Preparation and cycloaddition reactions of novel heterocyclic mesomeric betaines

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 5523±5534

Preparation and Cycloaddition Reactions of Novel Heterocyclic

Mesomeric Betaines

David O. Morgan,^a,bW. David Ollis^a,²and Stephen P. Stanforth^c,

*

^aDepartment of Chemistry, University of Shef®eld, Shef®eld, S3 7HF, UK

^bSmithKline Beecham Pharmaceuticals, Old Powder Mills, Leigh, Tonbridge, Kent, TN11 9AN, UK

^cSchool of Applied and Molecular Sciences, University of Northumbria at Newcastle, Newcastle upon Tyne, NE1 8ST, UK

Received 29 March 2000; accepted 8 May 2000

AbstractÐThe heterocyclic mesomeric betaines 6a±c reacted with dimethyl acetylenedicarboxylate and ethyl propiolate giving the 1,3-

dipolar cycloaddition products 7a±c and 8a±c, respectively. With esters of maleic, fumaric, acrylic and methacrylic acids, mesomeric

betaines 6a and 6b gave substituted tetralone derivatives. q 2000 Published by Elsevier Science Ltd.

Introduction

1,3-dipole. The 1,3-dipolar cycloaddition reactions of meso-

meric betaines 6a±c and the Diels±Alder reactions of their

vinylketene valence tautomers 10a±c are also described.

Heterocyclic mesomeric betaines¹have been broadly

classi®ed into two types; conjugated heterocyclic meso-

meric betaines which are associated with 1,3-dipoles and

cross-conjugated heterocyclic mesomeric betaines which

are associated with 1,4-dipoles. The dipolar cycloaddition

reactions of both types of heterocyclic mesomeric betaines

have been widely investigated and this has given access to a

diverse variety of heterocyclic molecules. In this paper we

report the synthesis of the conjugated heterocyclic meso-

meric betaines 6a±c which posses an azomethine-imine

Synthesis of the Heterocyclic Mesomeric Betaines

The general synthetic route to compounds 6a±c is shown in

Scheme 1. 2-Formylbenzoic acid 1a was treated with thio-

nyl chloride and then methanol²giving a 43:57 mixture of

the lactone 2a and the aldehyde 3a. This mixture was not

separated but was reacted directly with 2-nitrophenylhydrazine

Scheme 1. a, R¹H; b, R¹Me; c, R¹Ph.

Keywords: mesomeric betaines; cycloadditions; vinylketenes; 1; 3-dipoles.

* Corresponding author. Tel.: 1191-2274784; fax: 1191-2273519; e-mail: steven.stanforth@unn.ac.uk

Deceased.

²

0040±4020/00/$ - see front matter q 2000 Published by Elsevier Science Ltd.

PII: S0040-4020(00)00471-3

5524

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

yielding the hydrazone derivative 4a (84% from 2a/3a).

Acid promoted cyclisation of the hydrazone 4a using

toluene-4-sulfonic acid in boiling toluene solution gave

the phthalazone derivative 5a (69%).³Reductive cyclisation

of compound 5a with triethyl phosphite at 1208C yielded the

heterocyclic mesomeric betaine 6a (59%) as bronze needles.

A 74:26 mixture of the lactone 2b and ketone 3b was

obtained from the sulfuric acid catalysed esteri®cation

reaction of 2-acetylbenzoic acid 1b with methanol.⁴From

this mixture and 2-nitrophenylhydrazine, hydrazone 4b

(70% from 2b/3b) was obtained. The phthalazone derivative

5b⁵(63%) was then obtained from acid catalysed cyclisation

of 4b and subsequent triethyl phosphite mediated reductive

cyclisation of compound 5b afforded the heterocyclic meso-

meric betaine 6b (85%) as orange needles. Similarly, methyl

2-benzoylbenzoate 3c and 2-nitrophenylhydrazine gave the

hydrazone 4c (63%) from which the phthalazone 5c (71%)

was prepared. Reductive cyclisation of compound 5c with

triethyl phosphite gave the heterocyclic mesomeric betaine

6c (87%) as a dark orange solid.

reacted with ethyl propiolate in boiling benzene (3±168 h)

the cycloadducts 8a±c were obtained in reasonable yields

(60±78%). The infra-red spectra of all three cycloadducts

indicated the presence of amide (1651±1652 cm²¹) and

ester (1730±1731 cm²¹) groups. When these values are

compared with those of the cycloadducts 7a±c described

above, this strongly suggests that these cycloadducts are

not associated with an .N±CvC±CvO system. Structures

8a±c should therefore be assigned to these cycloadducts

rather than the corresponding regioisomeric structures

9a±c. In the ¹H NMR spectrum of compound 8a, the vicinal

coupling constant between the C5 and C6 protons was

2.0 Hz although it is conceivable that an allylic coupling

constant between the C5 and C7 protons in the regioisomer

9a might also be of this magnitude. The chemical shifts of

the ethoxycarbonyl methylene (d 4.18±4.24) and methyl

(d 1.23±1.29) protons also support the proposed regio-

selectivity of the cycloaddition reaction; in regioisomer 9c

the chemical shifts of these protons might be expected to be

signi®cantly different than in the compounds 9a and 9b

because of the proximity of the C5 phenyl substituent.

Semi-empirical molecular orbital calculations also support

the observed regioselectivity in the cycloaddition reaction

of mesomeric betaine 6a and ethyl propiolate and these are

described later.

Reaction of the Heterocyclic Mesomeric Betaines with

Acetylenes

All three heterocyclic mesomeric betaines 6a±c reacted

with dimethyl acetylenedicarboxylate in boiling benzene

(1.5±5 h) giving the 1,3-dipolar cycloaddition products

7a±c in good yields (76±93%). The infra-red spectrum

(CHCl₃) of cycloadduct 7a showed three carbonyl groups

at 1749, 1721, 1658 cm²¹which were attributed to the C7

ester, the C6 ester and the lactam groups, respectively. The

C6 ester group is observed at signi®cantly lower frequency

than the C7 ester group because it is part of an .N±CvC±

CvO system. Similarly, the cycloadducts 7b and 7c each

showed three carbonyl groups (1748, 1722, 1657 cm²¹for

7b; 1745, 1725, 1656 cm²¹for 7c) in their infra-red spectra.

The C5 proton of compound 7a (d 5.69) and the C5 methyl

group (d 1.99) of compound 7b were observed as singlets in

The heterocyclic mesomeric betaine 6a was unreactive

towards either diphenylacetylene or bis(trimethylsilyl)-

acetylene in boiling benzene solution.

Reaction of the Heterocyclic Mesomeric Betaines with

Alkenes

When the heterocyclic mesomeric betaines 6a and 6b were

reacted with either dimethyl maleate 11 (R²Me), diethyl

maleate 11 (R²Et), dimethyl fumarate 12 (R²Me) or

diethyl fumarate 12 (R²Et) in boiling benzene solution

(25±72 h), tetralone derivatives were obtained as outlined

in Scheme 2 and Table 1. The formation of these tetralone

derivatives can be readily rationalised by invoking a

cycloaddition reaction between the vinylketene valence

tautomers 10a and 10b of the mesomeric betaines 6a and

6b with these esters of maleic and fumaric acids. The

cycloaddition reactions of the vinylketene intermediates

10a and 10b are similar to those of structurally related

vinylketenes which have been generated by other routes.^6,7

1

their H NMR spectra.

In this paper we have considered the formation of the tetra-

lones 13±18 to occur via vinylketene intermediates 10a and

10b but we are aware that other reasonable mechanisms for

the formation of these products (Scheme 3) could be

proposed. In pathway A (Scheme 3) compounds 13±18

are formed via initial Michael addition reactions whereas

in pathway B fragmentation of the 1,3-dipolar cycloaddition

products could provide an alternative source of the Michael

adducts. Pathway B would also rationalise the different

product types obtained from the reactions of acetylenic

and ole®nic dipolarophiles with mesomeric betaines 6a

and 6b; fragmentation of the acetylene derived cycloadducts

7 and 8 could only result in the formation of vinylic anion

intermediates.

When the heterocyclic mesomeric betaines 6a±c were

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

5525

Mesomeric betaine 6a gave a mixture of diastereoisomers

14a (R²Me) and 18a (R²Me) with dimethyl maleate 11

(R²Me) which were separated by chromatography (entry

1). The relative stereochemistry of compounds 14a and 18a

were assigned from their ¹H NMR spectra (see below). The

formation of these two products can be readily rationalised

by assuming that a mixture of the exo 13a and endo 16a

cycloadducts are initially formed. Compound 13a tauto-

merises giving the enol form 14a which has the C3 ester

and C4 benzotriazole substituents in a favourable anti

relationship. As a consequence of the syn relationships

between the C2 and C3 ester substituents in compound

16a, epimerisation occurs giving the diastereoisomer 18a

via the corresponding enol tautomer 17a. The co-planar

arrangement of the benzene ring, the C1 and C2 carbon

atoms in the enol 17a forces the C3 ester and C4 benzo-

triazole substituents to lie in almost the same plane, whereas

in the ketone 18a these substituents can lie in different

planes. The keto tautomer 18a is therefore favoured over

the corresponding enol tautomer 17a.

The ¹H NMR spectrum of compound 18a (R²Me)

exhibited a 12.6 Hz coupling constant between the C2 and

C3 protons which is consistent with their proposed trans-

diaxial relationship. The C4 proton can therefore be trans-

axial or cis-equatorial relative to the C3 proton. The

observed coupling constant (4.6 Hz) between the C3 and

C4 protons con®rms their axial-equatorial relationship.

Having established the relative stereochemisry in com-

pound 18a and hence in the cycloadduct 16a, the second

Scheme 2. a, R¹H; b, R¹Me.

Table 1.

Entry

Mesomeric betaine

Ester

Products^a

1

2

3

4

6a

11 (R²Me)

12 (R²Me)

11 (R²Et)

12 (R²Et)

11 (R²Me)

12 (R²Me)

11 (R²Et)

12 (R²Et)

14a (R²Me) (31%), 18a

(R²Me) (8%)

14a (R²Me) (43%), 18a

(R²Me) (3%)

14a (R²Et) (38%), 18a

(R²Et) (17%)

14a (R²Et) (73%), 18a

(R²Et) (4%)

5

6

7

8

6b

14b/15b (R²Me), 7:3^b(54%)

14b/15b (R²Me), 7:3^b(56%)

14b/15b (R²Et), 13:7^b(31%)

14b/15b (R²Et), 13:7^b(42%)

^aIsolated yields.

^bRatios determined in by ¹H NMR spectroscopy in CDCl₃solution.

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D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

Scheme 3.

cycloadduct and its enol tautomer must have the relative

stereochemistry depicted in formulae 13a and 14a. The

coupling constant (2.1 Hz) between the C3 and C4 protons

in product 14a is consistent with their proposed diequatorial

orientation.

18a. However, we know that in the cycloaddition reactions

of 10a, the enolic product 17a is disfavoured, and similarly

structure 17b would be expected to be disfavoured. Since an

enolic product has been formed, the enol must have the

structure 14b.

With dimethyl fumarate 12 (R²Me), mesomeric betaine 6a

gave the same mixture of products as with dimethyl maleate

11 (R²Me) (entry 2, Table 1). In this reaction, the initially

formed cycloadducts are the diastereoisomers 15a and 18a

with the former compound 15a tautomerising giving the

product 14a. As noted above, tautomer 18a is preferred

over 17a. Dimethyl maleate 11 (R²Me) was not

isomerised to dimethyl fumarate 12 (R²Me) under the

reaction conditions.

Diethyl maleate 11 (R²Et) and diethyl fumarate 12

(R²Et) both reacted with mesomeric betaine 6a giving

analogous products 14a and 18a to their dimethyl counter-

parts (entries 3 and 4, respectively, Table 1).

Mesomeric betaine 6b also reacted with the dimethyl and

diethyl esters of maleic and fumaric acids giving an insepar-

able mixture of diastereoisomers. Crystallisation enabled

the isolation of a tautomeric mixture 14b (R²Me, Et)/

15b (R²Me, Et) in the ratios indicated in Table 1. The

enol tautomers 14b are the predominant structures and

this contrasts with the exclusive formation of the keto

1

tautomers 15a described above. The H NMR spectrum of

tautomers 15b showed coupling constants (13.7 Hz for

R²Me; 9.5 Hz for R²Et) between the C2 and C3 protons

indicating their trans-diaxial relationship. These coupling

constants would be consistent with either structure 15a or

Mesomeric betaines 6a and 6b reacted with methyl acrylate,

ethyl acrylate and ethyl methacrylate in boiling benzene

solution (7±54 h) giving the products indicated in Table 2.

All of these reactions were regioselective proceeding with

the regiochemistry shown. With methyl and ethyl acrylate,

the initially formed cycloadducts 19a/19b (R²Me, Et)

Table 2.

Entry Mesomeric betaine

Acrylate

Product(s)^a

1

2

3

4

5

6

6a

6b

6a

6b

6a

6b

Methyl acrylate 20a (R²Me) (54%)

Methyl acrylate 20b (R²Me) (65%)

1

tautomerised giving the enols 20a/20b (R²Me, Et). H

Ethyl acrylate

20a (R²Et) (96%)

20b (R²Et) (97%)

22a (18%), 23a (73%)

22b (15%), 23b (69%)

NMR and infra-red spectroscopy fully support the proposed

enolic structures and the regiochemistry of these cyclo-

addition reactions is therefore established; the alternative

regiochemistry would not give a b-keto ester and hence

enolisation could not occur.

21

^aIsolated yields

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

5527

Table 3.

Reactant

6a

HOMO energy (eV)

28.16

HOMO coef®cients

LUMO energy (eV)

LUMO coef®cients

C7 (0.522)

21.26

0.20

C7 (20.276)

N5 (20.321)

C1 (0.550)^a

C2 (20.382)

C12 (20.538)^b

C7 (20.394)

C1 (0.652)^a

N5 (20.489)

C1 (20.004)^a

C2 (20.003)

C12 (20.274)^b

C7 (0.587)

Ethyl propiolate

10a

211.38

28.14

21.41

20.11

Methyl acrylate

211.06

C1 (20.648)^a

C2 (20.664)

C2 (20.497)

^aC1b-carbon; C2a-carbon

^bThe numbering system in 10a corresponds with 6a for simplicity.

The cycloaddition reaction of compound 6a with ethyl

methacrylate 21 was regioselective giving a mixture of

two stereoisomers 22a and 23a. The regioselectivity of the

reaction was clear from the ¹H NMR spectra of the reaction

products. Thus, for compounds 22a and 23a an ABX system

(d_A3.12, d_B3.10, d_X6.63; J_AB13.2, J_AX10.6,

J_BX5.0 Hz) and an AMX system d_A2.62, d_M3.79, d_X

6.49; J_AM13.3, J_AX5.2, J_MX12.2 Hz), respectively for

the C3 and the C4 protons were observed. In the alternative

regio-isomers 24a these coupling patterns and coupling

constants would not be expected. Mesomeric betaine 6b

also reacted with ethyl methacrylate 21 giving a mixture

of stereoisomers 22b and 23b. Clearly, the structure of the

cycloadducts 22b and 23b would be anticipated to be

analogous to the cycloadducts 22a and 23a and this is

of the 1,3-dipolar cycloaddition reaction between meso-

meric betaine 6a and ethyl propiolate the Diels±Alder

reaction between the vinylketene 10a and methyl acrylate.

The HOMO/LUMO energies of these reactants and their

orbital coef®cients at the reaction centres are collected in

Table 3.

For the mesomeric betaine 6a/ethyl propiolate reaction the

HOMO (6a)/LUMO (ethyl propiolate) energy difference is

8.36 eV whereas the HOMO (ethyl propiolate)/LUMO (6a)

value is 10.57 eV, indicating that this 1,3-dipolar cyclo-

addition reaction will be controlled by the former inter-

action. The largest coef®cients at the reaction centres of

the HOMO of 6a and the LUMO of ethyl propiolate are

located at the C7 and the C1 atoms, respectively, which

would predict that the C7 (6a)±C1 (ethyl propiolate) bond

will be formed. This corresponds with the observed regio-

selectivity. Additionally, with mesomeric betaines 6b and

6c, steric interactions between the R¹substituent and the

ethoxycarbonyl group of the ethyl propiolate would also

favour this regioselectivity.

1

supported by H NMR spectral evidence in which the C3

protons are observed with similar chemical shifts. The

assignment of the relative stereochemistry of the cyclo-

adducts 22b and 23b is based on the chemical shifts of the

methyl protons (d 1.22 and 0.72, respectively) of the

ethoxycarbonyl groups. In the major cycloadduct 23b, a

1,3-diaxial interaction between the C2 and C4 methyl

groups forces the tetralone ring to adopt a conformation in

which the methyl protons of the ethoxycarbonyl group lie in

the shielding region of the C4 benzotriazole ring and the

aromatic ring of the tetralone moiety. Consequently, these

protons resonate at lower frequency. The relative stereo-

chemistry of cycloadducts 22a and 23a was tentatively

assigned as shown because of their general ¹H NMR spectral

similarity with compounds 22b and 23b.

For the vinylketene 10a/methyl acrylate reaction the

HOMO (10a)/LUMO (methyl acrylate) energy difference

is 8.03 eV whereas the HOMO (methyl acrylate)/LUMO

(10a) value is 12.47 eV, indicating that this Diels±Alder

reaction will be dominated by the former interaction. The

largest coef®cients at the reaction centres of the HOMO of

10a and the LUMO of methyl acrylate are located at the C7

and the C1 atoms, respectively, which would predict that the

C7 (10a)±C1 (methyl acrylate) bond will be formed and this

also corresponds with the observed regioselectivity.

Treatment of mesomeric betaines, 6a and 6b, with acrylo-

nitrile in boiling benzene gave a mixture of diastereo-

isomers (by ¹H NMR spectroscopy) but attempted

puri®cation of the reaction mixture by chromatography

resulted in decomposition. However, the crude reaction

product 25b from the reaction of mesomeric betaine 6b

was successfully oxidised with 2,3-dichloro-5,6-dicyano-

benzoquinone (DDQ) in boiling benzene giving compound

26b although in poor (26%) yield.

Transformations of Cycloadducts

In order to con®rm the structures of the cycloaddition

products of the valence tautomers 10a and 10b of the meso-

meric betaines 6a and 6b, respectively, some transforma-

tions of these cycloadducts were undertaken.

Acetylation of compound 14a (R²Et) with acetic

anhydride-pyridine gave 2,3-diethoxycarbonylnaphth-1-yl

acetate 27 (84% yield). In this reaction the benzotriazole

unit was eliminated and 1-acetylbenzotriazole was detected

in the reaction mixture but was partially hydrolysed upon

isolation. In contrast, acetylation of the enol esters 20a

(R²Et) and 20b (R²Et) with acetic anhydride-pyridine

did not result in the elimination of benzotriazole and the

Mesomeric betaine 6c was unreactive towards the alkenes

described above and mesomeric betaines 6a was inert

towards ethyl vinyl ether.

Semi-empirical Molecular Orbital Calculations

The PM3 method was used to determine the regioselectivity

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D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

acetates 28a (57% yield) and 28b (76% yield), respectively,

were isolated. In the case of compound 14a (R²Et) the C3

proton is relatively acidic due to the presence of the C3 ester

substituent and hence elimination of benzotriazole is

relatively easy.

solution unless stated otherwise. Chromatography refers to

preparative thick layer chromatography using silica gel

coated glass plates.

3-Methoxyphthalide 2a and 2-methoxycarbonylbenzal-

dehyde 3a.²Compound 1a (20 g, 0.13 mol) and thionyl

chloride (20 mL, 0.28 mol) were heated (2 h) at re¯ux.

The reaction mixture was allowed to cool to room tempera-

ture and evaporated. Methanol (60 mL) was added to the

residue and the mixture was heated (4 h) at re¯ux, allowed

to cool to room temperature, evaporated and then distilled

under reduced pressure giving a 43:57 mixture (18.2 g) of

compounds 2a and 3a as a colourless oil, bp 150±1528C,

1 mm Hg. Compound 2a: d_H(220 MHz) 7.62 (4H, m, ArH),

6.31 (1H, s, C3±H) and 3.62 (3H, s, ±OCH₃). Compound

3a: d_H(220 MHz) 10.57 (1H, s, ±CHO), 7.91 (4H, m, ArH)

and 3.97 (3H, s, ±CO₂CH₃).

3-Methyl-3-methoxyphthalide 2b and methyl 2-acetyl-

A mixture of compound 1b (20 g,

benzoate 3b.⁴

0.12 mol), methanol (40 mL) and concentrated sulphuric

acid (2 mL) was stored (15 h) at room temperature. The

mixture was poured into water (70 mL) and extracted with

ether (3£40 mL). The combined organic extracts were

washed with water, dried (MgSO₄) and evaporated. The

residue was distilled under reduced pressure giving a

74:26 mixture (16.2 g) of compounds 2b and 3b as a colour-

less oil, bp 120±1228C, 8 mm Hg. Compound 2b: d_H

(220 MHz) 2b 7.57 (4H, m, ArH), 3.05 (3H, s, ±OCH₃)

and 1.84 (3H, s, ±CH₃). Compound 3b: d_H(220 MHz)

7.82 (4H, m, ArH), 3.90 (3H, s, ±OCO₂CH₃) and 2.54

(3H, s, ±COCH₃).

Compound 14a (R²Et) reacted with a catalytic quantity of

1,5-diazabicyclo[4.3.0]non-5-ene (DBN) in boiling benzene

giving the naphthalene derivative 29a⁸(68%) and benzo-

triazole (64%). Similarly, treatment of a tautomeric mixture

of compounds 14b/15b (R²Et) with DBN afforded the

naphthalene derivative 29b (77%) and benzotriazole

(69%). In contrast, the enol ester 20a did not react under

these conditions indicating the necessity of a relatively

acidic C3 proton for the elimination of benzotriazole.

2-Methoxycarbonylbenzaldehyde 2⁰-nitrophenylhydra-

zone 4a. 2-Nitrophenylhydrazone (4.0 g, 26 mmol) was

dissolved in hot ethanol (150 mL). The solution was cooled

in an ice-bath and concentrated hydrochloric acid (1 mL)

followed by a mixture of 2a/3a (10.0 g) prepared as

described above was added. The reaction was kept (1 h) in

the cold and the orange precipitate of compound 4a (6.57 g,

84% from 3a) was collected, mp 186±1878C (with sublima-

tion before melting) (from methanol±chloroform). (Found:

C, 60.7; H, 4.6; N, 13.8. C₁₅H₁₃N₃O₄requires C, 60.2; H,

4.4; N, 14.0%), n_max.3310, 1717, 1619, 1578, 1503, 1483,

1334, 1275, 1258 and 1144 cm²¹, d_H(220 MHz) 11.09 (1H,

s, .NH), 8.87 (1H, s, ±CHv), 8.17 (2H, m, ArH), 7.96 (2H,

m, ArH), 7.54 (2H, m, ArH), 7.41 (1H, dt, J7.7 and 1.3 Hz,

ArH), 6.83 (1H, dt, J7.9 and 1.2 Hz, ArH) and 3.94 (3H, s,

±CO₂CH₃).

Alkaline hydrolysis of the enol esters 20a (R²Et) and 20b

(R²Et) gave the substituted tetralone derivative 30a (88%

yield) and 30b (56%), respectively. Acidic hydrolysis of

compound 20a (R²Et) resulted only in partial hydrolysis

of the ester group and a mixture of the tetralone 30a (41%),

the ester 31a⁹(31%) and benzotriazole (41% yield) was

obtained. Ester derivative 20b (R²Et) gave a mixture of

compound 31b (58%) and benzotriazole (65%) under

similar conditions.

Oxidation of compound 20a (R²Et) with 2,3-dichloro-5,6-

dicyano-1,4-benzoquinone (DDQ) gave the naphthalene

derivative 32 (85%).

Conclusions

2-Methoxycarbonylacetophenone 2⁰-nitrophenylhydra-

zone 4b. A mixture of compounds 2b/3b (10.0 g), prepared

as described above, was added to a solution of 2-nitro-

phenylhydrazone (2.24 g, 15 mmol) and concentrated

hydrochloric acid (1 mL) in methanol (40 mL). The mixture

was heated (1 h) at re¯ux, allowed to cool to room tempera-

ture and methanol (160 mL) and water (40 mL) were added.

The solution was decanted from the resulting oil and water

was added. The cloudy mixture was allowed to stand (15 h)

and the orange precipitate collected yielding compound 4b

(3.2 g, 70% from 3b), mp 101±1028C (from 70% aqueous

ethanol). (Found: C, 61.6; H, 4.9; N, 13.6. C₁₆H₁₅N₃O₄

requires C, 61.3; H, 4.8; N, 13.4%), n_max.3335, 1723,

The heterocyclic mesomeric betaines 6a±c underwent

typical 1,3-dipolar cycloaddition reactions with DMAD and

ethyl propiolate. With electron de®cient alkenes they gave

tetralone derivatives possibly via Diels±Alder reactions of

their valence tautomers 10a±c. The regioselectivity of both

types of cycloaddition reaction has been established and

rationalised by semi-empirical molecular orbital calculations.

Experimental

¹H NMR spectra were determined at 220 or 400 MHz in

CDCl₃solution. Infra-red spectra were recorded in CHCl₃

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

5529

1609, 1581, 1503, 1294, 1271 and 1145 cm²¹, d_H

(220 MHz) 10.89 (1H, s, .NH), 8.15 (1H, dd, J8.8 and

1.7 Hz, ArH), 7.82 (2H, m, ArH), 7.48 (4H, m, ArH), 6.81

(1H, dt, J7.6 and 1.3 Hz, ArH) 3.81 (3H, s, ±CO₂CH₃) and

2.36 (3H, m, ±CH₃).

7.5 mmol) and freshly distilled triethyl phosphite (15 mL)

was heated (65 h) at 1208C under a nitrogen atmosphere.

The reaction mixture was allowed to cool to room tempera-

ture and the solid collected by ®ltration giving compound 6a

(1.04 g, 59%) as bronze needles, mp 249±2508C (with

sublimation before melting) (from CH₃CN). (Found: C,

71.2; H, 4.0; N, 17.6 C₁₄H₉N₃O requires C, 71.5; H, 3.9;

N, 17.9%), n_max.1665, 1609, 1539 and 1148 cm²¹, l_max.

(EtOH) 238, 253, 277, 319, 401, 444 and 460 nm, d_H

(440 MHz) 8.66 (1H, ddd, J8.2, 1.2 and 0.8 Hz, ArH),

8.50 (1H, ddd, J8.2, 1.3 and 0.6 Hz, ArH), 8.39 (1H, s,

ArH), 7.72 (1H, dt, J8.1, 6.8 and 1.3 Hz, ArH), 7.62 (2H,

m, ArH), 7.56 (1H, dt, J8.4, 7.3 and 1.2 Hz, ArH), 7.50

(1H, dt, J8.2, 6.8 and 1.3 Hz, ArH) and 7.33 (1H, dt,

J8.2, 7.3 and 1.3 Hz, ArH).

2-Methoxycarbonylbenzophenone 2⁰-nitrophenylhydra-

zone 4c. Compound 3c¹⁰(7.0 g, 29 mmol), 2-nitrophenyl-

hydrazone (4.46 g, 29 mmol), concentrated hydrochloric

acid (2 mL) and methanol (70 mL) were heated (22 h) at

re¯ux with stirring. The reaction mixture was allowed to

cool to room temperature and kept (15 h) giving compound

4c (6.86 g, 63%) as red crystals, mp 160±1618C (from

ethanol). (Found: C, 66.9; H, 4.5; N, 11.3. C₂₁H₁₇N₃O₄

requires C, 67.2; H, 4.6; N, 11.2%), n_max.3300, 1726,

1615, 1575, 1492, 1320, 1273 and 1140 cm²¹, d_H

(220 MHz) 10.55 (1H, s, .NH), 8.29 (1H, dd, J7.8 and

1.1 Hz, ArH), 8.13 (1H, d, J8.3 Hz, ArH), 8.08 (1H, dd,

J8.8 and 1.1 Hz, ArH), 7.79 (1H, dt, J8.8 and 1.3 Hz,

ArH), 7.62 (3H, m, ArH), 7.34 (5H, m, ±Ph), 6.79 (1H, dt,

J7.0 and 1.1 Hz, ArH) and 3.68 (3H, s, ±CO₂CH₃).

7-Methyl-5,12-dihydro-12-oxo-6l⁵-phthalazino[2,3-a]-

benzotriazole-6-ylium-5-ide 6b. Using a similar method to

that described above for the preparation of compound 6a,

compound 5b (2.0 g, 7 mmol) and triethyl phosphite

(15 mL) gave, after 48 h, compound 6b (1.51 g, 85%) as

orange needles, mp 268±2708C (with sublimation before

melting) (from CH₃CN). (Found: C, 72.0; H, 4.6; N, 16.7.

C₁₅H₁₁N₃O requires C, 72.3; H, 4.5; N, 16.9%), n_max.(KBr)

3-(2⁰-Nitrophenyl)phthalaz-4-one 5a.

A mixture of

compound 4a (5.8 g, 19 mmol), toluene-4-sulfonic acid

(1.0 g) and toluene (15 mL) was heated (47 h) at re¯ux.

The mixture was allowed to cool to room temperature,

evaporated and ethanol (40 mL) was added to the residue.

The solid was collected, washed with ethanol and recrystal-

lised from ethanol giving compound 5a (3.5 g, 69%) as

white needles, mp 204±2068C (lit.³mp 2018C). n_max.

1673, 1536, 1360 and 1338 cm²¹, d_H(440 MHz) 8.66

(1H, d, J0.9 Hz, C1±H), 8.30 (1H, ddd, J8.0, 1.1 and

0.9 Hz, ArH), 8.16 (1H, dd, J8.1 and 1.5 Hz, ArH), 8.06

(2H, m, ArH), 7.95 (2H, m, ArH), 7.83 (1H, dd, J8.1 and

1.5 Hz, ArH) and 7.75 (1H, dt, J8.1, 7.4 and 1.5 Hz, ArH).

1-Methyl-3-(2⁰-nitrophenyl)phthalaz-4-one 5b. Using a

similar method to that described above for the preparation

of compound 5a, compound 4b (4.7 g, 15 mmol), toluene-4-

sulfonic acid (1.0 g) and toluene (10 mL) at re¯ux (9 h)

gave compound 5b (2.65 g, 63%) as white crystals, mp

203±2048C (from ethanol) (lit.⁵mp 2028C). n_max.1669,

1609, 1597, 1534, 1353 and 1340 cm²¹, d_H(400 MHz)

8.49 (1H, d, J8.1 Hz, ArH), 8.08 (1H, dd, J8.0 and

1.5 Hz, ArH), 7.89 (1H, dt, J8.1, 7.0 and 1.2 Hz, ArH),

7.82 (2H, m, ArH), 7.76 (1H, dt, J7.8 and 1.5 Hz, ArH),

7.69 (1H, dd, J7.8 and 1.5 Hz, ArH), 7.57 (1H, dt, J7.8

and 1.8 Hz, ArH) and 2.65 (3H, s, ±CH₃).

1654, 1603, 1520, 1429, 1311, 1254, 1191 and 748 cm²¹

_max.(EtOH) 209, 225, 249, 252, 276, 407, 453 and 470 nm,

,

l

d_H(400 MHz) 8.67 (1H, ddd, J8.2, 1.2 and 0.7 Hz, ArH),

8.60 (1H, ddd, J8.2, 1.4 and 0.7 Hz, ArH), 7.84 (1H, ddd,

J8.5, 1.4 and 0.7 Hz, ArH), 7.80 (1H, dt, J8.5, 6.5 and

1.4 Hz, ArH), 7.66 (1H, ddd, J8.4, 1.0 and 0.6 Hz, ArH),

7.55 (1H, dt, J8.4, 7.3 and 1.2 Hz, ArH), 7.52 (1H, dt,

J8.5, 8.2 and 1.4 Hz, ArH), 7.30 (1H, dt, J8.2, 7.3 and

1.0 Hz, ArH) and 3.01 (3H, s, ±CH₃).

7-Phenyl-5,12-dihydro-12-oxo-6l⁵-phthalazino[2,3-a]-

benzotriazole-6-ylium-5-ide 6c. Using a similar method to

that described above for the preparation of compound 6a,

compound 5c (2.0 g, 5.8 mmol) and triethyl phosphite

(15 mL) gave, after 24 h, compound 6c (1.57 g, 87%) as a

dark orange solid, mp 291±2928C (with sublimation before

melting) (from CH₃CN). (Found: C, 76.9; H, 4.4; N, 13.4.

C₂₀H₁₃N₃O requires C, 77.2; H, 4.2; N, 13.5%), n_max.(KBr)

1673, 1607, 1515, 1479, 1434, 1129 and 750 cm²¹, l_max.

(EtOH) 208, 226, 253, 280, 288, 322, 416 and 472 nm, d_H

(400 MHz) 8.73 (1H, d, J8.3 Hz, ArH), 8.61 (1H, ddd,

J8.1, 1.3 and 0.8 Hz, ArH), 7.66 (5H, m, ArH), 7.60

(2H, m, ArH), 7.50 (3H, m, ArH) and 7.33 (1H, dt, J8.3,

7.1 and 1.1 Hz, ArH).

1-Phenyl-3-(2⁰-nitrophenyl)phthalaz-4-one 5c. Using a

similar method to that described above for the preparation

of compound 5a, compound 4c (5.0 g, 15 mmol), toluene-4-

sulfonic acid (1.0 g) and toluene (15 mL) at re¯ux (43 h)

gave compound 5c (3.26 g, 71%) as white crystals, mp 163±

1648C (from ethanol). (Found: C, 69.9; H, 3.8; N, 12.2.

C₂₀H₁₃N₃O₃requires C, 70.0; H, 3.8; N, 12.2%), n_max.

1670, 1609, 1589, 1533, 1359 and 1340 cm²¹, d_H

(400 MHz) 8.57 (1H, m, ArH), 8.09 (1H, ddd, J8.1, 1.3

and 0.5 Hz, ArH), 7.82 (3H, m, ArH), 7.76 (3H, m, ArH)

and 7.56 (5H, m, ±Ph).

6,7-Dimethoxycarbonyl-5a,8,13-nitrilodibenzo[b,f][1,4]-

diazecin-14(5H)-one 7a. A mixture of compound 6a

(0.75 g, 3.2 mmol), DMAD (0.8 mL, 6.5 mmol) and

benzene (30 mL) was heated at re¯ux (1.5 h). The reaction

mixture was allowed to cool to room temperature, evapo-

rated and the residue was triturated with ethanol (15 mL)

giving compound 7a (0.91 g, 76%) as pale yellow crystals,

mp 211±2128C (with softening at 1788C) (from ethanol).

(Found: C, 63.8; H, 4.2; N, 10.9,

M 377.1006.

C₂₀H₁₅N₃O₅requires C, 63.7; H, 4.0; N, 11.1%, M

377.1011). n_max.1749, 1721, 1658, 1482, 1441, 1410,

1348 and 1300 cm²¹, d_H(400 MHz) 8.24 (1H, ddd,

J7.7, 1.4 and 0.6 Hz, ArH), 8.06 (1H, ddd, J7.6, 1.2

and 0.6 Hz, ArH), 7.66 (2H, m, ArH), 7.57 (1H, dt,

5,12-Dihydro-12-oxo-6l⁵-phthalazino[2,3-a]benzotria-

zole-6-ylium-5-ide 6a. A mixture of compound 5a (2.0 g,

5530

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

J7.7, 6.8 and 1.8 Hz, ArH), 7.34 (1H, dt, J7.6 and

1.2 Hz, ArH), 7.28 (1H, ddd, J7.6, 1.2 and 0.6 Hz,

ArH), 7.13 (1H, dt, J7.6 and 1.2 Hz, ArH), 5.69 (1H, s,

C5-H), 3.76 (3H, s, ±OCH₃) and 3.63 (3H, s, ±OCH₃).

The solution was stored at room temperature (15 h) giving

a complex of compound 8b-0.5 benzene (185 mg, 60%), mp

115±1188C (with softening at 1008C). (Found: C, 71.7; H,

5.2; N, 10.8, M 347.1273. C₂₀H₁₇N₃O₃´0.5C₆H₆requires C,

71.5; H, 5.2; N, 10.9%, M 347.1270). n_max.1730, 1652,

1485, 1415, 1313, 1130 and 1072 cm²¹, d_H(220 MHz)

8.28 (1H, dd, J7.6 and 1.7 Hz, ArH), 8.02 (1H, dd,

J7.7 and 1.1 Hz, ArH), 7.62 (2H, m, ArH), 7.49 (2H, m,

ArH), 7.32 (3H, s, benzene), 7.25 (1H, dt, J7.7 and 1.4 Hz,

ArH), 7.10 (1H, dt, J7.7 and 1.1 Hz, ArH), 6.22 (1H, s,

C6±H), 4.18 (2H, m, ±OCH₂CH₃), 1.85 (3H, s, ±CH₃) and

1.23 (3H, t, J7.6 Hz, ±OCH₂CH₃).

6,7-Dimethoxycarbonyl-5-methyl-5a,8,13-nitrilodibenzo-

[b,f][1,4]diazecin-14(5H)-one 7b. Using a similar method

to that described above for the preparation of compound 7a,

compound 6b (0.75 g, 3.0 mmol) and DMAD (0.8 mL,

6.5 mmol) in benzene (15 mL) gave, after 1.5 h, compound

7b (1.05 g, 89%) as yellow crystals, mp 181±1838C (from

EtOH). (Found: C, 64.6; H, 4.4; N, 10.8, M 391.1146.

C₂₁H₁₇N₃O₅requires C, 64.5; H, 4.4; N, 10.7%, M

391.1168). n_max.1748, 1722, 1657, 1485, 1415 and

1301 cm²¹, d_H(400 MHz) 8.26 (1H, dd, J8.0 and

1.6 Hz, ArH), 8.05 (1H, dd, J7.8 and 1.3 Hz, ArH), 7.78

(1H, dd, J8.0 and 1.2 Hz, ArH), 7.67 (1H, dt, J8.0 and

1.6 Hz, ArH) 7.54 (1H, dt, J8.0 and 1.2 Hz, ArH), 7.33

(1H, dt, J7.8 and 1.2 Hz, ArH), 7.28 (1H, d, J7.8 Hz,

ArH), 7.13 (1H, dt, J7.8 and 1.3 Hz, ArH), 3.75 (3H, s,

±OCH₃), 3.63 (3H, s, ±OCH₃) and 1.99 (3H, s, ±CH₃).

7-Ethoxycarbonyl-5-phenyl-5a,8,13-nitrilodibenzo[b,f][1,4]-

diazecin-14(5H)-one 8c. A mixture of compound 6c

(200 mg, 0.64 mmol), ethyl propiolate (0.1 mL,

0.98 mmol) and benzene (10 mL) was heated at re¯ux

(168 h) with stirring. The reaction mixture was allowed to

cool to room temperature, evaporated and the residual

yellow oil was triturated with ether (5 mL) giving

compound 8c (205 mg, 78%) as yellow crystals, mp 208±

2108C (from ethanol). (Found: C, 73.3; H, 4.7; N, 10.1, M

409.1420. C₂₅H₁₉N₃O₃requires C, 73.3; H, 4.7; N, 10.3%,

M 409.1414). n_max.1731, 1651, 1485, 1413, 1310 and

1108 cm²¹, d_H(220 MHz) 8.33 (1H, dd, J7.3 and

1.7 Hz, ArH), 8.11 (1H, d, J7.7 Hz, ArH), 7.65±7.35

(8H, m, ArH), 7.29 (1H, dt, J7.7 and 1.1 Hz, ArH), 7.11

(1H, dt, J7.7 and 1.1 Hz, ArH), 6.92 (1H, m, ArH), 6.68

(1H, s, C6±H), 4.24 (2H, m, ±OCH₂CH₃) and 1.29 (3H, t,

J7.6 Hz, ±OCH₂CH₃).

(3a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2,3-di-

methoxycarbonylnaphth-1-ol 14a (R²Me) and

(2a,3b,4b)-4-(2⁰H-benzotriazol-2⁰-yl)-2,3-dimethoxy-

carbonyltetra-1-one 18a (R²Me). (Method A) From

dimethyl maleate 11 (R²Me): a mixture of compound 6a

(204 mg, 0.87 mmol) dimethyl maleate 11 (R²Me)

(0.13 mL, 1.04 mmol) and benzene (10 mL) was heated at

re¯ux (32 h) with stirring. The reaction mixture was allowed

to cool to room temperature, evaporated and the residue was

fractionated by chromatography (light petroleum bp 40±

608C: ethyl acetate, 3:1) giving compound 14a (R²Me)

(R_f0.47) (103 mg, 31%) as white needles, mp 148.5±

149.58C (from 70% aqueous ethanol) and compound 18a

(R²Me) (R_f0.27) (27 mg, 8%) as small white needles,

mp 188±1908C (from ethanol). Compound 14a (R²Me):

(Found: C, 63.1; H, 4.8; N, 11.3, M 379.1178. C₂₀H₁₇N₃O₅

requires C, 63.3; H, 4.5; N, 11.1%, M 379.1168). n_max.1744,

1659, 1625, 1578, 1445, 1359 and 1278 cm²¹, d_H

(220 MHz) 12.61 (1H, s, ±OH), 8.03 (1H, d, J8.0 Hz,

ArH), 7.79 (2H, m, ArH), 7.48 (3H, m, ArH), 7.31 (2H,

m, ArH), 6.57 (1H, d, J2.1 Hz, C4±H), 4.77 (1H, d,

J2.1 Hz, C3±H), 3.78 (3H, s, ±OCH₃) and 3.68 (3H, s,

±OCH₃). Compound 18a (R²Me): (Found: C, 63.5; H, 4.6;

N, 11.3, M 379.1166. C₂₀H₁₇N₃O₅requires C, 63.3; H, 4.5;

N, 11.1%, M 379.1168). n_max.1744, 1693, 1438, 1325, 1263

and 1160 cm²¹, d_H(220 MHz) 8.18 (1H, d, J7.6 Hz,

ArH), 7.78 (2H, m, ArH), 7.56 (3H, m, ArH), 7.35 (2H,

m, ArH), 6.77 (1H, d, J4.6 Hz, C4±H), 4.95 (1H, d,

J12.6 Hz, C2±H), 4.31 (1H, dd, J12.6 and 4.6 Hz,

C3±H), 3.88 (3H, s, ±OCH₃) and 3.63 (3H, s, ±OCH₃).

6,7-Dimethoxycarbonyl-5-phenyl-5a,8,13-nitrilodibenzo-

[b,f][1,4]diazecin-14(5H)-one 7c. Using a similar method

to that described above for the preparation of compound 7a,

compound 6c (1.0 g, 3.2 mmol) and DMAD (0.8 mL,

6.5 mmol) in benzene (30 mL) gave, after 5 h, compound

7c (93%) as yellow crystals, mp 261±2648C (from ethanol).

(Found: C, 68.9; H, 4.5; N, 9.0, M 453.1326. C₂₆H₁₉N₃O₅

requires C, 68.9; H, 4.2; N, 9.3%, M 453.1327). n_max.1745,

1725, 1656, 1483 and 1413 cm²¹, d_H(400 MHz) 8.29 (1H,

dd, J7.8 and 2.0 Hz, ArH), 8.09 (1H, dd, J7.8 and

1.1 Hz, ArH), 7.50 (3H, m, ArH), 7.46 (1H, dt, J7.8 and

2.0 Hz, ArH), 7.40 (3H, m, ArH), 7.33 (1H, dt, J7.8 and

1.1 Hz, ArH), 7.18 (1H, d, J7.8 Hz, ArH), 7.09 (1H, dt,

J7.8 and 1.1 Hz, ArH), 7.03 (1H, dd, J7.8 and 2.0 Hz,

ArH), 3.76 (3H, s, ±OCH₃) and 3.66 (3H, s, ±OCH₃).

7-Ethoxycarbonyl-5a,8,13-nitrilodibenzo[b,f][1,4]diazecin-

14(5H)-one 8a. A mixture of compound 6a (200 mg,

0.85 mmol), ethyl propiolate (0.1 mL, 0.98 mmol) and

benzene (10 mL) was heated at re¯ux (3 h) with stirring.

The reaction mixture was allowed to cool to room tempera-

ture, evaporated and the residual yellow oil was triturated

with ether (7 mL) giving compound 8a (195 mg, 69%) as

yellow needles, mp 146±1488C (from ethanol). (Found: C,

68.3; H, 4.6; N, 12.8, M 333.1110. C₁₉H₁₅N₃O₃requires: C,

68.5; H, 4.5; N, 12.6%, M 333.1113), n_max.1731, 1652,

1484, 1411, 1315 and 1102 cm²¹, d_H(220 MHz) 8.28

(1H, dd, J7.1 and 1.2 Hz, ArH), 8.06 (1H, d, J7.6 Hz,

ArH), 7.69 (1H, d, J7.6 Hz, ArH), 7.58 (2H, m ArH), 7.44

(1H, d, J7.6 Hz, ArH), 7.29 (1H, dt, J7.6 and 1.2 Hz,

ArH), 7.13 (1H, dt, J7.6 and 1.2 Hz, ArH), 6.22 (1H, d,

J2.0 Hz, C6±H), 5.59 (1H, d, J2.0 Hz, C5±H), 4.20 (2H,

m, ±OCH₂CH₃) and 1.25 (3H, t, J7.3 Hz, ±OCH₂CH₃).

7-Ethoxycarbonyl-5-methyl-5a,8,13-nitrilodibenzo[b,f][1,4]-

diazecin-14(5H)-one 8b. A mixture of compound 6c

(200 mg, 0.80 mmol) and ethyl propiolate (0.1 mL,

0.98 mmol) and benzene (10 mL) was heated at re¯ux

(24 h) with stirring. The reaction mixture was allowed to

cool to room temperature, evaporated and the residual oil

was dissolved in boiling benzene±hexane (1:8) (70 mL).

Method B. From dimethyl fumarate 12 (R²Me): when

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

5531

dimethyl maleate 11 (R²Me) was replaced with dimethyl

fumarate 12 (R²Me) in Method A above, compounds 14a

(R²Me) (43%) and 18a (R²Me) (3%), both identical with

authentic samples, were obtained after chromatography.

enol ±OCH₃), 3.60 (s, enol ±OCH₃), 3.27 (s, keto

±OCH₃), 2.28 (s, keto C4±CH₃) and 2.20 (s, enol C4±

CH₃). The enol: keto ratio in CDCl₃solution was deter-

mined as 7:3.

(3a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2,3-di-

ethoxycarbonylnaphth-1-ol 14a (R²Et) and (2a,3b,

4b)-4-(2⁰H-benzotriazol-2⁰-yl)-2,3-diethoxycarbonyl-

tetra-1-one 18a (R²Et). (Method A) From diethyl

maleate: using a similar method to that described above

for the preparation of compounds 14a (R²Me) and 18a

(R²Me) but with a re¯ux period of 72 h, compound 6a

(200 mg, 0.85 mmol) diethyl maleate 11 (R²Et) (0.3 mL,

1.84 mmol) and benzene (15 mL) gave compound 14a

(R²Et) (R_f0.59) (131 mg, 38%) as white needles, mp

95±978C (from 70% aqueous ethanol) and compound 18a

(R²Et) (R_f0.44) (60 mg, 17%) as white needles, mp 117±

1188C (from 50% aqueous ethanol) after chromatography.

Compound 14a (R²Et): (Found: C, 65.0; H, 5.4; N, 10.2,

M 407.1469. C₂₂H₂₁N₃O₅requires C, 64.9; H, 5.2; N,

10.3%, M 407.1481). n_max.1746, 1655, 1589, 1548, 1406,

1375, 1359, 1277, 1092 and 1020 cm²¹, d_H(220 MHz)

12.69 (1H, s, ±OH), 8.02 (1H, dd, J7.9 and 1.4 Hz,

ArH), 7.78 (2H, m, ArH), 7.46 (3H, m, ArH), 7.30 (2H,

m, ArH), 6.54 (1H, d, J2.4 Hz, C4±H), 4.73 (1H, d,

J2.4 Hz, C3±H), 4.20 (4H, m, 2£±OCH₂CH₃), 1.24

(3H, t, J7.2 Hz, ±OCH₂CH₃) and 1.15 (3H, t, J7.2 Hz,

±OCH₂CH₃). Compound 18a (R²Et): (Found: C, 65.0; H,

5.3; N, 10.4, M 407.1492. C₂₂H₂₁N₃O₅requires C, 64.9; H,

5.2; N, 10.3%, M 407.1481). n_max.1739, 1693, 1604, 1586,

1373, 1325, 1261 and 1106 cm²¹, d_H(400 MHz) 8.17 (1H,

dd, J8.5 and 2 Hz, ArH), 7.78 (2H, m, ArH), 7.57 (3H, m,

ArH), 7.34 (2H, m, ArH), 6.77 (1H, d, J4.9 Hz, C4±H),

4.95 (1H, d, J12.8 Hz, C2±H), 4.32 (3H, m, C3±H and

±OCH₂CH₃), 4.05 (2H, m, ±OCH₂CH₃), 1.36 (3H, t,

J7.4 Hz, ±OCH₂CH₃) and 1.07 (3H, t, J7.4 Hz,

±OCH₂CH₃).

Method B. From dimethyl fumarate 12 (R²Me): when

dimethyl maleate 11 (R²Me) was replaced with dimethyl

fumarate 12 (R²Me) in Method A above, compounds 14b/

15b (R²Me) (56%) were obtained after chromatography,

identical with an authentic sample.

(3a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2,3-di-

ethoxycarbonyl-4-methylnaphth-1-ol 14b (R²Et) and

(2a,3b,4a)-4-(2⁰H-benzotriazol-2⁰-yl)-2,3-diethoxycar-

bonyl-4-methyltetra-1-one 15b (R²Et). (Method A)

From diethyl maleate 11 (R²Et): using a similar method

to that described above for the preparation of compounds

14b/15b (R²Me) but with a re¯ux period of 168 h,

compound 6b (200 mg, 0.80 mmol), diethyl maleate 11

(R²Et) (0.3 mL, 1.86 mmol) and benzene (10 mL) gave

compounds 14b/15b (R²Et) (105 mg, 31%) as white

crystals, mp 115±1188C (from 50% aqueous ethanol) after

chromatography. (Found: C, 65.5; H, 5.5; N, 10.1, M

421.1677. C₂₃H₂₃N₃O₅requires C, 65.5; H, 5.5; N, 10.0%,

M 421.1638). n_max.1732, 1693, 1650, 1621, 1402, 1388,

1320, 1269 and 1024 cm²¹, d_H(220 MHz) 12.40 (s, enol

±OH), 8.12±7.23 (m, ArH), 6.53 (m, ArH), 5.25 (s, enol

C3±H), 5.01 (d, J9.5 Hz, keto C2±H), 4.21 (m, 2£enol

±OCH₂CH₃, keto ±OCH₂CH₃and keto C3±H), 3.78 (m,

keto ±OCH₂CH₃), 2.30 (s, keto C4±CH₃), 2.24 (s, enol

C4±CH₃), 1.31 (m, keto, ±OCH₂CH₃and enol

±OCH₂CH₃), 1.11 (t, J7.1 Hz, enol ±OCH₂CH₃) and

0.55 (t, J7.1 Hz, keto ±OCH₂CH₃). The enol: keto ratio

was determined to be 13:7 in CDCl₃solution.

Method B. From diethyl fumarate 12 (R²Et): when diethyl

maleate 11 (R²Et) was replaced with diethyl fumarate 12

(R²Et) in Method A above, compounds 14b/15b (R²Et)

(42%) were obtained after chromatography, identical with

an authentic sample.

Method B. From diethyl fumarate 12 (R²Et): when diethyl

maleate 11 (R²Et) was replaced with diethyl fumarate 12

(R²Et) in Method A above, compounds 14a (R²Et)

(73%) and 18a (R²Et) (4%) were obtained after chromato-

graphy, identical with authentic samples.

4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2-methoxycar-

bonylnaphth-1-ol 20a (R²Me). A mixture of compound

6a (150 mg, 0.64 mmol), methyl acrylate (0.10 mL,

1.11 mmol) and benzene (5 mL) was heated (7 h) under

re¯ux. The reaction mixture was allowed to cool to room

temperature and evaporated. The residue was puri®ed by

chromatography (light petroleum bp 40±608C: ethyl

acetate, 3:1) giving compound 20 (R_f0.59) (110 mg, 54%)

as a colourless oil which crystallised upon standing.

Recrystallisation from 70% aqueous ethanol gave white

crystals, mp 106±1088C. (Found: C, 67.4; H, 4.9; N, 13.3,

M 321.1108. C₁₈H₁₅N₃O₃requires C, 67.3; H, 4.7; N,

13.1%, M 321.1113). n_max.1658, 1620, 1573, 1445, 1359,

1313 and 1273 cm²¹, d_H(400 MHz) 12.48 (1H, s, ±OH),

7.96 (1H, dd, J7.5 and 1.3 Hz, ArH), 7.86 (2H, m, ArH),

7.44 (1H, dt, J7.5 and 1.0 Hz, ArH), 7.39 (2H, m, ArH),

7.34 (1H, dt, J7.5 and 1.3 Hz, ArH), 6.73 (1H, d,

J7.5 Hz, ArH), 6.24 (1H, dd, J9.2 and 6.5 Hz, C4±H),

3.81 (3H, s, ±OCH₃), 3.62 (1H, dd, J15.8 and 9.2 Hz, C3±

H) and 3.23 (1H, dd, J15.8 and 6.5 Hz, C3±H).

(3a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2,3-di-

methoxycarbonyl-4-methylnaphth-1-ol 14b (R²Me)

and (2a,3b,4a)-4-(2⁰H-benzotriazol-2⁰-yl)-2,3-dimethoxy-

carbonyl-4-methyltetra-1-one 15b (R²Me). (Method A)

From dimethyl maleate 11 (R²Me): using a method simi-

lar to that described above for the preparation of compounds

14a (R²Me) and 18a (R²Me) but with a re¯ux period of

196 h, compound 6b (201 mg, 0.81 mmol), dimethyl

maleate 11 (R²Me) (0.13 mL, 1.04 mmol) and benzene

(10 mL) gave compounds 14b/15b (R²Me) (170 mg,

54%) as white crystals, mp 156±1598C (from 50% aqueous

ethanol). (Found: C, 63.9; H, 5.0; N, 10.9, M 393.1349.

C₂₁H₁₉N₃O₅requires C, 64.1; H, 4.9; N, 10.7%, M

393.1325). n_max.1738, 1693, 1657, 1624, 1575, 1444,

1360, 1323, 1270 and 999 cm²¹, d_H(220 MHz) 12.34 (s,

enol ±OH) 8.15±7.20 (m, ArH), 6.49 (m, ArH), 5.22 (s, enol

C3±H), 5.01 (d, J13.7 Hz, keto C2±H), 4.29 (d,

J13.7 Hz, keto C3±H), 3.83 (s, keto ±OCH₃), 3.78 (s,

5532

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2-methoxycar-

bonyl-4-methylnaphth-1-ol 20b (R²Me). Using a similar

method to that described above for the preparation of

compound 20a (R²Me) but with a re¯ux period of 22 h,

compound 6b (200 mg, 0.8 mmol) and methyl acrylate

(0.10 mL, 1.1 mmol) gave compound 20b (R²Me)

(175 mg, 65%) as white plates, mp 156±1578C (from 50%

aqueous ethanol). (Found: C, 68.1; H, 5.3; N, 12.5, M

335.1285. C₁₉H₁₇N₃O₃requires C, 68.1; H, 5.1; N, 12.5%,

M 335.1269). n_max.1658, 1623, 1577, 1446, 1379, 1362,

1327, 1274 and 1263 cm²¹, d_H(220 MHz) 12.83 (1H, s,

±OH), 7.95 (1H, dd, J7.6 and 1.9 Hz, ArH), 7.88 (2H,

m, ArH), 7.38 (4H, m, ArH), 6.71 (1H, dd, J7.3 and

1.8 Hz, ArH), 4.11 (1H, d, J6.4 Hz, C3±H), 3.84 (3H, s,

±OCH₃), 3.04 (1H, d, J6.4 Hz, C3±H) and 2.21 (3H, s,

C4±CH₃).

ethanol). Compound 22a: (Found: C, 68.5; H, 5.4; N,

12.4, M 349.1432. C₂₀H₁₉N₃O₃requires C, 68.8; H, 5.5;

N, 12.0%, M 349.1427), n_max.1739, 1695, 1602, 1455,

1327, 1294, 1181 and 1119 cm²¹, d (220 MHz) 8.17 (1H,

m, ArH), 7.90 (2H, m, ArH), 7.43 (4H, m, ArH), 6.63 (1H,

dd, X part of ABX system, J10.6 and 5.0 Hz, C4±H), 6.56

(1H, m, ArH), 4.21 (2H, q, J7.2 Hz, ±OCH₂CH₃), 3.12

(2H, AB part of ABX system, d_A3.12 and d_B3.10,

J13.2, 10.6 and 5.0 Hz, C3±H₂), 1.64 (3H, s, C2±CH₃)

and 1.18 (3H, t, J7.2 Hz, ±OCH₂CH₃). Compound 23a:

(Found: C, 68.7; H, 5.4; N, 12.3, M 349.1429. C₂₀H₁₉N₃O₃

requires C, 68.8; H, 5.5; N, 12.0%, M 349.1426), n_max.1738,

1692, 1326, 1270, 1255 and 1113 cm²¹, d_H(220 MHz) 8.18

(1H, m, ArH), 7.92 (2H, m, ArH), 7.47 (4H, m, ArH), 6.58

(1H, m, ArH), 6.49 (1H, dd, J12.2 and 5.3 Hz, C4±H),

4.21 (2H, m, ±OCH₂CH₃), 3.79 (1H, dd, J13.3 and

12.2 Hz, C3±H), 2.62 (1H, dd, J13.3 and 5.3 Hz, C3±

H), 1.67 (3H, s, C2±CH₃), 1.23 (3H, t, J7.2 Hz,

±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2-ethoxycarbonyl-

naphth-1-ol 20a (R²Et). Using a similar method to that

described above for the preparation of compound 20a

(R²Me) but with a re¯ux period of 10 h, compound 6a

(1.0 g, 4.3 mmol) and ethyl acrylate (0.5 mL, 4.6 mmol)

gave compound 20a (R²Et) (1.37 g, 96%) as white

needles, mp 112±1138C (from ethanol). (Found: C, 68.0;

H, 5.0; N, 12.3, M 335.1275. C₁₉H₁₇N₃O₃requires C,

68.1; H, 5.1; N, 12.5%, M 335.1270). n_max.1652, 1621,

1575, 1406, 1383, 1314, 1273 and 1084 cm²¹, d_H

(400 MHz) 12.56 (1H, s, ±OH), 7.95 (1H, dd, J7.8 and

1.4 Hz, ArH), 7.88 (2H, m, ArH), 7.40 (3H, m, ArH), 7.32

(1H, dt, J7.6 and 1.4 Hz, ArH), 6.65 (1H, d, J7.6 Hz,

ArH), 6.26 (1H, dd, J10.2 and 6.6 Hz, C4±H), 4.27 (2H,

m, ±OCH₂CH₃), 3.60 (1H, dd, J16.0 and 10.2 Hz, C3±H),

3.24 (1H, dd, J16.0 and 6.6 Hz, C3±H) and 1.31 (3H, t,

J7.1 Hz, ±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-3,4-dihydro-2-ethoxycarbonyl-

4-methylnaphth-1-ol 20b (R²Et). Using a similar method

to that described above for the preparation of compound 20a

(R²Me) but with a re¯ux period of 30 h, compound 6b

(0.50 g, 2 mmol) and ethyl acrylate (0.25 mL, 2.3 mmol)

gave compound 20b (R²Et) (0.68 g, 97%) as a colourless

oil which crystallised upon standing, mp 110±1128C (from

70% aqueous ethanol). (Found: C, 68.5; H, 5.5; N, 12.1, M

349.1432. C₂₀H₁₉N₃O₃requires C, 68.8; H, 5.5; N, 12.0%,

M 349.1427). n_max.1652, 1620, 1404, 1381, 1323, 1272 and

1262 cm²¹, d_H(220 MHz) 12.53 (1H, s, ±OH), 7.89 (3H, m,

ArH), 7.35 (4H, m, ArH), 6.64 (1H, dd, J7.7 and 1.2 Hz,

ArH), 4.31 (2H, q, J7.1 Hz, ±OCH₂CH₃), 4.11 (1H, d,

J15.7 Hz, C3±H), 3.05 (1H, d, J15.7 Hz, C3±H), 2.21

(3H, s, C4±CH₃) and 1.34 (3H, t, J7.1 Hz, ±OCH₂CH₃).

(2a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-2-ethoxycarbonyl-

2,4-dimethyltetral-1-one 22b and (2a,4a)-4-(2⁰H-benzo-

triazol-2⁰-yl)-2-ethoxycarbonyl-2,4-dimethyltetral-1-

one 23b. Using a similar method to that described above for

the preparation of compounds 22a and 23a, compound 6b

(218 mg, 0.88 mmol) and ethyl methacrylate (0.13 mL,

1.04 mmol) in benzene (7 mL) at re¯ux (54 h) gave

compound 22b (R_f0.53) (47 mg, 15%), mp 111±1128C

(from 60% aqueous ethanol) and compound 23b (R_f0.34,

216 mg, 69%), mp 129±1328C (from 95% aqueous ethanol).

Compound 22b: (Found: C, 69.3; H, 5.6; N, 11.6, M

363.1554. C₂₁H₂₁N₃O₃requires C, 69.4; H, 5.8; N, 11.6%,

M 363.1582), n_max.1728, 1693, 1601, 1458, 1321, 1251 and

1130 cm²¹, d_H(220 MHz) 8.21 (1H, m, ArH), 7.87 (2H, m,

ArH), 7.42 (4H, m, ArH), 6.82 (1H, m, ArH), 4.22 (2H, q,

J7.2 Hz, ±OCH₂CH₃), 3.48 (1H, d, J14.3 Hz, C3±H),

3.07 (1H, d, J14.3 Hz, C3±H), 2.28 (3H, s, C4±CH₃), 1.44

(3H, s, C2±CH₃) and 1.22 (3H, t, J7.2 Hz, ±OCH₂CH₃).

Compound 23b: (Found: C, 69.1; H, 5.8; N, 11.8, M

363.1575. C₂₁H₂₁N₃O₃requires C, 69.4; H, 5.8; N, 11.6%,

M 363.1582), n_max.1732, 1696, 1602, 1458, 1325, 1255, 102

and 926 cm²¹, d_H(220 MHz) 8.23 (1H, dd, J8.8 and

1.6 Hz, ArH), 7.78 (2H, m, ArH), 7.64 (1H, dt, J8.8 and

1.6 Hz, ArH), 7.54 (1H, dt, J8.8 and 1.2 Hz, ArH), 7.46

(1H, dd, J8.8 and 1.2 Hz, ArH), 7.31 (2H, m ArH), 3.68

(1H, d, J14.4 Hz, C3±H), 3.25 (2H, m, ±OCH₂CH₃), 2.51

(1H, d, J14.4 Hz, C3±H), 2.26 (3H, s, C4±CH₃), 1.49 (3H,

s, C2±CH₃) and 0.72 (3H, t, J7.2 Hz, ±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-2-cyano-4-methyl-1-oxo-1,4-

dihydronaphthalene 26b. A mixture of compound 6b

(300 mg, 1.2 mmol), acrylonitrile (0.1 mL, 1.5 mmol) and

benzene (10 mL) was heated at re¯ux (30 h) with stirring.

The reaction mixture was allowed to cool to room tempera-

ture, evaporated and triturated with methanol giving a white

solid (198 mg) which was shown to be a mixture of dia-

stereoisomers by ¹H NMR spectroscopy. Attempts to

separate this mixture of products by chromatography

resulted in decomposition. These products, benzene

(5 mL) and DDQ (151 mg, 0.67 mmol) were heated (2 h)

at re¯ux, the mixture was ®ltered whilst hot, the ®ltrate was

allowed to cool to room temperature and evaporated. The

residue was triturated with ethanol (5 mL) giving compound

(2a,4b)-4-(2⁰H-Benzotriazol-2⁰-yl)-2-ethoxycarbonyl-2-

methyltetral-1-one 22a and (2a,4a)-4-(2⁰H-benzotriazol-

2⁰-yl)-2-ethoxycarbonyl-2-methyltetral-1-one 23a.

A

mixture of compound 6a (257 mg, 1.09 mmol), ethyl

methacrylate 21 (0.16 mL, 1.28 mmol) and benzene

(8 mL) was heated (26 h) at re¯ux with stirring. The reac-

tion mixture was allowed to cool to room temperature and

evaporated. The residue was puri®ed by chromatography

(light petroleum bp 40±608C: ethyl acetate, 3:1) giving

compound 22a (R_f0.65) (68 mg, 18%) as white needles

mp 103±1048C (from 60% aqueous ethanol) and compound

23a (R_f0.52) (279 mg, 73%), mp 149±1508C (from

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

5533

26b (95 mg, 26%), mp 230±2328C (from ethanol). (Found:,

C, 71.8; H, 4.4; N, 19.0, M 300.1007. C₁₈H₁₂N₄O requires

C, 72.0; H, 4.0; N, 18.7%, M 300.1011). n_max.2339, 1684,

1603, 1459, 1364, 1320, 1253, 1079 and 974 cm²¹, d_H

(220 MHz) 8.26 (1H, dd, J8.4 and 2.0 Hz, ArH), 7.89

(3H, m, ArH), 7.50 (5H, m, C3±H and ArH) and 2.47

(3H, s, ±CH₃).

Diethyl 1-hydroxy-2,3-naphthalene dicarboxylate 29a. A

mixture of compound 14a (R²Et) (269 mg, 0.66 mmol),

DBN (1 drop) and benzene (5 mL) was heated (0.5 h) at

re¯ux. The reaction mixture was allowed to cool to room

temperature and evaporated. The residue was puri®ed by

chromatography (light petroleum bp 40±608C: ethyl ace-

tate, 3:1) giving compound 29a (R_f0.71) (130 mg, 68%)

as white needles, mp 53±548C (from ethanol) (lit.⁸mp

52±548C) and benzotriazole (R_f0.16) (50 mg, 64%),

identical with an authentic sample.

2,3-Diethoxycarbonylnaphth-1-yl acetate 27a. A mixture

of compound 18a (R²Et) (191 mg, 0.5 mmol), acetic

anhydride (1.0 mL) and pyridine (0.2 mL) was heated

(2 h) at re¯ux. The mixture was allowed to cool to room

temperature, poured into water (10 mL) and extracted with

chloroform (3£7 mL). The combined organic extracts were

washed with water (10 mL), dried (MgSO₄) and evaporated.

The residue was puri®ed by chromatography (light

petroleum bp 40±608C: ethyl acetate, 3:1) giving a mixture

Diethyl 1-hydroxy-4-methyl-2,3-naphthalene dicarboxy-

late 29b. Using a similar method to that described above,

compound 14b (R²Et) (199 mg, 0.47 mmol), DBN (2

drops) and benzene (3 mL) at re¯ux (5.5 h) gave compound

29b (R_f0.61) (110 mg, 77%) as white needles, mp 79±818C

(from ethanol) and benzotriazole (R_f0.12) (39 mg, 69%),

identical with an authentic sample. Compound 29b: (Found:

C, 67.5; H, 6.0, M 302.1164. C₁₇H₁₈O₅requires C, 67.5; H,

6.0%, M 302.1155), n_max.1728, 1659, 1585, 1410, 1378,

1333, 1109, 1059 and 1025 cm²¹, d_H(220 MHz) 12.48

(1H, s, ±OH), 8.47 (1H, dd, J8.0 and 1.2 Hz, ArH), 7.96

(1H, dd, J8.4 and 1.2 Hz, ArH), 7.68 (1H, dt, J8.4, 6.9

and 1.2 Hz, ArH), 7.56 (1H, dt, J8.0, 6.9 and 1.2 Hz,

ArH), 4.44 (4H, m, 2£±OCH₂CH₃), 2.49 (3H, s, C4-CH₃)

and 1.40 (6H, m, 2£±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)tetral-1-one 30a. A mixture of

compound 20a (R²Et) (1.0 g, 3 mmol) and dilute sodium

hydroxide solution (2 M, 30 mL) was heated under re¯ux

(6.5 h) with stirring. The reaction mixture was allowed to

cool to room temperature, acidi®ed with dilute hydrochloric

acid and then extracted with chloroform (3£40 mL). The

combined chloroform extracts were dried (MgSO₄) and

evaporated giving compound 30a (0.69 g, 88%) as white

needles, mp 157±1598C (from ethanol). (Found: C, 72.9;

H, 5.2; N, 15.8, M 263.1062. C₁₆H₁₃N₃O requires C, 73.0;

H, 5.0; N, 16.0%, M 263.1059). n_max.1693, 1603, 1458,

1330 and 1292 cm²¹, d_H(400 MHz) 8.16 (1H, m, ArH),

7.88 (2H, m, ArH), 7.48 (2H, m, ArH), 7.41 (2H, m,

ArH), 6.89 (1H, m, ArH), 6.37 (1H, dd, J8.1 and 4.3 Hz,

C4±H), 3.13 (1H, m, C2±H), 3.03 (1H, m, C3±H) and 2.79

(2H, m, C2±H and C3±H).

1

(R_f0.73) of 1-acetylbenzotriazole and benzotriazole by H

NMR spectroscopy and compound 27a (R_f0.37) (130 mg,

84%) as white crystals, mp 90±918C (from benzene±

hexane). (Found: C, 65.7; H, 5.6, M 330.1118. C₁₈H₁₈O₆

requires C, 65.5; H, 5.5%, M 330.1103). n_max.1775, 1722,

1448, 1368, 1276, 1180, 142, 1079 and 1032 cm²¹, d_H

(220 MHz) 8.41 (1H, s, C4±H), 7.94 (1H, dd, J7.0 and

2.0 Hz, ArH), 7.82 (1H, dd, J7.0 and 1.8 Hz, ArH), 7.60

(2H, m, ArH), 4.42 (4H, 2£q, J7.3 and 7.3 Hz, 2£±

OCH₂CH₃), 2.42 (3H, s, ±OCOCH₃) and 1.38 (6H, t,

J7.3 Hz, 2£± OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-2-ethoxycarbonyl-3,4-dihydro-

naphth-1-yl acetate 28a. A mixture of compound 20a

(R²Et) (200 mg, 0.6 mmol), acetic anhydride (2 mL) and

pyridine (0.5 mL) was heated (2 h) under re¯ux. The reac-

tion mixture was allowed to cool to room temperature and

added to water (20 mL). The mixture was extracted with

chloroform (3£10 mL) and the combined organic extracts

were washed with water (10 mL), dried (MgSO₄) and

evaporated. The residual oil was triturated with ethanol

giving compound 28a (129 mg, 57%) as white crystals,

mp 111±1138C. (Found: C, 66.6; H, 5.3; N, 11.1, M

377.1377. C₂₁H₁₉N₃O₄requires C, 66.8; H, 5.1; N, 11.1%,

M 377.1376), n_max.1771, 1707, 1639, 1372, 1189, 1139 and

1075 cm²¹, d_H(220 MHz) 7.89 (2H, m, ArH), 7.48 (1H, dd,

J7.3 and 2.2 Hz, ArH), 7.35 (4H, m, ArH), 6.70 (1H, d,

J7.1 Hz, ArH), 6.37 (1H, dd, J11.0 and 7.3 Hz, C4±H),

4.23 (2H, q, J6.9 Hz, ±OCH₂CH₃), 3.84 (1H, dd, J17.1

and 11.0 Hz, C3±H), 3.39 (1H, dd, J17.1 and 7.3 Hz, C3±

H), 2.39 (3H, s, ±OCOCH₃) and 1.28 (3H, t, J6.9 Hz,

±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-4-methyltetral-1-one

30b.

Using a similar method to that described above for the

preparation of compound 30a, compound 20b (R²Et)

(200 mg, 0.58 mmol) gave compound 30b (125 mg, 56%),

mp 174±1758C (from ethanol). (Found: C, 73.4; H, 5.7; N,

14.9, M 277.1228. C₁₇H₁₅N₃O requires C, 73.6; H, 5.5; N,

15.2%, M 277.1215), n_max.1691, 1605, 1458, 1333 and

1292 cm²¹, d_H(400 MHz) 8.13 (1H, dd, J7.9 and

1.9 Hz, ArH), 7.86 (2H, m, ArH), 7.51 (1H, dt, J7.9 and

1.9 Hz, ArH), 7.45 (1H, dt, J7.9 and 1.3 Hz, ArH), 7.38

(2H, m, ArH), 7.05 (1H, dd, J7.9 and 1.3 Hz, ArH), 3.41

(1H, m, C3±H), 2.85 (2H, m, C2±H₂), 2.55 (1H, m, C3±H)

and 2.34 (3H, s, ±CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-2-ethoxycarbonyl-3,4-dihydro-

4-methylnaphth-1-yl acetate 28b. Using a similar method

to that described above, compound 20b (R²Et) (200 mg,

0.57 mmol), acetic anhydride (4 mL) and pyridine (1 mL)

gave compound 28b (170 mg, 76%), mp 133±1348C (from

ethanol). (Found: C, 67.3; H, 5.5; N, 10.6, M 391.1552.

C₂₂H₂₁N₃O₄requires C, 67.5; H, 5.4; N, 10.7%, M

391.1532), n_max.1769, 1708, 1640, 1382, 1305, 1254,

1190, 1139 and 1068 cm²¹, d_H(220 MHz) 7.90 (2H, m,

ArH), 7.38 (5H, m, ArH), 6.58 (1H, d, J7.0 Hz, ArH),

4.28 (3H, m, C3±H and ±OCH₂CH₃), 3.22 (1H, d,

J16.8 Hz, C3±H), 2.39 (3H, s, ±OCOCH₃), 2.28 (3H, s,

C4±CH₃) and 1.31 (3H, t, J7.0 Hz, ±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)tetral-1-one 30a, ethyl 1-hy-

droxy-2-naphthoate 31a and benzotriazole. A mixture

of compound 20a (R²Et) (218 mg, 0.65 mmol), ethanol

(5 mL) and dilute hydrochloric acid (2 M, 5 mL) was heated

under re¯ux (5 h) with stirring. The reaction mixture was

5534

D. O. Morgan et al. / Tetrahedron 56 (2000) 5523±5534

allowed to cool to room temperature and extracted with

chloroform (3£7 mL). The combined organic extracts

were dried (MgSO₄), evaporated and the residue was puri-

®ed by chromatography (petroleum ether bp 40±608C: ethyl

acetate, 3:1) giving compound 31a (R_f0.88) (43 mg, 31%)

as a colourless oil which crystallised upon standing, mp

48±498C (from ethanol) (lit.⁹mp 498C), compound 30a

(R_f0.49) (70 mg, 41%) and benzotriazole (R_f0.15)

(20 mg, 26%), both identical authentic samples.

was triturated with ethanol giving compound 32 (150 mg,

85%), mp 144±1458C (from ethanol). (Found: C, 68.2; H,

4.8; N, 12.7, M 333.1118. C₁₉H₁₅N₃O₃requires C, 68.5; H,

4.5; N, 12.6%, M 333.1114), n_max.1657, 1640, 1398, 1377,

1319, 1240 and 1098 cm²¹, d_H(220 MHz) 12.36 (1H, s,

±OH), 8.55 (1H, dd, J7.8 and 1.6 Hz, ArH), 8.29 (1H, s,

C3±H), 8.05 (3H, m, ArH), 7.67 (2H, m, ArH), 7.49 (2H, m,

ArH), 4.50 (2H, q, J7.3 Hz, ±OCH₂CH₃) and 1.42 (3H, q,

J7.3 Hz, ±OCH₂CH₃).

Ethyl 1-hydroxy-4-methyl-2-naphthoate 31b and benzo-

triazole. In a similar manner to that described above for the

acidic hydrolysis of compound 20a (R²Et), compound 20b

(R²Et) (227 mg, 0.9 mmol) gave compound 31b (R_f0.88)

(86 mg, 58%) as white needles, mp 85±868C (from ethanol)

and benzotriazole (50 mg, 65%), identical with an authentic

sample. Compound 31b: (Found: C, 73.0; H, 6.2, M

230.0937. C₁₄H₁₄O₃requires C, 73.0; H, 6.1%, M

230.0943), n_max.1662, 1646, 1588, 1409, 1375, 1340,

1248, 1158, 1100 and 1023 cm²¹, d_H(220 MHz) 11.88

(1H, s, ±OH), 8.43 (1H, d, J8.0 Hz, ArH), 7.84 (1H, d,

J7.8 Hz, ArH), 7.55 (3H, m, ArH), 4.42 (2H, q, J7.1 Hz,

±OCH₂CH₃), 2.52 (3H, s, C4±CH₃) and 1.42 (3H, t,

J7.1 Hz, ±OCH₂CH₃).

4-(2⁰H-Benzotriazol-2⁰-yl)-2-ethoxycarbonylnaphth-1-ol

32. A mixture of compound 20a (R²Et) (178 mg,

0.53 mmol), DDQ (122 mg, 0.54 mmol) and benzene

(5 mL) was heated (24 h) at re¯ux with stirring. The reac-

tion was ®ltered whilst hot and the ®ltrate was allowed to

cool to room temperature and then evaporated. The residue

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Article Doi

Preparation and cycloaddition reactions of novel heterocyclic mesomeric betaines

DOI: 10.1016/S0040-4020(00)00471-3

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