One-pot synthesis of rac-1,2-diphenylethylene-1,2-diamine

Full text of DOI:10.1023/A:1022164208811

2308
Russian Chemical Bulletin, International Edition, Vol. 51, No. 12, pp. 2308—2309, December, 2002
Oneꢀpot synthesis of racꢀ1,2ꢀdiphenylethyleneꢀ1,2ꢀdiamine
E. A. Mistryukov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: secretary@ioc.ac.ru
Derivatives of 1,2ꢀdiphenylꢀ1,2ꢀethylenediamine
The cyclization of hydrobenzamide 2 into amarine 3
by thermolysis at 130 °C 7 or treatment with stoichiometꢀ
ric amounts of strong bases was described.8 We have unꢀ
expectedly found that this cyclization occurs exothermiꢀ
cally and in ∼100% yield when catalytic (5—12 mol.%)
quantities of sodium hydroxide in dimethylsulfoxide are
used. It is most likely that the cyclization proceeds, under
all conditions, through the diazapentadienide anion (А),
whose formation is favored (under our conditions) by a
highly polar solvent (Scheme 1). Anion А is rapidly cyꢀ
clized to diazaallylic anion В, whose protonation affords
amarine 3.
In the presence of a catalytic amount of base only, the
transformations of compounds 2 and 3 proceeding through
anions А and В are reversible. When the temperature inꢀ
creases to 130 °C, the thermodynamically more stable
isoamarine 4 is formed (through the slowly formed anꢀ
ion С) (a similar mechanism has been described9). Previꢀ
ously,7,8 the isomerization of amarine 3 to isoamarine 4
by a base at high temperature required a separate step.
Thus, the oneꢀpot transformation of hydrobenzamide
2 into isoamarine 4 was performed. The reductive splitꢀ
ting of isoamarine 4 under the optimized conditions2 comꢀ
enantiomers ((R,R)ꢀ and (S,S)ꢀ1) are used as chiral conꢀ
trollers and catalysts in a series of various reactions (see
Refs. 1—3 and references cited herein). The main diffiꢀ
culty in obtaining these valuable compounds is to syntheꢀ
size the corresponding racemic compound (racꢀ1), whose
enantiomeric splitting as salts of tartaric acids is easy.3—5
Among numerous published syntheses of diamine racꢀ1,
the recently modified2 synthesis from benzaldehyde and
liquid ammonium is the best method in the present time.
It proceeds through the soꢀcalled hydrobenzamide (2),
amarine (3), and isoamarine (4). In this work we found
that this synthesis can substantially be simplified due to
the use of some earlier unknown mechanistic features of
the process.
Starting 1,3,5ꢀtriphenylꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene
(hydrobenzamide, 2) can most conveniently be obtained
in significant amounts from benzaldehyde using ammoꢀ
nia under pressure (∼7 atm). This affords an intermediate
oily product, presumably 2,4,6ꢀtriphenylꢀ1,3,5ꢀhexaꢀ
hydrotriazine (see Ref. 6), which is transformed into crysꢀ
talline hydrobenzamide 2 after removal of excessive
ammonia.
Scheme 1
Reagents and conditions: a. NH3, 20 °C; b. NaOH (cat.), DMSO; c. Al/Hg, H2O.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2142—2143, December, 2002.
1066ꢀ5285/02/5112ꢀ2308 $27.00 © 2002 Plenum Publishing Corporation

Synthesis of 1,2ꢀdiphenylethyleneꢀ1,2ꢀdiamine
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 12, December, 2002 2309
was added for 1.5 h. After 2 h, water (5 mL) was added, and the
mixture was left for ∼20 h. A concentrated aqueous solution of
NH4OH (10 mL) was added to the mixture. After 24 h, the
mixture was filtered, and the filtrate was concentrated. The
residue on the filter was washed with the distillate obtained by
evaporation of the above filtrate, and the new filtrate was also
concentrated. The combined residue was concentrated (oil),
dissolved on heating in a mixture of MeOH (30 mL), concenꢀ
trated hydrochloric acid (15 mL), and water (10 mL), and cooled.
The crystalline precipitate of diamine dihydrochloride was filꢀ
tered off, washed on the filter with dioxane, and dried. The yield
of racꢀ1•2HCl was 7.88 g (82.5%). To isolate the base, the
resulting salt in THF was treated with an excess of a 10 М
aqueous solution of NaOH, the suspension was concentrated to
dryness at 80 °C, and the residue was extracted with boiling
petroleum ether to obtain racꢀ1 in 77.6% yield (5.52 g), m.p.
82 °C.3,7 1H NMR (DMSOꢀd6), δ: 1.70 (s, 4 Н, 2 NH2); 3.90 (s,
2 H, 2 CH); 7.20 (m, 10 H, 2 Ph).
pletes the practical method proposed for the synthesis of
diamine racꢀ1 from benzaldehyde in 70% overall yield.
The 1Н NMR spectrum was recorded on a Bruker ACꢀ200
instrument (200.13 MHz). TLC analyses were carried out on
Silufol plates using Et2O with several droplets of aqueous amꢀ
monia (visualized by an aqueous solution of KMnO4). Melting
points were determined on a Kofler heating stage. Reaction
mixtures were concentrated on a rotary evaporator at 30—40 °С
in a vacuum of a water jet pump.
(Е,Е)ꢀ1,3,5ꢀTriphenylꢀ2,4ꢀdiazapentaꢀ1,4ꢀdiene (2). A soꢀ
lution of benzaldehyde (50.7 mL, 53.1 g, 0.50 mol) in THF
(50 mL) was placed in a pressureꢀdesigned vessel connected
through a capillary with the ammonia cylinder. The valve on the
cylinder was opened, and the system was left for ∼20 h. The
vessel was disconnected from the cylinder, and the pressure
(∼7 atm) was slowly brought to atmospheric. The aqueous (upꢀ
per) layer was removed from the remaining bilayer mixture. The
bottom layer after concentration in vacuo crystallized and gave
hydrobenzamide 2. The product thus obtained in ∼100% yield
(49.7 g) was used in the next step without purification.
References
racꢀtransꢀ2,4,5ꢀTriphenylꢀ4ꢀimidazoline (isoamarine, 4). Soꢀ
dium hydroxide in pellets (∼0.3 g, 7 mmol) was added (as
one portion) to a suspension of hydrobenzamide 2 (16.5 g,
55.3 mmol) in DMSO (25 mL) in argon, and the mixture was
vigorously stirred. After ∼5 min, the mixture was warmed to
∼50 °C, and after ∼1 h it cooled to room temperature. According
to TLC data, amarine 3 (Rf 0.50) formed in ∼100% yield and
could be isolated. Then the reaction mixture was heated to 130 °C
for 3 h. TLC analysis showed only isoamarine 4 (Rf 0.70). The
mixture was cooled to ∼80 °C and successively treated with EtOH
(30 mL) and a concentrated aqueous solution of NH4OH (30 mL,
gradually poured). The resulting mixture was left for ∼20 h. The
precipitate of isoamarine 4 was filtered off, washed on the filter
with PriOH (30 mL), and dried. The yield was 14.9 g (90%),
m.p. 198—200 °C.7,8 Further the product was used without adꢀ
ditional purification.
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racꢀ1,2ꢀDiphenylethyleneꢀ1,2ꢀdiamine (racꢀ1). A mixture of
isoamarine 4 (10 g, 33.5 mmol), an aluminum foil as pieces
0.5 cm2 each (2.7 g, 100 mmol), HgCl2 (0.6 g, 2.2 mmol), and
THF (60 mL) was stirred in an argon atmosphere for 15 min.
Then a solution of water (1.8 mL, 100 mmol) in THF (5 mL)
Received September 27, 2002