A Novel Approach to the Synthesis of [1,2- a ]Fused Polymethylenebenzimidazoles

This article was downloaded by: [University of Hong Kong Libraries]On: 05 September 2013, At: 08:21Publisher: 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 International Journalfor Rapid Communication of Synthetic OrganicChemistryPublication details, including instructions for authors and subscription information:http://www.tandfonline.com/loi/lsyc20

A Novel Approach to the Synthesis of [1,2-a]FusedPolymethylenebenzimidazolesKonstantin G. Nazarenko a , Tatyana I. Shyrokaya a , Konstantin V. Shvidenko a & Andrei A.Tolmachev aa Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv, UkrainePublished online: 21 Aug 2006.

To cite this article: Konstantin G. Nazarenko , Tatyana I. Shyrokaya , Konstantin V. Shvidenko & Andrei A. Tolmachev (2003) ANovel Approach to the Synthesis of [1,2-a]Fused Polymethylenebenzimidazoles, Synthetic Communications: An InternationalJournal for Rapid Communication of Synthetic Organic Chemistry, 33:24, 4303-4311, DOI: 10.1081/SCC-120026860

To link to this article: http://dx.doi.org/10.1081/SCC-120026860

PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) containedin the publications on our platform. However, Taylor & Francis, our agents, and our licensors make norepresentations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of theContent. Any opinions and views expressed in this publication are the opinions and views of the authors, andare not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon andshould be independently verified with primary sources of information. Taylor and Francis shall not be liable forany losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoeveror howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use ofthe Content.

This article may be used for research, teaching, and private study purposes. Any substantial or systematicreproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in anyform to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions

http://www.tandfonline.com/loi/lsyc20

http://www.tandfonline.com/action/showCitFormats?doi=10.1081/SCC-120026860

http://dx.doi.org/10.1081/SCC-120026860

http://www.tandfonline.com/page/terms-and-conditions

http://www.tandfonline.com/page/terms-and-conditions

©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

SYNTHETIC COMMUNICATIONS�

Vol. 33, No. 24, pp. 4303–4311, 2003

A Novel Approach to the Synthesis of

[1,2-a]Fused Polymethylenebenzimidazoles

Konstantin G. Nazarenko,* Tatyana I. Shyrokaya,

Konstantin V. Shvidenko, and Andrei A. Tolmachev

Institute of Organic Chemistry, National Academy of

Sciences of Ukraine, Kyiv, Ukraine

ABSTRACT

The synthesis of 2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazoles and

7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazoles from cyclic

amidines is described.

Two general synthetic routes to tricyclic [1,2-a]fused benzimidazolesare known. The first requires no prior formation of the benzimidazolenucleus, and consists of cyclization reactions between 1,2-disubstitutedderivatives of 1-phenylpyrroline, piperidine, hexamethyleneimine etc.[1]

The second method involved an annulation of a saturated ring ontothe imidazole or benzimidazole nucleus.[2] For example, the synthesis of

*Correspondence: Konstantin G. Nazarenko, Institute of Organic Chemistry,

National Academy of Sciences of Ukraine, Murmanskaya 5, Kyiv-94, 02094,

Ukraine; Fax: þ380 44 5590480; E-mail: [email protected].

4303

DOI: 10.1081/SCC-120026860 0039-7911 (Print); 1532-2432 (Online)

Copyright & 2003 by Marcel Dekker, Inc. www.dekker.com

Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



[1,2-a]fused imidazoles and benzimidazoles by radical cyclization ontothe imidazole-2-position using 1-phenylselenoalkyl radical precursors iswell described in.[3]

Here we study another synthetic approach to the compounds desired,viz. the cyclization of readily accessible amidines I a–l into 1,2-tri- and1,2-pentamethylenebenzimidazoles II a–h. The conversion of suchcompounds into benzimidazole derivatives by intramolecular arylationhas not yet been described in the literature. There is some evidence onthe cyclization undergone by the type I compounds containing a fluorineatom at the meta-position, if treated with butyllithium. In this case,benzimidazole derivatives are formed in the course of cine-substitution.[4]

Compounds I a–f [5] obtained in one step from g-pyrrolidone ande-caprolactam were cyclized by heating at 140–150�C (X¼F) or ontreatment with strong bases such as sodium methoxide or sodium hydride(X¼F, Cl). It was found that activated C-Hal bonds of amidines I d–f

(n¼ 3) readily underwent nucleophilic aromatic substitution to give theseven-membered cyclized products II b–d. However, compounds I a–c

(n¼ 1) proved less prone to cyclization, and we were able to obtain thedesired 2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole derivative only fromthe amidine containing a fluorine activated by a para-nitro group.

NH

(CH2)n

X

N

R

I a - f

N

N

R

II b - d

N

N

R

II a

1

2

34

5

6

78

910

1 2

3

4

567

8

Taking into account a relatively high tendency of fluorine atoms inpolyfluorobenzenes to be substituted and also in view of the fact that thefluoro substituted derivatives of 1,2-pentamethylenebenzimidazole aredifficult to obtain by the currently available methods, we synthesized anumber of fluorine-containing amidines (I g–l) and studied the features oftheir conversion into II (see Table 2).

It was observed that the nature of the fluorine substitution pattern onthe benzene ring of amidines I g–l has a significant affect on the ability toring-close the imidazole-ring. In agreement with well-established theorieson nucleophilic aromatic substitution of polyfluoro-benzenes andpyridines by Chambers et al,[6] ring closure to give compounds II onlyoccurred for amidines containing at least one other ortho or meta fluorosubstituent. Monofluoro- and para-difluoro amidines I g–h failed tocyclize, even after prolonged heating with sodium hydride in DMF. It

4304 Nazarenko et al.

Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



Table 1. The cyclization of compounds I a–f.

Substrate Product

Entry n R X Entry Method Yield (%) M.p. (�C)

Ia 1 NO2 F IIa A 75 207–208a

Ib 1 CF3 Cl A, B —

Ic 1 SO2NEt2 Cl A, B —

Id 3 NO2 F IIb A 78 166

Ie 3 CF3 Cl IIc B 80 114–115

If 3 SO2NEt2 Cl IId B 81 145–146

a209–210�C.[1a]

Table 2. The cyclization of fluorine-containing amidines.

Substrate Product

Yield (%)

M.p. (�C)Method A Method B

Ig

NH

N

F

N

N — —

Ih

NH

N

FF

N

NF — —

Ii

NH

N

F

F

IIe

N

N

F

76 50 120–122

Ij

NH

N

F

FIIf

N

NF 74 42 143–144

IkN

F

F F

NH

IIg

N

N

FF

81 46 128–129

Il

NH

N

F

F F

F

F

IIh

N

N

FF

F

F 72 52 91–92

[1,2-a]Fused Polymethylenebenzimidazoles 4305

Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



is well-established that fluorine atoms at the meta- and ortho-positionsfacilitate nucleophilic substitution, whereas fluorine at the para-positionhas an affect comparable to that of a hydrogen atom.

The observed increased tendency for ortho- and meta-substitutedcyclic polyfluoro-benzene amidines to cyclize was supported by the spon-taneous formation of 7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimid-azoles II from the intermolecular reaction of O-methylcaprolactim III

with anilines IV b,e at 140–150�C. Heating neat solutions of III withIV a,c under the latter conditions yielded the expected amidines.[8] Incontrast, anilines IV d,f do not react with III, because of the decreasednucleophilicity of the amino group due to the strong �I effect of theadjacent fluorine atoms.

The structure of the products obtained was determined by of 1H and19FNMR spectra. Amidines I exist as two tautomeric forms differing bythe endo- or exo-disposition of the double bond.[8] As a result, they displaytwo sets of spectral signals assigned to two tautomers, the intensity ratiodepending both on the nature of a compound and on the measuringconditions. Another distinction between 1HNMR spectra of compoundsI and II is the signal position for the methylene group adjacent to thenitrogen atom. In the spectra of amidines, the 7-CH2 multiplet is observedin the range 3.0–3.6 ppm, whereas benzimidazole derivatives exhibit thecorresponding 10-CH2 peak in a weaker field, at about 4.2 ppm.

EXPERIMENTAL

Melting points are uncorrected. 1H, 19F, and 13CNMR spectra wererecorded at 300, 282, and 75MHz respectively on a Varian VXR-300spectrometer with TMS as an internal standard (chemical shifts in� ppm).

NH2

F R3

R2

R1

R

IV a- f

N

OMe

III

Scheme 1. For compounds IV: (a) R¼R1¼R2

¼R3¼H; (b) R¼R2

¼R3¼H,

R1¼F; (c) R¼R1

¼R3¼H, R2

¼F; (d) R¼R1¼R2

¼H, R3¼F; (e) R¼R1

¼ F,

R2¼R3

¼H; (f) R¼R1¼R2

¼R3¼F.


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



The General Methods for the Preparation of

Compounds II a–h

Method A

Amidine I is heated at 150�C for 4 h. The fusion cake formed isdissolved in 1N hydrochloric acid and filtered; the filtrate is basified toapproximately pH 10. The resulting precipitate is separated, washed withwater, and dried.

Method B

Amidine I (21mmol) is boiled in DMF (10mL) in the presence offreshly prepared sodium methylate for 1.5–2 h. The reaction mixture iscooled and diluted with water. The precipitate formed is separated,washed with water, and dried.

Spectral Data and Elemental Analysis Data for 1,2-Polymethyl-enebenzimidazoles II a–h

7-Nitro-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazole (IIa) wasrecrystallized from ethanol as pale yellow crystals. 1HNMR (CDCl3):2.81 (2H, quintet, 2-CH2), 3.14 (2H, t, 3-CH2), 4.21 (2H, t, 1-CH2),7.35 (1H, d, 8-H), 8.12 (1H, d, 9-H), 8.55 (1H, m, 6-H). Anal. Calcd.for C10H9N3O2: C, 59.11; N, 20.68. Found: C, 59.37; N, 20.54.

3-Nitro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (IIb)was recrystallized from hexane and ethanol as pale yellow crystals.1HNMR (DMSO-d6): 1.73–1.89 (6H, m, 7-, 8-, 9-CH2), 3.08 (2H, m,6-CH2), 4.35 (2H, m, 10-CH2), 7.76 (1H, dd, 2-H), 8.10 (1H, dd, 1-H),8.39 (1H, m, 4-H). 13CNMR (DMSO-d6): 24.86 (7-CH2), 28.01 (8-CH2),29.11 (6-CH2), 29.13 (9-CH2), 44.39 (10-CH2), 109.96 (1-CH), 114.36(4-CH), 117.18 (2-CH), 140.06 (3-C), 141.07 (10b-C), 142.19 (4a-C),160.75 (6a-C). Anal. Calcd. for C12H13N3O: C, 62.33; N, 18.17. Found:C, 62.48; N, 17.94.

3-Trifluoromethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (IIc)was recrystallized from hexane and ethanol as colorless crystals.1HNMR (DMSO-d6): 1.71–1.93 (6H, m, 7-, 8-, 9-CH2), 3.06–3.10 (2H,m, 6-CH2), 4.29–4.32 (2H, m, 10-CH2), 7.44–7.47 (1H, dd, 2-H), 7.47(1H, dd, 1-H), 7.80 (1H, m, 4-H). 13CNMR (DMSO-d6): 25.07 (7-CH2), 28.22 (8-CH2), 29.18 (6-CH2), 29.95 (9-CH2), 44.06 (10-CH2),


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



110.47 (1-CH), 115.59 (4-CH), 118.05 (2-CH), 119.82–130.62 (CF3, quar-tet, JC-F¼ 270.0Hz), 121.34–122.58 (3-C, quartet, JC-F¼ 30.5Hz), 138.02(10b-C), 141.51 (4a-C), 160.00 (6a-C). Anal. Calcd. for C13H13F3N2: C,61.41; N, 11.02. Found: C, 61.32; N, 10.88.

N,N-Diethyl-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole-3-sulfonamide (IId) was recrystallized from hexane and ethanol as colorlesscrystals. 1HNMR (CDCl3): 1.05–1.10 (6H, t, J¼ 7.2Hz, -CH2 -CH3),1.79–1.95 (6H, m, 7-, 8-, 9-CH2), 3.09–3.13 (2H, m, 6-CH2), 3.16–3.23(4H, quartet, -CH2-CH3), 4.29–4.32 (2H, m, 10-CH2), 7.61–7.66 (2H, m,1-, 2-H), 7.98 (1H, m, 4-H). 13CNMR (DMSO-d6): 14.05 (CH3CH2),24.91 (7-CH2), 28.06 (8-CH2), 29.11 (6-CH2), 29.86 (9-CH2), 41.77(CH3CH2), 44.16 (10-CH2), 110.29 (1-CH), 117.44 (4-CH), 120.05(2-CH), 132.44 (3-C), 138.08 (10b-C), 141.18 (4a-C), 160.00 (6a-C).Anal. Calcd. for C16H23N3O2S: C, 59.79; N, 13.07. Found: C, 59.70;N, 12.91.

2-Fluoro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (IIe)was recrystallized from ethanol as colorless crystals. 1HNMR(DMSO-d6): 1.66–1.90 (6H, m, 7-, 8-, 9-CH2), 2.97–3.03 (2H, m, 6-CH2),4.20–4.24 (2H, m, 10-CH2), 6.90–7.01, 7.41–7.53 (3H, m, 1-, 3-, 4-H).19FNMR (DMSO-d6): �121.40 � � � �121.34 (m). 13CNMR (DMSO-d6):25.25 (7-CH2), 28.35 (8-CH2), 29.19 (6-CH2), 30.07 (9-CH2),43.92 (10-CH2), 95.53–96.34 (3-CH, d, JC-F¼ 27.7Hz), 108.34–108.67(1-CH, d, JC-F¼ 25.2Hz), 118.81–118.96 (4-CH, d, JC-F¼10.9Hz), 135.73–135.92 (10b-C, d, JC-F¼ 14.1Hz), 138.43 (4a-C), 157.88(6a-C), 156.90–160.01 (2-C, d, JC-F¼ 233.3Hz). Anal. Calcd. forC12H13FN2: C, 70.57; N, 13.72. Found: C, 70.31; N, 13.81.

4-Fluoro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (IIf)was recrystallized from hexane and ethanol as colorless crystals.1HNMR (DMSO-d6): 1.69-1.78(4H, m, 7-, 8-CH2), 1.90–1.91 (2H, m,9-CH2), 3.02–3.06 (2H, m, 6-CH2), 4.22–4.26 (2H, m, 10-CH2),6.83–6.89 (1H, m, 3-H), 7.08–7.15 (1H, m, 2-H), 7.27–7.29 (1H, d,J¼ 8.1Hz, 1-H). 19FNMR (DMSO-d6): �130.21 � � � �130.14 (m).13CNMR (DMSO-d6): 25.07 (7-CH2), 28.19 (8-CH2), 29.08 (6-CH2),29.97 (9-CH2), 44.11 (10-CH2), 105.65 (1-CH), 106.03–106.26 (3-CH, d,JC-F¼ 17.25Hz), 121.49–121.59 (2-CH, d, JC-F¼ 7.5Hz), 130.06–130.29(4a-C, d, JC-F¼ 17.25Hz), 138.65–138.77 (10b-C, d, JC-F¼ 9.07Hz),151.16–154.46 (4-C, d, JC-F¼ 147.5Hz), 157.48 (6a-C). Anal. Calcd. forC12H13FN2: C, 70.57; N, 13.72. Found: C, 70.73; N, 13.64.

1,2-Difluoro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole (IIg)was recrystallized from hexane as colorless crystals. 1HNMR (DMSO-d6): 1.70–1.91 (6H, m, 7-, 8-, 9-CH2), 2.99–3.03 (2H, m, 6-CH2), 4.40–4.43(2H, m, 10-CH2), 7.00–7.10 (1H, m, 3-H), 7.24–7.29 (1H, m, 4-H).


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



19FNMR (DMSO-d6): �162.61 � � � �162.40 (m, J¼ 5.1Hz), �148.83 � � ��148.71 (m, J¼ 9.6Hz). 13CNMR (DMSO-d6): 24.96 (7-CH2), 28.31(8-CH2), 28.79 (6-CH2), 29.86 (9-CH2), 45.73–45.83 (10-CH2, d,JC-F¼ 7.5Hz), 109.49–109.76 (3-CH, d, J¼ 20.47Hz), 113.91–114.06(4-CH, dd, JC-F¼ 11.77Hz ), 123.78 (10b-C, dd), 134.37–137.88 (1-C,dd, JC-F¼ 18.4Hz, JC-F¼ 246.95), 140.72 (4a-C), 143.79–147.07 (2-C,dd, JC-F¼ 236.1Hz, JC-F¼ 10.5Hz), 158.99 (6a-C). Anal. Calcd. forC12H12F2N2: C, 64.86; N, 12.61. Found: C, 64.67; N, 12.75.

1,2,3,4-Tetrafluoro-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimida-zole (IIh) was recrystallized from hexane as colorless crystals. 1HNMR(DMSO-d6 ): 1.68–1.91 (6H, m, 7-, 8-, 9-CH2), 3.03–3.07 (2H, m, 6-CH2),4.39–4.42 (2H, m, 10-CH2).

19FNMR (DMSO-d6): �169.48 � � � �169.33(m), �167.46 � � � �167.33 (m), �163.87 � � � �163.75 (m), �157.07 � � ��156.94 (m). Anal. Calcd. for C12H10F4N2: C, 55.82; N, 10.85. Found:C, 56.08; N, 11.02.

REFERENCES

1. (a) Nair, M.D.; Adams, Roger. Benzimidazole syntheses byoxydative cyclization with peroxytrifluoroacetic acid. J. Am. Chem.Soc. 1961, 83, 3518–3521; (b) Mohrle, Hans; Gerloff, Joachim.Tricyclische benzimidazolderivate. Arch. Pharm. 1978, 311 (5),381–393; (c) Alkhader, Mohamed A.; Perera, R. Clinton; Sinha,Rajeshwar P.; Smalley, Robert K. Synthesis ofpolynuclear heterocycles. Part 4. 1Imidazo[4,5-g][3,1]benzoxazinones,imidazo [4,5-g]quinazolinones, imidazo[4,5-g]quinazolinediones, andimidazo[4,5-f ]indazolinones. J. Chem. Soc. Perkin Trans. I 1979,(4), 1056–1062; (d) Piotrovskii, L.B.; Poznyakova, L.N.Replacement of nitro groups in 2,3-dinitrotoluene by piperidine.Zh. Org. Khim. 1982, 18 (9), 1931–1935; (e) Groves, Clive L.;Ralph, James T.; Temple, Arthur F. Some novel heterocyclicsystems derived from 7-amino-2,3-dihydro-8-nitro-1H-pyrrolo[1,2-a]benzimidazole and the corresponding diamine. J. HeterocyclicChem. 1987, 24, 27–29; (f ) Imadul; Islam; Skibo, Edward B.Synthesis and physical studies of azamitosene and iminoazamito-sene reductive alkylating agents. Iminoquinone hydrolytic stability,syn/anti isomerization, and electrochemistry. J. Org. Chem. 1990,55, 3195–3205.

2. (a) De Selms, Roy C. Benzimidazoles. II. Synthesis of N-heterocyclicring systems containing 1,2-fused benzimidazole moieties. J.Org. Chem. 1962, 27, 2165–2167; (b) Haque, M. Rezaul;


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



Rasmussen Malkolm. Ambient heterocyclic reactivity: intramolecu-lar alkylation of 2,4-disubstituted benzimidazoles. Tetrahedron.1997, 53 (20), 6937–6958; (c) McClure, James R.; Custer, John H.;Schwarz, H. Dean; Lill, Deborah A. Synthesis of annelatedimidazoles and benzimidazoles. Synlett 2000, 5, 710–712.

3. (a) Aldabbagh, Fawaz; Bowman, W. Russell. Radical cyclizationinto imidazoles and benzimidazoles. Tetrahedron Lett. 1997,38 (21), 3793–3794; (b) Aldabbagh, Fawaz; Bowman, W. Russell.Radical cyclization into imidazoles and benzimidazoles.Tetrahedron 1999, 55 (13), 4109–4122.

4. Caroon, Joan M.; Fisher, Lawrence E. Preparation of substituted,annulated benzimidazoles via benzyne mediated cyclization.Heterocycles 1991, 32 (3), 459–467.

5. (a) Bredereck, Hellmut; Bredereck, Karl. Umsetzungen mit saurea-mid-phosphoroxychlorid-addukten und amidchloriden. 1961, 94 (8),2278–2295; (b) Javorsky, P.; Vesela, Z.; Truchlik, S. Synthesis andpesticidal activity of the substituted 3-(1-aza-1-cycloalken-2-yl)-3-phenyl-1-methylureas. Chem. Zvesti. 1978, 32 (2), 223–231.

6. (a) Brooke, Gerald M. The preparation and properties of polyfluoroaromatic and heteroaromatic compounds. J. Fluor. Chem. 1997,86, 1–76; (b) Chambers, Richard D.; Musgrave, W. Kenneth R.;Waterhouse, John S.; Williams, D. Lyn, H. Orientation and reactivityin nucleophilic replacement in polyfluoro-benzenes and -pyridines.J. Chem. Soc. Chem. Commun. 1974, (1), 239–240; (c) Chambers,Richard D.; Waterhouse John S.; Williams, D. Lyn H. Mechanismsfor reactions of halogenated compounds. Part 1. Activating effects offluorine in polyfluoropyridines in reactions with ammonia. J. Chem.Soc. Perkin Trans. II 1977, (5), 585–588; (d) Chambers, Richard D.;Close, Deborah; Musgrave, W. Kenneth R.; Waterhouse, John S.;Williams, D. Lyn H. Mechanisms for reactions of halogenatedcompounds. Part 2. 1Orienting effects of chlorine substituents innucleophilic aromatic substitution. J. Chem. Soc. Perkin Trans. II1977, (13), 1774–1778; (e) Chambers, Richard D.; Close, Deborah;Williams, D. Lyn H. Mechanisms for reactions of halogenatedcompounds. Part 3. Variation in activating influence of halogensubstituents in nucleophilic substitution. J. Chem. Soc. PerkinTrans. II 1980, (5), 778–780.

7. Benson, Richard E.; Cairns, Theodore L. Chemical reactions ofcaprolactam. J. Am. Chem. Soc. 1948, 70 (6), 2115–2118.

8. (a) Kwok, Russell; Pranc, Paul. Synthesis and nuclear magneticresonance spectra of some N-substituted 2-iminopyrrolidines.J. Org. Chem. 1967, 32 (3), 738–740; (b) Grisar, J. Martin;


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



Claxton, George P.; Wiech, Norbert L.; Lucas, Ronald W.;MacKenzie, Robert D.; Goldstein, Sidney. Benzhydryl and fluorenyllactamimides with hypoglycemic, diuretic, blood platelet aggregationinhibitory, and antiinflammatory activities. J. Med. Chem. 1973,16 (8), 885–893; (c) Jackman, Lloyd M.; Jen, Timothy. 1H and 13Cnuclear magnetic resonance studies on the tautomerism, geometricalisomerism, and conformation of some cyclic amidines, guanidines,and related systems. J. Am. Chem. Soc. 1975, 97 (10), 2811–2818.

Received in the UK June 19, 2003


Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013



Dow

nloa

ded

by [

Uni

vers

ity o

f H

ong

Kon

g L

ibra

ries

] at

08:

21 0

5 Se

ptem

ber

2013

Documents

A Novel Approach to the Synthesis of [1,2- a ]Fused Polymethylenebenzimidazoles