINE (100 g. 9-toluidine hydrochloride; 320 g. ethyl alcohol; time, 8 hrs.; temperature, 175'-180m) EXPT.1 EXPT.2 EXPT.3
........... ........... ............ ........... .....................
.. .. ..
Catag%im bromide, grams, Calcium chloride, grams. Cupric chloride, grams. Copper powder, grams.. Total oil, grams.. 166 Acetylizable portion of oil, per cent, ..... 9.4 Calculated tertiary base per cent.. 90.6 Distillation. Temperatkre 224'-226' cc... .......... 2 226°-2280' cc.. 68
..... ........... 228~1~4~~j :E.. ........... 230
.............
10
.. . 5.
10 10
107 7.9
103 9.4
92.1
38
5
90.6
..
28 69
1 42 51
13
7
DIETHYL-11Z-TOLUIDINE
A product containing 11.8 per cent acetylizable material was formed by heating m-toluidine hydrochloride with ten molecules of ethyl alcohol (Expt. 1, Table 11). The degree of alkylation was slightly lower in this case than t h a t obtained when t h e para salt was treated under similar conditions. The proportion of tertiary base in t h e reaction product was raised by t h e use of catalysts (Expt. 3). On t h e other hand, i t is of interest t o note t h a t copper powder (Expt. 2) exerted a n inhibitive action. It is difficult t o explain this apparent anomaly, since in all previous alkylations its use has proved beneficial. The best experimental conditions (Expt. 3) for t h e preparation of diethyl-m-toluidine were therefore productive of oils which contained about 90 per cent of the tertiary base. This figure is about 2 per cent lower than t h e results obtained with t h e para base, and 5 per cent lower than those obtained with aniline. A procedure similar t o t h a t applied i n the case of t h e para derivatives was used for t h e isolation of diethylm-toluidine. The latter was thereby obtained as a light yellow oil which boiled a t 232' under 755 mm. pressure. Weinbergl reported a boiling point of 231.5O for this compound. TABLE I I - D I E T H Y L - ~ - ~ O L U I D I N ~
(50 g . m-toluidine hydrochloride; 160 8. ethyl alcohol; time, 8 hrs.; temperature, 175O-18Oo)
The results which were obtained by heating p-toluidine hydrochloride with ten molecules of ethyl alcohol are recorded in Expt. 1, Table I. The product of this reaction distilled for t h e most part within a range of 4' and contained but 9.45 per cent secondary amine. The addition of copper powder and sodium bromide (Expt. 2) t o t h e reaction mixture increased t h e formation of the tertiary base, while t h e second set of catalysts (Expt. 3) produced no positive effect. The best conditions for t h e formation of diethyl-$-toluidine are therefore represented in Expt. 2. I n order to isolate pure diethyl-p-toluidine, t h e crude oil was heated for 3 hrs. with an equ&l weight of acetic anhydride. The resulting product was then fractionally distilled a t atmospheric pressure. The tertiary base was obtained as a pale yellow oil which boiled a t 230' a t 755 mm. This result is in accord with t h e previous observations of Weinberg,? who reported a boiling point of 229' for this amine. p
Bm., 18 (1883), 29;D. R. P. 21,243 (1883). Ann., 93 (1855), 313; A m . Chem. J.. 7 (18851, 119.
8
voi. 11,477.
1
Cit. B n . , 28 (1892), 1613. (IQOZ), 3540.
4 LOC. 8
a Zbid., 36 1 L O G . cu.
EXPT.1
Catalysts: Sodium bromide, grams, Calcium chloride, grams. . . . . . . . . . . Cupric chloride, grams. . . . . . . . . . . . . Copper powder, grams.. Total oil, grams.. ................... 55 Acetylizable portion of oil, per cent.. . . 11.8 Calculated tertiary base, per cent. . . . . 8 8 . 2 Distillation. Temperature 226°-2280 cc ........... 2 228'-230°' c c . , 16 23Oo-232O' c c . . 20 232'-234': c c . . ......... 4 234'-236' CC. . . . . . . . . . . 4 236°-2380: cc., ......... 4
...........
...........
......... .........
ExP.T. 2
EXPT.3
5
5 5 2.5
2: 5 47 13.7 86.3
7
19 9 4
4 4
..
48 9.75 90.25 13
17
8 4 4 2
DIETHYL-0-TOLUIDINE
The steric influence of o-substituents upon t h e alkylation of amines is interestingly demonstrated, in the interaction of o-toluidine and ethyl alcohol. When ten moles of the latter were heated with o-toluidine hydrochloride (Expt. 1, Table 111), t h e product contained 32 per cent of the secondary base. It has already been shown t h a t t h e alkylation of t h e meta and para isomers by this method yields a preponderance of t h e tertiary amine. In fact, in neither case did t h e acetylizable portion of t h e oil exceed 12 per cent. The result with o-toluidine therefore offers a striking contrast. The effect of the catalysts (Expts. 2 and 3), however, was more apparent with this base than with the meta 1LOC.
cit.
June, 1921
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a n d para derivatives. T h e best results were obtained by t h e use of cupric chloride, sodium bromide, a n d calcium chloride (Expt. 3). T h e oil contained 2 4 per cent of t h e mono-alkylated base. Even this, however, is quite inferior t o t h e degree of alkylation obtained when the isomers were similarly treated.
of distillation of this oil, compared with t h a t obtained in Expt. 1, indicates t h e considerable increase in t h e amount of tertiary base produced b y this change of procedure. I n order t o ascertain whether or not 175' was t h e optimum temperature, a n experiment was carried out under t h e favorable conditions of Expt. 2, t h e temTABLE III-DIETHYL-~-TOLVIDINE (100 E. o-toluidine hydrochloride: 320 g. alcohol; time, 8 hrs.) perature, however, being raised t o 200'. As aresult, EXPT.-I EXPT.2 EXPT.3 E x P T . ~ ~ t h e amount of dibutylaniline was decreased about Catalvsts: Skdium bromide, grams. ........ .. 10 5 5 per cent. This was due, no doubt, t o a n intra..* . 10 .. 10 Calcium chloride. grams. ........ 5 Cupric chloride, grams. ......... .. 5 2.5 molecular rearrangement, in which nuclear alkylated Copper powder, grams.. ........ 5 175 175 Temperature, C .................. If: 200 amines were produced in accordance with t h e following 92 91 Total oil, grams.. .................. 87 40 32.3 28.6 24 Acetvlizable Dortion of oil. Der cent.. . 39.9 equation: O
...
Calc&lated tertiary base, p6r cent. 67.7 Distillation. Temperature 5 206°-2100, cc 210°-2140 cc 65 15 214'-218": c c . . 218O-222O cc 7 222°-2260: c c . . 226 O-23O0. ....... cc 230°-2$40 cc 234'-238': c c . , 238'-242'. C C . . 1 One-half the usual autoclave charge used in
.......... .......... ........ .......... ........ .......... .......... ........ ........
.. .. .. .. ..
71.4
76
5 67 19 7
6 64 15 8 3
.. .. .. ..
..
.. .. .. ..
60.1
.. .. 1
2 2 7 8 6 7
this experiment.
I n order t o ascertain t h e effect of higher temperatures, a n experiment was carried out a t 200' C. with most efficient catalysts. This modification of conditions (Expt. 4) greatly increased t h e proportion of acetylizable bases. It is quite evident from this observation t h a t intramolecular rearrangement will t a k e place t o some extent a t temperatures of 200" C. Owing, therefore, t o t h e inhibitive effect of t h e ortho substituent, t h e best experimental conditions failed t o produce a product containing more t h a n 76 per cent diethyl-o-toluidine. T h e pure tertiary base was isolated from the reaction mixtures by t h e use of t h e method previously described for t h e preparation of the meta a n d para isomers. It was obtained as a practically colorless oil which boiled a t 206' t o 208' C. a t 755 mm. Stade1,l who has previously prepared this base, states t h a t i t boils a t 208' t o 209'. DI-)Z-BUTYLANILINE
As stated above, t h e action of n-butyl alcohol upon aniline has recently been investigated by Reilly and his co-workers. Their investigations, however, are of particular value in their information respecting t h e intramolecular rearrangement of rt-butylaniline, while their observations with regard t o t h e degree of nitrogen alkylation b y this method are wholly qualitative. T h e writers have therefore sought t o establish t h e experimental conditions productive of t h e maximum yield of di-12-butylaniline. The results of these investigations are given in Table IV. When aniline hydrochloride was heated a t 175 ' with t e n moles of n-butyl alcohol (Expt. 1, Table IV), t h e alkylated product contained b u t 51 per cent dibutylaniline. It is interesting t o note t h a t under similar conditions ethyl alcohol yielded a n oil containing 88 per cent diethylaniline. T h e difference in t h e reactivity of these two alcohols is plainly evident from these observations. T h e effect of introducing t h e catalytic mixture (Expt. 2) was quite marked. T h e yield of dibutylaniline was raised from 51 t o 75 per cent. The range 1
LOG,cit.
C6Hb.NH.CaHg ----) ~ ~ - N H ~ . C B H ~ . C ~ H ~
Reilly utilized temperatures of 240' t o 260' in order t o obtain p-a-butylaniline, b u t t h e results of Expt. 3 suggest t h a t alkylation of t h e nucleus, although not predominant, may t a k e place a t 200' C., or even lower. We did not operate a t temperatures lower t h a n 175O, since t h e autoclave pressure, which is a n important factor, decreases materially below this temperature. T h e most favorable conditions for t h e formation of dibutylaniline are therefore shown in Expt. 2. Even these, however, produce a tertiary amine formation which is 20 per cent below t h a t obtained with ethyl alcohol. T h e wide difference in t h e reactivity of t h e two alcohols may be seen from inspection of t h e following table: COMPARISON
OF
ETHYLAND n-BUTYL ALCOHOLSIN THEIR REACTION
ANILINEHYDROCHLORIDE Ethyl Alcohol n-Butyl Alcohol Per cent Per cent Alcohol (ten moles). 88 75i.5 Alcohol (ten moles and catalysts).. 95 The above percentages refer to the amount of tertiary amine in the reaction products. WITH
................... ......
Pure di-12-butylaniline was prepared by the following procedure: Fifty grams of the crude amine, containing about 25 per cent of t h e secondary base, were heated for 3 hrs. with a n equal weight of acetic anhydride. The resulting product was repeatedly distilled in order t o separate the tertiary base from the acetobutylaniline. After careful fractionation, di-n-butylaniline was obtained as a light yellow oil, which boiled a t 262' t o 264" under 755 mm. pressure. Reillyl reported t h e boiling point of this compound as 260" t o 263' under 767 mm. pressure. ANALYSIS(Kjeldahl) Calculated for CirHtaN: N . . Found: N
Per cent 6.86
........... ...........................
7.00
TABLEIV-Dl-n-BUTYLANILINE (50 g . aniline hydrochloride; 285 g . n-butyl alcohol; time, 8 hrs.) EXPT. 1 EXPT.2 EXPT.3
Catalysts: Sodium bromide, grams, .......... Calcium chloride, grams. Cupric chloride, grams. . . . . . . . . . . . Temperature C.. Total oil, g r i m s . . .................... Acetylizable portion of oil, per cent.. ... Calculated tertiary base, per cent. Distillation. Temperature 244O-248:, c c . . 248'-252 cc. . . . . . . . . . . . 252 '-256 ', cc . . . . . . . . . . . . 256°-2600, c c . 260°-264' cc . . . . . . . . . . . . 264°-2680: c c . . 268O-272' cc ............ 272'-276": c c .
.......... .. ..
...................
.
..... ......... ...........
lii-180
47
49
51 7 15 9 7
5
. . . . . . . . . . .. .. . . . . . . . . . . . ..
mw;;::; E;:. ........... ..........
1
J . Chem. Soc., 118 (1918), 99.
.. ..
5 5
2.5
175-180 53 24 75
..4
4 13 10 13 9 4
.. ..
5 5 2.5 200
51 30.3 69.7
.. ..
8 15 13 5 3 1
..
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Vol. 13, No. 6
DI-n-BUTYLTOLUIDINES separate the tertiary base. This proved successful, The action of n-butyl alcohol upon the hydrochlorides and t h e tertiary base was obtained in a fair state of of t h e isomeric toluidines has not been investigated purity. Fractional distillation of this product yielded until recently, and then only in connection with t h e pure di-a-butyl-p-toluidine as a yellow oil boiling a t para derivative. Reilly heated t h e hydrochloride of 283" t o 285" under 7 5 5 mm. pressure. Reilly states1 p-toluidine with 1.3 molecules of n-butyl alcohol a t t h a t t h e boiling point of di-n-butyl-p-toluidine is 282 O 220" t o 260" for 7 t o 8 hrs., and states' t h a t t h e product t o 284" a t 764 mm. of the reaction is essentially a primary amine, preTABLEV-DI-n-BUTYI,-P-TOLUIDINE sumably an aminobutyltoluene. Nitrogen-alkylated (50 g. p-toluidine hydrochloride: 255 g . n-butyl alcohol) EXPT.1 EXPT.2 EXPT.3 EXPT.4 derivatives were apparently produced in such small Catalysts: quantities in this reaction t h a t t h e extent of their Sodium bromide grams.. , . . , . ., 5 5 5 Calcium chloride', grams.. . . . . . . . 5 5 5 formation was not determined. The secondary amine Cupric chloride, grams 2.5 2.5 2.5 Time hours.. . . . . . . 8 12 8 is formed a t 140°, but t h e yield of this base rapidly Tem 'erature C . 175-180 175-180 175-180 200 gra)ms.::::.. . . . . . . . . . . . 65 65 66 64 diminishes with increasing temperature. Reilly, how- TotaToil, Acetylizable portion of oil, per cent. 28 22.6 22.5 29.1 72 77.4 77.5 70.9 Calculated tertiary base, per cent. . ever, has prepared t h e mono-n-butyl-o- and -p-tolu- Distillation. Temperature 256'-260:, C C . ....... 3 .. .. .. idines and the di-iz-butyl-p-toluidine2 by the action of 260"-264 C C . . ...... 4 .. .. .. n-butylchloride upon t h e corresponding amines. So 2 2 .. 6 2 4 f a r as the writers are aware, t h e di-n-butyl derivatives 18 6 24 29 l4 15 of m- and o-toluidine have not hitherto been prepared. 14 16 18 284°-2880, cc ........ 3 7 , 12 I n Tables V, VI, and VI1 are recorded t h e results of 288=2920, c c , . . . . . . . . . ..3 3 12 the experiments designed t o determine the factors'leadDI-%-BUTYL-m-TOLUIDINE ing t o the maximum degree of tertiary amine formation in t h e reaction between t h e toluidine hydrochlorides The results obtained with m-toluidine were slightly better t h a n t h e corresponding ones with the p a r a and n-butyl alcohol. derivative. The hydrochloride, when heated with t e n DI-a-BUTYL-P-TOLUIDINE molecules of n-butyl alcohol, gave a product containing A product containing 2 8 per cent of the secondary 7 3 per cent of di-n-butyl-m-toluidine (Expt. 1, Table base was obtained by t h e action of ten moles of n-butyl V I ) , while t h e introduction of t h e catalysts (Expt. 2 ) alcohol upon p-toluidine hydrochloride (Expt. 1, Table reduced the acetylizable material about 7 per cent. V). This result is considerably better t h a n t h e cor- Our best conditions for t h e preparation of di-n-butylresponding one with aniline, which gave 49 per cent m-toluidine are therefore represented by Expt. 2. of the secondary base. The utilization of t h e catalysts Under t h e conditions of t h e latter, the yields of tertiary (Expt. 2) produced an increase of about 5 per cent in base were slightly better t h a n those obtained with either the degree of alkylation. I n order t o ascertain t h e aniline or p-toluidine. Yet these are far inferior t o effect of longer heating, t h e time period was extended the results obtained with ethyl alcohol under similar t o 12 hrs. (Expt. 3). The results were substantially conditions. Hinsberg's method was used for t h e the same as those resulting from t h e usual time factor. isolation of di-n-butyl-m-toluidine, which has not hithAn increase in temperature t o 200" (Expt. 4) not only erto been described in t h e literature. By this profailed t o aid in t h e formation of the tertiary base, b u t cedure the amine was obtained as a pale yellow oil even facilitated t h e formation of nuclear alkylated which boiled a t 278" t o 280" a t 755 mm. amines. The best conditions, represented by Expt. 2 , ANALYSIS(Kjeldahl) Per cent Calculated for CisHzaN: N . .. gave results somewhat better t h a n those obtained with Found: N . . . . . . . . . . . . . . . . . . ..... 66.. 35 94 aniline under similar conditions. TABLE VI-DI-n-BuTYI,-m-~oLuIDINE We were unable satisfactorily t o isolate and purify (30 g . m-toluidine; 235 g. n-butyl alcohol; time, 8 hrs.; temp., 175°-1800) EXPT. 1 EXPT.2 di-n-butyl-p-toluidine by the use of acetic anhydride. Catalysts : . . Sodium bromide, grams. . . . . . . . . . . . . . . . 5 Hinsberg's method3 was therefore used. The proCalcium chloride, grams. ..................... 5 cedure employed was as follows: The crude amine, 2.5 Cupric chloride, grams.. .................... : .. 50 OB, grams,,.......................... . 63 previously analyzed, was shaken with twice the cal- Total 20.2 Acetylizable portion of oil, per cent, . . . . . . . . . . . . . 27.4 7 9.8 7 2 . 6 Calculated tertiarv base, per cent. .............. culated quantity of benzenesulfonyl chloride in the Distillation. Temperature . . . . . . . . . . . . . . . . . . . 13 .. 266°-2700, C C . . presence of four molecular proportions of alkali, as 1 270°-274', c c , . . . . . . . . . . . . .. . . . . . . 17 6 recommended by Hinsberg. After t h e initial reaction, 274O-278:, c c . . . . . . . . . . . . . .. . . . . . . 13 8 278O-282 c c . . . . . . . . . . . . . . . . . . . . . 9 5 5 which was strongiy exothermic, had subsided, the 282"-286', C C . . ............ ....... 4 286'-290°, C C . . . . . . . . . . . . . .. . . . . . . 4 mixture was heated until all odor of t h e acid chloride had disappeared. It was then extracted with ether DI-12-BUTYL-0-TOLUIDINE and the ether extract dried with anhydrous sodium The steric influence of t h e ortho-substituted methyl sulfate. After removal of the ether an attempt was group was even more apparent in the alkylation with made t o separate t h e tertiary amine from t h e benzene- butyl alcohol t h a n when ethyl alcohol was used. T h e sulfon derivative of t h e secondary base b y distillation. interaction of a-toluidine hydrochloride with ten moles This proved but a partial success. The distillate was of n-butyl alcohol (Expt. 1, Table VII) gave a product accordingly subjected t o steam distillation in order t o which contained 66 per cent acetylizable oil, and was 1 J . Chem. Soc., 118 (19181, 983. thus largelyzmono-n-butyl-o-toluidine. 2 I b i d . , 118 (ISIS), 974. SYNTHESIS
OF
THE
ISOMERIC
.
'
%.
.
8
Bcr.,
as
(1890). 3862.
1 LOC.
cit.
June, 1.921
T H E J O U R N A L OF I N D U S T R I A L A N D E N G I N E E R I N G C H E M I S T R Y
509
The use of t h e catalysts (Expt. 2) materially increased t h e degree of alkylation and reduced t h e proportion of acetylizable material t o about 51 per cent, a n improvement of 15 per cent. Even t h e latter result is distinctly inferior t o those obtained with either aniline or m- and p-toluidine under similar conditions. It is evident t h a t considerable experimentation would be required in order t o secure better yields of di-nbut yl-o-t oluidine. Di-n-butyl-o-toluidine was isolated by t h e same procedure which was employed in connection with t h e purification of t h e ortho and para bases. Considerable difficulty was experienced in obtaining t h e tertiary base in a high degree of purity, a comparatively pure product being finally prepared by two successive treatments of t h e crude di-n-butyl-o-toluidine with benzenesulfonyl chloride. After this purification t h e reaction product boiled a t 245' t o 260". This material was carefully redistilled, and t h e oil boiling between 255 O and 260 O was taken as t h e representative fraction. The latter cut boiled largely a t 256' t o 258' a t 755 mm. and appeared t o be a definite product. The analysis of this base confirmed t h e fact t h a t we were dealing with di-n-butyl-o-toluidine. ANALYSIS(Kjeldahl) Calculated for CISHZSN: N . Found: N
............ ............................
Per cent 6.39 6.58, 6 . 5 6
TABLE VII-DI-?Z-BUTSL-~-TOLUIDIN~ (50 g. o-toluidine hydrochloride; 265 g. n-butyl alcohol; time, 8 hrs.; temp., 175°-1800) EXPT.1 EXPT.3 Catalysts: Sodium bromide, grams. 5 5 Calcium chloride, grams. Cupric chloride, grams. 2.5 Total oil, grams .............................. 55 53 66.1 51.5 Acetylizable portion of oil, per cent.. Calculated tertiary base, per cent. 33.9 48.5 Distillation. Temperature 246"-250:, c c . . 4 13 3 259'-254 cc 21 10 2540-25S0: C C . . 25S0-2620, cc ..................... 9 13 4 7 262'-266' CC.. 266'-274" cc.. 8 274'-278O: cc.. 6
..................... ..................... ...................... ............
.............. ................... ..................... ................... ................... ..................... .....................
..
ANILINE
PARA ToLUiDrNE
ME TA
TOLU f D h E
ORTHO TOLUIDINE
I-ETHYL ALCOHOL(ten moles) A N D CATALSSTS (NaBr-CaCln-CuClr) 11-ETHYL ALCOHOL 111-BWTYL ALCOHOL (ten moles) A N D CATALYSTS (NaBr-CaClz-CuCln) IV-BUTYL ALCOHOL
t h e poorest yields of tertiary base were obtained in t h e alkylation of o-toluidine. These results are presumably due t o t h e spatial influence of t h e o-substituted methyl group. &--Two new amines have been prepared by t h e abovedescribed methods, namely, di-lz-butyl-o-toluidine (I), and di-n-butyl-m-toluidine (11).
SUMMARY
1-The action of ethyl alcohol upon t h e hydrochlorides of t h e isomeric toluidines has been investigated. T h e formation of t h e tertiary bases has been promoted by certain catalysts, namely, cupric chloride, sodium bromide, and calcium chloride, and t h e utilization of a large excess (ten moles) of t h e alcohol. The accompanying figure graphically illustrates t h e results of these experiments. For purposes of comparison, t h e results of t h e previous investigation on t h e action of ethyl alcohol upon aniline hydrochloride have also been included. Graph I represents t h e degree of tertiary amine formation which results from heating t h e hydrochlorides of t h e bases with ten moles of ethyl alcohol, while Graph I1 indicates t h e beneficial effect of t h e catalysts. The inactivity of o-toluidine, as compared with t h e other bases in either series, is very striking. 2--The/inter'action of n-butyl alcohol with t h e hydrochlorides of aniline and t h e isomeric toluidines has also been investigated. I n this series, catalysts have also increased tertiary amine formation. This is illustrated by Graph IV, which represents t h e results when t h e catalysts were employed, and Graph 111, when t h e latter were omitted. As with ethyl alcohol,
(1)
(11)
&The comparative activity of n-butyl alcohol and ethyl alcohol with regard t o alkylation is illustrated i n t h e figure. It will be noted t h a t t h e butyl alcohol curve is appreciably below t h a t of ethyl alcohol. On t h e other hand, t h e effects produced by t h e catalysts were far more pronounced in t h e butyl alcohol series. Annual Tables of Constants Owing t o delays incident t o the printers' strike, i t has been found necessary t o advance the date a t which subscriptions at the special reduced rates will be received for the forthcoming Volume IV of Annual Tables of Constants and Numerical Data of Physics, Chemistry and Technology. Details concerning this volume, the subscription rates, and a subscription blank will be found on pages 967 and 968 of the April number of the Journal of the American Chemicul Society. The size of the edition is determined by the number of advance Subscriptions received, and promptness in subscribing is the only guarantee of delivery.
