COMPETITIVE FORMATION OF -AMINO ACIDS, PROPENOIC, AND YLIDENEMALONIC ACIDS 1123
Reaction of aldehydes I and V and cyclohexa-
none with malonic acid and ammonium acetate
(general procedure). A mixture of aldehyde I or V,
or cyclohexanone, 114.4 g of malonic acid, and
177.1 g of ammonium acetate in 600 ml of 1-butanol
was refluxed for 1.5 3 h until CO2 no longer evolved.
with, is a colorless film of ammonium malonate de-
posited in the Liebig condenser, the reaction mixture
was diluted with 300 ml of 1-butanol, and distillation
was repeated. The residue was distilled in a vacuum
of 10 20 mm Hg, until the boiling point of the distil-
late reached 128 130 C or 130 135 C (with al-
The precipirate that formed (with aldehydes Ia Io, Iw, dehydes Vp Vt). In latter case, the distillate was
Ia , Va, Vc, Vd, or Vg Vm) was filtered off while hot, distilled once more to isolate acrylic acids VIIp Vs.
washed in succession with boiling 1-butanol (2
250 ml), 250 ml of boiling ethanol, 250 ml of water,
and 50 ml of ethanol at 25 C to obtain compounds
IIa IIf, IIh IIo, IIw, IVg, IVa , VIa, VIc, VId, VIg
and mixtures of compounds VIh, VIIIh and VIIIi
VIIIl, that were dried at 100 C. The mother liquor
was cooled to 20 C to obtain additional crops of
compound IIj, cinnamic acids IIIl and IIIm, and
amino acid VIk. They were filtered off, washed with
cold ethanol, and dried. After cooling, the mother
liquors were reduced by half and poured into 750 ml
of water. The precipitate that formed was filtered off,
washed with water, and dried at 100 C to obtain com-
pounds IIIa IIIf, IIIh IIIk, IIIo, and IIIw, a mix-
ture of compounds IIIa and IVa (2:1), and com-
pounds VIIa, VIIc, VIId, and VIIg VIIk, that were
additionally purified, if required, by recrystallization
from ethanol (IIIb IIIf), precipitation with water
from acetone (IIIj), or by reprecipitation with HCl
form aqueous alkalini washed with ether (IIIh, IIIi,
and IIIk). Most of amino acids II and VI are pure by
no less than 98%. Compounds IIl and IIm were
brought to this purity by additional recrystallization
from water.
The viscous still bottom was cooled to 20 C and
treated with stirring with 700 ml of acetone, allowed
to stand for no less than 10 h, and the precipitates that
formed were filtered off, washed with acetone, and
dried at 100 C to obtain compounds IIp and IIr,
mixtures of acids IIv and IIIv and IIt and IIIt, acids
IIu and IIy, a mixture of acids VIf, VIIf, and acids
VIp VIt, and XII. To separate mixtures of acids IIs
and IIIs, IIt and IIIt, and VIf and VIIf, amino acids
IIs, IIt, and VIf were extracted with water, the
aqueous extracts were evaporated, and acids IIs, IIt,
VIf, and VIIf were washed with acetone. Water-in-
soluble compounds IIIs and IIIt were then isolated by
recrystallization from 60% aqueous ethanol. The
mother liquors were reduced by 35% and poured into
650 ml of water. The precipitates that formed were
filtered off, washed with water, and dried to obtain
acids IIIp and IIIr (purified by recrystallization from
50% aqueous ethanol) and IIIu, IIIx, IIIy, and VIIe.
Cinnamic acid IIIz is a viscous oily substance. It was
isolated by decantation of the aqueous layer which
was then diluted with 300 ml of water, extracted with
ether, and removal of the solvent.
Furan and thiophene derivatives were synthesized
from aldehydes Vl, Vm, Vn, and Vo in a similar way
using as solvent 1-butanol instead of ethanol. With
aldehydes Vl and Vm, the reaction mixture was
poured into 4 l of water, the tarry residue was filtered
off, the filtrate was treated with ether (2 350 ml), and
the ether was removed. Amino acids VIl and VIm
were isolated from the aqueous layer and acrylic acids
VIIl and VIIm, from the ether extract. With al-
dehydes Vn and Vn, the synthesis was 8 h long, after
which 154 g of ammonium acetate was added to the
reaction mixture, and it was refluxed for an additional
4 h. After cooling, compounds VIn and VIIIo, res-
pectively, precipitated and were filtered off and dried
at 100 C. The mother liquors were evaporated, the
residue was poured into 500 ml of water, and the
precipitate was filtered off and recrystallized from
aqueous ethanol to obtain acids VIIn and VIIo,
repsectively.
Amino acid IIq was filtered off from the reaction
mixture cooled to 15 C, washed in with cold ethanol,
water, and acetone. The mother liquor was reduced
by half, poured into 500 ml of water, compound IIIq
precipitated and was filtered off and recrystallized
from 50% aqueous ethanol.
The reaction mixture was cooled to 15 C to pre-
cipitate acid IIv that was filtered off and washed with
cold ethanol, water, and ethanol (100 each). The
mother liquor was poured into 700 ml of water, and
the precipitate that formed was filtered off and dried.
The precipitate was washed with acetone to extract
cinnamic acid IIIv that was then precipitated with
water and filtered off. The acetone-insoluble precipi-
tate contained an additional portion of acid IIv. Acid
VIIb was obtain in a similar way.
The postreaction mixtures of aldehydes Ip, Ir Iu,
Ix Iz, Ve, Vf, and Vp Vt, as well as cyclohexanone
with malonic acid in the presence of ammonium
acetate looked like transparent solutions. All volatile
compounds boiling to 135 C were distilled off. There-
In the case of the reaction of aldehyde Vu with
malonic acid and ammonium acetate, the reaction
mixture was filtered to separate insoluble acid X, and
the filtrate was cooled to 15 C to precipitate acid XI.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 7 2005
Lebedev
