Dec.

, 1951 Notes 5865

ro-Amino-3,6-dimethoxy 2 -nitroacetophenone Hydro-

-
Reduction of Organic Azides to Primary Amines
chloride.—To a stirred suspension of 21 g. of hexamethylene with Lithium Aluminum Hydride
tetramine in 150 ml. of chlorobenzene at room temperature
was added in one portion 45.6 g. of <v-bromo-3,6-dimethoxy- By J. H. Boyer
2-nitroacetophenone. The mixture was stirred at 60-70°
for 4.5 hours, then chilled in an ice-bath and filtered. The The reduction of aliphatic and aromatic azides
dried, yellow powder, which weighed 62 g., was stirred at to primary amines with lithium aluminum hydride
room temperature for 18 hours with 140 ml. of 95% ethanol
and 70 ml. of concentrated hydrochloric acid. The yellow has been realized (1). The reaction provides a new
solid was recovered by filtration and stirred for 20 minutes procedure for the preparation of a-aminocarbinols
with 70 ml. of water. The suspension was chilled and from a-azidoketones (2). Stoichiometrically the
filtered. The yellow product weighed 31.5 g. (71%). A reactions may proceed according to the following
small sample was recrystallized with high recovery from 10%
hydrochloric acid as long yellow needles, m.p. 222-223° equations, although in the preliminary experi-
(dec.). ments shown here a two- to five-fold excess of lithium
Anal. Caled, for C,oHi3OsN2C1: C, 43.4; , 4.71; N, aluminum hydride was used to assure a positive
10.12. Found: C, 43.1; H, 4.73; N, 10.18. reaction.
-Acetamido-3,6-dimethoxy 2 nitroacetophenone.—
- -

Twenty-seven and one-half grams of 6>-amino-3,6-dimethoxy- 4R—N, + LiAlH, —> (R—NH—)4AlLi + 4N2 (1)
2-nitroacetophenone hydrochloride was acetylated by the 2R—C—CH2N3 + LiAlH, —>
procedure of Long and Troutman3 with 19.2 ml. of acetic
anhydride and 27.6 g. of sodium acetate trihydrate, followed o
II

by 60 ml. of concentrated hydrochloric acid. The dried

product weighed 25 g. (87%). A small portion was re- (R—CHCILNH—)2AlLi + 2N2 (2)
crystallized with high recovery from ethyl acetate. The
short, thick yellow needles melted with reddening and O—
partial sublimation at 170-173°.
Anal. Caled, for C12H140„N2: C, 51.1; , 5.00; N, Experimental1
9.92; -OCH,, 22.0. Found: C, 51.4; H, 5.24; N, 9.93; Reduction of the azides was carried out under the gen-
-OCH,, 21.9. eral conditions for lithium aluminum hydride reduction de-
l-(3,6-Dimethoxy-2-nitrophenyl)-2-acetamidoethanol.— scribed by Nystrom and Brown.1 In each case a suspension
Twenty-four grams of -acetamido-S, 6-dimethoxy-2-nitro- of the hydride in dry ether was treated with an ethereal
acetophenone was reduced with a solution of 24.2 g. of solution of the azide at such a rate that reflux was main-
aluminum isopropoxide in 205 ml. of isopropyl alcohol by tained. Following addition of the azide the mixture was
the procedure of Long, et al.3’* The reaction mixture was kept at reflux temperature for two hours. Moist ether was
hydrolyzed with 25 ml. of water and the product extracted then added to destroy the excess lithium aluminum hydride,
out with hot 80% isopropyl alcohol. Light tan crystals followed by distilled water to break up the complex. The
weighing 17.5 g. (73%), m.p. 168° (dec.), were obtained inorganic salts were removed by filtration and the amines
by chilling, then concentrating the extracts. A small were isolated from the ethereal layer of the filtrate. Modi-
sample was recrystallized from hot water as thick, tan crys- fications found useful for the isolation of the aminoalcohols
tals, m.p. 169° (dec.). from the filtrates obtained at this stage in the reduction of
Anal. Caled, for C,2H1606N2: C, 50.7; H, 5.68; N, the azidoketones are described below.
9.85; -OCH3, 21.9. Found: C, 50.4; H, 5.88; N, 9.83; «-Naphthylamine.—From 1.7 g. (0.01 mole) of «-naph-
-OCH,, 21.7. thyl azide3 in 100 ml. of anhydrous ether and 0.60 g. (0.015
l-(3,6-Dimethoxy-2-nitrophenyl )-2-amino ethanol. —A mole) of lithium aluminum hydride in 200 ml. of anhydrous
mixture of 17.5 g. of l-(3,6-dimethoxy-2-nitrophenyl)-2- ether there was obtained 1.13 g. (79% based on the azide)
acetamidoethanol and 200 ml. of 5% hydrochloric acid was of -naphthylamine, m.p. 50°, alone and when mixed with
an authentic sample of -naphthylamine. The picrate de-
stirred at 100° for six hours. Th% resulting solution was
filtered and made basic with 25% sodium hydroxide while rivative was prepared in ether and recrystallized from aque-
still hot. Twelve and one-half grams (84%) of light tan ous ethanol, m.p. 183-185°, alone and when mixed with an
authentic sample.
crystals was obtained on cooling. A small sample was re-
crystallized twice from hot water (Norite). The light tan, /S-Phenylethylamine.—From 3.0 g. (0.02 mole) of ß-
shining platelets melted at 171° (dec.) using the technique phenylethyl azide4 56in 100 ml. of anhydrous ether and 1.0 g.
of Córtese and Bauman.11 (0.025 mole) of lithium aluminum hydride in 250 ml. of
Anal. Caled, for Ci„H1405N2: C, 49.6; H, 5.83; N, anhydrous ether there was obtained 2.15 g. (89% based on
the azide) of /S-phenylethylamine (absorbs carbon dioxide),
11.56. Found: C, 49.4; , 6.00; N, 11.41.
b.p. 190-192°,· carbonate, m.p. 105-106°,· picrate m.p.
l-(3,6-Dimethoxy-2-nitrophenyl)-2-dichloroacetamidoeth- 169-170°,· and hydrochloride, m.p. 217°.·
anol.—A mixture of 12.5 g. of l-(3,6-dimethoxy-2-nitro- «-Phenyl-/S-aminoethanol.—From 4.6 g. (0.029 mole of
phenyl)-2-aminoethanol and 75 ml. of methyl dichloroace- phenacyl azide,7 89m.p. 17°, in 250 ml. of anhydrous ether and
tate was warmed at 75° for two hours with occasional swirl- 1.5 g. (0.04 mole) of lithium aluminum hydride in 300 ml.
ing. The dark solution was filtered and the filtrate evapo- of anhydrous ether was obtained 1.94 g. of the light yellow
rated to dryness on a steam-bath under reduced pressure (30 -phenyl-/S-aminoethanol, b.p. 135-137° (1 mm.), m.p.
mm.). The residue was washed with two small portions of 43-45°· (49.5% based on the azide). Appreciable solu-
chloroform. The yellow powder which remained weighed bility in both water and ether accounted for the isolation
10.5 g. and was recrystallized from 2.1 liters of 33% eth- of this product in roughly equal quantities from the aqueous
anol. The long yellow needles weighed 8.1 g. (46%), and ethereal layers of the filtrate obtained from the filtration
m.p. 163-165°. A second recrystallization raised the melt- of the inorganic salts. A picrate derivative was prepared in
ing point to 164-166°. benzene and recrystallized from a mixture of chloroform and
Anal. Caled, for C,2H,40»N2C12: C, 40.8; , 4.00; alcohol, m.p. 154-155°.·
N, 7.93; Cl, 20.1. Found: C, 41.1; , 4.14; N, 7.85; Cl,
19.6. (1) Microanalyses by the Clark Microanalytical Laboratory, Ur-
bana, Illinois. Melting and boiling points are uncorrected.
Acknowledgment.—The authors wish to express (2) R. F. Nystrom and W. G. Brown, This Journal, 69, 1197
their appreciation to the Wm. S. Merrell Co. for a (1947).
(3) . O. Forster and . E. Fierz, J. Chem. Soc.t 91, 1942 (1907).
grant infsupport of this work. (4) Generously submitted by Dr. P. A. S. Smith.
Venable Chemical Laboratory (5) A. Wohl and E. Berthoid, Ber., 43, 2183 (1910).
University of North Carolina (6) E. Erlenmeyer and A. Lipp, Ann., 219, 179 (1883).
Chapel Hill, N. C. Received July 23, 1951 (7) . O. Forster and R. Müller, J. Chem. Soc., 97, 126 (1910).
(8) C. Mannich and E. Thiele, Arch. Pharm., 268, 181 (1915).
(11) F. Córtese and L. Bauman, This Journal, 67, 1394 (1935). (9) German Patent 193,634, cf., Chem. Centr., 79, I, 430 (1908).
5866 Notes Vol, 73

«-Methyl-0-aminoethanol.—A solution of 5.65 g. (0.056 pressure using the optimum conditions of Penne-
mole) of triazoacetone,“ b.p. 54-56° (1 mm.) in 250 ml. of man and Audrieth.8
anhydrous ether was slowly added to a suspension of 2.90 g.
(0.04 mole) of lithium aluminum hydride in 400 ml. of an- In utilizing this procedure for the preparation
hydrous ether. Since the product, «-methyl-fl-aminn- of anhydrous deuterohydrazine, the hydrochloride
ethanol, is much more soluble in water than it is in ether, it salt was first deuterated by two or three successive
was found convenient to acidify the aqueous layer of the
filtrate obtained from the filtration of the inorganic salts exchanges with sufficient quantities of deuterium
with hydrochloric acid and isolate the amine hydrochloride oxide to readily dissolve the salt at the boiling
by evaporation of the solvent in an air stream. Purification point of the solution. After each exchange the
of the black tarry residue from a boiling mixture of absolute exchange water was evaporated off and the salt
ethanol-ethyl acetate gave colorless hygroscopic prisms residue dried at room temperature under reduced
only after five to seven days in the refrigerator, wt. 2.25 g.
(36.2% yield based on the azide), m.p. 70-73° (lit.11 m.p. pressure in the usual manner. Subsequent steps
72.5-74°). in the procedure were conducted so as to prevent
From the ethereal layer of the filtrate 0.50 g. (11.9% re-exchange of the deuterium atoms in the chloride
based on the azide) of the free aminoalcohol, b.p. 150-160°, salt with hydrogen atoms in atmospheric moisture or
was obtained. The total yield of the reaction was 48.1%.
A picrate derivative was prepared in ether and recrystal- in the reagents. The anhydrous deuterohydrazine
lized from a mixture of chloroform and ethanol, m.p. 144- produced by this procedure contained less than 0.5%
145° (lit.12 m.p. 142°). A picrolonate was prepared in deuterium oxide. From analysis of the infrared and
ether and recrystallized to a constant m.p. 224-225° (de- Raman spectra, it was estimated that the resulting
composition) from a benzene-alcohol mixture.
Anal. Caled, for CuH170„N5: C, 46.01; , 5.05; N, compound was more than 90% deuterated.
20.64. Found: C, 46.20; H.4.87; N, 20.45. Experimental Procedure.—Seventy grams of crushed so-
dium hydroxide was added on top of 40 g. of recrystallized
(10) . O. Forster and . E. Fierz, J. Chem. Soc., 93, 72 (1908). Eastman hydrazine dihydrochloride in a 150-ml. round-
(11) S. Gabriel and H. Oble, Bir„ SO, 804 (1917). bottom flask. This flask was connected by means of a stand-
(12) E. Peeters, Rec. trav. chim., 20, 259 (1901). ard taper joint to a short (10 cm.) coarse packed fractionat-
Chemistry Department ing column which in turn was connected to a water-cooled
condenser and receiver. This all glass system could be
University op Michigan
Ann Arbor, Michigan Received maintained at any desired reduced pressure by allowing dry
July 11, 1951
nitrogen to leak in through a controllable bleeder valve
while the system was being evacuated. After thoroughly
The Preparation of Anhydrous Hydrazine and flushing with dry nitrogen the system was evacuated and
maintained at a pressure of 200-250 mm. while the flask and
Deutero-hydrazine from Hydrazine its contents were being heated on an oil-bath. Reaction
Dihydrochloride1 at the interface between the two solids usually commenced
when the bath temperature reached about 100°. The re-
By E. L. Bulgozdy and E. L. Wagner sulting reaction proceeded vigorously and was completed in
20-40 minutes. This is the crucial step in the process as
In the course of an investigation to determine the well as the most dangerous and care must be exercised to
molecular spectra of anhydrous hydrazine and prevent the reaction from becoming too violent. In general,
immediate removal of the oil-bath at the inception of the re-
deutero-hydrazine a method for obtaining the action was a sufficient control. After completion of the
anhydrous material was desired which could readily initial neutralization reaction the temperature of the reac-
be adapted to preparing the deutero compound on tion mixture was lowered to 65° (bath 75-80°) and the
utilizing the appropriate deuterium substituted pressure reduced to 100-110 mm. Under these conditions a
cut of 6-7 of the possible 12 ml. of anhydrous hydrazine was
starting materials. Since the reported methods2 distilled over in two hours.
of synthesizing hydrazine in a practical way are Analyses.—The direct iodate titration method using
generally carried out in aqueous solution or in other carbon tetrachloride2 to extract the iodine was used to ana-
hydrogen-rich media, and the principal methods lyze the products of this procedure for purity. The ac-
of concentrating the anhydrous substance utilize companying table lists the results of several different prepa-
rations.
hydrazine hydrate as a starting material,8 a new
0.025 M
procedure was sought which, when adapted to the Sample
weight, g. KIOs, ml. NiH«, %
preparation of deutero-hydrazine, would be more 0.0432 53.61 99.8
parsimonious in its use of deuterium. The method .0436 55.98 99.4
ultimately employed involves the removal of .0438 54.01 98.6
hydrogen chloride from solid hydrazine dihydro- .0437 54.40 99.6
chloride by low temperature fusion with the .0625 77.56 99.3
stronger base sodium hydroxide. Sufficient solid .0623 77.54 99.5
sodium hydroxide is required to neutralize the
hydrogen chloride plus that necessary to tie up Acknowledgment.—The helpful suggestions of
the water formed in the neutralization as sodium Dr. C. J. Nyman during the phase of the work
hydroxide monohydrate. The fusion was carried reported here are gratefully acknowledged.
out above the melting point of the monohydrate Dept, op Chemistry
so that after neutralization had taken place the State College of Washington
reaction mixture was a relatively homogeneous Pullman, Washington Received June 18, 1951
liquid. Anhydrous hydrazine was removed from
this resulting mixture by distillation under reduced
(1) Taken from a thesis submitted by Eugene L. Bulgozdy in partial The 2,4-Dinitrophenylhydrazones of the Alkyl
fulfillment of the requirements for the degree of Master of Science at Phenyl Ketones
the State College of Washington.
(2) L. F. Audrieth and B. A. Ogg, “The Chemistry of Hydrazine,” By L. I. Braddock and Mary L. Willard
John Wiley and Sons, Inc., New York, N. Y., 1951.
Í3) R. A. Penneman and L. F. Audrieth, This Journal, 71, 1644 Attempts to prepare the 2,4-dinitrophenylhydra-
('1949). zones of the symmetrical, aliphatic ketones with