Cobalt (II) chloride or manganese (II) chloride or tin (II) chloride promoted one pot synthesis of dihydropyrimidin-2(1H)-ones using microwave irradiation
†Sanjay Kumar, Anil Saini & Jagir S Sandhu*
Department of Chemistry, Punjabi University, Patiala 147 002, India
*E-mail: j_sandhu2002@yahoo.com
Received 23 November 2004; accepted (revised) 4 March 2005
Various substituted 3, 4-dihydropyrimidin-2(1H)-ones have been synthesized in a one pot reaction of β-ketoesters, aldehydes and urea using cobalt chloride hexahydrate or manganese chloride tetrahydrate or tin chloride dihydrate under microwave irradiation in excellent yields without the addition of any proton source or any additive and without any side reactions as observed by Biginelli and others.
IPC: Int.Cl.7 C 07 D 239/00
In recent years multicomponent reactions (MCRs) have received considerable attention and emerged as one of the most important protocols in organic synthesis and medicinal chemistry2. The importance of MCRs lies in the fact that steps of synthetic sequence can be carried out without the isolation of intermediates. As a result the diversity, efficiency and rapid access to small and highly functionalized organic molecules make this approach of current interest in developing combinatorial libraries and optimization in drug discovery process3. In the past decade, there has been tremendous developments in three and four component reactions involving Passevini4, Ugi5, Mannich-type reaction6 and great efforts have been and still are being made to find and develop new MCR’s7.
In last decade, much attention has been focused particularly on dihydropyrimidinones (DHPMs), which are an important class of compounds due to their therapeutic and pharmacological properties8. They have emerged as integral backbones of several calcium channel blockers, nifedipine group of antihypertensive agents and alpha-la-antagonists and neuropeptide antagonists9. Alkaloids containing the dihydropyrimidine unit have been isolated from marine sources10 and among these are the batzelladine alkaloids which were found to be potent HIV gp-120- CD4 inhibitors11. This is an impressive profile that rests well for the interaction of this heterocyclic
building block (for structural resemblance see Figure 1) with a variety of biological targets of interest.
As shown in Figure 1 structural resemblance to widely used antihypertensive agents of nefidipine and its analogues, some of the aza analogues showed similar biological activity. This led to the develop- ment of variety of methods for the synthesis of this heterocyclic nucleus of continuing interest. The classical Biginelli reaction first described more than a century ago12 and reviewed8a,b recently involved condensation of an aldehyde, a β-dicarbonyl compound and urea under strongly acidic conditions.
However, the main drawback of Biginelli reaction is low yields13 and sensitive functional groups are lost during the reaction conditions14. This has led to the discovery of multistep strategies15 that produce somewhat higher yields but lack the simplicity of the original Biginelli one-pot synthesis. Several improvements in this reaction have recently been reported16. But the practical application of these methods suffers from disadvantages like use of mineral acids12,16e, strong lewis acids17,18 such as BF3.Et2O (ref. 17), expensive reagents such as lanthanide triflate19, indium halides20, zirconium tetrachloride21 as well as organic solvents22 which are not generally environmentally benign23. Therefore, a need still exists for versatile, simple and environ- mentally friendly process whereby DHPMs may be obtained under mild conditions. In continuation to our studies in the synthesis of DHPMs1,24 and cobalt
⎯⎯⎯⎯⎯⎯
†For preliminary communication see ref. 1
mediated organic reactions25, we were prompted to employ CoCl2.6H2O in Biginelli reaction under microwave irradiation. Also we have explored the use of MnCl2.4H2O and SnCl2.2H2O under microwaves for the synthesis of DHPMs (Scheme I).
In typical experiment, mixture of ethyl aceto- acetate, benzaldehyde, urea and cobaltous chloride hexahydrate were taken in a reaction vessel and placed in a Prolabo Synthwave Microwave Reactor and irradiated for 2 min. After completion (monitored by TLC), the reaction was cooled to room temperature and treated with water. The solid thus obtained was recrystallized from ethanol to afford pure 4a, m.p.
201-02 ºC (lit.26 m.p. 202-03ºC) in 98% yield.
Similarly, other substituted aldehydes, β-dicarbonyl compounds and urea were reacted together to produce the corresponding dihydropyrimidin-2(1H)-ones. The
results are summarized in Table I. A number of substituted aromatic, aliphatic and heterocyclic aldehydes have been employed successfully. Acetyl- acetone was also used with similar success to provide the corresponding 3,4-dihydropyrimidin-2(1H)-ones.
Under this condition, the yields were significantly improved and the reaction time period was reduced dramatically. For comparison sake when reactions were carried out in dry acetonitrile as solvent under reflux condition, the time taken was farely long (see Table I, method B; for experimental details see experimental section). This condensation procedure is fairly general and several functionalities including nitro, chloro, hydroxyl, methoxy and conjugated carbon-carbon double bond do survive during the course of the reaction. Meanwhile, even for aliphatic aldehydes such as butyraldehyde and iso-buty-
N H
CO2R
Me RO2C
Me O2N
N H
Me
CO2(CH2)2N Me O2C
Me C H3
Bn Me
Nifedipine I; R=Me, 2-NO2 , Nicardipine III Nitrendipine II; R=Et, 3-NO2
N
N H RO2C
Me
E
Z
N
N H
O CONH2 i-Pr O2C
Me O2 N O2N
IV R= alkyl, Z=O, S V SQ 32926,
X=2/3-NO2, 2-CF3
E= ester, acyl, amide
Figure 1 ⎯ Structures of nifedipine, its derivatives and aza-analogs
R1 H
O
Me O
R2 O
N
H2 NH2 O
CoCl2. 6H2O or MnCl2. 4H2O
or SnCl2. 2H2O, MWI
NH
NH O
R1
Me O
R2
1 2 3
4
+ +
Scheme I
Table I ⎯ CoC12.6H2O/MnC12.4H2O/SnCl2.2H2O mediated synthesis of dihydrophyrimidin-2(1H)-ones 4a-o
Reaction time Yieldb (%) m.p. lit.m.p.
Producta R1 R2 Catalyst Method A (min.)
Method B
(hr) A B °C °C 4a C6H5 OEt CoCl2.6H2O 2 3.5 98 92 201-02 202-0326 4b 4-(OCH3)C6H4 OEt CoCl2.6H2O 2 4 99 92 200-201 199-20119 4c 4-(OH)C6H4 OEt CoCl2.6H2O 2 3 88 80 227-28 227-2926 4d 3-(NO2)C6H4 OEt CoCl2.6H2O 2 3 86 81 224-27 226-2719 4e 4-(NO2)C6H4 OEt CoCl2.6H2O 2.5 3 88 84 208-10 207-1019 4f 4-(Cl)C6H4 OEt CoCl2.6H2O 3 3.5 94 86 212-13 210-1219 4g C6H5 CH = CH OEt CoCl2.6H2O 2.5 4 85 81 231-32 232-3519 4h 2-Furyl OEt CoCl2.6H2O 3 3.5 85 76 205-06 204-0526 4i 2,4-(Cl)2C6H3 OEt CoCl2.6H2O 2.5 3.5 91 86 238-39 238-4019
4j n-Bu OEt CoCl2.6H2O 2.5 4 80 75 156-18 157-5819
4k (CH3)2CH OEt CoCl2.6H2O 3 4 75 72 193-95 194-9519 4l C6H5 Me CoCl2.6H2O 3 3.5 86 81 208-10 209-1226 4m 4-(OCH3)C6H4 Me CoCl2.6H2O 2.5 4 95 86 190-91 191-9319 4n 4-(NO2)C6H4 Me CoCl2.6H2O 3 3 93 84 234-38 235-3719 4o 2,4-(Cl)2C6H3 Me CoCl2.6H2O 3 4 92 84 252-54 254-5519 4a C6H5 OEt MnCl2.4H2O 3 3.5 87 80 201-02 202-0326 4b 4-(OCH3)C6H4 OEt MnCl2.4H2O 2.5 4 88 82 200-201 199-0119 4d 3-(NO2)C6H4 OEt MnCl2.4H2O 2.5 3.5 82 80 225-27 226-2719 4f 4-(Cl)C6H4 OEt MnCl2.4H2O 2 3 85 74 211-13 210-1219 4g C6H5 CH = CH OEt MnCl2.4H2O 2 3.5 79 71 231-32 232-3519 4h 2-Furyl OEt MnCl2.4H2O 3.5 3.5 78 67 205-06 204-0526
4j n-Bu OEt MnCl2.4H2O 3 4 76 68 156-58 157-5819
4l C6H5 OEt MnCl2.4H2O 2.5 3.5 79 68 208-10 209-1226 4m 4-(OCH3)C6H4 Me MnCl2.4H2O 2.5 4 81 74 190-91 191-9319 4n 4-(NO2)C6H4 Me MnCl2.4H2O 3 3 73 68 234-36 235-3719 4o 2,4-(Cl)2C6H3 Me MnCl2.4H2O 3 3.5 74 72 252-54 254-5519 4a C6H5 OEt SnCl2.2H2O 3.5 6 96 901 201-02 202-0326 4b 4-(OCH3)C6H4 OEt SnCl2.2H2O 4 7 88 801 200-201 199-20119 4c 4-(OH)C6H4 OEt SnCl2.2H2O 3 5.5 86 801 227-28 227-2926 4d 3-(NO2)C6H4 OEt SnCl2.2H2O 3 5 83 811 224-27 226-2719 4e 4-(NO2)C6H4 OEt SnCl2.2H2O 3 5 92 851 209-11 207-1019 4f 4-(Cl)C6H4 OEt SnCl2.2H2O 3.5 5.5 94 881 211-13 210-1219 4g C6H5 CH = CH OEt SnCl2.2H2O 4 7 84 801 231-32 232-3519 4h 2-Furyl OEt SnCl2.2H2O 3.5 6 85 801 205-06 204-0526 4I 2,4-(Cl)2C6H3 OEt SnCl2.2H2O 3 6 88 861 238-39 238-4019 4j n-Bu OEt SnCl2.2H2O 3.5 6 81 74 156-57 157-5819 4k (CH3)2CH OEt SnCl2.2H2O 4 6.5 80 72 190-92 194-9519 4l C6H5 Me SnCl2.2H2O 3.5 6 88 81 207-10 209-1226 4m 4-(OCH3)C6H4 Me SnCl2.2H2O 3 6.5 92 83 188-90 191-9319 4n 4-(NO2)C6H4 Me SnCl2.2H2O 3 5.5 86 79 233-35 235-3719 4o 2,4-(Cl)2C6H3 Me SnCl2.2H2O 3 6 87 83 252-54 254-5519 A – using microwave irradiation
B – using thermolytic conditions
a Products are characterized by m.p. and spectral (IR, 1H NMR and MS) data
b Yields refer to pure isolated product
raldehyde which normally show extremely poor yield in the Biginelli reaction, the corresponding dihydro- pyrimidinones could be obtained in 75-80% yields27 (Table I). Moreover, acid sensitive aldehydes such as furfural also worked well without the rupture of furan ring and formation of any other side products as observed with nickel chloride or ferric chloride16e. Roughly 0.1 equivalent of CoCl2 was found to be sufficient for these reactions and use of less than 0.1 equivalent was not optimal one. The use of large amount of CoCl2.6H2O or addition of a few drops of hydrochloric acid, is found to be not fruitful i.e. does not increase the yields. We further extended this reaction under same condition to SnCl2.2H2O and MnCl2.4H2O and results obtained are presented in Table I. Notably, the reaction also proceeds with NiCl2.6H2O and FeCl3.6H2O when carried out without using any acids as additional proton source. It is worth mentioning here that NiCl2.6H2O and FeCl3.6H2O have been used earlier in Biginelli reaction16e in presence of hydrochloric acid and ethanol. In contrast, we have performed this three- component Biginelli condensation in refluxing aceto- nitrile also and got the corresponding DHPMs in
68-92% yields without the use of any acid or alcohol.
But with CoCl2.6H2O, MnCl2.H2O or SnCl2.H2O the corresponding DHPMs were obtained in 75-99%
yields when carried out under microwave irradiations.
The use of anhydrous metal salts i.e. CoCl2, MnCl2 or SnCl2, also affords equivalent results. When in this reaction nickel and cobalt halides were replaced by corresponding metal acetates i.e. nickel acetate dihydrate or cobalt acetate dihydrate, equally good results were obtained. It is worth mentioning here that the use of CaCl2.2H2O or AlCl3.6H2O in this reaction did not perform well rather yields obtained were 10- 15% lower.
Recently, the mechanism of the Biginelli reaction was studied in detail by Kappe28. The proposed mechanism is based on the steps as shown in Scheme II, viz. formation of 6 under the addition of acid catalysis, here we feel metal salts used are assisting the step followed by Michael type 2 to yield 8 through the intermediacy of 7. It is worth mentioning here that in earlier study also this amino alcohol 7 has been isolated and water elimination is effected separately by using toluene sulphonic acid to yield final product 4. The role of transition metal salts
RCHO H2N NH2 O
R
NH OH
O NH2
-H2O
R N H
O NH2
M Me OR'
O O
NH R R'O2C
Me O
N H2
O
1 3 5
6
2 7
NH
N H R R'O2C
Me O
O H
NH
N H R
O Me
R'O2C -H2O
M
8 4
2+
2+ +
+
M = Co, Mn or Sn Scheme II +
+
here seems to be two-fold, firstly to assist the forma- tion of 6 and also render active methylene compound 2 readily enolizable, means active methylene compound is further activated for Michael reaction.
As one can see there is elimination of H2O in two steps, therefore in our opinion water free conditions used by us are highly favourable to this reaction.
In conclusion, the present investigation discloses a new and simple modification of the Biginelli reaction by using relatively non-toxic and inexpensive CoCl2.6H2O or MnCl2.4H2O or SnCl2.2H2O as a mediator under microwave irradiation. The yield of the DHPMs can be increased from 20-50% (ref. 17) to 75-99% while the reaction time was reduced from 18- 48 hr to 2-3 min. It not only led to economical auto- mation but also reduced hazardous pollution to achieve environmentally friendly process. This cobalt/manganese/tin mediated one-pot synthesis of DHPMs is therefore, simple, high yielding, time saving, environment friendly and employs readily available cheap mild lewis acid. In addition to its simplicity and selectivity this reaction has one salient feature in its ability to tolerate a variety of aldehydes and constitute a useful alternative to the commonly accepted procedures.
Experimental Section
Materials were obtained from commercial suppliers and were used without further purifications. Melting points were determined by using a Buchi melting point apparatus and are uncorrected. IR spectra were recorded in KBr discs on a Perkin-Elmer 24°C analyzer; 1H NMR spectra on a 90 MHz spectrometer (chemical shifts in δ, ppm) relative to TMS as internal standard. The 100 MHz NMR spectra were recorded with TMS as internal standard (by RSIC, Shillong).
Elemental analyses were performed with TMS as internal standard (by RSIC, Shillong) on a Hitachi 026 CHN analyzer. All solvents were distilled before use. The reactions were carried out in Prolabo Microwave Module Synthwave S-402 (preliminary experiments were carried out in domestic microwave oven). The progress of reactions was monitored by TLC and chromatographic purification was performed with silica gel 60 (120 Mesh, Merck).
Biginelli condensation under microwave irradia- tion: General procedure. In a typical procedure, a mixture of ethyl acetoacetate (1.30g, 10 mmoles), benzaldehyde (1.06g, 10 mmoles), urea (0.6g, 10 mmoles) and cobaltous chloride hexahydrate (0.23 g,
1 mmole) was placed in a reaction vessel and heated in a Prolabo Synthwave Microwave Reactor for 2 min. After completion (monitored by TLC), the reaction was cooled to room temperature and poured into water (30 mL). The solid separated was filtered, washed with water and then recrystallized from ethanol to afford pure 4a, m.p. 201-02°C (lit.26 m.p.
202-03°C), yield 98%.
Similarly, other substituted aldehydes, β- dicarbonyl compounds and urea were reacted together to produce the corresponding dihydropyrimidin- 2(1H)-ones. The results are summarized in Table I.
Biginelli condensation under thermolytic conditions: General procedure. In a typical procedure, a mixture of ethy1 acetoacetate (1.30 g, 10 mmoles), benzaldehyde (1.06 g, 10 mmoles), urea (0.6 g, 10 mmoles) and cobaltous chloride hexahydrate (1.9 g, 15 mmoles) in dry acetonitrile was heated under reflux for 3-4 hr. After completion (monitored by TLC), the reaction was cooled to room temperature and the solvent was evaporated in vacuo.
The residue was treated with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure. The solid thus obtained was recrystallized from ethanol to afford pure 4a, m.p.
201-202°C (lit.26 m.p. 202-03°C), yield 80%.
Similarly, other substituted aldehydes, β- dicarbonyl compounds and urea were reacted together to produce the corresponding dihydropyrimidin-2 (1H)-ones.
5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3, 4-di- hydropyrimidin-2(1H)-one 4a: IR (KBr): 3235, 1726, 1639 cm-1; 1H NMR (CDCl3): δ 9.15 (s, 1H), 7.72 (s, 1H), 7.23 (m, 5H), 5.15 (s, 1H), 3.94 (q, J = 7.1Hz, 2H), 2.26 (s, 3H), 1.12 (t, J = 7.1Hz, 3H).
5-(Ethoxycarbonyl)-4-(4-methoxyphenyl)-6-me- thyl-3,4-dihydropyrimidin-2(1H)-one 4b: IR (KBr):
3237, 1705, 1642 cm-1; 1H NMR (CDCl3): δ 9.17 (s, 1H), 7.70 (s, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.87 (d, J
= 8.4Hz, 2H), 5.12 (s, 1H), 3.95 (q, J = 7.1 Hz, 2H), 2.27 (s, 3H), 1.11 (t, J = 7.1 Hz, 3H).
4-(4-Chlorophenyl)-5-(ethoxycarbonyl)-6-methyl- 3,4-dihydropyrimidin-2(1H)-one 4f:: IR (KBr):
3232, 1708, 1636 cm-1; 1H NMR (CDCl3): δ 9.18 (s, 1H), 7.71 (d, J = 3.4Hz, 1H), 7.31 (d, J = 8.3Hz, 2H), 7.18 (d, J = 8.3Hz, 2H), 5.15 (s, 1H), 3.93 (q, J = 7.1 Hz, 2H), 2.25 (s, 3H). 1.12 (t, J= 7.1 Hz, 3H).
5-(Ethoxycarbonyl)-4-(2-furfuryl)-6-methyl-3,4- dihydropyrimidin-2(1H)-one 4h: IR (KBr): 3252,
1705, 1662 cm-1; 1H NMR (CDCl3): δ 9.15 (s, 1H), 7.70 (s, 1H), 7.51 (s, 1H), 6.12 (d, J = 2.9Hz, 1H), 5.62 (d, J = 2.9Hz, 1H), 5.11 (s, 1H), 3.90 (q, J = 7.3 Hz, 2H), 2.21 (s, 1H), 1.14 (t, J = 7.3Hz, 3H).
4-Butyl-5-(ethoxycarbonyl)-6-methyl-3,4-dihydro- pyrimidin-2(1H)-one 4j: IR (KBr): 3240, 1715, 1652 cm-1; 1H NMR (CDCl3): δ 9.01 (s, 1H), 7.51 (s, 1H), 5.12 (s, 1H), 3.97 (q, J = 6.8 Hz, 2H), 2.26 (s, 3H), 1.41-1.22 (m, 9H), 1.10 (t, J = 6.8 Hz, 3H).
Acknowledgement
Authors wish to thank CSIR, New Delhi for financial assistance and authorities of Punjabi University, Patiala for providing laboratory facilities.
Also some experimental assistance and other liberal assistance by Dr P Saikia, SRF and Dr D Prajapati, Scientist, of RRL-Jt is duly acknowledged.
References
1 Kumar S, Saini A & Sandhu J S, Indian J Chem, 43B, 2004, 1485.
2 (a) Clark J H, Chemistry of Waste Minimization, (Chapman and Hall, London), 1995, 43.
(b) Clark J H & Macquarrie D J, Chem Soc Rev, 1996, 303.
(c) Sheldon R A, Chem Ind (London), 1997, 12.
(d) Weber L, Drug Disc Today, 7, 2002, 143.
(e) Domling A, Curr Opin Chem Biol, 6, 2002, 306.
3 (a) Dolle R E & Nelson K H, J Comb Chem, 1, 1999, 235.
(b) Thompson L A & Ellman J A, Chem Rev, 96, 1996, 555.
(c) Gordon E M, Gallop M A & Patel D V, Acc Chem Res, 29, 1996, 144.
4 (a) Kobayashi K, Matoba T, Susumu I, Takashi M, Morikawa O & Korishi H, Chem Lett, 1998, 551.
(b) Bossio R, Marcos C F, Marcaceini S & Pepino R, Tetrahedron Lett, 38, 1997, 2519.
5 (a) Keating T A & Armstrong R W, J Am Chem Soc, 117, 1995, 7842.
(b) Yamada T, Omote Y, Yamanaka Y, Miyazawa T &
Kuwata S, Synthesis, 1998, 991.
(c) Ross G F, Herdtweek E & Ugi I, Tetrahedron,58, 2002, 6127.
6 Arend M, Westermann D & Risch N, Angew Chem Int Ed.,37, 1998, 1045.
7 (a) Bagely M C, Dale J W & Bower J, Chem Commun, 2002, 1682.
(b) Kappe C O, Tetrahedron, 49, 1993, 6973.
(d) Shestopalov A M F, Emeliyanova Y M, Shestopalov A A, Rodinovskaya L A, Niazimbetova Z I & Evans D H, Org Lett, 2002, 423.
8 (a) Kappe C O,Tetrahedron, 49, 1993, 6937.
(b) Kappe C O, Acc Chem Res, 33, 2000, 879.
9 (a) Atwal K S, Swanson B N, Unger S E, Floyd D M, Moreland S, Hedberg A & O’Reilly B C, J Med Chem, 34, 1991, 806 and references cited therein.
(b) Kappe C O, Fabian W M F & Semones M A, Tetrahedron, 53, 1997, 2803.
10 Overman L E, Rabinowitz M H & Renhowe P A, J Am Chem Soc, 117, 1995, 2657.
11 Patil A D, Kumar N V, Kokka W C, Bean M F, Freyer A J, DeBrosse C, Mai S, Truneh A, Faulkner D J, Carte B, Breen A L, Hertzberg R P, Johnson R K, Westley J W & Ports B C M, J Org Chem, 60, 1995,1182.
12 Biginelli P, Gazz Chim Ital, 23, 1893, 360.
13 (a) Zavyalov S I & Kulikova L B, Khim Farm Zh, 26, 1992, 116.
(b) Gupta R, Gupta A K, Paul S & Kachroo P L, Indian J Chem, 34B, 1995, 151.
(c) Hu E H, Sidler D R, Dolling U H & Patane M A, PCT Int.
Appl. WO 97 21 687; Chem Abstr, 127, 1997, 121750v.
14 For a study of the pH dependence of the reaction see: Ehasn A
& Karimullah, Pak J Sci Ind Res, 10, 1967, 83.
15 (a) O’Reilly B C & Atwal K S, Heterocycles, 26, 1987, 1185.
(b) Atwal K S, O’Reilly B C, Gougoutas J Z & Malley M F, Heterocycles, 26, 1987, 1189.
(c) Shutalev A D & Kuksa V A, Khim Geterotsiki Soedin, 1997, 105.
(d) Shutlev A D, Kishko E A, Sivova N V & Kuznetsov A Y, Molecules, 3, 1998, 100.
16 (a) using KHSO4 see: Tu S, Fang F, Zhu S, Li T, Zhang X &
Zhuang Q, Synlett, 2004, 537.
(b) using Cu (OTf)2 see: Paraskar A S, Dewkar G K &
Sudalai A, Tetrahedron Lett, 44, 2003, 3305 and ref. 2 cited therein.
(c) using soluble polymer support see: Xia M & Wang Y, Tetrahedron Lett, 43, 2002, 7703.
(d) using ferric chloride/nickel chloride see: Lu J & Bai Y, Synthesis, 2002, 466.
17 Hu E H, Sidler D R & Dolling U H, J Org Chem, 63, 1998, 3454.
18 Ramalinga K, Vijaylakshmi P & Kaimal T N B, Synlett, 2001, 863.
19 Ma Y, Qian C, Wang L & Yang M, J Org Chem, 65, 2000, 3864.
20 Fu N, Yuan Y, Cao Z, Wang S, Wang J & Peppe C, Tetrahedron, 43, 2002, 2657.
21 Reddy C V, Mahesh M, Raju P V K, Romeshbabu T & Reddy V V N, Tetrahedron Lett, 43, 2002, 2657.
22 Robert H, Ganigues B & Bubac J, Tetrahedron Lett, 39, 1998, 1161.
23 Toussaint M W, Rosencrance A B, Breman L M, Breman J R, Wolfe M J, Hoffmann F J & Gardner H S, Environmental Health Perspective, 109, 2001, 35.
24 (a) Baruah P P, Gadhwal S, Prajapati D & Sandhu J S, Chem Lett, 2002, 1038.
(b)Gohain M, Prajapati D & Sandhu J S, Synlett, 2004, 235.
25 Baruah M, Hussain A, Prajapati D & Sandhu J S, Chem Lett, 1997, 789.
26 Folkers K, Harwood H J & Johnson T B, J Am Chem Soc, 54, 1932, 3751.
27 Eynde J J V, Audiart N, Canonne V & Kappe C O, Heterocycles, 1997, 1799.
28 (a) Kappe C O, J Org Chem,67, 1997, 7201.
(b) Kappe C O, Kumar D & Varma R S, Synthesis, 1999, 1799.
