Simplified Procedures for 1-Amino-2-propyne and Some Homologues

Article abstract of DOI:10.1055/s-2003-42401

1-Amino-2-propyne has been obtained in good yields by successive solvolysis of propargyl bromide in liquid ammonia, metalation of the dissolved amine with sodamide, and hydrolysis after complete removal of the ammonia by evaporation. Some homologues, RC≡CCH₂NH₂, have been obtained in fair yields by addition of alkyl bromides to the solution of the sodium derivative of 1-amino-2-propyne.

Full text of DOI:10.1055/s-2003-42401

PRACTICAL SYNTHETIC PROCEDURES
2427
Simplified Procedures for 1-Amino-2-propyne and Some Homologues
S
implifie
d
a
Procedure
n
s
for 1-Amino-2-pr
W
opyne and Some
H
om
o
.
logues Zwikker,a Lambert Brandsma,*b Hermann D. Verkruijssec
a
Department of Physical Organic Chemistry, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands
Julianalaan 273, 3722-GN, Bilthoven, The Netherlands
b
E-mail: l.brandsma@wxs.nl
PSP
c
Department of Chemical Education, Sorbonnelaan 16, 3584 CH Utrecht, The Netherlands
Received 16 June 2003; revised 14 July 2003
No10
Dedicated to Academician Professor Boris.A. Trofimov (A. E. Favorsky Institute of Chemistry of the Russian Academy of Sciences,
Siberian Branch, Irkutsk, Russia) on the occasion of his 65th birthday on 2 October, 2003.
Abstract: 1-Amino-2-propyne has been obtained in good yields by successive solvolysis of propargyl bromide in liquid ammonia, metala-
tion of the dissolved amine with sodamide, and hydrolysis after complete removal of the ammonia by evaporation. Some homologues,
RC≡CCH2NH2, have been obtained in fair yields by addition of alkyl bromides to the solution of the sodium derivative of 1-amino-2-pro-
pyne.
Key words: aminations, amines, alkynes, metalations, alkylations
NH2
R
1. liq. NH3, -34 oC
RBr
55-61 %
Na
2. 2 equiv. NaNH2, < -40 oC
NH2
NH2
Br
H2O
60-65%
R = n-C4H9, n-C6H13
Scheme 1
The
potentially
interesting
1-amino-2-propyne, undergo a smooth ammonolysis. A qualitative experiment
HC≡CCH2NH2 has been obtained in fair overall yields by showed that this is indeed the case. The bromide (5 mL)
successive N-propargylation of phthalimide, treatment of was added to boiling ammonia (50 mL). When after half
the product with dilute sulfuric acid and liberation of the an hour the solution was poured onto crushed ice (150 g),
amine by addition of alkali hydroxide.1 In an alternative no lower layer or turbidity was visible. Repetition of this
synthesis of this amine and some homologues, 1-halo-2- operation after a reaction time of ten minutes still showed
alkynes or analogous acetylenic arenesulfonates were re- the presence of some propargyl bromide. These experi-
acted with hexamethylenetetramine, after which the salt ments gave useful information with respect to the reaction
was treated with dilute hydrochloric acid.2 Zwierzak and time after the addition of the bromide in the synthetic pro-
co-workers4–7 developed some substitutes for the synthe- cedure.
sis of primary amines among which was 1-amino-2-pro-
pyne.
The subsequent reaction of propargyl bromide with the
corresponding amine, which affords dipropargylamine,
All syntheses published so far are, in general, laborious. (HC≡CCH2)2NH, proceeds (as in the case of saturated
The use of reagents with relatively high molecular alkyl halides) much more easily than the preceding reac-
weights in some syntheses makes performance on a larger tion of propargyl bromide with ammonia. In order to sup-
scale inconvenient.
press this undesired reaction, the use of a large molar
excess of liquid ammonia seemed necessary.
We considered the possibility of preparing propargyl-
amine by solvolysis of the corresponding bromide in liq- The next problem to be solved was to prevent entraining
uid ammonia. It was expected that, in contrast to the of the volatile propargylamine with the evaporating am-
homologues of methyl bromide, propargyl bromide would monia. In an earlier performed synthesis of propargyl-
amine, the ammonia was allowed to evaporate
completely. The amine was isolated in yields of only ca.
40%.8 In the procedure described below this problem is
solved by adding the reaction mixture to an excess of
SYNTHESIS 2003, No. 15, pp 2427–2428
Advanced online publication: 29.09.2003
DOI: 10.1055/s-2003-42401; Art ID: T05303SS.pdf
© Georg Thieme Verlag Stuttgart · New York
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Jan W. Zwikker et al.
PRACTICAL SYNTHETIC PROCEDURES
1-Amino-2-heptyne and 1-Amino-2-nonyne
The reactions were conducted on 0.20 molar scale, 250 mL of liquid
ammonia for the ammonolysis; the suspension of sodamide was
prepared in 200 mL of ammonia.
sodamide in liquid ammonia. In this way, the amine is
fixed as the sodium compound. After complete evapora-
tion of the ammonia, the amine could be liberated by ad-
dition of water, just enough to effect a smooth dissolution
of the solid. 1-Amino-2-heptyne and 1-amino-2-nonyne
were obtained in fair yields by reaction of the sodium de-
rivative with bromobutane and bromohexane.
In order to avoid problems during the aqueous work-up with the
separation of the layers, the suspension of sodamide was prepared
by using the minimal amount of iron(III) nitrate as described in the
references.9 After the addition of the ammoniacal solution of 1-ami-
no-2-propyne to this suspension (with strong cooling as described
above), n-butyl bromide (0.20 mol, 27.4 g) or n-hexyl bromide
(0.20 mol, 33.0 g) was added to the very dark solution. The mixture
was vigorously stirred for 3 h at the bp of ammonia, the reaction
flask being insulated in cotton wool. In the reaction with bromohex-
ane THF (50 mL) was added after 1 h. The last ammonia was re-
moved by placing the flask in a bath at 40 °C. H2O (150 mL) was
added followed by extractions with Et2O (4 × 50 mL). The com-
bined extracts were washed with H2O (2 ×), dried (K2CO3) and then
concentrated under reduced pressure. Careful distillation through a
30-cm Vigreux column gave 1-amino-2-heptyne and 1-amino-2-
nonyne.
1-Amino-2-propyne
Freshly distilled propargyl bromide (0.50 mol, 59.5 g) was added
dropwise over 45 min to anhyd liquid ammonia (500 mL) in a 1 L
round-bottomed flask with three vertical necks. This was equipped
with a dropping funnel, a mechanical stirrer and a combination of
thermometer and outlet. The dropping funnel was connected with a
tube (internal diameter ca. 5 mm) ending just above the surface of
the ammonia. During the addition nitrogen was passed through the
tube at a rate of ca. 100 mL/min in order to avoid preceding contact
of the bromide with the ammonia vapour (cf. 9) while the reaction
mixture was cooled in a bath with dry ice and acetone kept at ca.
–35 °C. After an additional 45 min the resulting solution was cooled
in a bath with liquid nitrogen to below –50 °C and subsequently
cautiously poured (in portions) over 10 min to a stirred suspension
of sodium amide (1.1 mol) in liquid ammonia (300 mL) in a 1-L
three-necked, round-bottomed flask. This suspension, prepared
from sodium (1.2 mol, 27.6 g),9 had been pre-cooled to between
–65 and –75 °C. After this operation the cooling bath and the stirrer
were removed. On the outer necks were placed stoppers. The mid-
dle neck was connected with a drying tube filled with KOH pellets.
In order to ensure the constant presence of a protecting atmosphere
of ammonia in the last stage of the evaporation, the drying tube was
placed on a level below the bottom of the flask.9 When, after one
night, liquid ammonia was no longer present, the flask was placed
in a bath at ca. 30 °C and evacuated (water aspirator) until the pres-
sure had dropped to below 10–20 Torr (this operation took about 1
h). Inert gas (preferably argon) was then admitted and the flask was
equipped with a dropping funnel (on the middle neck), a reflux con-
denser filled with dry ice and acetone (‘cold finger’-type) and an in-
let. The flask was placed in a bath at ca. 0 °C (or, preferably, at
lower temperature). Nitrogen or argon was slowly introduced and
H2O (100 mL) was added over 30 min, in the beginning dropwise,
but at a later stage, when the intensity of reflux (some ammonia) in
the cold finger had subsided, portion-wise. At the end, the flask was
swirled by hand for a few min in order to achieve complete contact
of the solid with the water. The flask was then equipped for a distil-
lation under atmospheric pressure (20 cm Vigreux column, con-
denser and receiver cooled in a bath at 0 °C). The flask was
immersed in an oil bath and heated until the temperature in the head
of the column had reached 100–102 °C. The distillate, a mixture of
propargyl amine and H2O, was saturated with KOH pellets (or, if
available, machine-powdered KOH) and a redistillation was carried
out, now collecting all liquid passing over below 95 °C. After addi-
tion of KOH pellets and vigorous shaking, a last distillation was car-
ried out giving the almost pure amine, distilling between 75–85 °C.
1-Amino-2-heptyne
Yield: 61%; bp 80 °C/20 Torr (lit.2 gives 68 °C/15 Torr), purity
100% (GC).
1H NMR (CDCl3): = 0.91 (t, CH3), 1.34 (s, NH2), 1.45 [m,
(CH2)2], 2.17 (t, CH2C≡), 3.39 (t, CH2N).
13C NMR spectrum (CDCl3): = 13,28, 18.09, 21.64, 30.67, 31.43,
80.61, 82.29.
MS: m/z calcd for (M + H+): 112.1126; found: 112.1221.
1-Amino-2-nonyne
Yield: 55%; bp 100 °C/15 Torr, purity 95% (lit.2 gives 82 °C/7
Torr).
The proton spectrum of C6H13C≡CCH2NH2 was closely similar to
the spectrum of 1-amino-2-heptyne; the (CH2)4 chain appeared as a
multiplet between = 1.30–1.51.
13C NMR: = 14.07, 18.76, 22.60, 28.61, 28.90, 31.43, 31.77,
80.94, 82.68.
Acknowledgment
The authors are indebted to Ms. A. C. T. H. M. van der Kerk, Ms.
V. E. M. Kaats and Mr. J. Schuring for technical assistance.
References
(1) Gloset, C.; Coupe, R. Bull. Soc. Chim. Fr. 1963, 2464.
(2) Marszak, L.; Koulkes, M. Bull. Soc. Chim. Fr. 1956, 93 and
references mentioned therein.
(3) Marszak-Fleury, A. Ann. Chim. (Paris, France) 1958, 3,
656.
(4) Koziara, A.; Zwierzak, A. Synthesis 1992, 1063.
(5) Klepacz, A.; Zwierzak, A. Synth. Commun. 2001, 1683.
(6) Zwierzak, A. Synth. Commun. 2001, 2287.
(7) Koziara, A.; Zawadski, S.; Zwierzak, A. Synthesis 1985,
202.
(8) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier:
Amsterdam, 1988, 2nd. ed..
(9) Brandsma, L. Synthesis of Acetylenes, Allenes, and
Cumulenes, Methods and Techniques, Elsevier, to appear in
2003 or 2004.
Yields: between 60 and 65%; n D 1.4492 (lit.3 gives bp 83 °C,
20
nD14.5 1.4500).
1H NMR spectrum (CDCl4, Me4Si): = 1.49 (s, NH2), 2.26 (t,
HC≡), 3.42 (d, CH2).
13C NMR (CDCl3, Me4Si): = 31.32, 70.40, 85.01.
Synthesis 2003, No. 15, 2427–2428 © Thieme Stuttgart · New York