New growth regulators of corn based on N-mono- and N,N-bis-3-butenyldichloroacetamides

Article abstract of DOI:10.1007/s11172-018-2080-0

Allylboration of imines, nitriles (including hydrocyanic acid), amides, lactams, aromatic azaheterocycles (pyridines, isoquinoline, and pyrrole) was used to synthesize a series of mono- and bis-3-butenylamines with different structures, which were converted to dichloroacetamides, new analogs of a known safener (herbicide antidote) Dichlormid successfully used in the cultivation of corn throughout the world. Biological tests for the germination of corn seeds showed that most of the dichloroacetamides obtained have growth-stimulating activity, which is mainly directed on the development of the root system. Compounds 2f, trans- and cis-2n, cis-2s, and 2t demonstrated outstanding activity, exceeding from two to three times the stimulating effect of Dichlormid on the developing root system of maize seedlings.

Full text of DOI:10.1007/s11172-018-2080-0

Russian Chemical Bulletin, International Edition, Vol. 67, No.2, pp. 345—358, February, 2018
345
New growth regulators of corn based on
Nꢀmonoꢀ and N,Nꢀbisꢀ3ꢀbutenyldichloroacetamides
Yu. N. Bubnov,a,b Yu. Ya. Spiridonov, and N. Yu. Kuznetsova
c
аA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
2
8 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085
b
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
7 Leninsky prosp., 119991 Moscow, Russian Federation
4
c
Russian Research Institute of Phytopathology (VNIIF),
Vlad. 5 ul. Institut, 143050 Bol´shye Vyazyomy, Moscow Region, Russian Federation
Allylboration of imines, nitriles (including hydrocyanic acid), amides, lactams, aromatic
azaheterocycles (pyridines, isoquinoline, and pyrrole) was used to synthesize a series of
monoꢀ and bisꢀ3ꢀbutenylamines with different structures, which were converted to dichloroꢀ
acetamides, new analogs of a known safener (herbicide antidote) Dichlormid successfully
used in the cultivation of corn throughout the world. Biological tests for the germination of
corn seeds showed that most of the dichloroacetamides obtained have growthꢀstimulating
activity, which is mainly directed on the development of the root system. Compounds 2f,
transꢀ and cisꢀ2n, cisꢀ2s, and 2t demonstrated outstanding activity, exceeding from two to
three times the stimulating effect of Dichlormid on the developing root system of maize
seedlings.
Key words: allylboranes, allylboration, plant growth regulators, Dichlormid, safeners.
Ensuring food security of the population is one of the
priority tasks of Russia´s development. The most imporꢀ
herbicides, but also increase the stress resistance of
1
4—7
plants.
Figure 1 shows the structures of a number of
tant factor in solving this problem is increasing the soil
fertility and yields of agricultural crops, which is largely
determined by the level of weed population in the places
commercially available antidotes, while the types of herꢀ
bicides used in combination with them are listed in Table 1.
Cyprosulfamide is one of the newest antidotes (developed
in 2005 by Bayer company) for the use in combination
with sulfonylureas and chloro derivatives of benzoic acid
(Dicamba) and triazine (Atrazine). These compounds are
particularly efficient for the protection of maize.
2
of cultivation. Balanced chemicalization of plant growing
using growth regulators and herbicides allows one to
3
achieve a significant increase in yields. However, it must
be understood that herbicides widely used in modern
industrial agriculture adversely affect both weeds and culꢀ
There are also a number of successfully used antiꢀ
dotes, which are amide derivatives of dichloroacetic acid
(see Fig. 1, Table 2). Dichlormid, the first representative
of this class, was patented in 1972 by Pallos as the antiꢀ
dote of thiocarbamate herbicides for the use in maize.6
Apart from that, Dichlormid is a more efficient safener
than, for example, naphthalic anhydride (see Table 1),
and is used in combination with a herbicide for soil appliꢀ
4
tivated plants. Poorly controlled use of herbicides results
in contamination of soil with their residues, which causes
serious damage to crops in the following years, while unꢀ
derestimation of this effect leads to tangible losses in the
yield of the main agricultural crops. Thus, when spraying
fields with xenobiotics from 30 to 70% of them gets
into the soil, contaminates it, and has a negative effect on
the yield in subsequent years (sometimes, the yield losses
reach 50%). This problem is especially acute when herbiꢀ
cides based on sulfonylureas are used, which, possessing
7
cation, like other antidotes of this class, for example,
4
benoxacor and AD 67. Currently, the worldwide use of
dichloroacetamideꢀbased safeners exceeds 8,000 tonnes
per year, while in the USA it reaches 2,000 tonnes per
–
1
unique biological activity (in doses of 10—25 g ha ), can
5
8,9
persist in the soil for a long time. Therefore, to efficientꢀ
year, confirming their high efficiency. The antidotes
ly use herbicides and other chemicals in modern agriculꢀ
ture, additives of the soꢀcalled safeners (antidotes, inducꢀ
tors of stability) are used in the preꢀsowing treatment,
which not only increase the selectivity of the action of
Dichlormid and DKAꢀ24 are derivatives of diꢀ and
monoallylamine.
In different years, our team in the ZIOC and INEOS
of RAS has developed efficient and simple singleꢀstep
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0345—0358, February, 2018.
066ꢀ5285/18/6702ꢀ0345 © 2018 Springer Science+Business Media, Inc.
1

3
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Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
Antidotes
Fluxofenim (CGA133205)
Naphthalic anhydride (NA)
Flurazole (MON4606)
Dietholate
Fenchlorazoleꢀethyl (AD67)
Cloquintocetꢀmexyl
Cyprosulfamide
Dichlormid (R25788)
NꢀAllylꢀNꢀdichloroacetylglycine
Benoxacor
CGA154281)
allylamide (DKAꢀ24)
(
2
ꢀDichloromethylꢀ2ꢀ
methylꢀ1,3ꢀdioxolane
MG191)
ADꢀ67
BAS145138
R29148
(
Herbicide
Clodinafopꢀpropargyl
Fig. 1. Structures of commercially available antidotes and herbicides.
methods for the synthesis of various 3ꢀbutenylamines conꢀ
taining mainly two allylic fragments.
Since the amines we synthesized are homologs of allylꢀ
amines, we anticipated that their dichloroacetyl derivaꢀ
tives would also exhibit antidotal activity. It is obvious
that the preparation of new compounds with higher safenꢀ
er activity is of great practical importance in the developꢀ
ment of new composite mixtures for the treatment of
Table 1. Antidotes of herbicides
Antidote
Herbicide
Cultures of cultivated plants for use
Fluxofenim (CGA133205)
Sulfonylureas, imidazolinones
Sorghum, rice, corn,
cotton, soybeans, sugar beets
Corn, cotton, sorghum
Naphthalic anhydride (NA)
Ureas, sulfonylureas, carbamates,
and many other herbicides
Acetanilides, imidazolinones
PhenoxapropꢀPꢀethyl
Thiocarbamates
Clodinafopꢀpropargyl
Flurazole (MON4606)
Fenchlorazoleꢀethyl (AD67)
Dietholate
Cloquintocetꢀmexyl
Cyprosulfamide
Corn, sorghum, rice
Wheat, triticale
Corn, cotton, wheat, rice
Wheat, triticale, rye
Wheat, corn, cotton
Sulfonylureas, Dicamba, Atrazine

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
347
Table 2. Antidotes of herbicides based on dichloroacetic acid derivatives
Antidote
Herbicide
Cultures of cultivated plants for use
Wheat, sorghum, rice, corn, oats
Dichlormid (R25788)
Thiocarbamates, including Sꢀ ethyldipropylꢀ
thiocarbamate (EPTC), butylate
Thiocarbamates
NꢀAllylꢀNꢀdichloroacetyl
glycine allylamide (DKAꢀ24)
Benoxacor (CGA154281)
ADꢀ67
Soybean, cotton, rapeseed
Chloroacetamides (metolachlor)
EPTC
Corn
Corn
BAS145138
R29148
Sulfоnylureas, thiocarbamates
Chloroacetamides
Corn, sorghum, wheat, rice
Wheat, corn, sunflower, rice, soybean,
cotton, rapeseed, tobacco
Corn, sorghum, rice
2
ꢀDichloromethylꢀ2ꢀmethylꢀ
,3ꢀdioxolane (MG191)
Chloroacetamides, thiocarbamates
1
seeds and plants. The parent dichloroacetamide safener,
Dichlormid, exhibits a complex biological activity when
acting on seeds or seedlings. The comprehensive studies
of the effect of Dichlormid, as well as of a number of its
analogs, on plants (and especially corn) have shown that
these compounds initiate an entire complex of biological
processes related to both the enhancement of the metaꢀ
bolic activity responsible for the protective action and the
component reaction of an aldehyde (ketone), ammonia
(4—10 equiv.), and allyl dibutoxyborane (1.6 equiv.)12
(Scheme 1).
The most efficient approach to the synthesis of bisꢀ3ꢀ
butenylamines with linear structure, namely, 1ꢀRꢀ1ꢀalꢀ
lylꢀ3ꢀbutenylamines 1c—f, is the reaction of organic niꢀ
1
3—15
triles with triallylborane
(Scheme 2). The synthesis
of amines 1d—f was described earlier.1 However, the
first member of this series, 1ꢀallylꢀ3ꢀbutenylamine (1c),
was synthesized by the oneꢀstep allylboration of hydroꢀ
cyanic acid for the first time. Earlier, amine 1c was obꢀ
tained from heptaꢀ1,6ꢀdienꢀ4ꢀol in three steps.16 As it
turned out, the reaction of triallylborane with HCN proꢀ
ceeds slower (4.5 h) than with organic nitriles and reꢀ
quires a higher temperature (140 °С, instead of 110 °С
for nitriles). Apparently, the absence of a substituent
at the cyano group decreases steric interactions in the
dimeric aminoboron intermediate and slows the transfer
of the second allyl group during formation of the boreꢀ
tidine ring. After the reaction mixture was deborated
with 20% NaOH, amine 1c was isolated by distillation in
69% yield.
5
biosynthesis of gibberellins responsible for the growth acꢀ
tivity.6
,10,11
In particular, the level of glutathione grows, the
activity of glutathioneꢀbound enzymes (transferase and
synthase), ATPꢀsulfurylase, acetohydroxyacid synthase,
1
0,11
monooxygenase, and others increases.
It is assumed
that the safener activity of dichloroacetamide derivatives
correlates with their biological stimulating activity.
The purpose of the present work is the synthesis
of dichloroacetamides from different homoallylamines
(
3ꢀbutenylamines) and the investigation of their biologiꢀ
cal effects on the germination of maize seeds. First, we
synthesized a series of 3ꢀbutenylamines 1a—u with variꢀ
ous structures (Schemes 1—9). The amines 1а and 1b
containing one allyl group were obtained by a threeꢀ
Scheme 1
Reagents and conditions: i. 7 M NH (10 equiv.) in MeOH, 25 °C, 16 h; ii. Cl CHC(O)Cl (DCAC), NaOH, CH Cl .
3
2
2
2

3
48
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
Scheme 2
t
1
, 2: R = H (c), Ph (d), Bu OC(O)CH (e), MeO(CH2)2 (f)
2
Reagents and conditions: i. 1) –30––20 °C, 2)100—140 °C, 1—5 h, 3) MeOH, 4) NaOH, 100 °C; ii. DCAC, NaOH, CH Cl .
2
2
Another method for preparation of bisꢀ3ꢀbutenylꢀ
amines is based on the reaction of triallylborane with
can be easily separated by acidꢀbase extraction (treatꢀ
ment with HCl and then with an alkaline solution) (see
Scheme 3).
amides containing at least one NH bond (RCONH or
2
RCONHR) (Scheme 3). These reactions require reflux in
THF and reach completion within 1.5 h. This method
was used to obtain primary amines 1g (48%) and 1h
2,2ꢀDiallylated Nꢀheterocycles 1j—m were synthesꢀ
ized using two pathways: the allylboration of 3ꢀchloroꢀ
propionitrile with subsequent closure of the azetidine ring (1j)
54%).15 A new substituted amine 1i was synthesized
upon treatment with an alkali or the allylboration of
17
(
lactams with fiveꢀ and sixꢀmembered ring (amines 1k,l)1
(Scheme 4). Derivative 1m was obtained as described in
the work,17 but as a racemate.
8
by allylboration of Nꢀmethylbenzamide. Moderate yields
of amines 1g—i are explained by the side formation
of diallylcarbinols Allyl C(R)OH, from which amines
2
Scheme 3
i
1
, 2: R = Bu , R´ = H (g), R = FCH , R´ = H (h), R = Ph, R´ = Me (i)
2
Reagents and conditions: i. 1) THF, 65 °C, 2) MeOH, 3) NaOH; ii. DCAC, NaOH, CH Cl .
2
2
Scheme 4
1
l
1
, 2: R = H, n = 1 (k), 2 (l); R = HOCH , n = 1 (m)
2
Reagents and conditions: i. 110 °C, 1 h; ii. NaOH, 70—100 °C; iii. DCAC, NaOH, CH Cl ; iv. 1) THF, 65 °C, 2) MeOH, 3) NaOH, H O.
2
2
2

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
349
Scheme 5
1
, 2: R = H (n), Me (o), OMe (p)
i
Compound
transꢀ1n
cisꢀ1n
transꢀ2n
cisꢀ2n
Yield (%)
Compound
1p
cisꢀ1p
cisꢀ2p
Yield (%)
59*
Reagents and conditions: i. 1) Pr OH (4 equiv.), 50 °C or 100 °C,
2 h, 2) MeOH, 3) NaOH, H O; ii. 1) (H C=CHCH ) B,
97
94
90
92
2
2
2 3
90
88
1
30—135 °C, 5 h, 2) MeOH, 3) NaOH, H O; iii. DCAC,
2
NaOH, CH Cl .
2
2
*
The ratio transꢀ1p : cisꢀ1p = 2.2 : 1.
The most convenient (and the simplest) approach to
ing transꢀisomer transꢀ1n and a mixture of isomers
trans/cisꢀ1p with triallylborane (130—135 °С, 5 h) (see
Scheme 5). Attempted chromatographic isolation of
individual transꢀisomer transꢀ1p from the mixture of
trans/cisꢀisomers trans/cisꢀ1p (2.2 : 1) was unsuccessful.
transꢀDimethallylꢀ4ꢀmethylꢀ3ꢀpiperideine (transꢀ1q)
(82%, trans : cis = 14 : 1) was synthesized by the reaction
of trimethallylborane with 4ꢀpicoline (50 °С, 2 h) and
isolated by chromatography (Scheme 6).
transꢀ and cisꢀα,α´ꢀdiallylated derivatives of 3ꢀpiperideine
and tetrahydrоisoquinoline is a reductive diallylation of
pyridines and isoquinolines with triallylborane in the presꢀ
ence of alcohols (methanol, ethanol, and, better, isoproꢀ
1
9—21
19,20,22
pyl alcohol).
It was found
that pyridine and
many its derivatives (but not 2ꢀpicoline and its analogs)
form 1 : 1 complexes with triallylborane, which do not
decompose upon distillation in vacuo. The complex pyridꢀ
ine—triallylborane treated with propanꢀ2ꢀol (20—100 °С,
2
h) undergoes a complete rearrangement with the forꢀ
Scheme 6
mation of transꢀ2,6ꢀdiallylꢀ3ꢀpiperideine (transꢀ1n) in up
to 80% yield. When the reaction was carried out in the
presence of 0.5—1.0 moles of pyridine, the yield of
transꢀ1n reached 97% (Scheme 5).
In the present work, we found that the reductive transꢀ
2
,6ꢀdiallylation of 4ꢀpicoline and 4ꢀmethoxypyridine
i
should be carried out at 50 °С (4 equiv. of Pr OH, 2 h).
Under these conditions, diallyl derivatives transꢀ1o and
trans/cisꢀ1p were obtained in 91% (trans : cis = 13 : 1)
and 59% yields (trans : cis = 2.2 : 1), respectively. At 100 °С,
the yield of compound 1o varied from 37 to 76%, while
no derivative 1p was formed at all. The studies of this
reaction by 1Н NMR spectroscopy showed that at the
temperatures above 50 °С, the protolysis of the B—allyl
bonds with the formation of propylene accompanied by the
degradation of the complex of triallylborane with 4ꢀsubstitꢀ
uted pyridine proceeds more actively instead of diallylation.
The thermodynamically more stable cisꢀderivatives
i
Reagents and conditions: i. 1) Pr OH (4 equiv.), 50 °C, 2 h,
2
2,23
cisꢀ1n (94%)
and cisꢀ1p (90%) were obtained by heatꢀ
2) MeOH, 3) NaOH, H O; ii. DCAC, NaOH, CH Cl .
2
2
2

3
50
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
The method of allylboration of pyridines is so univerꢀ
Scheme 8
sal method that it allows synthesis of not only the diallylꢀ
type derivatives 1n—q, but also nonsymmetrically substiꢀ
tuted compounds. Sequential treatment of pyridine with
lithium derivatives RLi (R = Alk, Ar) and triallylborane
can be used to obtain products containing alkyl (aryl) and
allyl substituents.2
4,25
Methyllithium smoothly adds to
pyridine in diethyl ether with the formation of lithium
ꢀmethyldienamide, which is captured by triallylborane
Scheme 7). Treatment of the intermediate triallylborane
2
(
ate complex with methanol and subsequent deboration
lead to transꢀ2ꢀallylꢀ6ꢀmethylꢀ1,2,3,6ꢀtetrahydrоpyridine
(
1r) in 93% yield.
Scheme 7
Reagents and conditions: i. 1) (H C=CHCH ) B, MeOH (3 equiv.),
2
2 3
2
1
0 °C, 2 h, 2) MeOH, 3) NaOH, H O; ii. 1) (H C=CHCH ) B,
30—135 °C, 2 h, 2) crystallization from hexane; iii. DCAC,
2 2 2 3
NaOH,CH Cl .
2
2
Reagents and conditions: i. MeLi, Et O, 0 °C, 1 h;
2
ii. (H C=CHCH ) B; iii. 1) MeOH, 2) NaOH, H O;
2
2 3
2
Scheme 9
iv. DCAC, NaOH, CH Cl .
2
2
Isoquinoline is more reactive toward triallylborane.
The reaction in the presence of methanol (3 equiv.) proꢀ
ceeds at room temperature (2 h) and leads to transꢀ1,3ꢀ
diallylꢀ1,2,3,4ꢀtetrahydrоisoquinoline (transꢀ1s) in up to
2
3,26,27
9
5% yield (Scheme 8).
Isomer transꢀ1s heated with
triallylborane undergoes isomerization with the formaꢀ
tion of the equilibrium mixture of cisꢀ and transꢀisomers
(
1 : 1), from which cisꢀisomer cisꢀ1s is isolated by crystalꢀ
lization from hexane (cisꢀ1s, m.p. 61 °С, transꢀ1s is an
2
3
oil) or by chromatography.
The reaction of triallylborane with pyrrole reached
completion at room temperature within 2—3 h (at 70 °С,
within 0.5 h) and led to two compounds: monoallylation
product 1t (15—30%) and transꢀ2,5ꢀdiallylpyrrolidine 1u
2
3,28,29
(
60—63%) (Scheme 9).
All the amines obtained (except a mixture of trans/cisꢀ
isomers trans/cisꢀ1p) were converted to dichloroacetꢀ
amides 2a—u upon treatment with dichloroacetyl chlorꢀ
ide (DCAC) (see Schemes 1—9). First, we tried an acylꢀ
ation procedure, which used Et N as a base at –30 °С,
3
however, these conditions led to the formation of a large
amount of resinification products of DCAC poorly separꢀ
Reagents and conditions: i. 1) 20 °C, 2—3 h, 2) MeOH,
3) NaOH, H O; ii. DCAC, NaOH, CH Cl .
2
2
2

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
351
able from dichloroacetamides, while a conversion of the
starting amine was not very high. The Schotten—Bauꢀ
Amides 2a—u were tested for stimulating activity.
Dichlormid was used as a comparison reference (see Fig. 1
and Table 2). The stimulating activity was evaluated on
germinating maize seeds (a hybrid Krasnodarsky 370 MV).
The monitoring of seed germination was performed with
photographic fixation. It was found that the most inforꢀ
mative was the measurement of the length of seedlings
and rootlets on the seventh day of the experiment. The
regularities of the stimulating activity of Dichlormid were
revealed, which made it possible to methodically correct
study the new dichloroacetamide derivatives of homoalꢀ
lylamines. The test results are given in Table 3.
mann acylation in a twoꢀphase system CH Cl /20%
2
2
aqueous NaOH at –15—–10 °С proceeds smoothly, but
the rate of saponification of DCAC turns out to be higher
and the conversion of the most hindered amines such as
transꢀ1n—q lies within 20—40% even upon treatment with
a 4—5ꢀfold excess of DCAC. By reducing the rate of
DCAC addition through a syringe pump, it became posꢀ
sible to completely and smoothly convert the amines to
dichloroacetyl derivatives 2a—u in high yields (up to 99%).
The library of synthesized dichloroacetamides of
homoallylamines 2a—u is representative for the primary
screening of biological activity, since it presents the main
structural variations of the starting butenyl amines.
Dichlormid at the doses of 1 and 10 g (t of seeds)–
acts as a growth stimulant, increasing the length of seedꢀ
lings and rootlets by 56 and 31.8%, respectively, however,
1
Table 3. The influence of dichloroacetamide derivatives 2a—u on the germination of maize seeds (a simple midseasonꢀripening
hybrid of maize Krasnodarsky 370 MV)
Entry
Variant
of experimentа
Doseb
of agent
g (t of seeds)
Length of sprouts
average value in %
Length of roots
average value
–
1
in %
/
/
cm
to control
/cm
to control
1
2
3
4
Dichlormid
0.1
1
2.7
2.8
3.9
2.5
2.8
3.1
3.6
2.9
4.5
5.1
5.4
4.8
4.3
5.3
6.2
5.1
+8.0
+12.0
+56.0
0.0
–3.4
+6.9
+24.1
0.0
–6.3
+6.2
+12.5
0
–15.7
+3.9
+21.6
0
4.0
5.5
5.8
4.4
3.9
4.7
4.8
4.9
4.1
5.0
4.6
3.9
3.5
5.2
5.6
3.7
–9.1
+25.0
+31.8
0.0
–20.4
–4.1
–2.0
0.0
+5.1
+28.2
+17.6
0
–5.4
+40.5
+51.4
0
1
—
0
b
Control
2a
0.1
1
1
—
0
b
Control
2b
0.1
1
1
—
0
b
Control
2c
0.1
1
1
—
0
b
Control
5
6
7
2d
0.1
1
3.3
3.3
3.3
2.9
4.9
4.7
4.8
4.8
6.7
6.9
+13.8
+13.8
+13.8
0.0
+2.1
–2.1
0
4.4
4.8
6.1
4.9
4.1
4.1
3.7
3.9
6.7
8.3
–10.2
–2.0
+24.5
0.0
+5.1
+5.1
–5.1
0
1
—
0
b
Control
2e
0.1
1
1
—
1
0
b
Control
0
2f
+26.4
+30.2
+48.9
+84.4
1
0
Control
—b
5.3
0.0
4.5
0.0
8
9
2g
1
6.3
6.1
5.3
+18.9
+15.1
0.0
4.5
5.4
4.5
0.0
+20.0
0.0
1
0
b
Control
—
2h
0.1
1
2.7
3.7
3.5
2.7
0.0
+37.0
+29.6
0.0
5.2
6.0
7.5
5.0
+4.0
+20.0
+50.0
0.0
1
0
b
Control
—
(
to be continued)

3
52
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
Table 3 (continued)
Entry
Variant
of experimentа
Doseb
of agent
g (t of seeds)
Length of sprouts
average value in %
Length of roots
–
1
average value
/cm
in %
/
/
cm
to control
to control
1
1
0
1
2i
1
5.7
6.2
5.3
3.3
3.1
3.9
2.7
2.5
2.6
2.7
2.4
2.7
3.6
3.0
2.7
6.8
5.8
5.3
3.2
3.5
3.67
2.9
+7.5
+17.0
0.0
+22.2
+14.8
+44.4
0.0
+4.2
+8.3
+12.5
0.0
3.6
4.0
4.5
5.3
5.4
6.5
5.0
5.3
4.5
5.3
3.5
4.7
5.8
7.2
5.0
5.6
4.4
4.5
4.9
5.3
9.8
4.9
–20.0
–11.1
0.0
+6.0
+8.0
+30.0
0.0
+51.4
+28.6
+51.4
0.0
–6.0
+16.0
+44.0
0.0
1
0
b
Control
—
0.1
1
2j
1
0
b
Control
—
0.1
1
1
1
2
3
2k
1
0
b
Control
—
0.1
1
2l
0.0
+33.3
+11.1
0.0
+28.3
+9.4
0.0
+10.3
+20.7
+24.1
0.0
1
0
b
Control
2m
—
1
1
1
4
5
+24.4
–2.2
0.0
1
0
b
Control
transꢀ2n
—
0.1
1
0.0
+8.2
+100.0
0.0
1
0
b
Control
—
1
1
1
1
2
6
7
8
9
0
transꢀ2o
1
5.4
5.9
5.3
5.9
7.0
5.3
6.6
6.5
5.3
4.6
6.0
5.7
3.2
3.4
3.3
2.9
5.2
5.6
5.8
4.8
6.8
6.3
5.3
7.2
6.7
5.3
6.0
6.0
5.3
+1.9
+11.3
0
+11.3
+32.1
0
+24.5
+22.6
0
–19.3
+5.3
0
+10.3
+17.2
+13.8
0.0
+8.3
+16.7
+20.8
0
+28.3
+18.9
0
+35.8
+26.4
0
4.2
5.6
4.5
4.7
6.2
4.5
8.2
7.1
4.5
3.1
3.9
5.2
4.0
4.6
5.0
4.9
4.5
5.2
5.1
3.9
7.1
8.3
4.5
9.2
5.6
4.5
4.9
6.6
4.5
+6.7
+24.4
0
+4.4
+37.8
0
+82.2
+57.8
0
–40.4
–25.0
0
–18.4
–6.1
+2.0
0.0
+15.4
+33.3
+30.8
0
+57.8
+84.4
0
+104.4
+24.4
0
1
—
1
0
b
b
b
b
Control
2q
1
—
1
0
Control
cisꢀ2n
1
—
1
0
Control
cisꢀ2p
1
0
Control
—
0.1
1
2r
1
0
b
Control
transꢀ2s
—
0.1
1
2
1
1
0
b
b
b
b
Control
cisꢀ2s
—
1
2
2
2
2
3
4
1
—
1
0
Control
2t
1
—
1
0
Control
2u
+13.2
+13.2
0
+8.9
+46.7
0
1
0
Control
—
a
b
Control experiments were carried out using distilled water.
–1
Control was distilled water in a dose of 10 L (t of seeds)
.

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
353
at a minimum dose of 0.1 g (t of seeds)–1 the root growth
slows by 9.1%. Amide 2a possesses a slightly higher toxꢀ
icity and acts more as a growth retarder at the doses of 0.1
and 1 g (t of seeds)–1, but at the dose of 10 g (t of seeds)–1
manifested itself as a stimulant to sprouts with an activity
of 24.1%, while retaining the toxic effect on rootlets
on the other hand, homoallylic. Amide transꢀ2n with
transꢀarrangement of the allyl groups showed outstandꢀ
ing growth activity: an increase in the length of seedlings
was 24.1% and that of rootlets was 100% (at the dose of
10 g (t of seeds)– ). Its cisꢀisomer cisꢀ2n possesses a smallꢀ
er but also significant growth activity (24.5 and 82.2%),
the maximum of which was achieved at the dose of
1 g (t of seeds)– . The introduction of a methyl group into
the heterocycle of transꢀ2о sharply reduces the growth
activity to 11.3 and 24.4% (at the dose of 10 g (t of seeds)– ),
thus demonstrating the importance of the steric environꢀ
ment at position 4 of the heterocycle. Some increase in
the activity occurs when methallyl groups are introduced
instead of allyl ones (compound 2q). Note that comꢀ
pound 2q has a balanced effect on the rootlets and seedꢀ
lings: the growth activity was 32.1 and 37.8% (at the dose
of 10 g (t of seeds)– ). The influence of 4ꢀmethoxy derivꢀ
ative cisꢀ2p has proved quite unexpected, which at the
dose of 1 g (t of seeds)– showed the herbicidal instead of
growth activity –19.3% (for sprouts) and –44% (for rootꢀ
1
(
–2.0%). It is interesting to compare the effect of Dichlorꢀ
1
mid and its homolog, compound 2c, which possesses
a similar growth activity, but has the opposite distribution
of activity, i.e., sprouts are stimulated less actively (21.6%)
and rootlets more actively (51.4%). The introduction of the
1
phenyl group (compound 2d) decreases the growth activity
1
(
13.8 and 24.5%) at the same dose of 10 g (t of seeds)–
,
while the methylation of the nitrogen atom (compound
i) leads to a general decrease in the growth activity on
seedlings to 17% and exhibits a herbicidal effect on roots
–11%). The introduction of a substituent with the lipoꢀ
2
1
(
philic bulky ester group (compound 2e) gave an unusual
effect, namely, the stimulating influence was almost comꢀ
pletely lost and was observed only at a minimum dose of
1
.1 g (t of seeds)–1. In the case of compound 2f (a reꢀ
lets); at the higher dose of 10 g (t of seeds) , the herbiꢀ
–1
0
duced and Оꢀmethylated analog of 2e), the growth activꢀ
ity was not only recovered, but even enhanced, which at
the dose of 10 g (t of seeds)–1 was 30.2% for sprouts and
cidal activity was slightly lower, +5.3 and ꢀ25%, respectiveꢀ
ly. The substitution of one of the allyl groups with the
methyl one (compound 2r) also leads to a decrease in the
growth activity, which was 13.8 and 2.0% (10 g (t of seeds)– ),
while a herbicidal effect was observed at lower doses.
In general, the presence of α ꢀallyl or αꢀmethallyl
groups enhances the stimulating activity of the test comꢀ
pounds.
1
8
4.4% for rootlets. The introduction of the bulky isobutyl
group (compound 2g) reduces the growth activity of
sprouts and rootlets by 15.1 and 20.0% (at the dose of
1
0 g (t of seeds)–1), respectively, indicating a general
pattern associated with bulky substituents in the series of
compounds 2c—g.
Tetrahydrоisoquinoline derivatives transꢀ and cisꢀ2s
manifested good growth activity. For transꢀisomer 2s, it
The monofluoromethyl group in compound 2h pracꢀ
tically did not change the growth activity as compared to 2c,
which was found to be 29.6 and 50% for a 10 g (t of seeds)–
dose. It should be noted a stable tendency of a greater
stimulating effect of our compounds on the root system
growth as compared to Dichlormid.
–
1
was (sprouts and rootlets) 16.7 and 33.3% (a 1 g (t of seeds)
1
–1
dose); 20.8 and 30.8% (a 10 g (t of seeds) dose), while
–
1
for cisꢀisomer 2s it was 28.3 and 57.8% (a 1 g (t of seeds)
dose); 18.9 and 84.4% (a 10 g (t of seeds)– dose). The
activity of compound cisꢀ2s was considerably higher, esꢀ
pecially with respect to the root system development. The
last compounds to be tested were derivatives of pyrroline
2t and pyrrolidine 2u. Compound 2t, which, like comꢀ
pounds 2n—s, is a hybrid of allylꢀ and homoallylamine,
has proved the most potent growth stimulant (sprouts
and rootlets): the growth activity was 35.8 and 104.4% (at
the dose of 1 g (t of seeds)– ), with an increase in the dose
of the substance leading to a decrease in the stimulating
effect, presumably, due to toxicity. Compound 2u is an
isomer of 2,2ꢀdiallylated derivative 2k with a different
arrangement of the allyl groups. The growth activity of 2u
was found to be close to the activity of compound 2k and
equal to (sprouts and rootlets) 13.2 and 46.7% (at the
dose of 10 g (t of seeds)– ).
1
Heterocyclic dichloroacetamides 2j—l also possess
a pronounced growth activity. The azetidine derivative 2j
exhibits a stimulating effect in all doses, giving a maxiꢀ
mum value of 44.4% (for sprouts) and 30% (for rootlets)
–
1
(
obtained when used at the dose of 10 g (t of seeds) ).
–
1
Pyrrolidine 2k (at the dose of 10 g (t of seeds) ) has
1
a similar effect, but it is directed more on the roots being
1
2.5% (for sprouts) and 51.4% (for rootlets). Further inꢀ
crease in the ring size does not lead to large changes; the
growth activity of piperidine derivative 2l (at the dose of
1
0 g (t of seeds)–1) is 11.1 and 44.0%. The introduction of
a hydroxymethyl group leads to the derivatives, which are
more toxic for maize. Thus, for example, the activity of
compound 2m with respect to sprouts and rootlets at the
1
–
1
dose of 1 g (t of seeds) is 28.3 and 24.4%, while at the
dose of 10 g (t of seeds)–1 it is 9.4 and –2.2%, respectively.
Heterocycles of tetrahydrоpyridine series, namely,
transꢀ2n, transꢀ2o, cisꢀ2n,p, 2q, and 2r have a dual strucꢀ
ture, since, on the one hand, they are allylic amides and,
From the examination of biological activity, it can be
concluded that dichloroacetic acid 3ꢀbutenylamides have
a high potential as plant growth stimulators. Unlike the
stimulating activity of Dichlormid, the influence of
3ꢀbutenylamides has proved to be more potent and selective

3
54
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
with respect to the root system. The most active were
aliphatic analogs of Dichlormid, especially that with
hexane and cooled, the organic layer was separated and washed
with water. Then, the organic phase was washed with 3 М HCl
(
20 mL), the aqueous layer was separated and twice extracted
2ꢀmethoxyethyl group (compound 2f). Heterocyclic
,2ꢀdiallylated derivatives 2j—l with different ring sizes also
with a mixture of hexane—Et O (1 : 1). After that, the aqueous
2
2
layer was alkalized by addition of solid NaOH (5 g) and exꢀ
exhibited pronounced growth activity. The maximum acꢀ
tivity was demonstrated by pyrrolidine derivative 2k. The
recordꢀhigh activity on the root system growth was exꢀ
hibited by 2,6ꢀdiallylꢀ1,2,3,6ꢀtetrahydrоpyridine derivaꢀ
tives transꢀ2n (100%) and cisꢀ2n (82%). A similar activity
was also observed in the case of diallylated derivatives of
tetrahydrоisoquinoline transꢀ and cisꢀ2s. Pyrroline amide
tracted with hexane (3×10 mL), the combined extracts were
dried with К СО , concentrated, and distilled in vacuo, colꢀ
2
3
lecting the fraction with b.p. 77—79 °C (0.5 Torr). Compound
1i (7.37 g, 67%) was obtained as pale yellow liquid. 1H NMR,
δ: 7.42—7.39 (m, 2 Н, Ph); 7.36—7.32 (m, 3 Н, Ph); 5.58 (ddt,
2 Н, 2 СН=, J = 7.2 Hz, J = 10.3 Hz, J = 16.5 Hz); 5.09—5.04
(
m, 4 Н, СН =); 2.57—2.52 (m, 4 Н, 2 СН ); 2.17 (s, 3 H,
2
2
1
3
NMe); 1.73 (br.s, 1 Н, NH). C NMR, δ: 144.57; 133.85
2 C); 128.00 (2 C); 126.62 (2 C); 126.28; 117.99 (2 C); 60.55;
1.49 (2 C); 28.54. Found (%): С, 83.66; H, 9.58; N, 7.01.
2
t, a unique hybrid of allylꢀ and homoallylamines, was
(
4
also exceptionally active (104%). We plan to study furꢀ
ther the effect of the structure of 3ꢀbutenylamines on the
growth regulating activity, as well as its relationship with
the potential antidotal activity of homoallylic compounds.
С14Н19N. Calculated (%): С, 83.53; Н, 9.51; N, 6.96.
Reductive allylation of 4ꢀsubstituted pyridines (general proꢀ
cedure). A 4ꢀsubstituted pyridine (0.2 mol) was added dropwise
to triallylborane (13.4 g, 16.8 mL, 0.1 mol) cooled to –30 °С
under argon atmosphere. Then, the reaction mixture was alꢀ
lowed to stand to warmꢀup to 0 °С, followed by the addition of
Experimental
i
Pr OH (24.0 g, 30.6 mL, 0.4 mol) in one portion and heating
Reactions were carried out under atmosphere of dry argon.
All the solvents used were purified according to the standard
procedures. NMR spectra were recorded on Bruker Avanceꢀ300
the mixture at 50 °С for 2 h. Then, 5 М NaOH (40 mL, 0.2 mol)
was added with stirring, the organic phase was diluted with
hexane, the organic layer was separated, dried with K CO ,
2
3
(
compound cisꢀ1p) and Bruker Avanceꢀ400 spectrometers (other
and concentrated on a rotary evaporator. The residue was disꢀ
tilled in vacuo.
compounds) in CDCl . Column chromatography was carried
3
out using silica gel 60—230 mesh (Merck). Allylated amines
transꢀ2,6ꢀDiallylꢀ4ꢀmethylꢀ1,2,3,6ꢀtetrahydrоpyridine
(transꢀ1o) was synthesized according to the general procedure
from 4ꢀpicoline (0.2 mol) and triallylborane (0.1 mol) in 32.04 g
1
2
16
15
18
17
1
a, 1b, 1c—h, 1j and 1m, 1k and 1l , transꢀ1n and
cisꢀ1n , transꢀ1o and cisꢀ1s, 1r,24,25 transꢀ1s, 1t and 1u
2
2
23
26
28,29
1
were obtained according to the described procedures.
(91%) yield. According to the H NMR spectrum, the ratio of
1
1
ꢀAllylbutꢀ3ꢀenylamine (1c). Triallylborane (7.37 g, 9.51 mL,
5.0 mmol) was added dropwise to a solution of HCN (syntheꢀ
sized in situ from TMSCN (4.96 g, 6.25 mL, 50.0 mmol) in
trans/cisꢀisomers was 13 : 1. H NMR, δ: 5.80—5.70 (m, 2 H,
5
2 CH=); 5.35 (m, 1 H, CH= of ring); 5.11—5.02 (m, 4 H,
2 СН =); 3.34 (br.s, 1 H, CHN); 2.96—2.89 (tt, 1 H, СHN,
2
a mixture of CH Cl2 (30 mL) and MeOH (1.60 g, 2.03 mL,
5
J = 4.1 Hz, J = 8.3 Hz); 2.23—2.05 (m, 4 H, 2 CH ); 1.85
2
2
0.0 mmol) with stirring at 25 °С for 20 min)3 cooled to –20 °С
0
(br.dd, 2 H, СН Н and NH, J = 4.1 Hz, J = 16.8 Hz); 1.70
А
В
under argon atmosphere. The resulting solution was gradually
heated to 140 °С, simultaneously distilling off CH Cl . The
(dd, 1 H, СН Н , J = 8.6 Hz, J = 16.8 Hz) 1.66 (s, 3 H, Ме)
(see Ref. 23).
А В
2
2
residual dense mass was heated at 140 °С for 4.5 h (until the
mixture became homogeneous and liquid). Then, a 5 M soluꢀ
tion of NaOH (33 mL, 165.0 mmol) was added slowly to the
reaction mixture cooled down to 80 °С, so that the temperature
did not exceed 110 °С. After the addition was completed, the
mixture was refluxed for 1 h, followed by the addition of
a saturated solution of KOH (50 mL) and, after cooling, by the
extraction with a mixture of nꢀC H —Et O (1 : 1) (3×20 mL).
cis/transꢀ2,6ꢀDiallylꢀ4ꢀmethoxyꢀ1,2,3,6ꢀtetrahydrоpyridine
(1p) was synthesized according to the general procedure from
4ꢀmethoxypyridine (6.0 g, 5.6 mL, 0.055 mol) and triallylborane
(3.69 g, 4.8 mL, 0.028 mol), the yield was 6.24 g (59%). Acꢀ
1
cording to the H NMR spectrum, the ratio of trans/cisꢀisoꢀ
mers was 2.2 : 1. Found (%): С, 74.39; H, 10.12; N, 7.32.
С12Н19NO. Calculated (%): С, 74.57; Н, 9.91; N, 7.25.
transꢀ2,6ꢀDimethallylꢀ4ꢀmethylꢀ1,2,3,6ꢀtetrahydrоpyridine
(1q) was synthesized according to the general procedure from
4ꢀpicoline (0.05 mol) and trimethallylborane (0.025 mol), the
yield was 4.20 g (82%), oil, b.p. 79—80 °С (0.5 Torr). Acꢀ
5
12
2
The extracts were dried with KOH, concentrated, and distilled,
collecting the fraction with b.p. 76 °С (90 Torr). The yield was
1
3
.82 g (69%). H NMR, δ: 5.83—5.73 (m, 2 Н, 2 СН=); 5.10—5.06
1
(
m, 4 Н, СН =); 2.85 (tt, 1 H, CH, J = 4.7 Hz, J = 7.6 Hz);
cording to the H NMR spectrum, the ratio of trans/cisꢀisoꢀ
2
1
2
.25—2.19 (m, 2 Н, 2 СН Н ); 2.01 (dt, 2 H, 2 СН Н , J = 7.9 Hz,
mers was 14 : 1. H NMR, δ: 5.35—5.31 (m, 1 Н, СН=); 4.81—4.78
А
B
А
B
1
3
J = 13.7 Hz); 1.60 (br.s, 2 Н, NH ) (see Ref. 16). C NMR,
(m, 2 Н, СН =); 4.76—4.75 (m, 1 Н, СН Н =); 4.67—4.66
2
2 А В
δ: 135.54 (2 C); 117.42 (2 C); 50.02; 41.89 (2 C).
(m, 1 Н, СН Н =); 3.52—3.45 (m, 1 H, СНN); 3.00 (tt, 1 H,
А В
Nꢀ(1ꢀAllylꢀ1ꢀphenylbutꢀ3ꢀenyl)ꢀNꢀmethylamine (1i). Triꢀ
allylborane (11.72 g, 15.14 mL, 87.5 mmol (a 1.6ꢀfold excess))
was added to a solution of Nꢀmethylbenzamide (7.40 g, 54.7 mmol)
in THF (20 mL). After the completion of the exothermic reacꢀ
tion, the mixture was refluxed for 1.5 h and cooled, after the
careful addition of MeOH (10 mL) the mixture was refluxed for
CHN, J = 4.5 Hz, J = 8.6 Hz); 2.12—2.07 (m, 3 H, 2CH H of
A В
methallyl and СН Н of ring); 1.92 (dd, 1 H, CH H of methꢀ
А
В
A
В
allyl, J = 0.5 Hz, J = 4.4 Hz); 1.92 (dd, 1 H, CH H of methꢀ
A
В
allyl, J = 0.5 Hz, J = 4.4 Hz); 1.81—1.77 (m, 1 H, СН НВ of
А
ring); 1.72—1.71 (m, 6 Н, 2 СН ); 1.68—1.67 (m, 3 Н, СН ).
3
3
1
3
C NMR, δ: 142.76; 142.17; 132.55; 123.05; 113.26; 113.17;
49.60; 44.34; 44.32; 43.08; 36.64; 23.32; 22.23; 22.06. Found (%):
С, 81.82; H, 11.17; N, 6.84. С Н N. Calculated (%): С, 81.89;
3
0 min followed by the addition of 5 М NaOH (70 mL, 0.35 mol)
and reflux for 1.5 h. After the complete deboration (test for
green color of flame), the reaction mixture was diluted with
1
4
23
Н, 11.29; N, 6.82.

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
355
cisꢀ2,6ꢀDiallylꢀ4ꢀmethoxyꢀ1,2,3,6ꢀtetrahydrоpyridine (cisꢀ1p).
Triallylborane (2.95 g, 3.8 mL, 22.0 mmol) was added dropwise
to a mixture of cis/transꢀisomers of compound 1p (3.93 g,
Nꢀ(1ꢀAllylꢀ1ꢀphenylbutꢀ3ꢀenyl)dichloroacetamide (2d) was
recrystallized from hot nꢀС Н . The yield was 89%. R 0.52
6
14
f
1
(nꢀС Н14—EtOAc (6 : 1)), m.p. 121—122 °С. H NMR, δ:
6
2
1
0 mmol) with stirring and the resulting mixture was heated at
30—135 °С for 6 h. Then, it was treated with МеОН (1.8 mL)
7.38—7.34 (m, 2 Н, Ph); 7.29—7.25 (m, 3 Н, Ph); 6.79 (br.s,
1 Н, NH); 5.85 (s, 1 H, CHCl ); 5.58 (dddd, 2 H, 2 CH=,
2
and 20% solution of NaOH (5.2 mL). After addition of hexane
10 mL), the organic layer was separated, dried with K CO ,
J = 6.4 Hz, J = 8.3 Hz, J = 10.2 Hz, J = 16.5 Hz); 5.20—5.16
(
(m, 4 H, 2 СH =); 2.98 (dd, 2 Н, 2 СН Н , J = 6.4 Hz,
2
3
2 А В
and concentrated on a rotary evaporator, the residue was disꢀ
tilled in vacuo, b.p. 88—90 °С (0.5 Torr). Compound cisꢀ1p
J = 14.0 Hz); 2.77 (dd, 2 Н, 2 СН Н , J = 8.3 Hz, J = 14.0 Hz).
А В
1
3
C NMR, δ: 162.73; 132.38 (2 C); 128.47 (2 C); 127.13; 125.19
(2 С); 119.98 (2 С); 67.10; 60.65; 42.58 (2 C). Found (%):
С, 60.46; H, 5.83; N, 4.64. C H Cl NO. Calculated (%):
(
3.36 g, 86%) was obtained as light yellow liquid. According to
1
the H NMR spectrum, the ratio of cis/transꢀisomers was
1
5
17
2
1
1
5
3
5.2 : 1. Н NMR, δ: 5.96—5.73 (m, 2 H, 2 СН= of allyls);
С, 60.41; Н, 5.75; N, 4.70.
tertꢀButyl 3ꢀallylꢀ3ꢀ[(dichloroacetyl)amino]ꢀ5ꢀhexenoate
(2e) was recrystallized from cold nꢀС Н . The yield was 88%.
.22—5.12 (m, 4 H, 2 СН =); 4.58 (br.s, 1 H, СН= of ring);
2
.57 (s, 3 H, ОМе); 3.53—3.47 (m, 1 H, C(2)HN); 2.95—2.86
6
14
1
(
(
m, 1 H, C(6)HN); 2.43—2.16 (m, 4 H, 2 CH of allyls); 2.06—2.03
m, 2 H, СН2 of ring); 2.00 (br.s, 1 H, NH). C NMR, δ:
R 0.75 (nꢀС Н —EtOAc (6 : 1)), m.p. 67—68 °С. H NMR,
f 6 14
2
1
3
δ: 7.49 (br.s, 1 Н, NH); 5.81 (s, 1 H, CHCl ); 5.78—5.70 (m, 2 H,
2
1
5
54.79; 135.18; 134.78; 117.67; 117.51; 96.65; 53.97; 53.10;
2.47; 41.77; 40.68; 34.63. Found (%): С, 74.48; H, 10.02;
2 CH=); 5.17—5.12 (m, 4 H, 2 СH =); 2.77 (dd, 2 Н, 2 СН Н ,
2 А В
t
J = 7.0 Hz, J = 14.0 Hz); 2.54 (s, 2 H, CH СOOBu ); 2.50 (dd,
2
t
N, 7.26. С Н NO. Calculated (%): С, 74.57; Н, 9.91; N, 7.25.
2 Н, 2 СН Н , J = 7.9 Hz, J = 14.0 Hz); 1.46 (s, 9 H, Bu ).
1
2
19
А
В
1
3
Synthesis of dichloroacetamides 2a—u (general procedure).
Some signals are split in the C NMR spectrum, δ: 170.82;
163.22; (132.31; 132.24) (2 C); (119.92; 119.90; 119.85)
(2 C); 81.79; 67.04; 57.67; 40.85; 40.31 (2 C); (28.27; 28.04;
28.01; 27.78) (3 C). Found (%): С, 53.47; H, 6.85; N, 4.16.
A solution of dichloroacetyl chloride (DCAC) (4—8 mmol) in
CH Cl (2 mL) was added through a syringe pump over 2 h to
a vigorously stirred mixture of amine 1a—u (2.0 mmol), 20%
solution of NaOH (10 mmol), and CH Cl (5 mL) at –15 °С,
2
2
C15H23Cl NO . Calculated (%): С, 53.58; Н, 6.89; N, 4.17.
2
2
2
3
so that the temperature did not exceed –10 °С. The reaction
progress was monitored by TLC. After the disappearance of the
starting amine 1a—u, the reaction mixture was stirred for 15 min
at 25 °С, the organic layer was separated, washed with 1 М HCl
Nꢀ[1ꢀAllylꢀ3ꢀbutenylꢀ1ꢀ(2ꢀmethoxyethyl)]dichloroacetamide
(2f) was subjected to chromatography on SiO2 in the system
nꢀС Н —EtOAc (20 : 1). The yield was 92%, light liquid.
6
14
1
R 0.2 (nꢀС Н —EtOAc (20 : 1)). H NMR, δ: 7.81 (br.s, 1 Н,
f
6
14
and water, dried with K CO , and concentrated on a rotary
NH); 5.77 (s, 1 H, CHCl ); 5.76—5.66 (m, 2 H, 2 CH=);
2
2
3
evaporator. The residue was subjected to chromatography or
recrystallized from an appropriate solvent.
5.10—5.06 (m, 4 H, 2 СH =); 3.56 (t, 2 Н, СН O, J = 5.4 Hz);
2 2
3.31 (s, 3 Н, MeO); 2.75 (dd, 2 Н, 2 СН Н , J = 7.0 Hz,
А
В
Nꢀ(1,1ꢀDimethylbutꢀ3ꢀenyl)dichloroacetamide (2a) was subꢀ
J = 14.0 Hz); 2.48 (dd, 2 Н, 2 СН Н , J = 8.0 Hz, J = 14.0
А В
1
3
jected to chromatography on SiO2 in the system nꢀС Н14—
Hz); 1.83 (t, 2 Н, СН CN, J = 5.4 Hz). C NMR, δ: 163.27;
6
2
EtOAc (6 : 1). The yield was 94%. R 0.56 (nꢀС Н14—EtOAc
132.88 (2 C); 118.93 (2 C); 68.76; 67.13; 58.66; 58.60; 40.13
(2 C); 34.55. Found (%): С, 51.38; H, 6.87; N, 4.92.
f
6
1
(
6 : 1)), m.p. 39—40 °С (nꢀС Н ). H NMR, δ: 6.33 (br.s, 1 Н,
6 14
NH); 5.79 (s, 1 H, CHCl ); 5.77 (ddt, 1 Н, CH=, J = 7.3 Hz,
C12H19Cl NO . Calculated (%): С, 51.44; Н, 6.83; N, 5.00.
2
2 2
J = 10.2 Hz, J = 17.2 Hz); 5.16—5.11 (m, 2 H, СH =); 2.44
Nꢀ(1ꢀAllylꢀ1ꢀisobutylbutꢀ3ꢀenyl)dichloroacetamide (2g) was
recrystallized from cold nꢀС Н . The yield was 90%. R 0.7
2
1
3
(
d, 2 Н, СН F, J = 7.6 Hz); 1.37 (s, 6 H, 2Me). C NMR,
2
6
14
f
δ: 162.97; 133.00; 119.42; 67.03; 53.98; 44.47; 26.15 (2 C).
Found (%): С, 45.70; H, 6.28; N, 6.73. C H13Cl NO. Calcuꢀ
(nꢀС Н —EtOAc (6 : 1)), m.p. 84—85 °С. The NMR spectrum
6 14
1
showed the presence of rotamers in the ratio of 8 : 1. H NMR,
δ, major rotamer: 6.25 (br.s, 1 Н, NH); 5.78 (s, 1 H, CHCl );
8
2
lated (%): С, 45.73; Н, 6.24; N, 6.67.
Nꢀ(1ꢀPhenylbutꢀ3ꢀenyl)dichloroacetamide (2b) was recrysꢀ
tallized from a mixture of Et O—nꢀС Н . The yield was 89%.
2
5.80—5.70 (m, 2 H, 2 CH=); 5.17—5.12 (m, 4 H, 2 СH =);
2
2.56 (dd, 2 Н, 2 СН Н , J = 7.3 Hz, J = 14.0 Hz); 2.48 (dd,
2
6
14
А
В
1
R 0.31 (nꢀС Н —EtOAc (6 : 1)), m.p. 91—92 °С. H NMR, δ:
2 Н, 2 СН Н , J = 7.3 Hz, J = 14.0 Hz); 1.83—1.72 (m, 1 Н,
А В
f
6
14
7
.40—7.36 (m, 2 Н, Ph); 7.33—7.28 (m, 3 Н, Ph); 6.85 (br.s, 1 Н,
СН); 1.69 (d, 2 Н, СН СН, J = 5.7 Hz); 0.96 (d, 6 Н, 2 СН ,
2 3
J = 6.7 Hz). 1 C NMR, δ: 162.63; 132.63 (2 C); 119.53 (2 C);
67.18; 59.13; 43.48; 39.99 (2 C); 24.46 (2 С); 23.79. The NMR
spectra of the minor rotamer are not reported because of the
low intensity and the overlap of the signals. Found (%): С, 56.16;
3
NH); 5.94 (s, 1 H, CHCl ); 5.78—5.67 (m, 1 H, CH=);
5
2
2
.22—5.16 (m, 2 H, СH =); 5.06 (q, 1 Н, СНN, J = 7.0 Hz);
2
1
3
.66 (dd, 2 Н, СН , J = 6.7 Hz, J = 7.0 Hz). C NMR,
2
δ: 163.32; 140.17; 132.98; 128.76 (2 C); 127.72; 126.17 (2 C);
19.13; 66.50; 53.04; 40.21. Found (%): С, 55.94; H, 5.12;
1
H, 7.59; N, 4.99. C H Cl NO. Calculated (%): С, 56.12;
13 21 2
N, 5.50. C12H13Cl NO. Calculated (%): С, 55.83; Н, 5.08;
Н, 7.61; N, 5.03.
2
N, 5.43.
Nꢀ(1ꢀAllylꢀ1ꢀfluoromethylbutꢀ3ꢀenyl)dichloroacetamide (2h)
Nꢀ(1ꢀAllylbutꢀ3ꢀenyl)dichloroacetamide (2c) was subjected
was subjected to chromatography on SiO2 in the system
to chromatography on SiO in the system nꢀС Н —EtOAc (6 : 1).
nꢀС Н —EtOAc (10 : 1). The yield was 96%, oil. R 0.23
6 14 f
(nꢀС Н —EtOAc (10 : 1)). H NMR, δ, 6.42 (br.s, 1 Н, NH);
6 14
5.82 (s, 1 H, CHCl ); 5.77 (ddt, 2 H, 2 CH=, J= 7.3 Hz, J = 10.2 Hz,
2
2
6
14
1
The yield was 94%. R 0.41 (nꢀС Н14—EtOAc (6 : 1)), m.p.
f
6
1
4
5
4
3 °С. H NMR, δ: 6.38 (br.s, 1 Н, NH); 5.88 (s, 1 H, CHCl );
2
.81—5.71 (m, 2 H, 2 CH=); 5.14—5.10 (m, 4 H, 2 СH =);
J = 17.2 Hz); 5.22—5.17 (m, 4 H, 2 СH =); 4.58 (d, 2 Н,
2
2
.06—3.98 (m, 1 Н, СНN); 2.37—2.24 (m, 4 Н, 2 СН2). 13C NMR,
СН F, J
= 47.0 Hz); 2.59 (dd, 2 Н, 2 СН Н , J = 7.3 Hz,
Н—F А В
2
δ: 163.55; 133.24 (2 C); 118.72 (2 C); 66.58; 48.92; 37.89 (2 C).
Found (%): С, 48.58; H, 5.87; N, 6.40. C H13Cl NO. Calcuꢀ
lated (%): С, 48.67; Н, 5.90; N, 6.31.
J = 14.0 Hz); 2.49 (dd, 2 Н, 2 СН Н , J = 7.6 Hz, J =
А В
1
3
= 14.0 Hz). C NMR, δ: 163.43; 131.29 (2 C); 120.50 (2 C);
9
2
(84.44, 82.69, 1 JCF = 175 Hz); 66.73 (58.49, 58.32, JCF
=
,2
1,3

3
56
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
=
16.8 Hz); (37.05, 37.02, 1,4JCF = 3.6 Hz) (2 С). Found (%):
J = 13.4 Hz); 2.09—1.91 (m, 2 Н, CHСН ); 1.82 (ddd, 1 Н,
2
С, 47.24; H, 5.47; N, 5.57. C10H14Cl FNO. Calculated (%):
СН Н CAll , J = 1.6 Hz, J = 6.4 Hz, J = 11.4 Hz); 1.53
А В 2
2
С, 47.26; Н, 5.55; N, 5.51.
(ddd, 1 Н, СН Н CAll , J = 2.2 Hz, J = 6.4 Hz, J = 12.1 Hz).
А В 2
1
3
Nꢀ(1ꢀAllylꢀ1ꢀphenylbutꢀ3ꢀenyl)dichloroꢀNꢀmethylacetamide
C NMR, δ: 163.39; 134.08; 133.60; 119.14; 118.70; 69.65;
67.03; 64.26; 60.34; 41.81; 40.41; 31.85; 25.31. Found (%):
С, 53.36; H, 6.48; N, 4.81. C13H19Cl NO . Calculated (%):
(
2i) was subjected to chromatography on SiO2 in the system
nꢀС Н —EtOAc (15 : 1). The yield was 82%, oil. R 0.31
6
14
f
2
2
1
(
nꢀС Н —EtOAc (12 : 1)). H NMR, δ: 7.33—7.30 (m, 2 Н, Ph);
С, 53.44; Н, 6.55; N, 4.79.
6
14
7
2
3
2
1
.23—7.21 (m, 3 Н, Ph); 6.13 (s, 1 H, CHCl ); 5.55—5.45 (m, 2 H,
1ꢀ[transꢀ2,6ꢀDiallylꢀ3,6ꢀdihydrоꢀ(2H)ꢀpyridino]ꢀ2,2ꢀdiꢀ
chloroethanꢀ1ꢀone (transꢀ2n) was subjected to chromatography
2
CH=); 5.13—5.08 (m, 4 H, 2 СH =); 3.26 (s, 3 Н, NMe);
2
.20 (dd, 2 Н, 2 СН Н , J = 8.4 Hz, J = 12.6 Hz); 2.80 (dd,
on SiO in the system nꢀС Н14—EtOAc (15 : 1). The yield was
А
В
2 6
1
3
Н, 2 СН Н , J = 6.2 Hz, J = 13.1 Hz). C NMR, δ: 163.00;
90%, oil. R 0.43 (nꢀС Н14—EtOAc (12 : 1)). The signals in
f 6
А
В
44.67; 132.84 (2 C); 128.15 (2 C); 126.67; 125.11 (2 C); 119.41
2 C); 67.45; 39.75 (2 С); 34.60. Found (%): С, 61.48; H, 6.01;
N, 4.54. C H Cl NO. Calculated (%): С, 61.55; Н, 6.13; N, 4.49.
the NMR spectra were broadened because of the hindered roꢀ
1
(
tation around the amide bond. H NMR, δ: 6.34 (br.s, 1 H,
CHCl ); 5.86 (br.s, 2 Н, 2 СН= of ring); 5.74—5.63 (m, 2 H,
16
19
2
2
1
ꢀ(2,2ꢀDiallylꢀ1ꢀazetidinyl)ꢀ2,2ꢀdichloroethanꢀ1ꢀone (2j)
was subjected to chromatography on SiO2 in the system
nꢀС Н —EtOAc (10 : 1). The yield was 96%, oil. R 0.36
2 CH=); 5.08—5.04 (m, 4 H, 2 СH =); 4.31 (br.s, 1 Н, СНN);
2
4.04 (br.s, 1 Н, СНN); 2.74 (br.s, 1 Н, СН Н ); 2.41—2.35
А
В
13
(br.m, 3 Н, СН Н , СН ); 2.25—2.19 (br.m, 2 Н, СН ). C NMR,
6
14
f
А
В
2
2
1
(
nꢀС Н —EtOAc (10 : 1)). H NMR, δ: 5.86 (dddd, 2 H,
δ: 164.09; 133.63 (br.); 133.04; 128.87 (br.); 122.62 (br.); 119.15
(br.); 118.29 (br.); 65.44 (br.); 52.72 (br.); 52.16 (br.); 39.34
(br.); 36.49 (br.); 27.06. Found (%): С, 56.83; H, 6.34; N, 5.07.
6
14
2
CH=, J = 7.0 Hz, J = 8.3 Hz, J = 10.5 Hz, J = 17.2 Hz); 5.78
s, 1 H, CHCl ); 5.20—5.15 (m, 4 H, 2 СH =); 4.11—4.07
2 2
m, 2 Н, СН N); 2.85 (dd, 2 Н, 2 СН Н , J = 6.7 Hz,
(
(
C13H17Cl NO. Calculated (%): С, 56.95; Н, 6.25; N, 5.11.
2
А
В
2
J = 14.0 Hz); 2.33 (dd, 2 Н, 2 СН Н , J = 8.0 Hz, J = 14.0 Hz);
1ꢀ[transꢀ2,6ꢀDiallylꢀ4ꢀmethylꢀ3,6ꢀdihydrоꢀ(2H)ꢀpyridino]ꢀ
2,2ꢀdichloroethanꢀ1ꢀone (transꢀ2o) was subjected to chromatoꢀ
А
В
1
3
2
.18—2.14 (m, 2 Н, СН СN). C NMR, δ: 161.79; 132.24
2
(
2 C); 119.65 (2 C); 72.37; 65.22; 47.04; 41.11 (2 С); 23.48.
graphy on SiO in the system nꢀС Н14—EtOAc (10 : 1). The
2
6
Found (%): С, 53.28; H, 5.96; N, 5.57. C H Cl NO. Calcuꢀ
yield was 88%, oil. R 0.55 (nꢀС Н14—EtOAc (4 : 1)). The
1
1
15
2
f
6
lated (%): С, 53.24; Н, 6.09; N, 5.64.
ꢀ(2,2ꢀDiallylꢀ1ꢀpyrrolidino)ꢀ2,2ꢀdichloroethanꢀ1ꢀone (2k)
was subjected to chromatography on SiO2 in the system
nꢀС Н —EtOAc (10 : 1). The yield was 92%, oil. R 0.42
signals in the NMR spectra were broadened because of the
hindered rotation around the amide bond. H NMR, δ: 6.34
1
1
(br.s, 1 H, CHCl ); 5.74—5.63 (m, 2 H, 2 CH=); 5.54—5.53
2
(br.s, 2 Н, 2 СН= of ring); 5.17—4.98 (br.m, 4 H, 2 СH =);
6
14
f
2
1
(
nꢀС Н —EtOAc (8 : 1)). H NMR, δ: 6.08 (s, 1 H, CHCl );
4.28 (br.s, 1 Н, СНN); 4.01 (br.s, 1 Н, СНN); 2.66 (br.s, 1 Н,
6
14
2
5
3
.72—5.62 (m, 2 H, 2 CH=); 5.10—5.06 (m, 4 H, 2 СH =);
СН Н ); 2.44—2.15 (br.m, 4 Н, СН Н , СН , СН Н of
2
А В А В 2 А В
.61 (t, 2 Н, СН N, J = 6.6 Hz); 2.97 (dd, 2 Н, 2 СН Н ,
ring); 2.01—1.92 (br.m, 1 Н, СН Н of ring); 1.76 (s, 3 Н,
А В
2
А
В
Me). 1 C NMR, δ: 163.83; 133.82 (br.); 133.44 (br.); 131.19
(br.); 121.91 (br.); 119.13 (br.); 118.08 (br.); 65.42 (br.); 52.85;
52.29 (br.); 39.56 (br.); 36.98 (br.); 31.79; 23.39. Found (%):
3
J = 6.7 Hz, J = 13.4 Hz); 2.37 (dd, 2 Н, 2 СН Н , J = 8.0 Hz,
J = 13.7 Hz); 1.93—1.81 (m, 4 Н, 2 СН ). C NMR, δ: 161.11;
1
3
А
В
1
3
2
33.39 (2 C); 118.88 (2 C); 68.94; 66.86; 49.37; 40.83 (2 С);
3.55; 23.13. Found (%): С, 55.02; H, 6.60; N, 5.31.
С, 58.37; H, 6.71; N, 4.76. C14H19Cl NO. Calculated (%):
2
C12H17Cl NO. Calculated (%): С, 54.97; Н, 6.54; N, 5.34.
С, 58.34; Н, 6.64; N, 4.86.
2
1
ꢀ(2,2ꢀDiallylpiperidino)ꢀ2,2ꢀdichloroethanꢀ1ꢀone (2l) was
1ꢀ[4ꢀMethylꢀtransꢀ2,6ꢀbis(2ꢀmethylꢀ2ꢀpropenyl)ꢀ3,6ꢀdiꢀ
hydrоꢀ(2H)ꢀpyridino]ꢀ2,2ꢀdichloroethanꢀ1ꢀone (2q) was recrysꢀ
subjected to chromatography on SiO in the system nꢀС Н14—
2
6
EtOAc (15 : 1). The yield was 90%, oil. R 0.49 (nꢀС Н14—
tallized from cold nꢀС Н14. The yield was 70%. Rf 0.46
f
6
6
1
EtOAc (10 : 1)). H NMR, δ: 6.12 (s, 1 H, CHCl ); 5.72 (ddt,
(nꢀС Н14—EtOAc (15 : 1)), m.p. 97—98 °С. The signals in the
2
6
2
H, 2 CH=, J = 7.3 Hz, J = 10.2 Hz, J = 16.8 Hz); 5.11—5.06
NMR spectra were broadened because of the hindered rotation
1
(
m, 4 H, 2 СH =); 3.54—3.51 (m, 2 Н, СН N); 2.96 (dd, 2 Н,
around the amide bond. H NMR, δ: 6.33 (br.s, 1 H, CHCl );
2
2
2
2
СН Н , J = 7.3 Hz, J = 13.6 Hz); 2.52 (dd, 2 Н, 2 СН Н ,
5.63 (br.s, 1 Н, СН= of ring); 4.85—4.68 (br.m, 4 H, 2 СH =);
4.41 (br.s, 1 Н, СНN); 4.16—4.12 (br.s, 1 Н, СНN); 2.66—
А
В
А
В
2
1
3
J = 7.6 Hz, J = 13.6 Hz); 1.77—1.63 (m, 6 Н, 3 СН2). C NMR,
δ: 163.06; 133.54 (2 C); 118.61 (2 C); 67.63; 62.30; 43.33; 40.09
2.07 (br.m, 6 Н, 3 СН ); 1.78 (s, 3 Н, Me); 1.76 (s, 6 Н, 2 Me).
2
1
3
(
2 С); 28.79; 21.69; 15.65. Found (%): С, 56.58; H, 6.89; N, 5.13.
C NMR, δ: 163.66; 142.22 (br.); 141.19 (br.); 131.07 (br.);
C13H19Cl NO. Calculated (%): С, 56.53; Н, 6.93; N, 5.07.
122.55 (br.); 114.81 (br.); 113.29 (br.); 64.88; 53.01 (br.); 51.48;
43.46 (br.); 42.16 (br.); 30.94 (br.); 23.54; 22.71 (br.); 22.07
2
1
ꢀ[2,2ꢀDiallylꢀ5ꢀ(hydroxymethyl)ꢀ1ꢀpyrrolidino]ꢀ2,2ꢀdiꢀ
chloroethanꢀ1ꢀone (2m), DCAC was used in an equivalent
(br.). Found (%): С, 60.81; H, 7.28; N, 4.35. C H Cl NO.
16 23 2
amount with respect to the aminoalcohol. The product was
Calculated (%): С, 60.76; Н, 7.33; N, 4.43.
subjected to chromatography on SiO in the system nꢀС Н14—
EtOAc (4 : 1). The yield was 47%, oil crystallizing on standꢀ
1ꢀ[cisꢀ2,6ꢀDiallylꢀ3,6ꢀdihydrоꢀ(2H)ꢀpyridino]ꢀ2,2ꢀdichloroꢀ
ethanꢀ1ꢀone (cisꢀ2n) was subjected to chromatography on SiO2
2
6
ing, m.p. 43—44 °С. Rf 0.28 (nꢀС Н14—EtOAc (4 : 1)).
in the system nꢀС Н14—EtOAc (10 : 1). The yield was 92%,
6
6
1
H NMR, δ: 6.75 (s, 1 H, CHCl ); 5.77—5.67 (m, 2 H, 2 CH=);
oil. R 0.47 (nꢀС Н —EtOAc (6 : 1)). The NMR spectrum
f 6 14
2
1
5
.13—5.05 (m, 4 H, 2 СH =); 4.12—4.07 (m, 1 Н, СНN); 3.58
showed the presence of rotamers in the ratio of 4 : 1. H NMR,
δ, major rotamer: 6.25 (s, 1 H, CHCl ); 5.91—5.69 (m, 4 H,
2
(
dd, 1 Н, СН Н ОН, J = 5.4 Hz, J = 10.8 Hz); 3.48 (dd, 1 Н,
А В
2
СН Н ОН, J = 9.9 Hz, J = 10.8 Hz); 3.04 (dd, 1 Н, СН Н ,
4 CH=); 5.14—5.08 (m, 4 H, 2 СH =); 4.61—4.56 (s, 1 Н, СНN);
А
В
А
В
2
J = 6.7 Hz, J = 13.7 Hz); 2.93 (dd, 1 Н, СН Н , J = 7.0 Hz,
4.31 (dd, 1 Н, СНN, J = 6.7 Hz, J = 13.6 Hz); 2.58—2.51
А
В
J = 13.7 Hz); 2.58 (br.s, 1 Н, ОН); 2.41 (dd, 1 Н, СНА´НВ´
J = 7.9 Hz, J = 13.6 Hz); 2.33 (dd, 1 Н, СНА´НВ´, J = 8.3 Hz,
,
(m, 1 Н, СН Н ); 2.46—2.33 (m, 3 Н, СН Н , СН );
А
В
А
В
2
1
3
2.25—2.14 (m, 2 Н, СН ). C NMR, δ, major rotamer: 162.27;
2

New dichloroacetamide growth regulators
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
357
1
5
34.44 (2 С); 125.92; 121.06; 118.59; 117.79; 66.29; 51.54;
1.31; 39.50; 38.07; 26.81. The NMR spectra of the minor
Found (%): С, 63.06; H, 5.88; N, 4.25. C17H19Cl NO. Calcuꢀ
lated (%): С, 62.97; Н, 5.91; N, 4.32.
2
rotamer are not reported because of the low intensity and the
overlap of the signals. Found (%): С, 56.92; H, 6.17; N, 5.13.
1ꢀ[cisꢀ1,3ꢀDiallylꢀ3,4ꢀdihydrоꢀ(1H)ꢀisoquinolino]ꢀ2,2ꢀdiꢀ
chloroethanꢀ1ꢀone (cisꢀ2s) was subjected to chromatography
C13H17Cl NO. Calculated (%): С, 56.95; Н, 6.25; N, 5.11.
on SiO in the system nꢀС Н14—EtOAc (10 : 1). The yield was
2 6
2
1
ꢀ[cisꢀ2,6ꢀDiallylꢀ4ꢀmethoxyꢀ3,6ꢀdihydrоꢀ(2H)ꢀpyridino]ꢀ
,2ꢀdichloroethanꢀ1ꢀone (cisꢀ2p) was subjected to chromatoꢀ
graphy on SiO in the system nꢀС Н14—EtOAc (12 : 1). The
98%, oil. Rf 0.75 (nꢀС Н14—EtOAc (6 : 1)). The NMR
6
2
spectrum showed the presence of rotamers in the ratio of 1 : 1.
1
H NMR, δ, a mixture of rotamers: 7.33—7.31 (m, 0.5 Н, Ar);
2
6
yield was 88%, oil. R 0.26 (nꢀС Н14—EtOAc (12 : 1)). The
7.27—7.16 (m, 2.5 Н, Ar); 7.12—7.10 (m, 1 Н, Ar); 6.34 (s, 0.5 H,
f
6
NMR spectrum showed the presence of rotamers in the ratio of
CHCl ); 6.30 (s, 0.5 H, CHCl ); 6.11—6.00 (m, 0.5 H, СН=);
5.92—5.69 (m, 1.5 H, СН=); 5.60—5.57 (m, 0.5 H, СHN);
2
2
1
7
.4 : 1. H NMR, δ, major rotamer: 6.03 (s, 1 H, CHCl ); 5.84
2
(
=
dddd, 1 H, CH=, J = 6.2 Hz, J = 8.1 Hz, J = 10.2 Hz, J =
17.0 Hz); 5.48 (dddd, 1 H, CH=, J = 6.0 Hz, J = 8.0 Hz,
J = 10.4 Hz, J = 16.8 Hz); 5.08—5.01 (m, 2 H, CH =);
5.20—5.05 (m, 4 H, 2 СH =); 5.03 (dd, 0.5 Н, СНN, J = 7.3 Hz,
J = 8.2 Hz); 4.58—4.53 (m, 0.5 Н, СНN); 4.41—4.34 (m, 0.5 Н,
2
СНN); 3.11 (t, 0.5 Н, СН Н of ring, J = 5.7 Hz); 3.07
2
А
В
4
.92—4.87 (m, 3 H, CH= of ring and СH =); 4.43 (t, 1 Н,
(t, 0.5 Н, СН Н of ring, J = 7.3 Hz); 2.95—2.88 (m, 1 Н,
А В
2
СНN, J = 2.6 Hz); 4.08—4.03 (m, 1 Н, СНN); 3.11 (s, 3 Н,
ОМе); 2.68—2.62 (m, 1 Н, СН Н ); 2.32—2.18 (m, 3 Н,
2 СН Н of ring); 2.85—2.78 (m, 1 H, СН Н ); 2.77—2.50
А В А В
(m, 0.5 H, СН Н ); 2.64—2.53 (m, 1.5 Н, СН Н and
А
В
А
В
А
В
1
3
13
СН Н , СН ); 2.08—2.00 (m, 2 Н, СН ). C NMR, δ, major
СН Н ); 2.40—2.30 (m, 1 H, СН Н ). C NMR, δ, a mixꢀ
А
В
2
2
А В А В
rotamer: 161.94; 151.07; 135.45; 134.78; 118.53; 117.56; 91.92;
7.04; 53.92; 51.90; 51.39; 41.33; 38.76; 30.34. The NMR specꢀ
tra of the minor rotamer are not reported because of the low
intensity and the overlap of the signals. Found (%): С, 55.22;
ture of rotamers: 162.78; 162.77; 136.07; 135.66; 135.43;
134.05 (2 С); 133.47; 133.14; 130.32; 129.22; 128.26; 127.99;
126.92; 126.63; 126.56; 126.48; 126.41; 119.16; 118.69; 118.09;
117.31; 66.43; 66.20; 58.75; 52.55; 52.13; 51.72; 43.34; 40.05;
40.01; 38.21; 32.04; 31.58. Found (%): С, 62.90; H, 5.98;
6
H, 6.19; N, 4.57. C14H19Cl NO . Calculated (%): С, 55.27;
2
2
Н, 6.30; N, 4.60.
ꢀ[transꢀ2ꢀAllylꢀ6ꢀmethylꢀ3,6ꢀdihydrоꢀ(2H)ꢀpyridino]ꢀ2,2ꢀ
dichloroethanꢀ1ꢀone (2r) was subjected to chromatography on
SiO2 in the system nꢀС Н14—EtOAc (10 : 1). The yield was
N, 4.18. C17H19Cl NO. Calculated (%): С, 62.97; Н, 5.91;
N, 4.32.
1ꢀ(2ꢀAllylꢀ2,5ꢀdihydrоꢀ1Hꢀpyrrolꢀ1ꢀyl)ꢀ2,2ꢀdichloroethanꢀ
1ꢀone (2t) was subjected to chromatography on SiO2 in the
2
1
6
9
4%, oil. R 0.56 (nꢀС Н14—EtOAc (6 : 1)). The signals in
system nꢀС Н —EtOAc (6 : 1). The yield was 93%, oil. R 0.3
f
6
6
1
4
f
the NMR spectra were broadened because of the hindered roꢀ
tation around the amide bond. H NMR, δ: 6.33 (br.s, 1 H,
(nꢀС Н — EtOAc (4 : 1)). The NMR spectrum showed
6 14
1
1
the presence of rotamers in the ratio of 7.3 : 1. H NMR, δ,
a mixture of rotamers: 6.24 (s, 0.12 H, CHCl ); 6.10 (s, 0.88 H,
CHCl ); 5.84—5.81 (br.m, 2 H, 2 СH= of ring); 5.75—5.65
2
2
(
m, 1 Н, СН=); 5.08—5.04 (m, 2 H, СH =); 4.33 (br.s, 1 Н, СНN);
CHCl ); 5.93—5.90 (m, 0.12 H, СH= of ring); 5.83—5.77
2
2
4
.05 (br.s, 1 Н, СНN); 2.39—2.23 (br.m, 4 Н, 2 СН ); 1.33
(m, 1.88 H, 2 СH= of ring); 5.71—5.61 (m, 1 H, СH= of allyl);
2
1
3
(
(
br.d, 3 Н, Me, J = 5.1 Hz). C NMR, δ: 164.04 (br.); 133.81
br.); 131.25 (br.); 121.19 (br.); 119.10 (br.); 52.73; 48.51 (br.);
5.16—5.11 (m, 0.24 H, СH = of allyl); 5.08—5.03 (m, 1.76 H,
2
СH = of allyl); 4.89—4.85 (m, 0.88 Н, СНN); 4.74—4.71
2
3
9.02 (br.); 26.58; 19.46 (br.). Found (%): С, 53.30; H, 6.15;
(m, 0.12 Н, СНN); 4.49—4.41 (m, 1 Н, СН Н N); 4.35—4.30
А В
N, 5.61. C H Cl NO . Calculated (%): С, 53.24; Н, 6.09;
(m, 0.88 Н, СН Н N); 4.11—4.05 (m, 0.12 Н, СН Н N);
1
1
15
2
2
А
В
А
В
N, 5.64.
ꢀ[transꢀ1,3ꢀDiallylꢀ3,4ꢀdihydrоꢀ(1H)ꢀisoquinolino]ꢀ2,2ꢀ
dichloroethanꢀ1ꢀone (transꢀ2s) was subjected to chromatography
on SiO in the system nꢀС Н14—EtOAc (10 : 1). The yield was
2.63—2.49 (m, 1.76 H, СН of allyl); 2.45—2.38 (m, 0.24 H,
2
СН2 of allyl). 1 C NMR, δ, major rotamer: 161.40; 132.40;
3
1
129.65; 124.05; 118.66; 65.79; 65.45; 53.64; 35.73. Found (%):
С, 49.26; H, 4.98; N, 6.32. C H Cl NO. Calculated (%):
2
6
9
11
2
9
7%, a crystallizing oil, m.p. 69—70 °С. R 0.5 (nꢀС Н14—
С, 49.11; Н, 5.04; N, 6.36.
f
6
EtOAc (6 : 1)). The NMR spectrum showed the presence of
rotamers in the ratio of 2.5 : 1. H NMR, δ, a mixture of rotaꢀ
1ꢀ(2,5ꢀDiallylꢀ1ꢀpyrrolidino)ꢀ2,2ꢀdichloroethanꢀ1ꢀone (2u)
was subjected to chromatography on SiO2 in the system
1
mers: 7.30—7.08 (m, 4 Н, Ar); 6.47 (s, 0.28 H, CHCl ); 6.43
nꢀС Н14—EtOAc (4 : 1). The yield was 99%, a slowly crystalꢀ
6
2
(
(
s, 0.72 H, CHCl ); 5.69—5.53 (m, 2 H, 2 СH=); 5.16—5.03
lizing oil, m.p. 59—60 °С. R 0.37 (nꢀС Н14—EtOAc (4 : 1)).
f 6
H NMR, δ: 6.17 (s, 1 H, CHCl ); 5.75—5.64 (m, 2 H, 2 СH=);
2
2
1
m, 2 H, СH =); 5.01—4.85 (m, 2.72 Н, СН = and 0.72,
2
2
СНN); 4.70—4.66 (m, 0.28 Н, СНN); 4.56—4.54 (m, 0.28 Н,
СНN); 4.23—4.18 (m, 0.72 Н, СНN); 3.20 (dd, 0.72 Н, СН Н
5.16—5.02 (m, 4 H, 2 СH =); 4.15 (td, 1 Н, СНN, J = 2.9 Hz,
J = 8.5 Hz); 3.93 (q, 1 Н, СНN, J = 6.8 Hz); 2.61—2.55
2
А
В
of ring, J = 4.5 Hz, J = 15.3 Hz); 3.07 (dd, 0.28 Н, СН НВ of
(m, 1 Н, СН Н of allyl); 2.25—2.22 (m, 2 Н, СН of ring);
А
А
В
2
ring, J = 4.8 Hz, J = 15.6 Hz); 2.93 (d, 0.28 Н, СН Н of ring,
2.18—1.93 (m, 3 Н, СН Н of allyl, СН of allyl); 1.83—1.75
А В 2
А
В
1
3
J = 15.6 Hz); 2.84 (dd, 0.72 Н, СН Н of ring, J = 1.9 Hz,
(m, 2 Н, СН of ring). C NMR, δ: 162.34; 134.26; 133.05;
А
В
2
J = 15.2 Hz); 2.66—2.61 (m, 0.72 H, СН Н ); 2.53—2.50 (two m,
119.04; 117.80; 65.07; 58.23; 58.11; 40.36; 35.41; 28.11; 25.42.
А
В
0
2
.28 H, СH ); 2.41 (dt, 0.72 Н, СН Н , J = 8.3 Hz, J = 13.0 Hz);
Found (%): С, 54.87; H, 6.60; N, 5.28. C H Cl NO. Calcuꢀ
lated (%): С, 54.97; Н, 6.54; N, 5.34.
2
А
В
12 17 2
.36—2.33 (br.s, 0.28 H, СН Н ); 2.02—1.89 (two m, 0.72 H,
А
В
СH ); 1.57 (dt, 0.28 Н, СН Н , J = 9.8 Hz, J = 13.0 Hz).
Study of biological activity of amides 2a—u was carried out
using germinating maize seeds (a simple midseasonꢀripening
hybrid of maize Krasnodarsky 370 MV). Before the experiꢀ
ment, a portion of test seeds (15 pieces) was treated with
a solution of Dichlormid or amides 2a—u (in doses 0.1, 1, and
10 g (t of seeds)–1). For statistical reliability, each experiment
2
А
В
1
3
C NMR, δ, major rotamer: 163.47; 135.60; 133.46; 132.80;
31.97; 128.66; 127.57; 127.48; 126.74; 119.42; 118.50; 65.06;
6.68; 53.02; 40.04; 39.74; 31.81. 1 C NMR, minor rotamer:
63.35; 134.93; 134.34; 133.10; 132.68; 129.23; 128.17; 127.11;
26.66; 119.65; 117.88; 64.70; 58.22; 52.51; 44.06; 35.78; 30.07.
1
5
1
1
3

3
58
Russ.Chem.Bull., Int.Ed., Vol. 67, No. 2, February, 2018
Bubnov et al.
was carried out in three Petri dishes (in triplicate). Distilled
water (4 mL) was added to the Petri dishes with test samples
treated with dichloroacetamides and with an aqueous control
sample. The Petri dishes with the treated seeds were incubated
for 7 days at 25 °С. The seeds were ventilated every day
by opening the dishes for 25—30 min, and distilled water
9. J. D. Sivey, H.ꢀJ. Lehmler, C. J. Salice, A. N. Ricko, D. M.
Cwiertny, Environ. Sci. Technol. Lett., 2015, 2, 260.
10. K. K. Hatzios, Z. Naturforsch., C: J. Biosci., 991, 46, 819.
11. Crop Safeners for Herbicides: Development, Uses, and Mechaꢀ
nisms of Action, Eds K. K. Hatzios, R. E. Hoagland, Acad.
Press, San Diego, 1989.
(
1—2 mL) was added if necessary to prevent the seeds from
12. N. Yu. Kuznetsov, R. M. Tikhov, I. A. Godovikov, V. N.
Khrustalev, Yu. N. Bubnov, Org. Biomol. Chem., 2016, 14,
4283 (supporting material).
13. Yu. N. Bubnov, B. M. Mikhailov, Bull. Acad. Sci. USSR,
Div. Chem. Sci., 1967, 16, 467.
drying out. After 7 days, the lengths of sprouts and rootlets of
germinating seeds were measured and their average values were
found. The measurement data were mathematically processed
using the following equation:
1
1
4. Yu. N. Bubnov, V. S. Bogdanov, B. M. Mikhailov,
Zh. Obshch. Khim. [Russ. J. Gen. Chem.], 1968, 38, 260
С = (L/D•100) – 100%,
(
in Russian).
where C is the change in the length of a sprout or a rootlet
relative to the water control; L is the average length of a sprout
or a rootlet) in the experimental, reference variants or in herꢀ
bicide control, cm; D is the average length of a sprout (or
a rootlet) in the control variant, cm.
5. N. Yu. Kuznetsov, V. I. Maleev, V. N. Khrustalev, A. F.
Mkrtchyan, I. A. Godovikov, T. V. Strelkova, Yu. N. Bubꢀ
nov, Eur. J. Org. Chem., 2012, 334.
6. S. Ma, B. Ni, Chem. Eur. J., 2004, 10, 3286.
7. N. Yu. Kuznetsov, G. D. Kolomnikova, V. N. Khrustalev,
D. G. Golovanov, Yu. N. Bubnov, Eur. J. Org. Chem.,
(
1
1
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 15ꢀ29ꢀ05870
ofiꢀm).
2
008, 5647.
1
1
8. Yu. N. Bubnov, F. V. Pastukhov, I. V. Yampolsky, A. V.
Ignatenko, Eur. J. Org. Chem., 2000, 1503.
9. Yu. N. Bubnov, Pure Appl. Chem., 1994, 66, 235.
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Received May 25, 2017;
in revised form June 9, 2017;
accepted November 12, 2017
4
6, 2187.