View
217
Download
2
Category
Preview:
Citation preview
This article was downloaded by: [Georgetown University]On: 02 October 2013, At: 11:10Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number: 1072954 Registered office:Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An InternationalJournal for Rapid Communication ofSynthetic Organic ChemistryPublication details, including instructions for authors and subscriptioninformation:http://www.tandfonline.com/loi/lsyc20
Reaction of Phenylglyoxal withCyclopentenylmorpholine and its ArylideneDerivativesSergey P. Ivonin a , Andrey V. Lapandin a & Anna V. Dolgikh aa PBMR Inc., Kiev, UkrainePublished online: 16 Aug 2006.
To cite this article: Sergey P. Ivonin , Andrey V. Lapandin & Anna V. Dolgikh (2006) Reaction of Phenylglyoxalwith Cyclopentenylmorpholine and its Arylidene Derivatives, Synthetic Communications: An InternationalJournal for Rapid Communication of Synthetic Organic Chemistry, 36:10, 1413-1417
To link to this article: http://dx.doi.org/10.1080/00397910500522132
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)contained in the publications on our platform. However, Taylor & Francis, our agents, and ourlicensors make no representations or warranties whatsoever as to the accuracy, completeness, orsuitability for any purpose of the Content. Any opinions and views expressed in this publicationare the opinions and views of the authors, and are not the views of or endorsed by Taylor &Francis. The accuracy of the Content should not be relied upon and should be independentlyverified with primary sources of information. Taylor and Francis shall not be liable for anylosses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilitieswhatsoever or howsoever caused arising directly or indirectly in connection with, in relation to orarising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantialor systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, ordistribution in any form to anyone is expressly forbidden. Terms & Conditions of access and usecan be found at http://www.tandfonline.com/page/terms-and-conditions
Reaction of Phenylglyoxalwith Cyclopentenylmorpholine and its
Arylidene Derivatives
Sergey P. Ivonin, Andrey V. Lapandin, and Anna V. Dolgikh
PBMR Inc., Kiev, Ukraine
Abstract: The reaction of phenylglyoxal with cyclopentenylmorpholine and its
arylidene derivatives leads to hydroxyalkylation products.
Keywords: Arylglyoxals, electrophilic aromatic substitution, enamines
INTRODUCTION
Enamines are extensively applied in organic,[1] and in particular heterocyclic
synthesis,[2 – 4] both as carbonyl compound equivalents and as an individually
significant class of organics. Enamines derived from cyclic ketones can add
aldehydes to give the corresponding arylidene derivatives.[5] If enamines
are reacted with a,a,a-trihalogenoalkylcarbonyl compounds, the products
can be isolated in the hydroxyalkylated form.[6,7] The reaction mostly
involves hydrolysis of the enamine moiety, whereas 1,3-bis-electrophilic
a,b-unsaturated ketones furnish bicyclic b-diketones because of the easily
migrating enamine double bond.[8,9] In the context of our research on the
chemical behavior of phenylglyoxal toward p-excessive heterocycles and
their derivatives,[10,11] our special interest is in the reactions of phenylglyoxal
with enamines derived from cyclic ketones.
Received in Poland October 21, 2005
Address correspondence to Sergey P. Ivonin, PBMR Inc., 1 Murmanskaya Street,
Kiev, 02094, Ukraine. Tel.: 38 044 5598877; E-mail: ivonin@dp.ukrtel.net
Synthetic Communicationsw, 36: 1413–1417, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500522132
1413
Dow
nloa
ded
by [
Geo
rget
own
Uni
vers
ity]
at 1
1:10
02
Oct
ober
201
3
RESULTS AND DISCUSSION
We have found that phenylglyoxal reacts with enamine 1 to yield the hydro-
xyalkylated product 3 containing two phenylglyoxal residues irrespective of
the reagent ratio in the reaction mixture (Scheme 1). It is likely that on
adding the first phenylglyoxal molecule, the enamine double-bond
migration and dehydration occur, leading to the intermediate enamine 2.
Then, in contrast to the reaction with chloral,[6] electrophilic hydroxyalkyla-
tion by the second phenylglyoxal molecule follows and a-hydroxyketone 3
results.
A sufficiently high reactivity of phenylglyoxal toward enamine 1 enables
its arylidene derivatives 4–6 to be hydroxyalkylated smoothly, with the cor-
responding products 7–9 obtained in high yields (Scheme 2). In the reaction
with the benzylidene derivative 4 of cyclopentenylmorpholine, the initially
produced a-hydroxyketone is oxidized to diketone 7.
The most characteristic 1H NMR signals of compounds 7–9 are those in
the region 6.62–6.94 ppm, which arise from methylidene protons. It is note-
worthy that the corresponding signal of a-hydroxyketone 3 is shifted
0.7 ppm upfield, presumably because of the keto-enol tautomerism of
molecule 3.
Most intensive signals in the mass spectra of a-hydroxyketones are
provided by the fission-fragment ions formed on the C–C bond cleavage in
hydroxyketone groups, with the charge mainly localized on the hydroxyalkyl
fragment bearing the enamine moiety. Interestingly, the ions are detected that
result from the successive elimination of the benzoyl radical and the CO
molecule (the m/z value points to Mþ-105-48) and correspond to the
s-complex structure in electrophilic substitution reactions of enamines.
EXPERIMENTAL
1H NMR spectra were recorded in DMSO-D6 on a Varian VXR-300 instru-
ment at 300 MHz with TMS as internal standard. IR spectra were measured
with a UR-20 spectrometer in KBr tablets. Mass spectra were registered
on a mass spectrometer MX-1321 in the electron-impact regime at 70 eV.
Scheme 1.
S. P. Ivonin, A. V. Lapandin, and A. V. Dolgikh1414
Dow
nloa
ded
by [
Geo
rget
own
Uni
vers
ity]
at 1
1:10
02
Oct
ober
201
3
The course of the reaction and product purities were controlled by TLC on the
Silufol-UV-254 plates in a benzene : acetone (5 : 1) system.
General Procedure for the Reaction between
Enamines and Phenylglyoxal
A solution of phenylglyoxal (5.00 mmol) and enamine (5.00 mmol) in diethyl
ether (10 ml) was held at room temperature for 12 h. In the reaction with
enamine 6, benzene was used as a solvent. The precipitate formed was
filtered off and recrystallized from ethanol.
Data
2-Hydroxy-2-[2-morpholin-4-yl-3-(2-oxo-2-phenylethyliden)cyclopent-1-
enyl]-1-phenylethanone (3). Yield 82%. Pale yellow powder. Mp 153–
1548C. IR, n, cm21: 3465, 3080, 2980, 2945, 2875, 1695, 1650, 1465,
1385, 1285, 1180, 1125, 1080, 980. 1H NMR, d, ppm (J, Hz): 1.18 (m, 2H,
H5a,5eCycl), 1.60 (m, 2H, H4a,4eCycl), 2.95 (t, 4H, N(CH2CH2)2O, J ¼ 4.5),
3.55 [t, 4H, N(CH2CH2)2O, J ¼ 4.5], 5.12 (d, 1H, CHOH, J ¼ 15.0), 5.17
(dd, 1H, CHOH, J ¼ 4.5, J ¼ 15.0), 5.90 (d, 1H, 55CHBz, J¼4.5), 7.44–
7.56 (m, 4H, H3,30,5,50
Ph), 7.59–7.66 (m, 2H, H4,40
Ph), 7.89 (d, 2H, H20,60
Ph,
J ¼ 6.9), 7.97 (d, 2H, H2,6Ph, J ¼ 6.9). MS, m/z (Irel,%): 403 Mþ (5), 298
(100), 250 (17), 105 (60). Found, %: C, 74.38; H, 6.17. C25H25NO4 calcd.,
%: C, 74.42; H, 6.25.
1-(3-Benzylidene-2-morpholin-4-ylcyclopent-1-enyl)-2-phenylethan-1,2-
dione (7). Yield 75%. Pale yellow powder. Mp 168–1708C. IR, n, cm21:
3170, 2985, 2940, 2910, 2875, 1670, 1610, 1520, 1455, 1425, 1375, 1315,
1260, 1240, 1200, 1180, 1120, 1080, 1045, 975, 900. 1H NMR, d, ppm (J,
Hz): 2.66 (m, 2H, H5a,5eCycl), 2.85 (m, 2H, H4a,4eCycl), 3.48 (t, 4H,
N(CH2CH2)2O, J ¼ 4.8), 3.75 (t, 4H, N(CH2CH2)2O, J ¼ 4.8), 6.94 (t, 1H,
55CHPh, J¼4.5), 7.25–7.40 (m, 5H, Ph0), 7.50 (t, 2H, H3,5Ph, J ¼ 8.4),
7.62 (d, 1H, H4Ph, J ¼ 8.4), 7.97 (d, 2H, H2,6Ph, J ¼ 8.4). MS, m/z
Scheme 2. R ¼ Ph (4, 7), Thien-2-yl (5, 8), C6H4NO2-4 (6, 9); Z ¼ O (7); H,
OH (8, 9).
Phenylglyoxal with Cyclopentenylmorpholine 1415
Dow
nloa
ded
by [
Geo
rget
own
Uni
vers
ity]
at 1
1:10
02
Oct
ober
201
3
(Irel,%): 373 Mþ (2), 268 (100). Found, %: C, 72.08; H, 6.96. C27H31NO5
calcd., %: C, 72.14; H, 6.98.
2-Hydroxy-2-(2-morpholin-4-yl-3-thien-2-ylmethylidenecyclopent-1-
enyl)-1-phenylethanone (8). Yield 75%. Pale yellow powder. Mp 124–
1258C. IR, n, cm21: 3455, 2975, 2900, 2865, 1680, 1590, 1515, 1435,
1305, 1260, 1180, 1090, 1010, 945. 1H NMR, d, ppm (J, Hz): 2.07 (m, 2H,
H5a,5eCycl), 2.39 (m, 2H, H4a,4eCycl), 2.97 [t, 4H, N(CH2CH2)2O, J ¼ 4.8],
3.55 [t, 4H, N(CH2CH2)2O, J ¼ 4.8], 5.45 (d, 1H, CHOH, J ¼ 5.2), 5.90
(d, 1H, CHOH, J ¼ 5.2), 6.65 (s, 1H, 55CHTh), 6.94 (t, 1H, H4Th,
J ¼ 5.4), 6.99 (d, 1H, H3Th, J ¼ 5.4), 7.33 (d, 1H, H5Th), 7.41 (t, 2H,
H3,5Ph, J ¼ 7.8), 7.51 (d, 1H, H4Ph, J ¼ 7.8), 7.87 (d, 2H, H2,6Ph, J ¼ 7.8).
MS, m/z (Irel,%): 381 Mþ (3), 276 (100), 228 (23), 105 (80). Found, %: C,
69.26; H, 6.08. C22H23NO3S calcd., %: C, 69.27; H, 6.08.
2-Hydroxy-2-[2-morpholin-4-yl-3-(4-nitrobenzylidene)cyclopent-1-enyl]-
1-phenylethanone (9). Yield 75%. Pale yellow powder. Mp 1338C. IR, n,
cm21: 3450, 2980, 2930, 2870, 1690, 1595, 1520, 1460, 1345, 1275, 1180,
1120, 1075, 1000, 960, 900. 1H NMR, d, ppm (J, Hz): 2.19 (m, 2H,
H5a,5eCycl), 2.75 (m, 2H, H4a,4eCycl), 3.10 [t, 4H, N(CH2CH2)2O, J ¼ 4.8],
3.68 [t, 4H, N(CH2CH2)2O, J ¼ 4.8], 5.71 (d, 1H, CHOH, J ¼ 5.4), 6.08
(d, 1H, CHOH, J ¼ 5.4), 6.62 (s, 1H, 55CHAr), 7.54 (t, 2H, H3,5Ph,
J ¼ 7.5), 7.61 (d, 2H, H2,6Ar, J ¼ 9.0), 7.65 (d, 1H, H4Ph, J ¼ 7.5), 8.00
(d, 2H, H2,6Ph, J ¼ 7.5), 8.16 (d, 2H, H3,5Ar, J ¼ 9.0). MS, m/z (Irel,%):
420 Mþ (2), 315 (100), 267 (10), 105 (77). Found, %: C, 68.54; H, 5.76.
C24H24N2O5. calcd., %: C, 68.56; H, 5.75.
REFERENCES
1. Rappoport, Z. The Chemistry of Enamines; Wiley: Chichester, 1994.2. Lue, P.; Greenhill, J. V. Enamines in heterocyclic synthesis. Adv. Heterocycl.
Chem. 1997, 67, 207–343.3. Granik, V. G.; Makarov, V. A.; Parkanyi, C. Enamines as synthons in the synthesis
of heterocycles. Adv. Heterocycl. Chem. 1999, 72, 272–359.4. Stanovnik, B.; Svete, J. Synthesis of heterocycles from alkyl 3-(dimethylamino)-
propenoates and related enaminones. Chem. Rev. 2004, 104 (5), 2433–2480.5. Birkofer, L.; Kim, S. M.; Engels, H. D. Aldehydaddition an enamine. Chem. Ber.
1962, 95, 1495–1504.6. Nolde, C.; Lawesson, S.-O. Enamine chemistry, XVI: Reactions between
enamines and chloral. Bull. Soc. Chim. Belg. 1977, 86 (4), 313–319.7. Palecek, J.; Paleta, O. Novel and convenient aldolization of methyl
3,3,3-trifluoropyruvate using enamines instead of ketones. Synthesis 2004 (4),521–524.
8. Byeon, C.-H.; Hart, D. J.; Lai, C.-S.; Uneh, J. Reactions of cyclohexanoneenamines with a,b-unsaturated thioesters and selenoesters. Synlett 2000 (1),119–121.
S. P. Ivonin, A. V. Lapandin, and A. V. Dolgikh1416
Dow
nloa
ded
by [
Geo
rget
own
Uni
vers
ity]
at 1
1:10
02
Oct
ober
201
3
9. Nenajdenko, V. G.; Druzhinin, S. V.; Balenkova, E. S. Reaction of a,b-unsaturated trifluoromethyl ketones with cyclic enamines. Russ. Chem. Bull.2004, 53 (2), 435–442.
10. Ivonin, S. P.; Lapandin, A. V.; Anishchenko, A. A.; Shtamburg, V. G. Reaction ofarylglyoxals with electron-rich benzenes and p-excessive heterocycles facilesynthesis of heteroaryl a-acyloins. Synth. Commun. 2004, 34 (3), 451–461.
11. Ivonin, S. P.; Lapandin, A. V.; Anishchenko, A. A.; Shtamburg, V. G. Mutualinfluence of (dimethylhydrazono)methyl groups and a-hydroxyketone moietiesin hetaryl analogues of unsymmetric benzoins. Eur. J. Org. Chem. 2004 (22),4688–4693.
Phenylglyoxal with Cyclopentenylmorpholine 1417
Dow
nloa
ded
by [
Geo
rget
own
Uni
vers
ity]
at 1
1:10
02
Oct
ober
201
3
Recommended