1-Acyl- and 1,2-dihydro-1H(acyl)deoxyvasicinones. Synthesis and chemical transformations

Article abstract of DOI:10.1007/s10600-007-0155-5

1-Acyl-and 1,2-dihydro-1H(methyl, acyl)deoxyvasicinones were synthesized. Their PMR and ¹³C NMR spectra were investigated. The chemical shifts and SSCC were determined. 1-Acyl derivatives were produced by acylation of 1,2-dihydrodeoxyvascinone

Full text of DOI:10.1007/s10600-007-0155-5

Chemistry of Natural Compounds, Vol. 43, No. 4, 2007
1-ACYL- AND 1,2-DIHYDRO-1 (ACYL)DEOXYVASICINONES.
H
SYNTHESIS AND CHEMICAL TRANSFORMATIONS
Kh. M. Shakhidoyatov, Yasser Barakat,
M. G. Levkovich, and N. D. Abdullaev
UDC 547.944/945:547.856.1
13
H
1-Acyl- and 1,2-dihydro-1 (methyl, acyl)deoxyvasicinones were synthesized. Their PMR and C NMR
spectra were investigated. The chemical shiftsandSSCCwere determined. 1-Acylderivatives were produced
by acylation of 1,2-dihydrodeoxyvascinone with caprylyl- and chloroacetylchlorides. It was shown that the
Cl atom of 1-chloroacetyldeoxyvasicinone was labile and underwent nucleophilic substitution by amines.
In contrast with this, it reacted with cyanide, hydroselenide, methoxide, phenoxide, and anions of compounds
with an activated methylene group in a completely different direction to cleave the chloroacetyl group and
form 1,2-dihydrodeoxyvasicinone. It was found that addition of 1,2-dihydrodeoxyvasicinone to
phenylacetylene occurred regio- and stereoselectively to form the cis-isomer of 1-(2-phenylvinyl)-1,2-
dihydrodeoxyvasicinone.
13C NMR, regioselectivity,
Key words: deoxyvasicinone, 1 (acyl)-1,2-dihydrodeoxyvasicinone salts, PMR,
H
phenylacetylene, nucleophilic substitution, addition.
We recently found that deoxyvasicinone reacted with acetylbromide and benzoyl- and -nitrobenzoylchlorides to form
p
salts of -acyldeoxyvasicinone [1-3], which turned out to be effective acylating agents for aliphatic and aromatic primary and
N
secondary amines [2] and for the natural compounds cytisine and α- and β-amino acids [3]. On the other hand, we discovered
thatthe N=C bond ofdeoxyvasicinone, its seven-membered homolog 2,3-pentamethylene-3,4-dihydroquinazol-4-one, andtheir
analogs is reduced selectively by NaBH [5-7], in contrast with reduction by zinc in HCl or HOAc and also by LiAlH [4].
4
4
However, the structural features of the products from reduction of the N=C bond were insufficiently elucidated in these studies,
in particular, of 1,2-dihydrodeoxyvasicinone and its transformation products [5].
In continuation of our research on chemical transformations of tricyclic quinazoline alkaloids, we reduced
deoxyvasicinone (1) with NaBH in alcohol [5] to produce 1,2-dihydrodeoxyvasicinone (2) in good yield (82%).
4
O
O
5
4
3
6
N
11
10
N
+ NaBH
4
7
N
H
N
1
9
8
1
2
The products of chemical transformations of 1 in this study were monitored by NMR spectroscopy. The general
13
characteristics of the PMR spectrum of deoxyvasicinone have been published [8]. Herein both the PMR and the C NMR
spectra of certain derivatives of 1 are investigated in detail.
Table 1 gives the NMR spectra of 2.
The three-dimensional structure of 1 is practicallyplanar. OnlyC-10 deviates from the common plane of the molecule
(the five-membered ring has the C-10 envelope conformation). Reduction of the N1=C2 double bond changes the conformation
of the saturated six-membered ring to a C2 chair; of the five-membered ring, a C9 envelope. The orientation of the two H11
protons is almost the same relative to the average plane of the molecule.
S. Yu. Yunusov Institute ofthe Chemistryof Plant Substances, Academyof Sciences, Republic of Uzbekistan, 700170,
Tashkent, fax (99871) 120 64 75. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 353-359, July-August, 2007.
Original article submitted November 20, 2006.
0009-3130/07/4304-0429 ©2007 Springer Science+Business Media, Inc.
429

TABLE 1. NMR Spectra of 2, CD3OD, H0 = 400 MHz, 0 = TMS
Atom
1H chemical shifts, ppm
4.05
Spin-spin coupling constants, Hz
5.73 (H-9), 7.26 (H-9 )
13C chemical shifts, ppm
2
4
4a
5
6
7
8
8a
9
9′
10
10′
11
11′
71.34
164.70
118.31
128.58
119.97
134.49
116.06
150.22
34.01
7.69
6.80
7.28
6.75
7.82 (H-6), 1.59 (H-7), 0.49 (H-8)
7.82 (H-5), 7.26 (H-7), 1.09 (H-8)
1.59 (H-5), 7.26 (H-6), 8.12 (H-8)
0.49 (H-5), 1.09 (H-6), 8.12 (H-7)
2.35
1.90-2.10
1.90-2.10
1.90-2.10
3.69
ΣSSCC = 23.8
Complex 3H multiplet
“-“
“-“
12.36 (Ha-11), 7.93 (Ha-10), 7.93 (He-10)
12.36 (He-11), 8.48 (Ha-10), 3.60 (He-10)
22.67
45.40
3.58
______
The spin-coupled partner is given in parentheses next to the SSCC.
Dihedral angles C4–N3–C11–H11 and C4–N3–C11–H11′ are 51° and 72° so that the polarizing and inductive effects
of the carbonyl and unshared electron pair of N3 on both H11 protons are very similar. The difference in the chemical shifts
of these protons is only 0.11 ppm. However, this is entirely adequate to observe reliably and separately the resonances of these
geminal protons.
The greatest changes in the orientation of geminal protons occurred for the H9 protons. Dihedral angles
H2–C2–C9–H9 and H2–C2–C9–H9′ are 45° and 167°. The cis- and trans-SSCC of the H2 protons with the H9 protons are 5.73
and 7.26 Hz, respectively. However, the H9 multiplet at 3.35 ppm forms a very complex unresolvable multiplet for which only
the total of all its SSCC can be estimated, 23.8 Hz. This is typical of an equatorial proton. The axial H9′ proton resonates at
1.90-2.10 ppm and unfortunately overlaps another two very complex multiplets of the H10 protons.
The resonances of the aromatic protons form a veryclear pattern of four separate resonances with three resolved SSCC
in each of them. Constant J(H5,H8) = 0.49 Hz was detected through five bonds. Chemical shifts of H6 and H8 are smaller than
those of H5 and H7, which agrees well with the rule of alternation in an aromatic system and the effect of the carbonyl group.
The PMR spectrum of 2 shows a distinct temperature dependence even in the range 20-55°C. On heating, the
individual lines of the multiplets narrow and become better resolved. This mayindicate the presence in 2 of several conformers
with a small transition barrier between them. Heating by 30-35°C above room temperature gives the average resonances and
the spectra become simpler.
13
The C NMR spectrum of 2 is typical of a quinazolone system [4]. The aromatic part of the spectrum contains seven
resonances, one from a carbonyl C atom and six from the aromatic ring. Assigning resonances of the quarternary C atoms is
not difficult because of the clear influence of N-1 on the resonance of C-8a (150.22 ppm). The rule of alternation of electron
density and, therefore, nuclear shielding, is clearly visible in resonances of the tertiary aromatic C atoms, like in the PMR
spectra (Table 1). Assignments of resonances of the phenyl C atoms of 2 is also in good agreement with the literature for
analogous bicyclic systems [9-11]. Resonances of C atoms of the saturated part of the molecule have very characteristic
increments in chemical shifts because of the two N atoms and are easily assigned (Table 1).
13
Changes in the PMR and C NMR spectra upon adding substituents in the 1-position of 2 are interesting. It was
shown earlier that reduction of 1 methyl iodide (3) by NaBH gives 1-methyl-1,2-dihydrodeoxyvasicinone (4) [5].
4
O
O
N
N
+ NaBH
4
N
N
CH
CH
3
3
I
4
3
430

TABLE 2. NMR Spectra of 4, CD3OD, H0 = 400 MHz, 0 = TMS
Atom
1H chemical shifts, ppm
4.61
Spin-spin coupling constants, Hz
4.97 (H-9e), 8.91 (H-9a)
13C chemical shifts, ppm
2
4
4a
5
6
7
8
8a
9e
76.49
164.25
119.62
128.68
120.11
135.00
113.60
151.53
34.34
7.77
6.88
7.42
6.86
7.66 (H-6), 1.70 (H-7), 0.51 (H-8)
7.66 (H-5), 7.33 (H-7), 1.01 (H-8)
1.70 (H-5), 7.33 (H-6), 8.34 (H-8)
0.51 (H-5), 1.01 (H-6), 8.34 (H-7)
2.46
2.02
2.10
1.93
3.72
3.63
2.79
10.62 (H-9a), 5.38 (H-10a), 4.97 (H-2), 0.40 (H-11a)
10.62 (H-9e), 8.91 (H-2), 6.42 (H-10e), 0.40 (H-11a)
12.00 (H-10a), 7.30 (H-11a), 6.42 (H-9a), 1.05 (H-11e)
12.00 (H-10e), 12.00 (H-11a), 10.08 (H-11e), 5.38 (H-9e)
12.12 (H-11a), 10.08 (H-10a), 1.05 (H-10e)
9a
10e
10a
11e
11a
N-Me
22.08
45.83
33.71
12.12 (H-11e), 12.00 (H-10a), 7.30 (H-10e), 0.40 (H-9e), 0.40 (H-9a)
H 10e
26.77 H z
H 11e
H 11e
H 9e
H 9a
26.35 H z
H 2
J11a J11e
J9a
J10a
J2
J9a
J9e
H 10a
39.46 H z
J10a
J10e
C H 3
H 11e
H 11e
H 9c
H 2
ppm
4.4
4.0
3.6
3.2
2.8
2.4
2.0
Fig. 1. PMR spectrum of the alkane part of 4 in CD OD. The total width of the multiplet is given for H9a, H10e, and H10a.
3
The PMR spectrum of 4 (methylated analog of 1,2-dihydrodeoxyvasicin-2-one) in CD OD is naturally very similar to
3
that of 2 itself. The most characteristic differences in the spectrum are the appearance of a resonance for the methyl (2.79 ppm)
and a weak-field shift (by 0.56 ppm) of the resonance for H-2. The presence of a relatively bulky substituent on N1 stabilizes
the conformation of the saturated part of the molecule. The resolution of the PMR spectrum improves substantially. Whereas
resonances of separate protons up to three SSCC could be observed in the spectrum of 2, those for four SSCC and even five
SSCC for the H-11a protons could be reproduced in the saturated part ofits methylated analog. The methyl group gives a poorly
resolved SSCC with H-2 ( 0.2 Hz) and possibly with H-8 ( 0.1 Hz). In these instances SSCC were measured from the change
of width of separate individual lines in resonances of H-2 and H-8. Furthermore, the methyl exerts an Overhauser effect on
resonances of H-8 (13%), H-2 (4.5%), and both H9 protons ( 3%). Table 2 lists the parameters of the NMR spectra of 4.
The individual multiplets of the H-2 protons and both H-11 and H-9a become regular and close to first order (Fig. 1).
The high resolution of these resonances enables practically all SSCC for this spin system to be determined. Three overlapping
resonances in 2 (H-9a, H-10a, and H-10e), although forming as before a single very broad multiplet, nevertheless can be
separated into individual multiplets. This turned out to be sufficient to determine the remaining three SSCC between these
protons. Thus, all chemical shifts and practically all SSCC for 4 could be reproduced.
431

13
4
2
The C NMR spectrum of agreed well with that of nonmethylated and with characteristic features of quinazolone
derivatives.
Acyl groups were added to and by acylation. It was shown earlier that reacts with benzoylchloride to form
1
2
1
5a
1-benzoyldeoxyvasicinone chloride ( ) [3, 6]. We carried out this reaction with caprylylchloride in order to determine if
chlorides of aliphatic acids could be used.
1
5c 1
Compound also reacts with acetylbromide to form 1-acetyldeoxyvasicinone bromide ( ) [6]. As it turned out,
5b
reacts with caprylylchloride to give salt
in good yield [6].
O
O
O
N
O
NaBH
4
RCOCl
RCOCl
N
N
N
N
N
N
N
H
COR Cl
COR
1
5a,b,c
6a,b, 7
2
5a, 6a:
5b, 6b:
5c:
R = C7H15;
7:
R = CH3; R = CH2Cl
R = C6H5;
+
1
3
4
The ability to reduce the quaternary N=C2 bond of methyl iodide ( ) with NaBH to give [5] suggested that salt
4
5
5a 5b
might also be reduced by it. However, the reaction of and with NaBH with heating in alcohol cleaved the acyl group
4
2
to form .
Compounds
6a
6b
2
were prepared by acylation of with benzoyl- or caprylylchlorides in the presence of Et N.
3
and
Acylation of 1,2-dihydrodeoxyvasicinone by chloroacetylchloride was interesting from two points of view; first, for
studying the relative reactivity of the acylating agents and; second, because of the presence in 1-chloroacetyl-1,2-
dihydrodeoxyvasicinoneofa labileCl atom that might undergonucleophilicsubstitution. Furthermore, theexpectedcompounds
were interesting as potential biologically active compounds. The reaction was carried out in benzene in the presence of Et N
3
7
(for binding the released HCl) and produced 1-chloroacetyl-1,2-dihydrodeoxyvasicinone ( ) in high yield (80%).
The Cl atom in compounds with electron-accepting substituents (CO, COO, SO H, NO , N–C=N, and others) in the
3
2
7
α-position to a methylene is known to be labile and can undergo nucleophilic substitution reactions. Compound that was
synthesized by us is such a compound, in particular, a derivative of α-chloroacetamide. We decided to study its reactions with
amines, alcohols, phenols, hydroselenides, andcompoundswith activatedmethylenesbecause these are nucleophiles and should
react.
7
Compound reacted with various amines. The reactions occurred under various conditions depending on the nature
and basicity of the amines.
O
O
O
O
HNRR
1
N
N
N
N
HCl
N
N
N
N
COCH N(C H )
2 5 3
Cl
COCH NRR
2 1
COCH NRR HCl
2
COCH Cl
2
2
1
16
7
8 - 11
12 - 15
8, 12:
9, 13:
10, 14:
R + R1 = (CH2)5
R = R1 = CH3;
R = R1 = C2H5;
11, 15:
R + R1 = (CH2)2O(CH2)2
We used aliphatic (dimethyl- and diethylamine) and heterocyclic (piperidine, morpholine) amines in the reactions,
7
which proceeded readily with heating the reagents in a 1:1 ratio ( :amine) in absolute benzene for 4 h.
16
7
Compound reacted with Et N to give quaternary salt
.
3
8 11
crystallized well from organic
The synthesized 1-dialkyl(hetaryl)aminoacetyl-1,2-dihydrodeoxyvasicinones
solvents. They were very soluble in alcohol, acetone, benzene, and other solvents and poorly soluble in water. They could be
-
12 15
16
recrystallized from hexane. They were strong bases and easily formed hydrochlorides
in water and alcohol and slightly soluble in other organic solvents.
-
. These, like , were very soluble
The structures of the prepared compounds were confirmed by IR, PMR, and mass spectra.
−1
8 11
The IR spectra of - contained absorption bands for carbonyl at 1675-1685 cm (νCO), typical of quinazol-4-ones
[4, 8]; at 1650-1659 cm −1 (νN–CO); and at 1603-1606 cm −1 (νCH=CH).
432

2
TABLE 3. PMR Spectra of and 1-Dialkyl(hetaryl)aminoacetyl-1,2-dihydrodeoxyvasicinones in CDCl3
C atom
Compound
2
5
6
7
8
9
9a,10e,a
11e,a
CO-CH2
NRR1
2
7
NH 4.47
5.07
5.12
5.12
5.12
7.95
8.09
8.05
8.06
6.87
7.39
7.32
7.52
7.47
6.69
7.24
7.45
2.43
2.87
2.87
2.82
1.77-2.32
1.83-2.70
1.67-2.57
1.72-2.57
3.57-3.97
3.57-3.82
3.57-3.77
3.57-3.77
4.19, 4.26
3.42, 3.42
3.27, 3.27
9
Eth 2.44, 0.92
α 2.37, β,γ 1.42
7.39
10
7.21-7.44
7.47 7.21-7.44
11
M-n 2.52, 3.67
5.12
8.05
7.20-7.57*
2.78
1.72-2.67
3.47-3.72
3.26, 3.30
______
*Values given for the 6th, 7th, and 8th C atoms.
M-n [Morpholine].
PMRspectra ofthe prepared derivatives had somewhat different chemical shiftsthan thoseoftheframeworkmolecules.
2
The greatest shift in the position of the resonances compared with those of in CDCl (Table 3) were observed for aromatic
3
protons H-6 and H-8 (weak-field shift of 0.5 ppm) and for equatorial proton H-9. The shifts of the remaining resonances were
considered insignificant. Apparently the shifts of the aromatic protons were due to conjugation with the carbonyl. According
to the redistribution of charge around the aromatic system, the changes of protons H-6 and H-8 were rather large whereas those
of H-5 and H-7 were much smaller. The change of equatorial proton H-9 was due most probably to the inductive effect of the
substituents in 7-11. The nature of the multiplicity in all spectra was almost unchanged.
+
Mass spectra of the compounds showed weak (10-20%) peaks for the molecular ions. Further fragmentation of [M]
led to loss of a cyclopentane ring or an aminoacetyl group.
It seemed interesting to study substitution of the Cl in 1-chloroacetyl-1,2-dihydro-1 (7) by other nucleophilic reagents
(cyanide, hydroselenide, methoxide, phenoxide, and anions of compounds with activated methylenes such as malonic,
acetoacetic, and cyanoacetic esters, acetylacetone, etc.). However, in all instances it turned out that the reaction was
accompanied by cleavage of the chloroacetyl group and formation of 1,2-dihydrodeoxyvasicinone (2).
Methylation of 2 by methyliodide in the presence of NaH in DMF is known to occur at N-1 [5]. Partial dehydration
of 1,2-dihydrodeoxyvasicinone and its seven-membered analog to 1 and its homolog occurred. We studied alkylation of 2 with
allylbromide. Formation of1-allyl-1,2-dihydrodeoxyvasicinoneanditsisomerization products, the1-cis-and1-trans-propen-1-
yl derivatives, was expected. The possibility of such isomerization was demonstrated using 9-allylcarbazole [12] and 10-
allylphenothiazine [13] as examples. Performing the reaction under methylation conditions [5] led to formation of the normal
allylation product (17). In addition, starting material and its dehydrogenation product (1) remained in the reaction mixture.
Thus, dehydrogenation is a general reaction of 2.
Possible addition of 2 to phenylacetylene was studied by carrying out the reaction in superbase (DMSO + KOH). It
proceeded regioselectively to form mainly 1-cis-(2-phenylvinyl)-1,2-dihydrodeoxyvasicinone (18).
O
O
O
C H C CH
N
6
5
N
N
N
N
H
N
C
C H
6
H
CH CH CH
2
5
2
C
H
2
17
18
The structure of 18 was confirmed by IR and PMR spectra. Its IR spectrum contained absorption bands for carbonyl,
−
1
double bonds of the benzene ring and others, and bands at 759 and 695 cm , typical of cis-ethenyl.
The PMR spectrum of protons in the sidechain double bond appeared as two doublets at 5.86 (1H, d, J = 9, α-H) and
6.30 (1H, d, J = 9, β-H). The SSCC of 9.0 Hz indicated that the protons of the double bond were in the cis-position. Thus,
addition to2ofphenylacetyleneoccurredregio-andstereoselectivelywith formation exclusivelyofcis-1-(2-phenylvinyl)-2 (18).
Similar regioselectivity was observed for nucleophilic addition of phenothiazines to phenylacetylene [14] and
isomerization of 10-allylphenothiazine into the cis-propenyl derivative [13].
433

It is known that cis-10-(2-phenylvinyl)- and 10-alkenylphenylthiazines are isomerized into the corresponding
trans-isomers [13, 14].
We attempted to carryout the isomerization of cis-17 into the trans-form byheating it at 100-110°C for 3 h. However,
such isomerization did not occur. The cis-form 18 remained unchanged.
EXPERIMENTAL
IR spectra were recorded on a Perkin—Elmer Model 2000 Fourier IR spectrometer in pressed KBr disks. Mass spectra
were recorded in MX-1310 and MS25RS (Kratos) spectrometers at ionizing potential 70 eV, source temperature 250°C, direct
sample introduction at 120°C, and accelerating potential 4 kV. NMR spectra were recorded on a UNITY-400+ spectrometer
1
13
at operating frequency 400 MHz for H and 100 MHz for C. Samples were prepared in CD OD with TMS internal standard
3
(0 ppm). Spectra (except variable temperature experiments with 2) were recorded at room temperature. Highly accurate
measurements of SSCC were obtained bysetting the detection time for signal decaybyfree induction to 8 s, using a digital filter
before Fourier transformation to increase resolution, and refining all resonances in PMR spectra using the LAME integration
program to two decimal places accuracy. Deoxyvasicinone was prepared by the literature method [8]. 1,2-Dihydro-
deoxyvasicinone was synthesized as before [5]. Salts of N-acyldeoxyvasicinone 5a and b were prepared by the literature
methods [3, 6].
1-Caprylyl-1,2-dihydrodeoxyvasicinone (6b). A stirred solution of 1,2-dihydrodeoxyvasicinone (0.5 g, 2.7 mmol)
in absolute benzene (30 mL) was treated with Et N (0.37 mL, 2.7 mmol) and dropwise with a solution of caprylylchloride
3
(0.45 mL, 2.7 mmol) in the same solvent (3 mL). The reactoin mixture was stirred at room temperature for 1 h, then at 85-90 C
for 1.5 h, cooled, treated with water (30 mL), and transferred to a separatory funnel. The organic layer was separated, washed
with water (2×), and dried over Na SO . Solvent was distilled off. The solid was recrystallized from hexane to afford 6b
2
4
(0.5 g, 60%), mp 190-192°C, R 0.73 (Silufol, CHCl :CH OH, 10:1).
f
3
3
1-Chloroacetyl-1,2-dihydrodeoxyvasicinone (7) 1,2-Dihydrodeoxyvasicinone(10g, 5.3mmol)wasplacedinathree-
necked flask equipped with a mechanical stirrer, dropping funnel, and reflux condenser; dissolved with stirring in absolute
benzene (100 mL); treated first with Et N (5 mL, 5.3 mmol) and then dropwise through the dropping funnel with a solution
3
of chloroacetylchloride (15 mL, 0.2 mmol) in absolute benzene (20 mL). The reaction mixture was heated on a water bath with
stirring and refluxing for 4 h and cooled. The resulting precipitate was filtered off. The residue was treated with water. The
resulting crystals were separated, dried, and recrystallized from hexane. Yield 14.2 g (80%), mp 141-142°C, R 0.70 (Silufol,
f
CHCl :CH OH, 10:1).
3
3
−
1
+
IR spectrum (cm ): 1688, 1661 (ν ), 1606, 1580, 1482 (ν
). Mass spectrum (%): 264/266 (4) [M] , 263/265
CH=CH
CO
+
(2) [M - 1] , 230 (89), 229 (68), 187 (23), 186 (11), 160 (5), 146 (100).
1-Dimethylaminoacetyl-1,2-dihydrodeoxyvasicinone (8). A solution of 1-chloroacetyl-2 (1.5 g, 5 mmol) in alcohol
(30 mL) was treated with aqueous dimethylamine (2.27 mL, 34 mmol, 33%), heated on a water bath for 4 h, diluted with water
(30 mL), extracted with CHCl (3×), and dried over MgSO . The solvent was distilled off. The solid was recrystallized from
3
4
hexane. Yield 1 g (65%), mp 123-124°C, R 0.70 (Silufol, CHCl :CH OH, 10:1).
f
3
3
−
1
IR spectrum (cm ): 1688, 1661 (ν ), 1606, 1580, 1482 (ν
). PMR spectrum (CDCl , δ, ppm): 3.50 (2H, s,
3
CO
CH=CH
N–CH ), 3.56-3.70 (2H, CH –11, m), 1.65-1.65 (4H, m, CH CH ), 3.60 [6H, s, N(CH ) ], 5.12 (1H, q, H-2), 7.22-7.50 (3H,
2
2
2
2
3 2
+
+
+
m), 7.91-8.05 (1H, dd, H-5). Mass spectrum (%): 273 (20) [M] , 272 (8) [M - 1] , 271 (14) [M - 2] , 229 (23), 215 (8), 214
(15), 188 (100), 187 (18), 186 (15), 161 (95), 147 (40), 119 (20).
1-Diethylaminoacetyl-1,2-dihydrodeoxyvasicinone (9). A mixture of 1-chloroacetyl-1,2-dihydrodeoxyvasicinone
(1.5 g, 5.7 mmol) and diethylamine (1.8 mL, 17 mmol) in benzene (30 mL) was refluxed for 4 h, cooled, and thoroughlywashed
with water. The organic layer was separated and dried over MgSO . The solvent was distilled off. The solid was recrystallized
4
from hexane. Yield 1.13 g (67%), mp 95-96°C, R 0.76 (Silufol, CHCl :CH OH, 10:1).
f
3
3
).
−
1
IR spectrum (cm ): 1685, 1659 (ν ), 1603, 1578, 1480 (ν
CO
CH=CH
1-Piperidinoacetyl-1,2-dihydrodeoxyvasicinone (10) was prepared analogously to that described above from 7
(1.5 g, 11 mmol) and piperidine (1.05 mL, 11 mmol) in benzene (30 mL) to afford the product (1.2 g, 68%), mp 93-94°C, R
f
0.75 (Silufol, CHCl :CH OH, 10:1).
3
3
434

−
1
IR spectrum (cm ): 1676, 1650 (ν ), 1607, 1578, 1484 (ν
).
CH=CH
CO
1-Morpholinoacetyl-1,2-dihydrodeoxyvasicinone (11) was prepared from 7 (1.5 g, 5.7 mmol) and morpholine
(1.57 mL, 18 mmol) in benzene (30 mL) analogouslyto the preparation of 8 to afford the product (1.23 g, 69%), mp 151-152°C
(hexane), R 0.72 (Silufol, CHCl :CH OH, 10:1).
f
3
3
−
1
+
IR spectrum (cm ): 1678, 1656 (ν ), 1608, 1577, 1472 (ν
). Mass spectrum (%): 315 (10) [M] , 314 (3)
CH=CH
CO
+
+
[M - 1] , 313 (4) [M - 2] , 285 (17), 245 (16), 229 (27), 228 (17), 215 (16), 160 (17), 146 (17), 146 (100), 132 (22), 119 (17).
Dimethylaminoacetyl-1,2-dihydrodeoxyvasicinone Hydrochloride (12). Compound 8 (500 mg) was dissolved in
absolute Et O (10 mL) and saturated with gaseous HCl until crystals formed to give 12 (550 mg, 97%), mp >300°C (dec.).
2
Salts 13-15 were prepared analogously and decomposed at >300°C.
1-Triethylammoniumacetyl-1,2-dihydrodeoxyvasicinoneChloride(16). 1-Chloroacetyl-1,2-dihydrodeoxyvasicinone
(1.5 g, 5.7 mmol) and Et N (0.8 mL, 5.7 mmol) in benzene (30 mL) were left at room temperature for 8 h. The resulting
3
−
1
precipitate was separated. Yield 1.62 g (78%), mp 229-230°C, R 0.77 (Silufol, CHCl :CH OH, 10:1). IR spectrum (cm ):
f
3
3
1677, 1651 (ν ), 1606, 1579, 1470 (ν
).
CH=CH
CO
Reaction of 7 with Cyanide. A solution of 1-chloroacetyl-1,2-dihydrodeoxyvasicinone (1 g, 3.8 mmol) in alcohol
(100 mL) was treated with acetocyanhydride (1.0 ml, 12 mmol) and K CO (0.38 g) in water (50 mL) and heated on a water
2
3
bath for 24 h. The solid was filtered off. The solvent was distilled off. The solid was recrystallized from benzene to afford
2 (0.57 g, 80%), mp 180-181°C.
Reaction of 7 with Sodium Hydroselenide. A 250-mL four-necked flask equipped with a stirrer, reflux condenser,
thermometer, and tube for adding He was charged with powdered selenium (0.41 g, 5.2 mmol) and water (25 mL), stirred for
20 min under He, treated with stirring in portions with NaBH (0.39 g, 10.4 mmol), stirred for 20 min at room temperature and
4
1 h at 40°C, cooled to 20-22°C, treated dropwise with 7 (0.7 g, 2.6 mmol), stirred for 1 h at room temperature and 1 h at 90-
95°C, and cooled. The resulting precipitate was filtered off. The filtrate was neutralized with acetic acid. The resulting solid
was filtered off, washed with water, dried, and recrystallized from benzene to afford 1,2-dihydrodeoxyvasicinone (0.36 g, 73%),
mp 179-180°C, R 0.79 (Silufol, CHCl :CH OH, 10:1).
f
3
3
Reaction of 7 with Sodium Methoxide. Sodium hydride (130 mg, 5.5 mmol) was added to absolute methanol (5 mL),
treated with 1-chloroacetyl-1,2-dihydrodeoxyvasicinone (1.3 g, 5 mmol) in methanol (5 mL), left for 3 h, anddiluted with water.
The resulting precipitate was filtered off, washed with water, dried, and recrystallized from benzene to afford 2 (0.72 g, 76%),
mp 179-180°C, R 0.78 (Silufol, CHCl :CH OH, 10:1).
f
3
3
Analogous results were obtained for the reaction of 2 with sodium phenoxide.
Reaction of 1-Chloroacetyl-1,2-dihydrodeoxyvasicinone with Sodium Malonic Ester. Metallic sodium (140 mg,
6 mmol) was placed in a flask with absolute alcohol (10 mL). The resulting solution of sodium ethoxide was treated with
malonic ester (80 mg, 5 mmol), stirred at room temperature for 20 min, treated with 7 (1.3 g, 5 mmol) in absolute alcohol
(5 mL), stirred for 2 h, and poured into water. The resulting precipitate was filtered off, washed with water, and dried to afford
1,2-dihydrodeoxyvacisinone (0.73 g, 78%), mp 179-180°C, R 0.76 (Silufol, CHCl :CH OH, 10:1).
f
3
3
The reactions with sodium acetoacetate (80% yield of 2) and cyanoacetate esters (76% yield) and acetylacetone (80%
yield) proceeded analogously.
Reduction of 5a with NaBH . A solution of NaBH (0.28 g, 7.6 mmol) in alcohol (25 mL) was treated with
4
4
N-benzoyldeoxyvasicinone chloride (0.5 g, 1 mmol) and heated on a water bath for 4 h. The alcohol was distilled off. The solid
was treated with water (30 mL) and extracted with CHCl (3 × 20 mL). The solvent was distilled off. The solid was
3
recrystallized from hexane to afford 1 (0.2 g, 70%).
Reaction of 5c with NaBH to form 1 proceeded analogously.
4
Alkylation of 2 with Allylbromide. A solution of 2 (1 g, 5 mmol) in absolute DMF (25 mL) was treated with NaH
(0.12 g, 5 mmol), stirred for 20 min, treated with allylbromide (0.44 mL, 5 mmol), heated and stirred on a water bath (70-80°C)
for 1.5 h, cooled, diluted with water (40 mL), and extracted with benzene. The organic layer was dried over Na SO . The
2
4
solvent was distilled off. The solid was recrystallized from hexane to afford 17 (1.4 g, 73%), mp 161-162°C, R 0.70 (Silufol,
f
CHCl :CH OH, 10:1).
3
3
−
1
+
+
IR spectrum (cm ): 1660 (ν ), 1608, 1572, 1478 (ν
). Mass spectrum (%): 228 (73) [M] , 227 (46) [M - 1] ,
CH=CH
CO
+
+
187 (53) [M - CH =CHCH ] , 186 (100) [M - 42] .
2
2
Addition of 2 to Phenylacetylene. A mixture of 2 (2.07 g, 11 mmol) and KOH (0.5 g) in DMSO (25 mL) was heated
to 100°C, treated dropwise with phenylacetylene (2.4 mL, 22 mmol), held at this temperature for 2 h, cooled, diluted with water,
435

and extracted with CHCl . The organic layer was dried over Na SO . The solvent was evaporated. The solid was recrystallized
3
2
4
from hexane to afford 18 (2.4 g, 78%), mp 191-192°C, R 0.76 (Silufol, CHCl :CH OH, 10:1).
f
3
3
−
1
IR spectrum (cm ): 1680 (ν ), 1605, 1581, 1477 (ν
), 759, 695 (CH=CH-cis). PMR spectrum (δ, ppm): 1.90-
CH=CH
CO
2.10 (2H, m, H-9), 2.46-2.72 (2H, m, H-10), 4.38-4.65 (2H, m, H-11), 6.75, 6.83, 6.47 (3H, m, H-8, H-7, H-6), 7.93-8.02 (1H,
d, H-5), 7.35 (5H, s, Ar), 5.86-5.94 (1H, dd, H-2), 6.25-6.35 (1H, dd, Hβ, J = 9 Hz).
ACKNOWLEDGMENT
The work was supported financially by GNTP-10 (State Scientific-Technical Program).
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