~Acetamino-cu-carboxy-y-(3-indole) -butyric Acid (V) A reaction mixture consisting of 4 g. of I Y , 2.2 g. of sodium hydroxide and 25 ml. of water was refluxed for four hours. The hot mixture was treated wit! Darco, filtered hot and the filtrate was then cooled t o 5 The addition of 5.7 ml. of cold concentrated hydrochloric acid t o the filtrate caused precipitation of slightly pink crystals of V. The mixture, after standing fifteen hours a t 5 O , was filtered. The solid was waslyd with 50 nil. ,of ice-water and dried for two hours a t 60 ; m. p . 140-141 ; yield 3.3 g. (97.5y0) of material suitable for conversion to VI. A sample of pur: V, recrystallized from 30% ethanol, melted at 153-154 Anal. Calcd. for ClsHleOsNz: N, 9.21. Found: K, 8.94. ~Acetamino-r-(J-indole)-butyric Acid (dl-N-Acetylhomotryptophan) (VI).-Decarboxylation of the substituted malonic acid V was readily effected by refluxing a suspension of 3O. g. of V in 25 ml. of water for three hours. The homogeneous reaction mixture was cooled t o 5 O and made acidic (congo red paper) by the careful addition of 18% hydrochloric acid. The acetyl derivative (VI) separated from the acidic solution as an oil which slowly crystallized. The mixture was filtered and the crude product (2.0 g.) was recrystallized from 40% ethanol. The product isolated from this recrysotalkation was the monohydrate of VI, m. p. 112-113 ; yield, 1.60 g. (58.3%). Anal. Calcd. for C ~ & H ~ ~ O ~ N ZN, .HZ 10.05. O : Found: N , 10.12. For the above analysis the crystals were dried for two hours at 25" under 2 mm. pressure. When the crystals were ikely pulverized and dried for an additional two
.
.
hours a t the same triiiperature and pressure the hydrat c apparently decomposed t o anhydrous VI. Anal. Calcd. for C14Hla0&: S, 10.77. Found: S , 10.53. a-Amino-y -( 3 -indole) -butyric Acid ( d l-Homotryptophan) (VII).-Recrystallized dl-N-acetylhomotryptophan monohydrate (VI, 1.60 g.), sodium hydroxide (1.00 9.) and water (10 ml.) were combined and the solution was refluxed for twenty hours. The hot reaction mixture was trzated with Darco, filtered and the filtrate was cooled t o 5 Glacial acetic acid (1.50 g.) was added t o the filtrate which was then allowed t o stand at 5" for twelve hours t o ensure complete precipitation of the amino acid VII. The reaction mixture was g t e r e d and the white solid was found t o be almost pure dl-homotryptophan, m. p. 306310"; yield 1.21 g. (96.5%). It was recrystallized from a large volume of 50% ethanol. The glistening platelets of pure VI1 melted sharply at 308' with decomposition. A n d . Calcd. for ClzHIrOzNz: C, 66.0; H, 6.47; N, 12.84. Found: C,66.15; H,6.51; N, 13.16.
.
Summary dl-Homotryptophan [a-amino-y-(3-indole)-butyric acid] has been synthesized eria the sequence: indole, tryptophol, /3-(3-indole)-ethyl bromide, ethyl a-acetamino-a-carbethoxy-y-(3 -indole) -butyrate, a-acetamino- a-carboxy- y - (3-indole) -butyric acid, a-acetamino-y-(3-indole)-butyricacid, dl-homotryptophan. URBANA, ILLINOIS RECEIVED JANUARY 2, 1948
NOTES Correlation of Rates of Halogenation of Methylbenzenes BY FRANCIS E. CONDON
The rate of chlorination of toluene relative to that of benzene is 345l; relative to that a t only one position in benzene, it is 345 X 6 = 2070. The product has been reported to be 42% p - and 58% o-chlorotoluene. Hence the partial relative rate of chlorination of toluene a t the para position is 0.42 X 2070 = 870; similarly, the ortho b L A T 1 V E RATES O F
Calculated Experimental' Calculated
TABLEI HALOGENATION OF POLYMFlTHYLBENZENES (BENZENE= 1)
*-Xylene
o-Xylene
m-Xylene
Mesitylene
Pentamethylbenzene
x x
2 . 5 X 10' 4 . 6 x 103
2 . 4 X lo6 4 . 3 x 106
1 . 6 X 108 1 . 8 X lo8
7 . 8 X 108
2.0 2.2
103 lo*
Pseudocumene
Hemimellitine
x
8 . 7 X lo6
7.4
10'
partial relative rate is (0.58/2) X 2070 = 600. The meta partial relative rate may be approxi(1) De la Mare and Robertson, J . Chem. Soc., 270 (1943). (2) Wertyporoch, Ana., 408, 153-168 (1932); C. A., SI, 2177
(i~az).
mated as 5, which seems reasonable in view of the value of 3 found for meta nitration.a If each of the methyls in a polymethylbenzene exerts the same activating influence as the one in toluene, a partial relative rate of chlorination a t each available nuclear position may be calculated as a product of two or more partial relative rates, each corresponding to a methyl and its position. The rate for the polymethylbenzene relative to that for benzene is then one-sixth the sum of the partial relative rates for all available positions.
Durene
3.0 X
lo6
Prehnitene
4.4
x
10'
13 X 108 Isodurene
5 . 2 X 108
In p-xylene, for example, each of the four available positions is influenced by two methyls, one ortho and one meta. The calculated partial rela(3) Ingold, Lapworth, Rothstein and Ward, J . Chrm. SOC.,1959 (1931).
NOTES
1964
tive rate a t each position is therefore 600 X 5 = 3000; and the rate for p-xylene relative to that for benzene is 4 X 3000/6 = 2000. Similarly,.inasmuch as the single available position in pentamethylbenzene is influenced by one para, two meta, and two ortho methyls, the rate of chlorination of pentamethylbenzene relative to that of benzene is 870 X 5 X 5 X 600 X 600/6 = 1.3 X lo9. Such calculated relative rates are compiled in Table I, together with available experimental values’ for chlorination or bromination. The agreement between the calculated and the experimental values, which is good in view of the 350,000-fold range, inspires considerable confidence in the five values for which experimental confirmation is a t present unavailable. A product of relative rates as calculated above is mathematically related to a sum of activation energy differences calculated from Arrheniustype equations for the individual rate constants k = Ae--E/RT For
Val, 70
-
+
defined by the neutralization equation NO+ C1NOC1. As in the analogous case of carbonyl chloride,2 the chloride ion should not be appreciably solvated, for the electronic structure of NOCl (resonance between :O=N+C1- and :O=N-6 .. : will not be affected by an electrondonor so weak as chloride. In agreement with this prediction, potassium chloride is insoluble in liquid nitrosyl chloride, contributing no conductance effect. The nitrosyl ion, on the other hand, should be solvated very strongly, on account of the resonance structures :O=X-Cl-N=O:] . .. . .. .. +,
..
)
.
[.
Hence it is expected that nitrosyl salts, many of which have been recognizedJ4should be soluble in liquid nitrosyl chloride, with high electrical conductance. Experimental Results.-These ideas have been tested in a preliminary investigation of the electrical conductance of solutions of typical nitrosyl ki/k = (Ai/A)e(E-Ei)/RT salts in liquid nitrosyl chloride. The monoand nitrosyl salts NOAlC14, NOFeC14 and NOSbCle X(E - Ei) = ZRT In ( k i l k ) ZRT In (ASIA) = are readily soluble strong electrolytes, as deR T In l I ( k i / k ) - RT In lI(Ai/A) manded by the theory (see Table I). The solvaIf the several A terms are equal,‘ the relationship tion is indicated by the reaction NOA1C14(s) simplifies to NOCl(g) S NOAICh.NOCl(s), recently discovered in our laboratories by Donald E. McKenzie. Z(E - Ei) = RTlnJI(ki/k) According to the theory of absolute reaction ratess The dissociation pressure of the product is approximately 240 mm. a t 0’. k = (KT/h)e-F/RT Less favorable results were obtained with where K = Boltzmann constant, h = Planck con- (N0)&3nClG, (N0)2TiCle, and (NOS04H), all of stant, and F = difference in free energy between which appeared quite insoluble and non-conductinitial and activated states, or “activation free i n g Dinitrosyl pyrosulfate, (N0)2S207,6showed a energy.’, Consequently, without any assumption slight conductance which very slowly passed of constancy for an A term, or “frequency factoPS through a maximum (see Table 11). Sulfuric acid was inert. k i / k =s e(F-Fi)/RT The inert character of potassium chloride was and not changed by an “acid” solution of nitrosyl Z(F Fi) = RT In lI(kI/k) chloroantimonate, which, by analogy with carso that a product of relative rates is simply related bonyl “acidsJJin carbonyl chloride, should have to a sum of activation free energy differences. dissolved it. The reason might be a protective (4) Cf.Bradfield and Jones, J . Chcm. Soc., 1006, 3073 (1928); coating of KSbCls. Trans. Faraday Soc., 87, 737 (1941). I n an attempt to estabish chloride ions in liq(5) Glasstone, Laidler and Eyring, “The Theory of Rate Procuid NOC1, the base-action of water was tried. esses,” McGraw-Hill Book Co., Inc., New York, N. Y . , 1941. However, the water only dissolved without conBARTLESVILLE, OKLAEOIU RECEIVED NOVEMBER 28,1947 ductance and was recovered by evaporating the nitrosyl chloride. The usual hydrolysis reaction 2NOC1+ NO NO2 2HC1 is slow a t H20 Liquid Nitrosyl Chloride as an Ionizing Solvent room temperature and the products are nonconducting in nitrosyl chloride. BY ANTONB. BURGAND GEORGE W. CAMPBELL, JR.‘ (a) Germann and Gagos, J . Phys. Chcm., 28, 965 (1924); Liquid nitrosyl chloride is expected to be a (b)(2) Germann and Timpanp, ibid., 29, 1423 (1925); ( c ) Germann and fairly effective ionizing solvent, for its dielectric Birosel, ibid., 29, 1469 (1925); (d) Germann, THIS JOURNAL,47, constant (18.2 a t 12’)la is comparable to that of 2465 (1925); (e) Germann and Timpany, i b i d . , 47, 2275 (19251 (3) Ketelaar and Palmer, ibid., 69,2629 (1937). liquid ammonia. The acid-base system would be (4) (a) Willke-Dorfurt and Balz, 2.onorg. ollgem. Chem., 169,210
-
+
-
+
(1) This note is based upon a thesis submitted by George W. Campbell, Jr., to the Graduate Faculty of the University of Southern California, in partial fulfillment of the requirements for the degree of Master of Science, June, 1947. (la) Ketelaar, Rcc traw. chim., 69,289 (1943).
+
+
(1927); (b) Gall and Mengdehl, B e . , 60B,86 (1927); ( c ) Rheinboldt and Wasserfuhr, ibid., 60B,732 (1927); (d) Angus and Leckie, Proc. Roy. Soc. (London), A160, 615 (1935); (e) Klingenberg, Rec. fro%chim., 66, 749 (1937). (5) Jones, Price and Webb, J . C k m . SOC.,186, 812 (1929).
