Reactions of nitroxides XIII: Synthesis of the Morita-Baylis-Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6- tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

Article abstract of DOI:10.3762/bjoc.8.171

The Morita-Baylis-Hillman adducts bearing a nitroxyl moiety were synthesized from 4-acryloyloxy-2,2,6,6-tetramethylpiperidine- 1-oxyl and aliphatic, aryl and heterocyclic aldehydes.

Full text of DOI:10.3762/bjoc.8.171

Reactions of nitroxides XIII:
Synthesis of the Morita–Baylis–Hillman adducts
bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-
tetramethylpiperidine-1-oxyl as a starting compound,
and DABCO and quinuclidine as catalysts
Jerzy Zakrzewski
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 1515–1522.
Institute of Industrial Organic Chemistry, Annopol 6, 03-236 Warsaw,
Poland
doi:10.3762/bjoc.8.171
Received: 23 May 2012
Email:
Accepted: 03 August 2012
Published: 12 September 2012
Jerzy Zakrzewski - zakrzewski@ipo.waw.pl
For part XII see [1].
Keywords:
4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl; DABCO;
Morita–Baylis–Hillman reaction; nitroxides; quinuclidine
Associate Editor: M. P. Sibi
© 2012 Zakrzewski; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The Morita–Baylis–Hillman adducts bearing a nitroxyl moiety were synthesized from 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-
1-oxyl and aliphatic, aryl and heterocyclic aldehydes.
Introduction
In the Morita–Baylis–Hillman (MBH) reaction, aldehydes react every year. The application and scope of the reaction has been
with a double bond activated by an electron-withdrawing group summarized in many review articles, e.g., [20], as well as the
(EWG). The vinylic carbon bearing an EWG undergoes substi- latest ones [21-24]. Some recent results concerning MBH reac-
tution. The reaction is carried out in the presence of either a tion have been presented [6,16,18,25-33]. MBH adducts them-
tertiary amine (e.g., DABCO [2-6], quinuclidine and its deriva- selves are reported to be antiproliferative agents [34]; however,
tives [7-12], DBU [13,14], DBN [13], DMAP and its deriva- they are often applied as a tool for building more complex
tives [4,15,16], urotropine [17], brucine N-oxide [18]) or a target structures, usually of biological importance [35-43]. The
phosphine [19] as a catalyst. The MBH reaction is a MBH reaction is a rather slow process (complete reaction
carbon–carbon bond forming process. This is the reason why a can take hundreds of hours), especially when acrylates are
huge amount of research devoted to the reaction is reported used [44]. As has been very well known since the 1960s,
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stable nitroxides can react without affecting the unpaired Results and Discussion
electron. However, there are also reactions that do involve the 4-Acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (3) was
free electron (e.g., many types of reductions, or a disproportion- obtained by esterification of acryloyl chloride (2) with 2,2,6,6-
ation in an acidic environment). To the best of our knowledge, tetramethyl-4-piperidinol-1-oxyl (1) [46,47] in 90–95% yield.
nitroxyl radicals have not yet been applied in the MBH reaction To synthesize MBH adducts (5a–o), 3 was reacted with ali-
(to date), and the potential influence of the nitroxide moiety on phatic (4a–c), aryl (4d–l) and heterocyclic (4m,n) aldehydes,
the MBH reaction is unknown. Herein we present the MBH and (to obtain a compound bearing both nitroxyl and ferrocenyl
reaction with a nitroxyl radical, 4-acryloyloxy-2,2,6,6-tetra- moiety) ferrocenyl aldehyde (4o). Two catalytic systems were
methylpiperidine-1-oxyl, used as a starting material as an olefin tested: DABCO, and quinuclidine with methanol as a cocata-
activated with EWG. Acrylates are considered as rather unreac- lyst. The latter system was chosen because it has been described
tive in the MBH reaction [44]. It was shown that the effects on as an excellent rate enhancer for the MBH reaction [9,11].
the reaction of aryl, benzyl, alkyl, and functionalized alkyl Methanol was chosen as an additive bearing a polar O–H bond,
acrylic esters with benzaldehyde and furfuraldehyde in the pres- which activates both the aldehyde and “Michael” intermediate
ence of DABCO, strongly depend upon the electronic and steric formed in the first step of the reaction, when an amine catalyst
effects of the ester part. The “unreactivity” of acrylates attacks an EWG activated olefin [11]. The reaction was carried
increases with steric hindrance and with increasing chain length out in THF as a solvent or the reagents were stirred neat. The
of the alcohol moiety in an acrylate [20,45]. The alcohol moiety synthesized MBH adducts (5a–o) are summarized in Scheme 1
in 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl is and Table 1.
undoubtly sterically hindered, so the expected reaction times
will be long; however, this nitroxide has been chosen based on MBH adducts (5a–o) were obtained with very diverse results.
the availability of such nitroxyl esters. As an electrophilic Reaction times varied from one day to tens of days (5f,g,o). The
partner in the MBH reaction, commonly used aldehydes were reaction was significantly faster in the presence of quinuclidine/
chosen, whose activity is broadly discussed in the literature. methanol system as a catalyst than in the presence of DABCO.
Aromatic aldehydes, especially those containing EWGs, are The yields of the MBH adducts successfully obtained varied
considered as reactive in the MBH reaction, in contrast to the from negligible (5o, see below) to almost quantitative (5c,m).
aliphatic aldehydes (both n-butanal and pivalaldehyde), which The use of 4-hydroxybenzaldehyde, 2-bromonicotinic aldehyde
are considered to be unreactive, although EWGs on the and 3-ferrocenylpropenal [48] did not result in any detectable
α-carbon atom (e.g., chloral) enhance their reactivity [20]. MBH adducts in either catalytic system. The reaction with 2,4-
2-Furaldehyde and nicotinic aldehyde were used because they dinitrobenzaldehyde (4l) provides some atypical intensely blue-
were considered to be especially reactive in the MBH reaction colored side-products. The appropriate blue zones were isolated
[43].
during column chromatography (Supporting Information
Scheme 1: MBH adducts 5a–o from 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl.
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Table 1: Yields and melting points (mp) of MBH adducts 5a–o.
5
R
DABCO
t [h]
DABCO
yield [%]
quinuclidine/methanol quinuclidine/methanol mp [°C]
t [h]
yield [%]
a
b
c
d
e
f
n-C4H9
333
330
91
36
—
48
78
—
—
27
24
76
59
22
69
99
24
—
96
81
33
99
92
42
27
23
56
77
47
79
56
65
48
2
83–85
(CH3)3C
480
26
red oil
CCl3
154–156
116–118
130–133
121–124
105–109
127–130
132–135
112–115
102–104
50–57 (glass)
92–97
C6H5
115
672
984
1008
672
768
528
376
90
48
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
336
1112
336
168
72
g
h
i
4-BrC6H4
4-CF3C6H4
3,5-(CF3)2C6H3
4-NO2C6H4
2,4-(NO2)2C6H3
3-pyridyl
j
432
96
k
l
30
m
n
o
592
664
1128
72
2-furyl
144
1680
114–118
118–124
ferrocenyl
File 1); however, attempts to obtain their physicochemical and [54]. 5d was reduced in situ with phenylhydrazine directly in an
spectral data were unsuccessful. The blue color of the side- NMR tube to a nonradical, corresponding N-hydroxylamine.
products suggests that a nitroso group may be formed as a result The 1H NMR and 13C NMR spectra were recorded, but only
of the reduction of the nitro group. Such transformations of 2,4- their aliphatic part was found to be valuable due to the signals
dinitrobenzaldehyde are well known. Under light, 2-nitroso-4- belonging to phenylhydrazine itself. The recorded spectral data
nitrobenzoic acid (characterized as its methyl ester) is formed are presented in the experimental part and the Supporting Infor-
[49]. In dilute aqueous sodium hydroxide solution, 4-nitroso-2- mation File 1 (together with spectra of phenylhydrazine itself,
nitrophenol and formic acid are formed [50-52]. Ferrocenyl as a background) as well. The observed singlet in 1H NMR at
aldehyde (4o) as the starting compound [53] did not afford any δ 5.54, and symmetric narrow multiplets at 5.76–5.90 and
product when DABCO was used as a catalyst. Use of the quinu- 6.28–6.45 assigned to the C6H5–CH(OH)–C(=CH2)- fragment
clidine/methanol system and thorough searching of a potential are well consistent with the spectra of the typical series of the
product by TLC, resulted in the separation of the expected MBH adducts of common aldehydes and methyl acrylate,
adduct 5o in 2% yield. However, its identity was confirmed presented in [32]. Synthesized compounds 5a–o showed a weak
unambiguously by (HR-)MS (both EI and ESI) and IR spec- antifungal activity. No insecticidal, acaricidal and herbicidal
troscopy. This poor result is probably caused by the cumulative activity were shown.
steric hindrance of both ferrocenyl and nitroxyl moieties (the
sensitivity of the MBH reaction to the steric hindrance of the Conclusion
alcohol moiety in an acrylate was commented on in the intro- In conclusion, it has been demonstrated that the use of 4-acryl-
duction [20,45]). Due to the radical nature of the adducts 5a–o, oyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (3) as a starting
their structures were confirmed by (HR-)MS (both EI and ESI), compound allows us to obtain new MBH adducts 5a–o bearing
and IR spectroscopy (see Supporting Information File 1 for a nitroxyl moiety. The use of quinuclidine with methanol as a
EIMS and IR spectra). Most of the EIMS spectra show the m/z catalyst instead of DABCO decreases the time of the reaction.
124 peak as the base one (except 5k,m,o), and the abundant No influence of the radical nature of 4-acryloyloxy-2,2,6,6-
intensity of m/z 109 peak (except 5c,f,l,o). The both fragments: tetramethylpiperidine-1-oxyl (3) on the reaction course was
m/z 124 and 109 are originated from the nitroxyl moiety of the observed.
investigated compounds 5. HRMS–EI for m/z 124: calcd for
C9H16: 124.12520; found: 124.12515; for m/z 109: calcd for Experimental
C8H13: 109.10173; found: 109.10079. However, direct charac- General: 2,2,6,6-Tetramethyl-4-hydroxypiperidin-1-oxyl (1)
terization of the adducts 5a–o by NMR is impossible, one of the was synthesized by the oxidation of 2,2,6,6-tetramethyl-4-
adducts (5d, R = C6H5) was subjected to the exemplary experi- piperidinol with 30% hydrogen peroxide (76.5% yield, mp
ment developed for nitroxides by Keana and coworkers in 1975 71–73 °C), according to [55-57]. Liquid aldehydes were puri-
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Beilstein J. Org. Chem. 2012, 8, 1515–1522.
fied by using vacuum distillation. THF was distilled over 10–20 mol % DABCO or quinuclidine), methanol (only if quin-
sodium under argon in the presence of benzophenone as an indi- uclidine is used as catalyst) (10 μL), and an excess of freshly
cator. The experiments were performed in a 5 mL round-bottom distilled aldehyde (4a, 4b, 4d, 4n, ≈1 mL) were stirred under
flask, equipped with a magnetic stirrer. Most of the MBH argon at room temperature for the time mentioned in Table 1.
adducts were obtained as red solids. TLC was carried out on The progress of the reaction was monitored by TLC (hexane/
silica gel Merck Alurolle 5562, Alufolien 5554. Column chro- ethyl acetate 9:1, benzene/ethyl acetate 9:1, benzene/methanol
matography was performed by using Merck 1.09385.1000 or 9:1). The MBH adduct 5 was isolated by direct column chroma-
Zeochem 60 hyd 40–63 μm (0.040–0.063 mm, 230–400 mesh). tography of the reaction mixture by using an appropriate mobile
TLC visualisation: UV 254 nm light and/or iodine vapours. phase (hexane/ethyl acetate 9:1, benzene/ethyl acetate 95:5,
EIMS data were recorded by using AMD 604 and Agilent Tech- benzene/methanol 95:5) to afford the desired adduct 5.
nologies 5975 B mass spectrometers. HRMS–EI data were
recorded by using an AMD 604 mass spectrometer. ESIMS and MBH adducts 5; general procedure in THF (5c, e–m, o): An
HRMS–ESI (positive ions, CH3OH as solvent) were recorded appropriate aldehyde, freshly distilled and added with a syringe
by using a Micromass LCT apparatus. IR (ν, cm−1) data were if liquid (0.8 mmol (4e, 4f, 4g, 4h, 4i, 4j, 4m), 0.6 mmol (4c),
recorded by using an FT/IR Jasco 420 spectrophotometer. 1H or 0.4 mmol (4k, 4l, 4o)), 4-acryloyloxy-2,2,6,6-tetramethyl-
and 13C NMR data were collected by using a Varian UNITY- piperidine-1-oxyl (3, 0.4 mmol), a catalyst (about 10–20 mol %
plus 200 spectrophotometer.
DABCO or quinuclidine), methanol (only if quinuclidine is
used as catalyst, 10 μL), and anhydrous THF (1.0–1.5 mL),
4-Acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (3): were stirred under argon at room temperature for the time
2,2,6,6-Tetramethyl-4-piperidinol-1-oxyl (1, 0.344 g, 2 mmol) mentioned in Table 1. The progress of the reaction was moni-
in benzene (≈5 mL) was placed in a round bottomed flask of tored by TLC (hexane/ethyl acetate 9:1, benzene/ethyl acetate
50 mL capacity equipped with a magnetic stirrer. A solution of 9:1, benzene/methanol 9:1). THF was evaporated under reduced
triethylamine (1.54 g, 15.3 mmol, 2.1–2.2 mL) in benzene pressure. The residue was subjected to column chromatography
(6 mL) was added dropwise from a pipette. A solution of acry- by using an appropriate mobile phase (hexane/ethyl acetate 9:1,
loyl chloride (2, 0.187 g, 2.08 mmol, 170 μL) in benzene benzene/ethyl acetate 95:5, benzene/methanol 95:5) to afford
(3.5 mL) was added dropwise from a syringe at room tempera- the desired adduct 5.
ture. The progress of the reaction was monitored by TLC
(benzene/ethyl acetate 9:1, benzene/methanol 9:1). The reac- 4-(2-((n-Butyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra-
tion mixture was stirred at room temperature for 20 h, then the methylpiperidine-1-oxyl (5a): Yield (DABCO): 46 mg (36%);
second portion of 2 (0.094 g, 1.04 mmol, 85 μL) in benzene Yield (quinuclidine): 101 mg (81%); orange solid; mp
(1.7 mL) was added dropwise from a syringe. The reaction mix- 83–85 °C; EIMS m/z (% relative intensity): M+ 312 (10), 255
ture was stirred at room temperature for 1 h. Depending on the (7), 240 (10), 155 (45), 154 (23), 141 (11), 140 (35), 139 (17),
results of the TLC control of the progress of the reaction the 124 (100), 109 (69), 100 (18), 98 (9), 95 (30), 85 (10), 83 (44),
third portion of 2 may be added (≈50 μL). After the reaction had 82 (19), 81 (16), 74 (14), 69 (31), 67 (17), 56 (18), 55 (29), 41
been terminated, the precipitate of triethylamine hydrochloride (32); HRMS–EI (m/z): calcd for C17H30NO4: 312.21748;
was filtered off and the filtrate was concentrated under reduced found: 312.21674; mass spectrum (ESI, m/z, %) 335 (100,
pressure. The red residue was subjected to column chromatog- [M + Na]+) 140 (46); HRMS–ESI (m/z): calcd for
raphy (hexane/ethyl acetate 9:1 as a mobile phase). The red C19H26NO4Na, 335.2073; found, 335.2067; IR (KBr): 1701
eluent was collected to give red crystals of 4-acryloyloxy- (C=O), 1633 (C=C) cm−1.
2,2,6,6-tetramethylpiperidine-1-oxyl (3), yield: 0.41–0.43 g
(90–95%); mp 102–104 °C (lit. [46]: 102.5–103 °C, [58]: 102 4-(2-((tert-Butyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra-
°C, [59]: 99 °C ); EIMS m/z (% relative intensity): M+ 226 (16), methylpiperidine-1-oxyl (5b): Yield (quinuclidine): 41 mg
194 (10), 154 (15), 141 (7), 140 (17), 139 (21), 124 (84), 109 (33%); red oil; EIMS m/z (% relative intensity): M+ 312 (11),
(95), 98 (6), 95 (8), 82 (21), 81 (20), 69 (11), 68 (20), 67 (19), 241 (6), 172 (7), 156 (44), 155 (64), 140 (73), 124 (100), 109
55 (100), 41 (34); HRMS–EI (m/z): calcd for C12H20NO3, (65), 100 (49), 98 (17), 95 (22), 85 (13), 83 (22), 82 (27), 81
226.14432; found, 226.14401; IR (KBr): 1720 (C=O), 1635 (24), 74 (55), 69 (46), 67 (23), 58 (17), 57 (98), 56 (38), 55
(C=C) cm−1.
(42), 41 (65); HRMS–ESI (m/z): calcd for C17H30NO4,
312.21748; found, 312.21818; ESIMS m/z (% relative
MBH adducts 5; general procedure without solvent with an intensity): [M + Na]+ 335 (100); HRMS–ESI (m/z): [M + Na]+
excess of aldehyde (5a,b,d,n): 4-Acryloyloxy-2,2,6,6-tetra- calcd for C17H30NO4Na, 335.2073; found, 335.2042; IR (KBr):
methylpiperidine-1-oxyl (3, 0.4 mmol), and a catalyst (about 1706 (C=O) 1627 (C=C) cm−1.
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Beilstein J. Org. Chem. 2012, 8, 1515–1522.
4-(2-((Trichloromethyl)hydroxymethyl)acryloyloxy)-2,2,6,6- 715 (3), [M + Na]+ 369 (100); HRMS–ESI (m/z): [M + Na]+
tetramethylpiperidine-1-oxyl (5c): Yield (DABCO): 72 mg calcd for C20H28NO4Na, 369.1905; found, 369.1916; IR (KBr):
(48%); yield (quinuclidine): 148 mg (99%); yellow powder; mp 1709 (C=O), 1630 (C=C) cm−1.
154–156 °C; EIMS m/z (% relative intensity): 374 (5), M+ 372
(5), 240 (9), 203 (4), 201 (5), 167 (9), 165 (15), 155 (24), 154 4-(2-((4-Methoxyphenyl)hydroxymethyl)acryloyloxy)-
(20), 140 (17), 139 (19), 124 (100), 110 (6), 100 (10), 98 (6), 95 2,2,6,6-tetramethylpiperidine-1-oxyl (5f): Yield (quinucli-
(5), 85 (11), 83 (7), 82 (17), 81 (14), 69 (22), 68 (11), 67 (13), dine): 39 mg (27%); orange solid; mp 121–124 °C; EIMS m/z
56 (14), 55 (20); HRMS–EI (m/z): calcd for C14H21NO4Cl3, (% relative intensity): M+ 362 (23), 208 (13), 207 (17), 191
372.05362; found, 372.05425; ESIMS m/z (% relative (23), 190 (14), 189 (19), 173 (12), 163 (9), 162 (8), 154 (42),
intensity): 397 (86), [M + Na]+ 395 (100); HRMS–ESI (m/z): 147 (10), 146 (14), 145 (20), 140 (31), 139 (19), 137 (23), 135
[M + Na]+ calcd for C14H21Cl3NO4Na, 395.0434; found, (36), 124 (100), 110 (7), 69 (23), 57 (6), 56 (11), 41 (21);
395.0429; IR (KBr): 1710 (C=O), 1633 (C=C) cm−1.
HRMS–EI (m/z): calcd for C20H28NO5, 362.19675; found,
362.19501; EIMS m/z (% relative intensity): [M + Na]+ 385
4-(2-((Phenyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra- (100), 119 (15); HRMS–ESI (m/z): [M + Na]+ calcd for
methylpiperidine-1-oxyl (5d): Yield (DABCO): 104 mg C20H28NO5Na, 385.1865; found, 385.1841; IR (KBr): 1707
(78%); yield (quinuclidine): 122 mg (92%); orange crystals; mp (C=O), 1611 (C=C) cm−1.
116–118 °C; EIMS m/z (% relative intensity): M+ 332 (9), 302
(3), 284 (2), 154 (16), 140 (11), 133 (8), 124 (100), 117 (28), 4-(2-((4-Fluorophenyl)hydroxymethyl)acryloyloxy)-2,2,6,6-
116 (14), 115 (27), 109 (82), 79 (21); HRMS–EI calcd for tetramethylpiperidine-1-oxyl (5g): Yield (DABCO): 38 mg
C19H26NO4, 332.1862; found, 332.1856; ESIMS m/z (% rela- (27%); Yield (quinuclidine): 33 mg (23%); yellow powder; mp
tive intensity): [M + Na]+ 355 (100); HRMS–ESI (m/z): 105–109 °C; EIMS m/z (% relative intensity): M+ 350 (13), 195
[M + Na]+ calcd for C19H26NO4Na, 355.1760; found, (5), 180 (5), 179 (7), 177 (4), 154 (33), 140 (22), 139 (16), 135
355.1742; IR (KBr): 1707 (C=O), 1628 (C=C) cm−1; 1H NMR (25), 134 (12), 133 (20), 124 (100), 109 (83), 97 (15), 83 (6), 82
(200 MHz, CDCl3, after reduction with phenylhydrazine in situ, (16), 69 (25), 67 (13), 56 (11), 55 (18), 41 (22); HRMS–EI
in an NMR tube, in CDCl3, aliphatic part of the spectrum, in (m/z): calcd for C19H25NO4F, 350.17676; found, 350.17570;
fact the spectrum of the corresponding hydroxylamine [54]) δ ESIMS m/z (% relative intensity): [M + Na]+ 373 (20), 288
1.16, 1.18, 1.19, 1.21 (4s, 12H, 4CH3), 1.40–1.64 (m, 2H, (100); HRMS–ESI (m/z): [M + Na]+ calcd for C19H25FNO4Na,
CH2), 1.75–1.95 (m, 2H, CH2), 4.96–5.18 (m, 1H, 373.1665; found: 373.1652; IR (KBr): 1712 (C=O), 1631 (C=C)
CH–OC(=O)), 5.54 (s, 1H, CH–OH), 5.76–5.90 (m, 1H, cm−1.
=CHH), 6.28–6.45 (m, 1H, =CHH) ppm; 13C NMR (50 MHz,
CDCl3, after reduction with phenylhydrazine in situ, in an NMR 4-(2-((4-Bromophenyl)hydroxymethyl)acryloyloxy)-2,2,6,6-
tube, in CDCl3, aliphatic part of the spectrum, in fact the spec- tetramethylpiperidine-1-oxyl (5h): Yield (DABCO): 39 mg
trum of the corresponding hydroxylamine [54]) δ 20.65 (2CH3), (24%); yield (quinuclidine): 92 mg (56%); orange powder; mp
32.00 (2CH3), 43.75 (CH2, confirmed by DEPT 135, piperidine 127–130 °C; EIMS m/z (% relative intensity): 412 (12), M+ 410
ring), 43.81 (CH2, confirmed by DEPT 135, piperidine ring), (11), 255 (5), 239 (7), 185 (6), 160 (23), 154 (43), 140 (15), 139
43.97 (CH2, confirmed by DEPT 135, piperidine ring), 59.48 (17), 124 (100), 116 (21), 109 (66), 69 (18), 55 (14), 41 (16);
(2C, absent in DEPT 135, piperidine ring), 67.68 (CHOC=O), HRMS–EI (m/z): calcd for C19H25NO4Br, 410.09669; found,
73.32 (CHOH), 126.12 (C=CH2, confirmed by DEPT 135), 410.09745; ESIMS m/z (% relative intensity): 435 (80),
126.84 (2CHar), 128.03 (CHar), 128.64 (2CHar), 141.63 [M + Na]+ 433 (80), 414 (95), [M + 2H]+ 412 (100);
(Car–CHOH, absent in DEPT 135), 142.50 (C=CH2, absent in HRMS–ESI (m/z): [M + 2H]+ calcd for C19H27NO4Br,
DEPT 135), 165.98 (C=O, absent in DEPT 135) ppm.
412.1123, found, 412.1109; HRMS–ESI (m/z): [M + Na]+ calcd
for C19H25NO4BrNa, 433.0865; found, 433.0868; IR (KBr):
4-(2-((4-Methylphenyl)hydroxymethyl)acryloyloxy)-2,2,6,6- 1708 (C=O), 1630 (C=C) cm−1.
tetramethylpiperidine-1-oxyl (5e): Yield (quinuclidine):
58 mg (42%); orange solid; mp 130–133 °C; EIMS m/z (% rela- 4-(2-((4-Trifluoromethylphenyl)hydroxymethyl)acryloyloxy)
tive intensity): M+ 346 (22), 191 (13), 175 (15), 173 (12), 156 -2,2,6,6-tetramethylpiperidine-1-oxyl (5i): Yield (DABCO):
(11), 155 (10), 154 (22), 147 (9), 140 (18), 139 (16), 131 (25), 122 mg (76%); yield (quinuclidine): 123 mg (77%); orange-
130 (9), 129 (15), 124 (100), 109 (67), 93 (11), 91 (19), 82 (13), yellow powder; mp 132–135 °C; EIMS m/z (% relative
81 (14), 77 (9), 74 (8), 69 (13), 68 (7), 69 (13), 56 (8), 55 (13), intensity): M+ 400 (13), 229 (6), 201 (10), 185 (15), 184 (8),
41 (14); HRMS–EI (m/z): calcd for C20H28NO4, 346.20183; 183 (12), 154 (39), 141 (7), 139 (16), 127 (16), 125 (15), 124
found, 346.20093; ESIMS m/z (% relative intensity): [2M + Na] (100), 109 (82), 85 (10), 83 (6), 82 (14), 81 (16), 74 (9), 69
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Beilstein J. Org. Chem. 2012, 8, 1515–1522.
(22), 68 (10), 67 (12), 57 (7), 56 (11), 55 (17), 41 (22); 162 (13), 154 (15), 144 (8), 140 (24), 135 (17), 124 (59), 118
HRMS–EI (m/z): calcd for C20H25NO4F3, 400.17357; (23), 117 (18), 109 (73), 82 (11), 81 (13), 80 (13), 79 (6), 78
found, 400.17225; ESIMS m/z (% relative intensity): [M + Na]+ (7), 69 (19), 68 (8), 67 (14), 56 (11), 55 (20), 53 (9), 41 (26);
423 (100); HRMS–ESI (m/z): [M + Na]+ calcd for HRMS–EI (m/z): calcd for C18H25N2O4, 333.18143; found,
C20H25F3NO4Na, 423.1633; found, 423.1629; IR (KBr): 1712 333.18050; ESIMS m/z (% relative intensity): [M + Na]+ 356
(C=O), 1630 (C=C) cm−1.
(100); HRMS–ESI (m/z): [M + Na]+ calcd for C18H25N2O4Na,
356.1712; found, 356.1708; IR (film) 1714 (C=O), 1632 (C=C)
4-(2-((3,5-Bis(trifluoromethyl)phenyl)hydroxymethyl)acryl- cm−1.
oyloxy)-2,2,6,6-tetramethylpiperidine-1-oxyl (5j): Yield
(DABCO): 111 mg (59%); yield (quinuclidine): 88 mg (47%); 4-(2-((2-Furyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra-
light-orange crystals; mp 112–115 °C; EIMS m/z (% relative methylpiperidine-1-oxyl (5n): Yield (DABCO): 31 mg (24%);
intensity): M+ 468 (16), 454 (4), 434 (10), 253 (10), 252 (5), yield (quinuclidine): 62 mg (48%); dark orange-yellow powder;
251 (4), 249 (6), 243 (6), 241 (9), 233 (10), 229 (8), 213 (7), mp 114–118 °C; EIMS m/z (% relative intensity): M+ 322 (20),
195 (13), 154 (36), 140 (22), 139 (17), 124 (100), 109 (74), 85 305 (4), 154 (25), 151 (29), 140 (30), 124 (100), 109 (84), 97
(12), 82 (14), 81 (14), 69 (15), 68 (9), 67 (11), 57 (6), 56 (10), (24), 83 (9), 82 (17), 81 (17), 69 (43), 67 (19), 56 (13), 55 (19),
55 (14), 41 (16); HRMS–EI (m/z): calcd for C21H24NO4F6, 41 (36); HRMS–EI (m/z): calcd for C17H24NO5, 322.16545;
468.16095; found, 468.16152; ESIMS m/z (% relative found, 322.16457; ESIMS m/z (% relative intensity): 346 (50),
intensity): [M + Na]+ 491 (100); HRMS–ESI (m/z): [M + Na]+ [M + Na]+ 345 (100); HRMS–ESI (m/z): [M + Na]+ calcd for
calcd for C21H24F6NO4Na, 491.1507; found: 491.1459; IR C17H24NO5Na, 345.1552; found, 345.1554; IR (KBr): 1706
(KBr): 1714 (C=O), 1638 (C=C) cm−1.
(C=O), 1633 (C=C) cm−1.
4-(2-((4-Nitrophenyl)hydroxymethyl)acryloyloxy)-2,2,6,6- 4-(2-((Ferrocenyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra-
tetramethylpiperidine-1-oxyl (5k): Yield (DABCO): 33 mg methylpiperidine-1-oxyl (5o): Yield (quinuclidine): 4 mg
(22%); yield (quinuclidine): 120 mg (79%); yellow powder; mp (2%); orange solid; mp 118–124 °C; EIMS m/z (% relative
102–104 °C; EIMS m/z (% relative intensity): M+ 377 (15), 363 intensity): 441 (8), M+ 440 (16), 439 (1), 438 (2), 426 (6), 425
(12), 189 (8), 160 (25), 154 (51), 140 (67), 139 (19), 124 (76), (14), 424 (2), 423 (7), 410 (2), 409 (4), 392 (3), 286 (64), 284
109 (100), 85 (13), 82 (22), 81 (21), 69 (29), 68 (13), 67 (16), (9), 270 (14), 269 (6), 268 (7), 243 (8), 241 (5), 224 (25), 186
57 (9), 56 (16), 55 (23), 41 (28); HRMS–EI (m/z): calcd for (7), 185 (9), 149 (18), 98 (35), 97 (22), 80 (78), 71 (34), 70
C19H25N2O6, 377.17126; found, 377.17090; ESIMS m/z (% (15), 69 (31), 58 (39), 57 (64), 56 (18), 55 (52), 45 (13), 44
relative intensity): [M + Na]+ 400 (100); HRMS–ESI (m/z): (67), 43 (36), 42 (22), 41 (48), 40 (100); HRMS–EI (m/z): calcd
[M + Na]+ calcd for C19H25N2O6Na, 400.1610; found, for C23H30NO4Fe; 440.15242; found, 440.15327; ESIMS m/z
400.1603; IR (KBr): 1713 (C=O), 1636 (C=C), 1521 (NO2), (% relative intensity): [M + Na]+ 463 (95), M+ 440 (100);
1351 (NO2) cm−1.
HRMS–ESI (m/z): calcd for C23H30NO4Fe, 440.1524; found,
440.1495; IR (KBr): 1701 (C=O), 1633 (C=C) cm−1.
4-(2-((2,4-Dinitrophenyl)hydroxymethyl)acryloyloxy)-
2,2,6,6-tetramethylpiperidine-1-oxyl (5l): Yield (DABCO):
117 mg (69%); yield (quinuclidine): 95 mg (56%); red glass;
mp 50–67 °C; EIMS m/z (% relative intensity): M+ 422 (8), 408
(5), 179 (8), 154 (34), 140 (34), 139 (15), 124 (100), 85 (10), 82
(15), 81 (15), 69 (21), 68 (9), 67 (13), 57 (10), 56 (13), 55 (21),
41 (22); HRMS–EI (m/z): calcd for C19H24N3O8, 422.15634;
found, 422.15561; ESIMS m/z (% relative intensity): [M + 2H]+
424 (100); HRMS–ESI (m/z): [M + 2H]+ calcd for
C19H26N3O8, 424.1720; found, 424.1729; IR (KBr): 1717
(C=O), 1628, (C=C), 1537 (NO2), 1347 (NO2) cm−1.
Supporting Information
Supporting Information features EIMS and IR spectra of
the synthesized compounds 5a–o, 1H and 13C NMR of 5d
with phenylhydrazine, and the chromatographic separation
of 5l.
Supporting Information File 1
Detailed spectrographic data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-171-S1.pdf]
4-(2-((3-Pyridyl)hydroxymethyl)acryloyloxy)-2,2,6,6-tetra-
methylpiperidine-1-oxyl (5m): Yield (DABCO): 132 mg
(99%); yield (quinuclidine): 87 mg (65%); orange-yellow Acknowledgments
powder; mp 92–97 °C; EIMS m/z (% relative intensity): 334 The work was supported by the Polish Ministry of Science and
(12), M+ 333 (17), 303 (6), 301 (7), 247 (9), 180 (100), 163 (7), Higher Education, 429/E-142/S/2010.
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Beilstein J. Org. Chem. 2012, 8, 1515–1522.
30.Zhong, F.; Chen, G.-Y.; Lu, Y. Org. Lett. 2011, 13, 82–85.
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