A convenient synthesis of alkenyl-substituted glycidonitriles and glycidates

Article abstract of DOI:10.1055/s-2006-958926

α-Chloronitriles or α-chloroesters reacted with α,β-unsaturated carbonyl compounds in the presence of powdered sodium hydroxide, in ethereal solvents, giving alkenyl-substituted glycidonitriles or esters. The straightforward process aTfords nitriles in pa

Full text of DOI:10.1055/s-2006-958926

PAPER
75
A Convenient Synthesis of Alkenyl-Substituted Glycidonitriles and Glycidates
Synthesis of
A
lken
n
yl Substitute
n
d
G
lycidoni
a
s
and
G
lycida
G
tes adaj, Andrzej Jończyk*
Warsaw University of Technology, Faculty of Chemistry, Koszykowa St. 75, 00662 Warsaw, Poland
Fax +48(22)6282741; E-mail: anjon@ch.pw.edu.pl
Received 20 June 2006; revised 5 July 2006
cyclohexene.11 On the other hand, neither ethyl chloro-
Abstract: a-Chloronitriles or a-chloroesters reacted with a,b-un-
saturated carbonyl compounds in the presence of powdered sodium
hydroxide, in ethereal solvents, giving alkenyl-substituted glyci-
donitriles or esters. The straightforward process affords nitriles in
particularly high yields.
nor bromo-acetate underwent the reaction with either ac-
rolein or methyl vinyl ketone under PTC conditions.22
Depending upon the structure of the halonitrile or ha-
loester used, their carbanions can attack a,b-unsaturated
carbonyl compounds either at the carbon–carbon double
bond, leading to the formation of the corresponding cyclo-
propanes (1,4-addition), or at the carbonyl carbon, giving
alkenylo-oxiranes (1,2-addition). Chloroacetonitrile11–15
and chloroacetates10,15,16 have been shown to react
through 1,2-addition, while (a-chloro)phenylacetates re-
act via 1,4-addition.15,16 On the other hand, a survey of the
literature reveals a discrepancy between the reported reac-
tivities of (a-halo)phenylacetonitriles. Thus, a-bromo de-
rivatives have been shown to behave in a manner similar
to chloroacetonitrile, affording the 1,2-addition prod-
ucts,13,14 while the corresponding a-chloro compounds
reacted by 1,4-addition, forming substituted cyclopro-
panes.15
Key words: aldehydes, ketones, carbanions, condensation, ep-
oxides
Nitriles and esters of glycidic acids (glycidonitriles and
glycidates) are useful substrates for the preparation of a
variety of important products, such as carbonyl com-
pounds,1,2 carboxylic acids,3 fluorine-substituted carboxy-
lic acids,4–6 cyanodioxolanes,7 aziridine carboxylic esters8
and cyanodienes.9 Chemical transformations of alkenyl-
substituted glycidonitriles and glycidates, however, have
only rarely been investigated. According to a few reports
concerning such processes, the alkenyl function is pre-
served in the product (e.g. during homologation of a,b-un-
saturated ketones to aldehydes,10,11 in the preparation of a
retinoic acid derivative12 and base-mediated oxirane ring
opening13) or, together with the oxirane ring, is involved
in the formation of the final products (e.g. thermal conver-
sion of epoxyhexenynes into 3,4-annulated 2-
vinylfurans14). In our opinion, the synthetic utility of the
title compounds in organic synthesis is still unrecognized.
Taking into account this literature data, we considered
that establishing a general, simple method with which to
prepare alkenyl-substituted glycidonitriles and glycidates
would be of value. To this end, we investigated the
Darzens condensation of chloronitriles 1, 2 and chlo-
roesters 3, 4 with a series of a,b-unsaturated aldehydes 5–
8 and ketones 9–12 under PTC conditions.23
Alkenyl-substituted glycidonitriles or glycidic esters are
usually prepared by the reaction of either a-halogeno ni-
triles or a-halogeno esters with a,b-unsaturated carbonyl
compounds. Such reactions are usually carried out in the
presence of potassium tert-butoxide,10,11,13–15 sodium hy-
dride,15 sodium hexamethyldisilazanide (NaHMDS)15 or
sodium ethoxide16 in tert-butanol, HMPT, THF, diethyl
ether or their mixtures, sometimes with the addition of
benzene (Darzens-type condensation17). Typical phase-
transfer catalysis (PTC) conditions18–21 [50% aq sodium
hydroxide and catalytic benzyltriethylammonium chlo-
ride (TEBAC) in acetonitrile] have been applied for the
preparation of cyanoepoxyhexenynes via the condensa-
tion of chloroacetonitrile or 2-bromo-2-phenylacetonitrile
with tetramethylsilane (TMS)-protected enynals.13,14 In
one case, the reaction of chloroacetonitrile with a dienone
was carried out with powdered sodium hydroxide and a
catalytic amount of DMF in toluene,12 though these con-
ditions proved unfeasible for the reaction with 1-acetylo-
Stirring chloroacetonitrile (1) with aldehyde 8, 50% aque-
ous sodium hydroxide, and catalytic TEBAC in benzene
(20–30 °C for 4 h), however, resulted in only 57% conver-
sion of 8 to the expected product 16 (determined by GC).
When powdered sodium hydroxide and the same catalyst
in THF were used, only an intractable mixture was
formed. According to literature, Darzens condensation of
halonitriles with carbonyl compounds can be realized
with solid alkali-metal hydroxides, in aprotic dipolar sol-
vents,24 even in a catalytic amounts.12 However, because
these solvents are rather expensive and difficult to recover
after work-up procedures, we decided to carry out the re-
action of nitrile 1 with aldehyde 8 in the presence of pow-
dered sodium hydroxide in THF, without any catalyst.
Though the reaction mixture charred a little under these
conditions, the product 16 was isolated in 91% yield
(Table 1, entry 4). Encouraged by this result, we conduct-
ed the same reaction with a range of a,b-unsaturated alde-
hydes 5–7 and ketones 9–12 with chloroacetonitrile (1); in
the majority cases the expected products were obtained in
high yields (Scheme 1, Table 1, entries 1–8).
SYNTHESIS 2007, No. 1, pp 0075–0080
x
x
.
x
x
.2
0
0
7
Advanced online publication: 12.12.2006
DOI: 10.1055/s-2006-958926; Art ID: Z12206SS
© Georg Thieme Verlag Stuttgart · New York

76
A. Gadaj, A. Jończyk
PAPER
R2
droxide, the glycidonitrile 16 was obtained in 78% yield,
though the conversion required significantly longer to go
to completion (~45 min). Importantly, after the sodium
hydroxide had been removed by filtration, at least 90% of
THF solvent used in the reaction of 1 with 8 could be re-
covered by distillation (16 was obtained in 84% yield).
R2
powdered NaOH,
R1
R3
R5
THF
R3
R5
+
20–30 °C,
10–105 min
R4
O
Cl
CN
R4
O
CN
R1
R1 = H,
1
13–20
21–25
5–12
Me, 2
Chloroacetates 3 and 4 also reacted with a,b-unsaturated
aldehydes 5–8 under the conditions described above, af-
fording alkenylglycidates 26–30 in 30–73% yield
(Scheme 2, Table 2).
Scheme 1
Equally satisfactory results were obtained from the reac-
tion of a-chloropropionitrile (2) with aldehydes 7, 8 and
ketone 10 (Table 1, entries 9, 10 and 11, respectively);
however, the expected products 24 and 25 from the open
chain and cyclic ketones, 11 and 12 respectively, were
only formed in rather low yields and were accompanied
by significant amounts of intractable materials (Table 1,
entries 12 and 13). Except for the reaction of nitrile 2 with
ketone 10 (Table 1, entry 11), the conversion was com-
pleted in less than one hour, and the products were usually
isolated by vacuum distillation. Again, typical PTC con-
ditions proved inefficient in the reaction of 2 with alde-
hyde 8, with ~44% of starting material remaining after
eight hours (determined by GC) .
powdered NaOH,
THF
O
CHO
R3
Cl
CO2R1
+
R3
CO2R1
10–30 °C,
0.5–6.5 h
R2
5–8
R2
R1 = iPr, 3
26–30
tBu, 4
Scheme 2
The progress of these reactions were followed by GC, and
it is important to note that upon complete consumption of
the carbonyl component, the reaction should be worked
up, since otherwise, the glycidonitriles or glycidic ester
products tended to degrade.
When the reaction of nitrile 1 with aldehyde 8 was carried
out using commercially available granules of sodium hy-
Table 1 Alkenyl-Substituted Glycidonitriles 13–25
Entry
R1
R2
R3
R4
R5
Time
(min)
Product,
Oxirane ring
stereochemical ratio
(by GC)
yielda (%)
1
2
1
H
5b
6b
H
Me
H
H
H
10
45
10
15
30
45
40
45
48
40
105
20
47
13, 57
14, 83
15, 69
16,c 91
17, 36
18, 75
19, 80
20, 79
21, 62
22, 88
23, 76
24,g 28
25, 36
1.9 (E/Z)
2.4 (E/Z)
1.7 (E/Z)
1.6 (E/Z)
1.8 (E/Z)d
1.6 (E/Z)d
1.8 (E/Z)
1.5f
n-Bu
H
H
H
3
7b
Ph
Ph
H
H
H
4
8b
Me
H
H
H
5
9b
H
Me
Me
Me
6
10b
11b
12e
7e
H
Me
Ph
H
Me
H
7
H
8
H
(CH2)3
9
2
Me
H
Ph
Ph
Me
Ph
H
H
H
1.3 (E/Z)d
1.7 (E/Z)d
3.4f
10
11
12
13
8e
Me
H
H
H
10b
11e
12e
Me
H
Me
Me
H
1.0
H
(CH2)3
1.8f
a Isolated by vacuum distillation.
b Conducted in 100 mL of THF.
c In DME, yield = 86%.
d Determined by 1H and NOESY NMR (500 MHz).
e Conducted in 50 mL of THF.
f Ratio of major to minor diastereoisomers.
g Isolated by column chromatography.
Synthesis 2007, No. 1, 75–80 © Thieme Stuttgart · New York

PAPER
Synthesis of Alkenyl-Substituted Glycidonitriles and Glycidates
77
Table 2 Alkenyl-Substituted Glycidates 26–30
Entry
R1
R2
R3
Timea (min) Product,
yieldb (%)
Oxirane ring
stereochemical ratio
(by 1H NMR)
1
2
3
4
5
3
4
i-Pr
8
5
6
7
8
Me
H
Ph
Me
H
390c
37
26, 32
27, 30
28, 69
29, 40
30,d 73
E
t-Bu
6.0 (E/Z)
10.3 (E/Z)
4.5 (E/Z)
E
n-Bu
H
48
Ph
Ph
30
Me
150
a Reaction conducted at 20–30 °C.
b Isolated by vacuum distillation.
c Reaction conducted at 10–15 °C.
d Isolated by crystallization from MeOH.
C2-H E), 3.58–3.63 (m, 2 H, C2-H + C3-H Z), 3.72 (dd, J = 8.0, 2.0
Hz, 1 H, C3-H E), 5.10 (ddq, J = 15.6, 8.0, 1.6 Hz, 1 H,
CH3CH=CH E), 5.39 (ddq, J = 15.6, 8.0, 1.6 Hz, 1 H, CH3CH=CH
Z), 6.08–6.22 (m, 1 H, CH3CH=CH E + Z).
13C NMR (100 MHz, CDCl3): d = 17.9, 18.0, 42.7, 43.1, 57.0, 58.6,
115.6, 116.2, 123.0, 124.1, 136.2, 137.2.
In summary, we have established a simple, fairly general
method for the synthesis of substituted alkenylglycidoni-
triles and alkenylglycidates from readily available a-chlo-
ronitriles, a-chloroesters, a,b-unsaturated aldehydes and
ketones. This method is particularly recommended for the
synthesis of alkenyl-substituted glycidonitriles.
HRMS (EI): m/z [M+] calcd for C6H7NO: 109.0528; found
109.0524.
Melting points (determined in a capillary tube apparatus) and boil-
ing points are uncorrected. 1H and 13C NMR spectra were measured
in CDCl3 on a Varian Mercury 400 or Varian Gemini 200 spectrom-
eter (400 MHz or 200 MHz for 1H and 100 MHz or 50 MHz for 13C).
3-(1-Methylenepentyl)oxirane-2-carbonitrile (14)
Yield: 6.07 g (83%); colorless oil; bp 93–96 °C (10 Torr); mixture
of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3 E),
0.93 (t, J = 7.2 Hz, 3 H, CH3 Z), 1.27–1.57 (m, 4 H, CH2 E + Z),
1.87–2.01 (m, 2 H, CH2C=C E), 2.15–2.20 (m, 2 H, CH2C=C Z),
3.28 (d, J = 2.0 Hz, 1 H, C2-H E), 3.58 (d, J = 3.6 Hz, 1 H, C2-H Z),
3.60 (d, J = 3.6 Hz, 1 H, C3-H Z), 3.74 (d, J = 2.0 Hz, 1 H, C3-H E),
5.10 (q, J = 1.2 Hz, 1 H, C=CH2 E), 5.16–5.18 (m, 1 H, C=CH2 Z),
5.21–5.22 (m, 1 H, C=CH2 Z), 5.22–5.26 (m, 1 H, C=CH2 E).
1
1H and H NOESY spectra were measured in CDCl3 on a Brucker
500 spectrometer at 500 MHz. Chemical shifts (d) are given in ppm
relative to TMS and coupling constants (J) are given in Hz. Gas
chromatography (GC) analyses were carried out with an Agilent
6850 chromatograph, equipped with HP50+ (30 m) capillary col-
umn. Elemental analyses were performed with a Perkin–Elmer
CHNO/S Series II 2400 microanalyser. HR-MS analyses were per-
formed with an AMD-604 spectrograph. Column chromatography
was carried out using MERCK Aluminum oxide 90 active basic
(70–230 mesh) with hexane as eluent. Chloroacetonitrile (1), iso-
propyl chloroacetate (3), carbonyl compounds 5–12 and all solvents
were commercially available, while 2-chloropropionitrile (2)1 and
tert-butyl chloroacetate (4)25 were synthesized according to litera-
ture procedures.
13C NMR (100 MHz, CDCl3): d = 13.8 (E + Z), 22.2, 22.3, 29.8,
29.9, 30.3, 32.7, 41.9, 43.9, 57.8, 59.7, 113.5, 115.1, 115.3, 116.3,
139.9, 141.5.
Anal. Calcd for C9H13NO: C, 71.49; H, 8.67; N, 9.26. Found: C,
71.73; H, 8.65; N, 9.32.
3-Styryloxirane-2-carbonitrile (15)
Yield: 5.88 g (69%); yellowish oil; bp 113–118 °C (0.2 Torr); mix-
ture of diastereoisomers.
Synthesis of Compounds 13–25; General Procedure
Powdered NaOH (6.00 g, 0.15 mol) and THF (100 mL or 50 mL,
Table 1) were stirred with a magnetic stirrer while a mixture of a-
chloronitrile 1 or 2 (0.055 mol) and carbonyl compound 5–12 (0.05
mol) was added dropwise at 20–30 °C over 20 min. The mixture
was stirred at the same temperature until GC analyses indicated the
total consumption of the starting carbonyl compound (Table 1). The
reaction mixture was then poured into a mixture of ice–water (~100
g) and CH2Cl2 (100 mL), the organic phase was taken and the aque-
ous phase was extracted with CH2Cl2 (3 × 50 mL). The combined
organic extracts were washed with brine (100 mL), dried over
MgSO4 and concentrated. The products 13–25 were isolated either
by vacuum distillation or by column chromatography (Table 1).
1H NMR (400 MHz, CDCl3): d = 3.43 (d, J = 2.0 Hz, 1 H, C2-H E),
3.71 (d, J = 4.0 Hz, 1 H, C2-H Z), 3.83 (ddd, J = 8.0, 4.0, 0.4 Hz,
1 H, C3-H Z), 3.94 (ddd, J = 8.0, 2.0, 0.8 Hz, 1 H, C3-H E), 5.78
(dd, J = 16.0, 8.0 Hz, 1 H, PhCH=CH E), 6.07 (dd, J = 16.0, 8.0 Hz,
1 H, PhCH=CH Z), 6.92 (d, J = 16.0 Hz, 1 H, PhCH=CH E), 7.00
(d, J = 16.0 Hz, 1 H, PhCH=CH Z), 7.31–7.47 (m, 5 H, Ar-H E + Z).
13C NMR (100 MHz, CDCl3): d = 43.2, 43.5, 57.4, 58.8, 115.5,
116.0, 120.2, 121.3, 126.7, 126.8, 126.9, 128.7, 128.8, 128.9, 129.0,
134.8, 134.9, 138.1, 139.2.
Anal. Calcd for C11H9NO: C, 77.17; H, 5.30; N, 8.18. Found: C,
76.95; H, 5.48; N, 8.21.
3-(1-Propenyl)oxirane-2-carbonitrile (13)
Yield: 3.12 g (57%); colorless oil; bp 87–89 °C (20 Torr); mixture
of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.77 (dd, J = 6.8, 1.6 Hz, 3 H, CH3
E), 1.83 (dd, J = 6.8, 1.6 Hz, 3 H, CH3 Z), 3.30 (d, J = 2.0 Hz, 1 H,
3-(1-Methylstyryl)oxirane-2-carbonitrile (16)
Yield: 8.38 g (91%); colorless oil; bp 108 °C (0.2 Torr); mixture of
diastereoisomers.
Synthesis 2007, No. 1, 75–80 © Thieme Stuttgart · New York

78
A. Gadaj, A. Jończyk
PAPER
1H NMR (400 MHz, CDCl3): d = 1.74 (d, J = 1.6 Hz, 3 H, CH3 E),
2.02 (d, J = 1.6 Hz, 3 H, CH3 Z), 3.47 (d, J = 2.0 Hz, 1 H, C2-H E),
3.64 (d, 1 H, J = 4.0 Hz, C2-H Z), 3.76 (dd, J = 4.0, 0.4 Hz, 1 H, C3-
H Z), 3.92 (dd, J = 2.0, 0.8 Hz, 1 H, C3-H E), 6.75 (s, 1 H,
PhCH=CCH3 Z), 6.77 (s, 1 H, PhCH=CCH3 E), 7.26–7.42 (m, 5 H,
Ar-H E + Z).
13C NMR (100 MHz, CDCl3): d = 11.5, 14.3, 40.9, 43.1, 59.8, 62.1,
115.3, 116.4, 127.2, 127.4, 128.1, 128.2, 128.4, 128.8, 128.9, 129.2,
129.4, 132.2, 135.7, 135.8.
13C NMR (50 MHz, CDCl3): d = 20.7, 20.8, 24.6, 24.7, 28.4, 30.3,
48.8 (E + Z), 61.5, 61.6, 115.8, 116.0, 123.0, 124.6, 139.5, 140.0.
Anal. Calcd for C8H9NO: C, 71.09; H, 6.71; N, 10.36. Found: C,
70.24; H, 6.59; N, 10.17.
2-Methyl-3-styryloxirane-2-carbonitrile (21)
Yield: 5.72 g (62%); yellowish oil; bp 123–127 °C (0.5 Torr); mix-
ture of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.66 (s, 3 H, CH3 E), 1.73 (s, 3 H,
CH3 Z), 3.59 (d, J = 8.0 Hz, 1 H, C3-H Z), 4.00 (d, J = 7.2 Hz, 1 H,
C3-H E), 5.92 (dd, J = 16.0, 7.2 Hz, 1 H, PhCH=CH E), 6.08 (dd,
J = 15.6, 8.0 Hz, 1 H, PhCH=CH Z), 6.88 (d, J = 16.0 Hz, 1 H,
PhCH=CH E), 6.95 (d, J = 15.6 Hz, 1 H, PhCH=CH Z), 7.29–7.48
(m, 5 H, Ar-H E + Z).
13C NMR (100 MHz, CDCl3): d = 16.1, 20.4, 50.0, 51.8, 62.6, 63.9,
117.5, 118.8, 119.0, 121.1, 126.7, 126.8, 128.7, 128.8, 128.9, 135.1,
138.6, 138.7.
HRMS (EI): m/z [M+] calcd for C12H11NO: 185.0841; found
185.0844.
HRMS (EI): m/z [M+] calcd for C12H11NO: 185.0841; found
185.0843.
3-Methyl-3-vinyloxirane-2-carbonitrile (17)
Yield: 1.95 g (36%); colorless oil; bp 47–51 °C (10 Torr); mixture
of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.53 (s, 3 H, CH3 Z), 1.67 (s, 3 H,
CH3 E), 3.33 (s, 1 H, C2-H E), 3.44 (s, 1 H, C2-H Z), 5.37 (dd,
J = 10.8, 0.8 Hz, 1 H, CH2=CH E), 5.47 (dd, J = 17.2, 0.8 Hz, 1 H,
CH2=CH E), 5.52 (dd, J = 10.8, 0.8 Hz, 1 H, CH2=CH Z), 5.57 (dd,
J = 17.2, 0.8 Hz, 1 H, CH2=CH Z), 5.61 (dd, J = 17.2, 10.8 Hz, 3 H,
CH2=CH E), 5.84 (dd, J = 17.2, 10.8 Hz, 3 H, CH2=CH Z).
2-Methyl-3-(1-methylstyryl)oxirane-2-carbonitrile (22)
Yield: 8.80 g (88%); colorless oil; bp 114–118 °C (0.5 Torr); mix-
ture of diastereoisomers.
13C NMR (100 MHz, CDCl3): d = 17.1, 19.0, 48.7, 49.0, 61.4, 61.7,
115.6 (E + Z), 119.9, 121.2, 133.4, 135.2.
Anal. Calcd for C6H7NO: C, 66.04; H, 6.47; N, 12.84. Found: C,
65.37; H, 6.49; N, 12.81.
1H NMR (400 MHz, CDCl3): d = 1.56 (s, 3 H, CH3 E), 1.76 (s, 3 H,
CH3 Z), 1.97–2.00 (m, 3 H, PhCH=CCH3 E), 2.01–2.03 (m, 3 H,
PhCH=CCH3 Z), 3.52 (s, 1 H, C3-H Z), 3.92 (s, 1 H, C3-H E), 6.48
(s, 1 H, PhCH=CCH3 E), 6.71 (s, 1 H, PhCH=CCH3 Z), 7.24–7.42
(m, 5 H, Ar-H E + Z).
13C NMR (100 MHz, CDCl3): d = 14.6, 14.7, 15.5, 20.8, 49.4, 51.7,
64.8, 66.3, 117.3, 119.2, 127.1, 127.3, 127.4, 128.2, 128.3, 128.8,
128.9, 129.0, 135.8, 136.1.
3-Methyl-3-(2-methyl-1-propenyl)oxirane-2-carbonitrile (18)
Yield: 5.14 g (75%); colorless oil; bp 90–92 °C (20 Torr); mixture
of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.46 (s, 3 H, CH3 Z), 1.60 (s, 3 H,
CH3 E), 1.69 [d, J = 1.2 Hz, 3 H, CH=C(CH3)2 E], 1.73 [d, J = 1.6
Hz, 3 H, CH=C(CH3)2 E], 1.78 [d, J = 1.6 Hz, 3 H, CH=C(CH3)2
Z], 1.80 [d, J = 1.2 Hz, 3 H, CH=C(CH3)2 Z], 3.30 (s, 1 H, C2-H E),
3.34 (s, 1 H, C2-H Z), 5.30–5.34 [m, 1 H, CH=C(CH3)2 E], 5.38–
5.41 [m, 1 H, CH=C(CH3)2 Z].
Anal. Calcd for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C,
78.24; H, 6.59; N, 7.06.
2,3-Dimethyl-3-(2-methyl-1-propenyl)oxirane-2-carbonitrile
(23)
Yield: 5.72 g (76%); colorless oil; bp 88–92 °C (20 Torr); mixture
of diastereoisomers.
13C NMR (100 MHz, CDCl3): d = 19.1, 19.4, 20.4, 22.3, 25.2, 25.4,
48.0, 48.1, 61.3, 61.8, 116.1, 116.2, 119.2, 121.0, 139.0, 140.7.
HRMS (EI): m/z [M+] calcd for C8H11NO: 137.0841; found:
137.0837.
1H NMR (400 MHz, CDCl3): d = 1.41 (s, 3 H, CH3 minor), 1.51 (s,
3 H, CH3 major), 1.61 (s, 3 H, CH3 major), 1.65 (s, 3 H, CH3 minor),
1.70 [d, J = 1.2 Hz, 3 H, CH=C(CH3)2 major], 1.73 [d, J = 1.6 Hz,
3 H, CH=C(CH3)2 major], 1.74–1.76 [m, 6 H, CH=C(CH3)2 minor],
5.16–5.19 [m, 1 H, CH=C(CH3)2 major], 5.41–5.44 [m, 1 H,
CH=C(CH3)2 minor].
13C NMR (100 MHz, CDCl3): d = 17.4, 18.2, 18.4, 19.3, 19.4, 21.7,
25.1, 25.2, 54.1, 54.4, 64.5, 65.0, 118.7, 118.8, 119.3, 121.7, 139.1,
139.2.
3-Methyl-3-styryloxirane-2-carbonitrile (19)
Yield: 7.36 g (80%); yellowish oil; bp 119–125 °C (0.4 Torr); mix-
ture of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.65 (s, 3 H, CH3 Z), 1.80 (s, 3 H,
CH3 E), 3.43 (s, 1 H, C2-H E), 3.52 (s, 1 H, C2-H Z), 5.95 (d,
J = 16.0 Hz, 1 H, PhCH=CH E), 6.17 (d, J = 16.0 Hz, 1 H,
PhCH=CH Z), 6.75 (d, J = 16.0 Hz, 1 H, PhCH=CH E), 6.86 (d,
J = 16.0 Hz, 1 H, PhCH=CH Z), 7.28–7.46 (m, 5 H, Ar-H E + Z).
HRMS (EI): m/z [M+] calcd for C9H13NO: 151.0997; found:
151.0991.
13C NMR (100 MHz, CDCl3): d = 17.8, 19.7, 49.2, 49.5, 61.7, 62.0,
115.6, 115.7, 124.1, 125.8, 126.6, 126.8, 128.6, 128.7, 134.2, 135.1,
135.2, 135.8.
2,3-Dimethyl-3-styryloxirane-2-carbonitrile (24)
Yield: 2.82 g (28%); yellowish oil; mixture of diastereoisomers.
Anal. Calcd for C12H11NO: C, 77.81; H, 5.99; N, 7.56. Found: C,
77.69; H, 6.21; N, 7.56.
1H NMR (400 MHz, CDCl3): d = 1.60 (s, 3 H, CH3), 1.61 (s, 3 H,
CH3), 1.74 (s, 3 H, CH3), 1.80 (s, 3 H, CH3), 6.11 (d, J = 16.0 Hz,
1 H, PhCH=CH), 6.24 (d, J = 16.0 Hz, 1 H, PhCH=CH), 6.66 (d,
J = 16.0 Hz, 1 H, PhCH=CH), 6.82 (d, J = 16.0 Hz, 1 H,
PhCH=CH), 7.27–7.46 (m, 5 H, Ar-H).
1-Oxaspiro[2.5]oct-4-ene-2-carbonitrile (20)
Yield: 5.32 g (79%); colorless oil; bp 110–114 °C (15 Torr); mix-
ture of diastereoisomers.
1H NMR (200 MHz, CDCl3): d = 1.62–2.32 (m, 6 H, CH2), 3.41 (s,
1 H, C2-H major), 3.44 (s, 1 H, C2-H minor), 5.06–5.16 (m, 1 H,
CCH=CH major), 5.43–5.53 (m, 1 H, CCH=CH minor), 6.20–6.42
(m, 1 H, CCH=CH).
13C NMR (100 MHz, CDCl3): d = 16.2, 17.2, 17.7, 20.5, 55.6, 55.8,
64.7, 65.5, 118.4, 118.5, 123.2, 126.2, 126.6, 126.8, 128.5, 128.5,
128.6, 128.7, 134.6, 134.9, 135.3, 135.4.
Anal. Calcd for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C,
78.08; H, 6.48; N, 6.78.
Synthesis 2007, No. 1, 75–80 © Thieme Stuttgart · New York

PAPER
Synthesis of Alkenyl-Substituted Glycidonitriles and Glycidates
79
2-Methyl-1-oxaspiro[2.5]oct-4-ene-2-carbonitrile (25)
Yield: 2.65 g (36%); colorless oil; bp 109–114 °C (15 Torr); mix-
ture of diastereoisomers.
13C NMR (100 MHz, CDCl3): d = 13.9 (E + Z), 22.3, 22.5, 27.9,
28.0, 30.0, 30.4, 33.3, 54.2, 55.3, 57.6, 59.2, 82.1, 82.4, 112.2,
113.9, 140.4, 143.6, 165.8, 167.8.
1H NMR (400 MHz, CDCl3): d = 1.63 (s, 1 H, CH3 major), 1.64 (s,
1 H, CH3 minor), 1.76–2.25 (m, 6 H, CH2), 5.22–5.32 (m, 1 H,
CCH=CH major), 5.50–5.60 (m, 1 H, CCH=CH minor), 6.22–6.40
(m, 1 H, CCH=CH).
13C NMR (100 MHz, CDCl3): d = 16.9, 17.2, 20.6, 20.8, 24.6, 24.9,
26.7, 29.9, 55.1, 55.4, 63.5, 64.1, 118.4, 118.5, 121.8, 124.7, 139.0,
139.9.
Anal. Calcd for C13H22O3: C, 68.99; H, 9.80. Found: C, 69.14; H,
9.71.
tert-Butyl 3-Styryl-oxirane-2-carboxylate (29)
Yield: 2.48 g (40%); colorless oil; bp 147 °C (0.6 Torr); mixture of
diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.50 [s, 9 H, C(CH3)3 Z], 1.52 [s,
9 H, C(CH3)3 E], 3.39 (d, J = 2.0 Hz, 1 H, C2-H E), 3.66 (d, J = 4.4
Hz, 1 H, C2-H Z), 3.69 (dd, J = 8.0, 2.0 Hz, 1 H, C3-H E), 3.75 (dd,
J = 8.4, 4.4 Hz, 1 H, C3-H Z), 5.87 (dd, J = 16.0, 8.0 Hz, 1 H,
PhCH=CH E), 6.16 (dd, J = 16.0, 8.4 Hz, 1 H, PhCH=CH Z), 6.85
(d, J = 16.0 Hz, 1 H, PhCH=CH E), 6.89 (d, J = 16.0 Hz, 1 H,
PhCH=CH Z), 7.24–7.42 (m, 5 H, Ar-H E + Z).
Anal. Calcd for C9H11NO: C, 72.46; H, 7.43; N, 9.39. Found: C,
72.41; H, 7.47; N, 9.28.
Synthesis of Compounds 26–30; General Procedure
Powdered NaOH (3.00 g, 75 mmol) and THF (25 mL) were stirred
with a magnetic stirrer while a mixture of a-chloroester 3 (5.12 g,
37.5 mmol) or 4 (4.52 g, 30 mmol) and the carbonyl compound 5–
8 (25 mmol) was added dropwise at 10–30 °C (Table 2) over 10
min. The mixture was stirred at the same temperature for the time
indicated in Table 2 (until GC analyses indicated the total consump-
tion of the starting carbonyl compound) and worked up as described
above. The products 26–30 were isolated either by vacuum distilla-
tion or by crystallization from MeOH (Table 2).
13C NMR (100 MHz, CDCl3): d = 27.9, 28.0, 55.0, 55.6, 57.5, 58.0,
82.5 (E + Z), 121.6, 124.2, 126.5, 128.4, 128.6, 135.5, 136.1, 137.5,
166.8, 167.5.
Anal. Calcd for C15H18O3: C, 73.15; H, 7.37. Found: C, 72.91; H,
7.20.
tert-Butyl 3-(1-Methylstyryl)oxirane-2-carboxylate (30)
Yield: 4.75 g (73%); white solid; mp 66–67 °C (MeOH).
Isopropyl 3-(1-Methylstyryl)oxirane-2-carboxylate (26)
Yield: 1.97 g (32%); yellowish oil; bp 141–145 °C (1.5 Torr).
1H NMR (400 MHz, CDCl3): d = 1.52 [s, 9 H, C(CH3)3], 1.74 (d,
J = 1.2 Hz, 3 H, CH3), 3.42 (d, J = 2.0 Hz, 1 H, C2-H), 3.67 (dd,
J = 2.0, 0.4 Hz, 1 H, C3-H), 6.72 (s, 1 H, PhCH=CCH3), 7.23–7.38
(m, 5 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 11.9, 27.9, 53.1, 61.6, 82.5,
127.0, 128.2, 128.9, 130.9, 131.9, 136.5, 167.9.
1H NMR (400 MHz, CDCl3): d = 1.31 [d, J = 6.4 Hz, 3 H,
CH(CH3)2], 1.32 (d, J = 6.4 Hz, 3 H, CH(CH3)2], 1.75 (d, J = 1.6
Hz, 3 H, CH3), 3.50 (d, J = 1.6 Hz, 1 H, C2-H), 3.72 (dd, J = 1.6,
0.8 Hz, 1 H, C3-H), 5.14 [qq, J = 6.4, 6.4 Hz, 1 H, CH(CH3)2], 6.72
(s, 1 H, PhCH=CCH3), 7.22–7.38 (m, 5 H, Ar-H).
13C NMR (100 MHz, CDCl3): d = 11.9, 21.6, 21.7, 52.7, 61.8, 69.4,
127.1, 128.1, 128.2, 128.9, 130.9, 131.7, 136.5, 168.4.
Anal. Calcd for C16H20O3: C, 73.82; H, 7.74. Found: C, 73.68; H,
7.85.
Anal. Calcd for C15H18O3: C, 73.15; H, 7.37. Found: C, 73.12; H,
7.37.
Acknowledgment
We are grateful to the Ministry of Science and Higher Education,
Warsaw (Poland) for financial support (Grant No 3 T09B 084 29).
tert-Butyl 3-(1-Propenyl)oxirane-2-carboxylate (27)
Yield: 1.40 g (30%); colorless oil; bp 57–60 °C (0.2 Torr); mixture
of diastereoisomers.
1H NMR (400 MHz, CDCl3): d = 1.44 [s, 9 H, C(CH3)3 E], 1.45 [s,
9 H, C(CH3)3 Z], 1.70–1.75 (m, 3 H, CH3 E + Z), 3.20 (d, J = 2.0 Hz,
1 H, C2-H E), 3.43 (dd, J = 8.0, 2.0 Hz, 1 H, C3-H E), 3.48–3.52
(m, 2 H, C2-H + C3-H Z), 5.13 (ddq, J = 15.6, 8.0, 1.6 Hz, 1 H,
CH3CH=CH E), 5.34–5.42 (m, 1 H, CH3CH=CH Z), 5.94–6.08 (m,
1 H, CH3CH=CH E + Z).
13C NMR (100 MHz, CDCl3): d = 17.8, 18.0, 27.8, 28.0, 54.6, 55.1,
57.2, 57.7, 82.2, 82.3, 123.6, 126.5, 133.7, 135.1, 166.9, 167.7.
HRMS (EI): m/z [M+] calcd for C10H16O3: 184.1099; found:
184.1099.
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80
A. Gadaj, A. Jończyk
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Synthesis 2007, No. 1, 75–80 © Thieme Stuttgart · New York