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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

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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

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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.

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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).

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(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.

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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.

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enamines and chloral. Bull. Soc. Chim. Belg. 1977, 86 (4), 313–319.7. Palecek, J.; Paleta, O. Novel and convenient aldolization of methyl

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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.

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