Reactions of alkyl (halomethyl)furancarboxylates with hexamethylenetetramine

Article abstract of DOI:10.1134/S1070363206080251

All isomers of (aminomethyl)furancarboxylic acids were prepared by the Delepine reaction from alkyl (halomethyl)furancarboxylates. Treatment of the initially formed quaternary salt with an ethanolic HCl solution yielded the salts of the corresponding unst

Full text of DOI:10.1134/S1070363206080251

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 8, pp. 1304 1309.
Pleiades Publishing, Inc., 2006.
Original Russian Text I.M. Lapina, L.M. Pevzner, A.A. Potekhin, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 8, pp. 1359 1364.
Reactions of Alkyl (Halomethyl)furancarboxylates
with Hexamethylenetetramine
I. M. Lapina, L. M. Pevzner, and A. A. Potekhin
St. Petersburg State University,
Universitetskii pr. 26, St. Petersburg, 198504 Russia
Received March 27, 2006
Abstract All isomers of (aminomethyl)furancarboxylic acids were prepared by the Delepine reaction from
alkyl (halomethyl)furancarboxylates. Treatment of the initially formed quaternary salt with an ethanolic HCl
solution yielded the salts of the corresponding unstable amino acid esters. A procedure for their purification
to a high degree of purity was developed. Hydrolysis of the crude esters yielded stable amino acid salts.
DOI: 10.1134/S1070363206080251
Aminomethyl derivatives of the furan series are
studied for a considerably long time as intermediates
in the synthesis of biologically active compounds.
Among them are precursors of muscarine and mus-
carine-like compounds [1]. Introduction of amino-
methyl group into the furan fragment of a diterpenoid,
lambertianic acid, led to the development of a new
group of nootropic remedies [2]. Aminomethylfurans
are used as convenient intermediates in the synthesis
of biologically active compounds of perhydroazine
and perhydroazole series [3]. 6-(Furfurylamino)purine
was the first discovered compound stimulating the cell
fission [4].
Among methods for preparing primary amines, the
Delepine reaction is distinguished by the availability
of the starting substances, high selectivity, and mild
reaction conditions. In the furan series, it was used
for preparing 2-aminomethylfuran-5-carboxylic acid
and 2-aminomethyl-5-benzoylfuran [9], but these
studies were not developed further. We decided to
apply the Delepine reaction tn a series of substituted
(halomethyl)furancarboxylic acid esters with different
mutual arrangement of the halomethyl and alkoxy-
carbonyl groups in the ring.
The Delepine reaction consists of two steps. In the
first step, one of hexamethylenetetramine nitrogen
atoms is alkylated to form a quaternary salt. The pos-
sibility and conditions of performing this step depend
on the substrate electrophilicity.
Thus, aminomethyl derivatives of furans are prom-
ising precursors for preparing new biologically
active compounds and drugs.
In the second step, acid-catalyzed alcoholysis of
this salt is performed to obtain the amine hydrochlo-
ride. In the course of this process, intermediate elec-
trophilic species are formed, which can enter the sub-
stitution reactions with, e.g., phenolic ethers [10] and
the simplest furans [11]. Therefore, the possibility of
successful alcoholysis will be determined by the
hydrolytic stability of the furan ring and its inertness
to oxonium cations formed by alcoholysis of the
hexamethylenetetramine fragment. Both these factors
primarily depend on the nature and location of sub-
stituents in the furan ring.
At the same time, existing methods for preparing
amines of the furan series have certain limitations
concerning the structure of the furan moiety, because
in most cases either the aminoalkylation of furans
having free -position and an electron-donating sub-
stituent in the ring or the reduction of furfural deriva-
tives is used [5 7]. Furthermore, most of the amines
obtained are tertiary, which strongly limits the ap-
plication sphere of these compounds in the reactions
involving the amino group.
It was shown previously [8] that the halomethyl
group can be introduced into any position of the
furancarboxylic acid heteroring. This fact allowed
preparation of a series of compounds that we decided
to use as starting substances in the synthesis of
(aminomethyl)furancarboxylic acids with primary
amino group, which are presently the most poorly
studied.
Finally, formation of the amine competes with the
redox process yielding the aldehyde (Sommelet reac-
tion). The occurrence of the reaction along one or
another pathway is determined by acidity of the
medium.
Thus, the first and the second steps of the Delepine
1304

REACTIONS OF ALKYL (HALOMETHYL)FURANCARBOXYLATES
1305
Table 1. Alkylation of hexamethylenetetramine with alkyl halomethylfurancarboxylates
R2 R3
R2 R3
CH2[(CH2)6N4]+Hlg
CH2Hlg
*
O
*
O
R4
R4
R1
R1
Starting
comp.
no.
Reaction Hexamethylene- Yield,
mp,
(solvent)
C
R1
R2
R3
R4
time, h tetramine salt
%
I
II
III
COOC2H5
COOC2H5
COOCH3 CH2Br
H
H
H
CH2Cl
H
CH2Cl
CH3
H
4
2
8
XIIIa
XIVb
XVc
82
88
83
219 (chloroform)
215 (petroleum ether)
182 183 (chloroform
hexane)
IV
V
VI
COOCH3
CH2Br
CH2Br
H
CH2Cl
H
COOC2H5
t-C4H9
H
H
10
2
4
XVI
XVIII
XIX
54
89
79
248 (ethyl acetate)
186 (ethyl acetate)
184 185 (petroleum
ether)
189 190 (ethyl acetate)
221 (petroleum ether)
141 (ethyl acetate)
217 (ethyl acetate
petroleum ether)
209 (ethyl acetate
petroleum ether)
COOC2H5
H
VII CH3
VIII i-C4H9
IX
CH2Cl
CH2Cl
H
COOC2H5 CH3
COOC2H5 CH3
COOC2H5 CH2Br
COOC2H5 CH2Br
11
2
2
XXd
XXI
XXII
XXIII
94
71
74
92
t-C4H9
C6H5
X
H
2
XI
CH2Br
H
COOC2H5 C6H5
2
XXIV
78
a
b
Found, %: C 50.65; H 6.26; N 16.82. C
N 16.32. C
Calculated, %: C 43.45; H 5.29; N 15.60. Found, %: C 53.59; H 7.11; N 15.61. C
H ClN O . Calculated, %: C 51.14; H 6.39; N 17.05. Found, %: C 52.45; H 6.64;
14 21 4 3
c
H ClN O . Calculated, %: C 52.55; H 6.72; N 16.35. Found, %: C 44.01; H 5.68; N 15.24. C H BrN O .
15 23 4 3 13 19 4 3
d
H ClN O . Calculated, %: C 53.86; H 7.01;
16 25 4 3
N 15.71.
reation are independent processes. Their character is
determined by different factors, and they must be
considered separately.
Therefore, the optimal reaction time was found from a
series of experiments using the hexamethylene-
tetramine salt yield as a criterion.
Table 1 shows that the halomethyl group position
and the kind of the halogen do not significantly affect
the hexamethylenetetramine salt yield. In all the cases,
they are high and in some cases almost quantitative.
We found that the volume of the substituent in the
position adjacent to the halomethyl group plays an
important role. Introduction of the tert-butyl group
into the -position of the furan ring (compound IV)
decreases the quaternary salt yield from 88% for II to
54%. Similar trend was observed in a series of com-
pounds VII, VIII, XII with -methyl, -isobutyl, and
-tert-butyl substituents, respectively. For the first
two compounds, the quaternary salt yield decreases
from 94 to 71%, and in the case of XII the reaction
does not occur at all.
Alkylation of hexamethylenetetramine with (halo-
methyl)furancarboxylic acid esters was performed in
chloroform at 1:1 molar ratio of the reactants [12]. The
structure of the starting products, the reaction time,
the isolation conditions, and the yields of the quatern-
ary salts are listed in Table 1. The character of the
process was determined by location of the halomethyl
group in the furan ring and the kind of the halogen.
The reactions of -(bromomethyl)furans V, VI, and
IX XI are strongly exothermic. Without efficient heat
removal, 3-4 min after the start of the process the re-
action mixture comes to boil. In the case of -chloro-
methyl- and -bromomethylfurans, the reaction mix-
ture temperature increases by 10 15 C. For the reac-
tion completion, the mixture was refluxed for a time
given in Table 1. For compounds of the furan series,
the reaction progress cannot be monitored by TLC on
silica gel because of their high lability under these
conditions.
CH2Cl
EtOOC
t-C4H9
H3C
O
XII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

1306
LAPINA et al.
Hexamethylenetetramine salts were decomposed to
hydrochloride or without it. Base hydrolysis was
carried out in aqueous ethanol for 2.5 3 h. Amino-
furancarboxylic acids are colorless high-melting crys-
talline compounds which are poorly soluble in water
and organic solvents, but give difficultly settling
suspensions.
amines by treatment with ethanolic HCl. Similarly to
the previous step, the reaction time was found from
the series of experiments because monitoring of the
reaction progress appeared to be unreliable.
Variation of the HCl to quaternary salt molar ratio
showed that at the stoichiometric ratio (3:1) the target
product yield is relatively low. At the molar ratio
With the aim to obtain the compounds more
suitable for identification, we have converted the
increased to (4.5 5):1, it reaches the highest value, and amino acids into their hydrochlorides. These salts are
further increase in the hydrogen chloride amount does
not affect the reaction progress.
colorless crystalline compounds readily soluble in
water and DMSO and usually only moderately soluble
in methanol and ethanol. When heated, amino acid
hydrochlorides start to sublime at 180 C, and at
250 260 C they carbonize without melting. The
yields of amino acid hydrochlorides and their 1H
NMR characteristics are listed in Table 2.
Amino ester hydrochlorides are crystalline com-
pounds. They may be isolated from ethanol or some
other organic solvents, but, as a rule, they contain
residual ammonium chloride. For example, amino
ester hydrochlorides prepared from hexamethylene-
tetramine salts XIV, XV, XIX, and XX, according to
1H NMR data, contain 11, 7.7, 14, and 6.5% ammo-
nium chloride, respectively. Removal of this impurity
appeared to be labor-consuming and was accompanied
by the target product losses. Therefore, the yields of
the amino ester hydrochlorides cannot be used for
characterizing the efficiency of the decomposition of
hexamethylenetetramine salts.
In the synthetic practice, the reactions involving
the amino group require protection of the carboxy
group by esterification. In this connection, we at-
tempted to carry out esterification of the amino acid
hydrochlorides obtained with the aim to prepare
samples of these compounds free from the ammonium
chloride impurity.
We tested three esterification procedures: in the
methanol thionyl chloride system at 0 and 65 C [13],
the procedure involving intermediate formation of a
mixed anhydride by treating the amino acid with tri-
fluoroacetic anhydride [14, 15], and the reaction of
the amino acid with triethyl orthoformate [16]. Amino
acid hydrochlorides XXVII and XXXIII were used
as substrates.
Free amino esters, similarly to the native amino
acid esters, slowly enter polycondensation in the cold,
and at approximately 100 C this reaction is complete
in several minutes. Therefore, purification of these
substances, which are viscous oils, by vacuum distilla-
tion was unfeasible.
To characterize the chemical properties of the
amino group in the aminomethyl compounds prepared,
we involved these substances in acylation reactions
typical of amines. Accessible furancarboxylic acid
chlorides were used as acylating agents. With the
majority of them, the amines under study form well
crystallizing compounds. Although amino ester hy-
drochlorides were not purified to remove the residual
ammonium chloride, we obtained pure (furoylamino-
methyl)furancarboxylic acids.
We found that the amino acid conversion with the
first system does not exceed 15 20% according to the
1H NMR data, and the amino ester hydrochloride
cannot be separated from the corresponding amino
acid salt. The second and third systems appeared to
be ineffective. In both cases, only the starting acid
hydrochloride was recovered.
Therefore, the development of a procedure for
purification of amino ester hydrochlorides to remove
residual ammonium chloride is a practically important
problem. We have developed the following procedure.
Contaminated amino ester hydrochloride was sus-
pended in toluene and treated with a saturated potas-
sium carbonate solution. Free amino ester dissolved
in toluene, and the impurity remained in the aqueoeus
phase. After the extraction with toluene, the aqueous
layer was rejected. The toluene solution was dried for
a short time over sodium sulfate and acidified with an
ethanolic HCl solution. Evaporation of the solvents
gave the product free from ammonium chloride. The
yields of purified amino ester hydrochlorides vary
Further studies showed that, after the base hydrol-
ysis of the esters, aminofurancarboxylic acids readily
precipitate from aqueous-ethanol solutions as free
acids at pH 6.5 7 and as hydrochlorides at pH below
4. Therefore, the amino acid yield in the second step
of the Delepine reaction can be most reliably es-
timated from the overall yield of the acid alcoholysis
of the quaternary salt and of the base hydrolysis of
the resulting amino ester hydrochloride.
Preparation of the target product in the form of the
amino acid or its hydrochloride was performed either
with isolation of the crude crystalline amino ester
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

REACTIONS OF ALKYL (HALOMETHYL)FURANCARBOXYLATES
1307
Table 2. Yields and spectral characteristics of (aminomethyl)furancarboxylic acids
R2 R3
HCl
R4
R1
O
Comp.
no.
Yield,
%
R1
R2
R3
R4
CH2NH2
CH2NH2 CH3
1H NMR spectrum, , ppm
XXVII
COOH
H
H
H
42
72
63
24
48
42
77
60
4.13 s (CH2N), 6.69 d (H4-furan), 7.22 s (H3-furan),
8.75 br.s (NH3)
XXVIIIa COOH
2.35 s (CH3), 3.85 s (CH2N), 7.30 s (H5-furan),
8.34 br.s (NH3)
XXIX
XXX
COOH
COOH
CH2NH2
H
H
H
4.16 s (CH2N), 6.97 s (H4-furan), 7.84 s (H5-furan),
8.73 br.s (NH3)
CH2NH2 t-C4H9
1.29 s [(CH3)3C], 4.00 s (CH2N), 7.37 s (H3-furan),
8.59 br.s (NH2)
XXXI
XXXII
CH2NH2 COOH
CH2NH2
H
H
4.27 s (CH2N), 6.74 s (H4-furan), 7.79 s (H5-furan),
8.72 br.s (NH3)
H
COOH
H
4.07 s (CH2H), 6.81 s (H3-furan), 8.44 s (H5-furan),
8.63 br.s (NH3)
XXXIIIb CH3
CH2NH2 COOH
CH2NH2 COOH
CH3
CH3
2.13 s (CH23-furan), 2.49 s (CH53-furan), 3.95 s
(CH2N), 8.25 br.s (NH3)
XXXIV
i-C4H9
0.90 d (CH2-isobutyl), 1.90 m (CH-isobutyl), 2.50 br.s
(CH3-furan + CH2-furan + residual DMSO), 3.94 s
(CH2N), 8.05 br.s (NH3)
1.27 s [(CH3)3C], 4.26 s (CH2N), 6.33 s (H4-furan),
8.81 br.s (NH3)
4.39 s (CH2N), 7.08 s (H4-furan), 7.32 t (Hp-phenyl),
7.41 t (Hm-phenyl), 7.81 d (Ho-phenyl), 8.98 br.s (NH3)
4.15 s (CH2N), 6.86 s (H3-furan), 7.50 m (Hp + Hm-
phenyl), 8.00 d (Ho-phenyl), 8.63 br.s (NH3)
1.24 s [(CH3)3C], 4.12 s (CH2N), 6.63 s (H4-furan),
8.61 br.s (NH3)
XXXV
t-C4H9
H
H
H
H
COOH
COOH
COOH
CH2NH2
CH2NH2
C6H5
67
69
44
35
XXXVIc C6H5
XXXVII CH2NH2
XXXVIII t-C4H9
CH2NH2 COOH
a
b
Found, %: C 39.88; H 5.35; N 6.74. C H NO HCl. Calculated, %: C 40.10; H 5.73; N 6.68. Found, %: C 46.15; H 5.77; N 6.56.
7
11
4
c
C H NO HCl. Calculated, %: C 46.72; H 5.84; N 6.81. Found, %: C 65.94; H 5.28; N 6.44. C
H NO . Calculated, %:
8
11
3
12 11 3
C 66.36; H 5.07; N 6.45 (for the free amino acid).
from 50 to 76%. The product loss in this operation is
evidently caused by the amino ester hydrolysis in an
alkaline medium.
furancarboxylic acid are poorly esterified with
commonly used systems.
EXPERIMENTAL
Thus, application of the Delepine reaction to alkyl
(halomethyl)furancarboxylates allows preparation of
aminomethyl derivatives of furancarboxylic acids with
any mutual arrangement of the carboxy and amino-
methyl groups in the furan ring. Among the simplest
alkyl substituents under study, only the adjacent tert-
butyl group prevents the reaction. The process may
be directed toward formation of both amino acids and
hydrochlorides of their esters. The latter fact is of
special value, because aminomethyl derivatives of
1
The H NMR spectra were taken on a Bruker WM-
250 spectrometer in DMSO-d6. Chemical shifts were
measured relative to internal TMS.
Alkylation of hexamethylenetetramine with
alkyl
(halomethyl)furancarboxylates
(general
procedure). To a solution of hexamethylenetetramine
in chloroform (5 ml of chloroform per gram of hexa-
methylenetetramine), an equivalent amount of alkyl
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

1308
LAPINA et al.
(halomethyl)furancarboxylate was added, and the
mixture was refluxed for the required time (Table 1).
Then the mixture was left overnight, after which the
hexamethylenetetrammonium salt was filtered off, or
chloroform was removed and the residue was crystal-
lized from a mixture of solvents indicated in Table 1.
The crystals obtained were dried at 40 50 C. The
structures of the starting compounds, reaction condi-
tions, and melting points of the salts obtained are
given in Table 1.
precipitated amino acid was filtered off and dried at
40 50 C. The structures of the compounds obtained,
yields of amino acids, and H NMR data for their
1
hydrochlorides are listed in Table 2.
Purification of amino ester hydrochlorides.
Crude amino ester hydrochloride obtained from hexa-
methylenetetramine salt XIV, XV, XX, XXII, or
XXIV was suspended in toluene (5 ml per gram of
salt), and the saturated aqueous solution of potassium
carbonate was added (2 mol of K2CO3 per mole of
salt). The resulting mixture was stirred for 10 15 min,
the organic layer was separated, and the aqueous layer
was washed with toluene. The combined toluene solu-
tions were dried over sodium sulfate and acidified to
pH 1 with a saturated solution of HCl in ethanol. The
acidified solution was evaporated at reduced pressure
until the onset of crystallization. Hydrochlorides XIV,
XV, and XX were filtered off, and compounds XXII
and XXIV were preliminarily triturated with a small
amount of petroleum ether. The obtained crystals of
amino ester hydrochlorides were dried at 40 50 C.
Hydrolysis of hexamethylenetetramine salt to
amino acid (general procedure). a. Without isolation
of the amino ester hydrochloride. Hexamethylene-
tetramine salt XVI, XVIII, XXI, or XXV was dis-
solved on heating in ethanol to prepare an almost
saturated solution, and then a saturated solution of
HCl in ethanol was added (4.5 mol per mole of the
salt). The mixture was refluxed with stirring for 2.5
3 h and then filtered while hot to separate the am-
monium chloride precipitate. The major part of the
solvent was distilled off at reduced pressure, and the
residue was dissolved in water and alkalized with a
20% NaOH solution to pH 8.5 9. After that, the same
solution (2 mol per mole of the starting hexame-
thylenetetramine salt) was added, and the resulting
mixture was boiled with stirring for 3 h. After remov-
ing the residual ethanol, the solution was acidified
with HCl to pH 1 2. The amino acid hydrochloride
crystallized from the solution within certain time.
Ethyl 4-aminomethyl-5-methylfuran-2-carboxy-
1
late hydrochloride. Yield 59%, mp 188 C. H NMR
spectrum, , ppm: 1.32 t (CH3-ethyl), 2.40 s (CH53-
furan), 3.81 s (CH2N), 4.25 q (CH2O), 7.39 s (H3-
furan), 8.57 s (NH+3).
Ethyl 3-aminomethylfuran-2-carboxylate
1
hydrochloride. Yield 59%, mp 154 156 C. H NMR
spectrum, , ppm: 1.28 t (CH3-ethyl), 4.16 s (CH2N),
b. With isolation of the crystalline amino ester
hydrochloride. A nearly saturated solution of hexa-
methylenetetramine salt XIII XV, XIX, XX, or
XXII XXIV was prepared by heating it in ethanol.
After that, a saturated solution of HCl in ethanol
(4.5 mol per mole of the salt) was added, and the
mixture was refluxed for 2.5 3 h. Then the mixture
was filtered while hot, and the ammonium chloride
precipitate was washed with hot ethanol. The com-
bined filtrate was concentrated at reduced pressure by
a factor of 2 2.5, until the crystallization started, and
was left in the refrigerator ( 6 C). Usually on the next
day, crystals of the amino ester hydrochloride were
filtered off and washed with a small amount of
acetone or ethyl acetate. In the case of the synthesis
of the amino ester hydrochloride from hexamethy-
lenetetramine salt XXIV, the solution obtained after
removing ammonium chloride must be concentrated
and triturated with ethyl acetate before cooling. The
crystals of the amino ester hydrochloride dried at 40
50 C were dissolved in a small amount of ethanol,
and 3 equiv of 20% aqueous NaOH solution was
added. The resulting mixture was boiled with stirring
for 3 h. After removing the residual ethanol, the reac-
tion mixture was acidified with HCl to pH 6.5 7. The
4.23 q (CH2O), 6.97 s (H4-furan), 7.89 s (H5-furan),
8.72 br.s (NH+3).
Ethyl 5-aminomethyl-2-phenylfuran-3-car-
1
boxylate hydrochloride. Yield 60%, mp 128 C. H
NMR spectrum, , ppm: 1.27 s (CH3-ethyl), 4.15 s
(CH2N), 4.22 q (CH2O), 6.86 s (H4-furan), 7.51 m
(Hp + Hm), 8.01 m (2Ho), 8.63 br.s (NH+3).
Ethyl 2-aminomethyl-5-tert-butylfuran-3-car-
1
boxylate. Yield 59%, mp 125 C. H NMR spectrum,
, ppm: 1.28 br.s [(CH3)3C + CH3-ethyl], 4.22 m
(CH2O + CH2N), 6.33 s (H4-furan), 8.82 br.s (NH+3).
Ethyl 4-aminomethyl-2,5-dimethylfuran-3-car-
1
boxylate. Yield 76%, mp 218 C. H NMR spectrum,
, ppm: 1.32 t (CH3-ethyl), 2.47 s (CH23-furan +
residual DMSO), 2.99 s (CH53-furan), 3.92 s (CH2N),
4.24 q (CH2O), 7.99 s (NH+3).
Acylation of alkyl (aminomethyl)furancar-
boxylates (general procedure). A weighed portion of
alkyl (aminomethyl)furancarboxylate hydrochloride
was dissolved in a small amount of acetonitrile, and
2 equiv of triethylamine was added with stirring. The
resulting mixture was treated with 1 equiv of furan-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006

REACTIONS OF ALKYL (HALOMETHYL)FURANCARBOXYLATES
carboxylic acid chloride (50% solution in acetonitrile).
1309
REFERENCES
The mixture was stirred for 2 h at room temperature
and then left overnight. After that, triethylamine
hydrochloride was filtered off, the filtrate was evap-
orated, and the residue was dissolved in chloroform
and washed with water. The resulting solution was
dried over calcium chloride and then evaporated. If no
crystalline acylated aminomethylfurancarboxylic acid
ester could be obtained, the residue was hydrolyzed
with aqueous-ethanolic alkali. For this purpose, a
weighed portion of the acylated ester was dissolved in
a small amount of ethanol, and 2 equiv of 50% KOH
solution was added. The resulting mixture was re-
fluxed for 6 h, and then, if necessary, ethanol was
distilled off at reduced pressure. After that, the mix-
ture was acidified with an HCl solution to pH 2. The
crystals that formed were filtered off and dried at
40 50 C.
1. Eugster, C.H., Haplinger, F., Denss, R., and Yirol, E.,
Helv. Chim. Acta, 1958, vol. 41, p. 886.
2. Tolstikova, T.G., Dolgikh, M.P., and Tolstikov, G.A.,
Dokl. Ross. Akad. Nauk, 2000, vol. 374, no. 2, p. 565.
3. Shikhaliev, Kh.S., Falaleev, A.V., Kryl’skii, D.V.,
and Solov’ev, A.S., Azotistye geterotsikly i alkaloidy
(Nitrogen-Containing Heterocycles and Alkaloids),
Kartsev, V.G. and Tolstikov, G.A., Eds., Moscow:
Iridium, 2001, p. 587.
4. Iroog, F. and Armstrong, D.J., Ann. Rev. Plant
Physiol., 1970, vol. 21, p. 359.
5. Winberg, H.E., Fawcett, F.S., Mochel, W.E., and
Theobold, C.W., J. Am. Chem. Soc., 1960, vol. 82,
no. 4, p. 1428.
6. Heaney, K. and Papageorgion, J., Tetrahedron Lett.,
5-[N-(5-tert-Butyl-2-methyl-3-furoyl)amino]-
1988, vol. 29, no. 19, p. 2377.
1
methylfuran-2-carboxylic acid: mp 172 C. H NMR
7. Novitskii, K.Yu., Yur’ev, Yu.K., Afanas’eva, Yu.A.,
Bolesov, I.E., and Oleinik, A.M., Zh. Obshch. Khim.,
1960, vol. 30, no. 10, p. 2199.
spectrum, , ppm: 1.24 s [(CH3)3C], 2.48 m (CH23),
4.41 s (CH2N), 6.38 s (H4-furan), 6.43 s (H4-furan),
7.07 s (H3-furan), 8.33 s (NH), 12.7 br.s (COOH).
Found, %: C 63.96; H 6.28; N 4.54. C16H19NO5.
Calculated, %: C 62.95; H 6.23; N 4.59.
8. Pevzner, L.M., Ignat’ev, V.M., and Ionin, B.I., Zh.
Obshch. Khim., 1992, vol. 62, no. 4, p. 797.
9. Mndzhoyan, A.L., Panayan, G.L., and Galstyan, A.S.,
2-[N-(3-Methyl-2-furoyl)amino]methylfuran-3-
Arm. Khim. Zh., 1959, vol. 22, no. 3, p. 34.
1
carboxylic acid: mp 130 C. H NMR spectrum, ,
ppm: 2.31 s (CH3), 4.75 s (CH2N), 6.45 s (H4-furan),
10. Vavon, J., Bolle, D., and Calin, P., Bull. Soc. Chim.
Fr., 1939, vol. 5, no. 6, p. 1025.
6.62 s (H4-furan), 7.60 d.s (2H5-furan), 8.39 s (NH),
12.73 br.s (COOH).
11. Dunelli, D. and Marini, C., Gazz. Chim. Ital., 1937,
vol. 67, p. 312.
5-[N-(4-Carboxy-3-furoyl)amino]methylfuran-2-
12. Organic Reactions, Adams, R., Ed., New York: Wiley,
1944. Translated under the title Organicheskie reak-
tsii, Moscow, 1956, vol. 8, p. 270.
1
carboxylic acid: mp 222 C. H NMR spectrum, ,
ppm: 4.55 s (CH2N), 6.48 s (H4-furan), 7.09 s (H3-
furan), 8.38 d.s (H2 and H5-furan), 9.89 s (NH).
Found, %: C 51.37; H 3.64; N 5.00. C12H9NO7. Cal-
culated, %: C 51.61; H 3.23; N 5.02.
13. Gershkovich, A.A. and Kibirev, V.K., Sintez peptidov.
Reagenty i metody (Peptide Synthesis. Reagents and
Methods), Kiev: Naukova Dumka, 1987, p. 171.
5-[N-(2-Methyl-3-furoyl)amino]methylfuran-2-
14. Bourne, E.J., Stacey, M., Tatlow, J.C., and Ted-
1
carboxylic acid: mp 176 C. H NMR spectrum, ,
der, J.M., J. Chem. Soc., 1949, p. 2976.
ppm: 2.51 m (CH23), 4.42 s (CH2N), 6.39 s (H4-furan),
6.84 d (H4-furan), 7.18 s (H3-furan), 7.42 s (H5-furan),
8.48 m (NH), 12.72 br.s (COOH). Found, %: C 57.11;
H 4.56; N 5.60. C12H11NO5. Calculated, %: C 57.83;
H 4.42; N 5.62.
15. Parish, R.C. and Stock, L.M., J. Org. Chem., 1965,
vol. 30, no. 4, p. 927.
16. Cohen, H. and Mier, D., Chem. Ind. (London), 1965,
no. 2, p. 349.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 8 2006