Pyrrolodiazine derivatives as blue organic luminophores: synthesis and properties. Part 3

DOI: 10.1016/j.tet.2010.04.050

Source and publish data:

Tetrahedron p. 4298 - 4306 (2010)

Update date:2022-08-10

Topics:

Authors:

Zbancioc, Gheorghita N.

Huhn, Thomas

Groth, Ulrich

Deleanu, Calin

Mangalagiu, Ionel I.

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1016/j.tet.2010.04.050

A fast, efficient, general and environmentally friendly method for preparation of highly fluorescent derivatives containing the pyrrolodiazine moiety using microwave (MW) irradiation, in liquid phase, is reported. Under MW irradiation the yields are much

Full text of DOI:10.1016/j.tet.2010.04.050

Tetrahedron 66 (2010) 4298e4306

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

Pyrrolodiazine derivatives as blue organic luminophores: synthesis and

properties. Part 3^q

Gheorghita N. Zbancioc ^a, Thomas Huhn ^b, Ulrich Groth ^b, Calin Deleanu ^c, Ionel I. Mangalagiu ^a

^a‘Al. I. Cuza’ University, Faculty of Chemistry, Organic Chemistry Department, Bd. Carol I no. 11, 700506 Iasi, Romania

€

University of Konstanz, Organic Chemistry Department, Fach M720, Universitatsstr. 10, D-78464 Konstanz, Germany

^c‘P. Poni’ Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41-A, RO-700487 Iasi, Romania

a r t i c l e i n f o

a b s t r a c t

Article history:

A fast, efﬁcient, general and environmentally friendly method for preparation of highly ﬂuorescent

derivatives containing the pyrrolodiazine moiety using microwave (MW) irradiation, in liquid phase, is

reported. Under MW irradiation the yields are much higher, sometimes substantially (by almost double)

and, the amount of solvent used is at least 5-fold less. The pyrrolopyridazine (PP) derivatives are very

intense blue emitters and have high quantum yields (up to 90%) while pyrrolophthalazine (PHP)

compounds are still intense blue emitters but the quantum yield is negligible. A certain inﬂuence of the

substituents concerning ﬂuorescence was found, those ones at the 7 position being crucial for ﬂuores-

cence. The number of the substituents from the pyrrolo ring seems not to play an important role in

regard with the ﬂuorescence but, with an increasing number of substituents a certain hypsochromic shift

in the absorption spectra was found.

Received 4 January 2010

Received in revised form 24 March 2010

Accepted 12 April 2010

Available online 4 May 2010

Keywords:

Pyrrolodiazine

Fluorescence

Blue luminophores

Microwave

Cycloadditions

1. Introduction

little self-quenching, proper energy levels, pure RGB colour and

high stability.

Synthesis of highly ﬂuorescent derivatives with extended

-conjugation continues to arouse strong interest because of

Microwave irradiation became a new trend in organic chemistry

offering a versatile and facile pathway in a large variety of

syntheses.^10,11So far, few studies have been reported regarding

dipolar cycloaddition reactions of dazinium ylides and most of

these have been conducted by our group.^7,12

As a part of our work in the ﬁeld of blue luminous materials for

practical applications,⁷we decided to study the relationship

between optical properties and structure (the effect of substituents

and conjugation), and to develop efﬁcient, general and environ-

mentally friendly methods for preparation of these derivatives

using MW technologies.

their applications as sensors and biosensors, electroluminescent

materials, lasers, and other optoelectronic devices.^1e4Various

classes and various strategies have been adopted to reach this

goal.^1,5e8Fused N-heterocyclic rings offer very interesting optical

properties. Pyrrolodiazine (PD) derivatives represent such a class

(containing both a

p-excessive pyrrole and a p-deﬁcient diazine

ring with one bridgehead nitrogen), being a ‘pure’ blue-emitting

moiety.^6,7The absorption and ﬂuorescence spectra of N-hetero-

cycles are solvent sensitive and depend, on one hand, on the

nature of the substituents at the heterocycle, and on the other

hand, on the positions of the substituents. Investigations on the

synthesis of new blue luminous materials for applications in

electroluminescent displays have attracted great attention, but

there are very few single component deep blue- and pure

red-emitting dyes.^1,2Because of the industrial demand,⁹it is still

essential to ﬁnd molecules, which exhibit high ﬂuorescence,

2. Results and discussion

Considering the pyrrolopyridiazine (PP) moiety responsible for

blue ﬂuorescent properties,^6,7a rational design showed that the

most suitable and accessible modiﬁcation can be done on 3,4-po-

sition of the pyridazine (PY) heterocycle (expansion of the

p system

conjugation with a benzene ring) and the 5-, 6- and 7-positions of

the pyrrolo (PYR) ring (ester, amide or ketone substituents; with or

without double bond in 4a,5- and 6,7-positions). In equal measure

our interest was to study the inﬂuence of these modiﬁcations

concerning the synthesis.

Ref. 7.

* Corresponding author. Tel.: þ40 232 201343; fax: þ40 232 201313; e-mail

address: ionelm@uaic.ro (I.I. Mangalagiu).

doi:10.1016/j.tet.2010.04.050

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

4299

tetrahydro-pyrrolodazine intermediate 4, leading to more ther-

modynamically stable compounds 3a,b and 5aed. We may also

notice that the saturated intermediates derived from acrylate

(pathway iiib) have a greater tendency towards dehydrogenation,

leading to a mixture of dihydropyrrolo-PY (5a,b) and pyrrolo-PY

(3a,b) while intermediates derived from acrylonitrile (pathway iiia)

are leading to dihydropyrrolo-PY (5c,d) only.

However, this strategy has some major disadvantages: longer

reaction time (around 2e3 h), lower yields (around 30%), higher

energy consumption and the need for large amounts of solvents,

etc. This is why we decided to use MW technology, a non-con-

ventional method, for syntheses. The MW assisted reactions were

carried out using a monomode reactor, using a constant irradiation

power and varying the temperature (the so-called ‘power

control’). The best results were obtained when we used 20% of the

The strategies adopted for construction of ﬂuorescent PD

derivatives I, are depicted in Scheme 1. The preparation of all PD

derivatives, 2e5, involves two steps: initially N-alkylation of the

diazine [PY or phthalazine (PH)] followed by a 3þ2 dipolar cyclo-

addition of diazinium ylides 1⁰(generated in situ from the corre-

sponding salts) to the corresponding dipolarophiles (activated

alkenes or alkynes).

COR¹

COOR²

2. a. R¹= OMe; R²= Me

b. R¹= OEt; R²= Me

c. R¹= NH₂; R²= Et

R²OOC

COOR²

R²OOC

COOR²

R²OOC

2. g. R¹= NH₂; R²= Me 2. h. R¹= OEt; R²= Me

3. g. R¹= OMe; R²= Me

h. R¹= OEt; R²= Me

i. R¹= NH₂; R²= Me

d. R¹= C₆H₄F4; R²= Me

COR¹

iia

e. R¹= C₆H₄Cl4; R²= Me

f. R¹= C₆H₄Me4; R²= Me

R²OOC

3. a. R¹= OMe; R²= Me

b. R¹= OEt; R²⁼Me

COR¹

c. R¹= NH₂; R²= Et

COOR²

R²OOC

d. R¹= C₆H₄F4; R²= Et

e. R¹= C₆H₄Cl4; R²= Et

f. R¹= C₆H₄Me4; R²= Et

R²OOC

COOR²

BrCH₂COR¹

Et₃N

CH₂COR¹

R¹= OMe, NH₂,

CH COR¹

C₆H₄X4 (X=F, Cl, Me)

CH COR¹

Y= H, C₆H₄

1. a. PY, R¹= OMe; e. PY, R¹= C₆H₄Cl4; i. PH, R¹=NH₂

b.PY, R¹= OEt; f. PY, R¹= C₆H₄Me4;

c. PY, R¹= NH₂; g. PH, R¹= OMe;

d. PY, R¹=C₆H₄F4;h. PH, R¹=OEt

iii

iiia

COR¹

Z= CN; COOMe

COR¹

c. R¹= OMe, Z= CN

d. R¹= OEt, Z= CN

iiib

3a,b

5. a. R = OMe, Z= COOMe

4. b. R¹= NH₂, Z=CN

[a. R¹= OMe, Z= CN]

4. c. R¹= NH₂, Z=CN

b. R = OEt, Z= COOMe

Scheme 1. Cyloaddition reactions of dazinium ylides with alkynes (pathways i and ii) and alkenes (pathways iii and iv), under microwaves and classical heating conditions.

The reaction mechanism occurs as a typical Huisgen [3þ2]

dipolar cycloaddition. When alkynes are used as dipolarophiles

(pathways i, ii), the PD moieties 2 and 3 are obtained. As in-

termediates are obtained the dihydropyrrolodazine derivatives 2⁰

and 3⁰, which have a greater tendency towards dehydrogenation

leading to fully aromatised PDs, thermodynamically more stable

(with the exception of compound 2g, which undergo an intra-

molecular rearrangement). In the case of alkenes (pathways iii, iv),

the reactions occur differently according to the R-substituent and

dipolarophiles structure, the ﬁrst factor being determined. Thus,

when R is an amide moiety the cycloaddition stops at the tetra-

hydro-pyrrolodazine 4b,c stage. When R is an ester moiety the

cycloaddition is followed by an oxidative dehydrogenation of the

full power of the magnetron (800 W). Table 1 lists optimised

conditions we employed, under MW irradiation as well as under

classical heating.

As indicated in Table 1, under MW heating the reaction times

decrease dramatically (from several hours to 5 min) and, the

amount of solvent used is at least 5-fold less (see Experimental), so

these reactions may be considered as environmentally friendly.

Most remarkably the yields are higher with the use of MW heating,

sometimes substantially (by almost double). We could also notice

that the yields are higher when the substituent from the seventh

position is an ester or amide group. A certain inﬂuence concerning

yields between PY/PH heterocycle or between double/triple bound

dipolarophiles is difﬁcult to be determine.

4300

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

Table 1

(up to 90%), partially saturated dihydropyrrolo-PY (5aed) are red-

shifted (l_maxof ﬂuorescence around 425e435 nm, l_maxof absorp-

tion around 470e510 nm) and have a low quantum yield (around

5e40%), while tetrahydro-pyrrolodiazine (4b,c) have a negligible

quantum yield (les than 5%), the ﬂuorescence are even more red-

shifted (l_maxof ﬂuorescence around 427e442 nm) and, intriguing,

Syntheses of PD derivatives under MW and classical heating conditions, in liquid

phase

Compound

Classical heating

Microwaves

time (min)

Reaction

Yield (%) Reaction

Yield (%)

time (min)

2a (PY, R¹¼OMe; R²¼Me)

2b (PY, R¹¼OEt; R²¼Me)

2c (PY, R¹¼NH₂; R²¼Et)

2d (PY, R¹¼C₆H₄F4; R²¼Me)

2e(PY, R¹¼C₆H₄Cl4; R²¼Me)

120

the absorption if blue-shifted

304e326 nm), Scheme 2.

(

l_maxof absorption around

2f (PY, R¹¼C₆H₄Me4; R²¼Me) 120

2g (PH, R¹¼NH₂; R²¼Me)

2h (PH, R¹¼OEt; R²¼Me)

3a (PY, R¹¼OMe; R²¼Me)

3b (PY, R¹¼OEt; R²¼Me)

3c (PY, R¹¼NH₂; R²¼Et)

3d (PY, R¹¼C₆H₄F4; R²¼Et)

3e(PY, R¹¼C₆H₄Cl4; R²¼Et)

3f (PY, R¹¼C₆H₄Me4; R²¼Et)

3g (PH, R¹¼OMe; R²¼Me)

3h (PH, R¹¼OEt; R²¼Me)

3i (PH, R¹¼NH₂; R²¼Me)

4b (PY, R¹¼NH₂; Z¼CN)

4c (PH, R¹¼NH₂; Z¼CN)

5a (PY,R¹¼OMe; Z¼COOMe)

5b (PY, R¹¼OEt; Z¼COOMe)

5c (PY, R¹¼OMe; Z¼CN)

5d (PY, R¹¼OEt; Z¼CN)

120

180

However, fully aromatised pyrrolo-PH (2h and 3gei) have an

unexpected behaviour. Even so they are very intense blue emitters

(

l_maxof ﬂuorescence around 430e448 nm), they have a negligible

quantumyield (less than10%) and anunusual blue-shiftedabsorption

l_maxof absorption around 314e322 nm). This is very unusual be-

(

cause normally extension of conjugation should have an opposite

effect: a red-shift in absorption and increasing of quantum yield.¹We

presume that this is a question of aromaticity mostly (p-stacking

interactions, favourable or unfavourable, could playa role). Unless the

pyrrolo-PH have a more extended conjugated system (three rings

compared withpyrrolo-PY withonly two), the pyrrolopyridazine unit

is more delocalised in pyrrolo-PY compounds (resonance structure I).

The resonance structure II will have a major contribution to the

structure of pyrrolo-PH, due to the strong tendency of the fused

benzene ring to remain aromatic. Consequently, the delocalisation in

pyrrolo-PH compounds will decrease and they will appear

blue-shifted in absorption spectra. Similar consideration has been

published for related cases.⁶

In the next stage of our work, we studied the absorption and

emission spectra of the obtained compounds. The spectra of all the

compounds were recorded in ethanol, chloroform and cyclohexane

solutions at room temperature. Relative quantum yields were

determined by using anthracene in ethanol (

¼0.27 at 25 ^ꢀC).¹³The

studied PDs, although relatively similar in molecular structure,

exhibit clear differences in their experimental absorption and

emission spectra, as summarised in Table 2.

Table 2

(-NH₂)

l_max(nm) of absorption spectra, ﬂuorescence spectra and relative quantum yields

(%) of PD compounds 2e5

Highly

fluorescence

No (very low)

fluorescence

Compound Fluorescence (l_max, nm)

Absorption (l_max, nm)

(quantum yields (%)

EtOH

CHCl₃

Cyclohexane EtOH CHCl₃Cyclohexane

The data from Table 2 indicates also a certain inﬂuence of the

substituents, those ones from position

ﬂuorescence.

7 being crucial for

431 (70) 430 (90) 430 (83)

431 (70) 429 (90) 430 (83)

429 (63) 431 (82) 434 (76)

343

356

334

332

374

314

349

365

333

330

333

315

316

319

326

316

470

485

484

351

352

362

335

334

333

375

319

357

358

370

335

332

334

319

320

322

321

304

479

488

355

366

329

327

Insoluble

322

361

When the substituent is an ester or amide group the pyrrolo-PY

compounds have an intense blue ﬂuorescence and a very high

quantum yield. When the substituent is a ketone the pyrrolo-PY

compounds still are blue emitters (red-shifted, l_maxof ﬂuorescence

around 430e450 nm) but the quantum yield is negligible. Again,

a feasible explanation should be related to the conjugation: pyr-

rolo-PY compounds bearing esters (amide, respectively) in position

7 have a stronger conjugation compared with those ones bearing

a keto-moiety.

The number of the substituents from the pyrrolo ring doesn’t

seem to play an important role with regard to the ﬂuorescence

properties. Data from Table 2 indicates that both classes of com-

pounds, with three or two substituents (e.g., 2aec vs 3aec), have

almost the same ﬂuorescent properties (very blue) and quantum

yield (around 90%). However, we may notice in the absorption,

a certain hypsochromic shift with the increasing of the number of

substituents [l_maxabsorption around 343e366 nm (for three sub-

stituents) and around 349e370 nm (for two substituents)].

446 (1)

448 (2)

451 (1)

487 (1)

448 (4)

436 (8)

439 (3)

438 (7)

471 (1)

431 (5)

433 (11)

434 (d)

436 (10)

Insoluble

434 (8)

430 (66) 423 (91) 416 (85)

429 (66) 422 (91) 416 (85)

436 (89) 437 (76) Insoluble

361

Insoluble

329

322

Insoluble

496

508

442 (1)

430 (2)

433 (1)

446 (4)

448 (3)

442 (2)

427 (1)

430 (9)

432 (3)

433 (4)

436 (5)

436 (7)

437 (4)

430 (5)

430 (4)

432 (2)

439 (2)

439 (5)

427 (18) 415 (40)

424 (4)

Insoluble

432 (8)

432 (9)

432 (8)

Insoluble

420 (4)

419 (4)

508

As expected, conjugation is determined concerning ﬂuorescence

and quantum yields. As shown in Table 2, fully aromatised and

conjugated pyrrolo-PY (2aec and 3aec) are very intense blue

emitters (l_maxof ﬂuorescence around 415e435 nm, l_maxof ab-

sorption around 340e370 nm) and extremely high quantum yield

3. Conclusions

We report herein a fast, efﬁcient and straightforward method for

MW preparation of highly ﬂuorescent derivatives containing the PD

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

4301

Fluorescence red-shifted,

quantum yield decreasing

Fluorescence red-shifted,

quantum yield decreasing

Scheme 2. Fluorescence and quantum yield variation in the pyrrolodiazine series.

moiety. Remarkably, under MW irradiation the yields are much

higher, sometimes substantially (by almost double) and, the amount

of solvent used is at least 5-fold less. Presence of an ester or amide

group in the position 7 of the pyrrolopyridazine skeleton increases

the chemical yield. The fully aromatised pyrrolo[1,2-b]pyridazines

are very intense blue emitters and have high quantum yields while

pyrrolophthalazine compounds are still intense blue emitters but

the quantum yield is negligible. A feasible explication for this

behaviour is presented. A certain inﬂuence of the substituents

concerning ﬂuorescencewasfound, thoseone at theposition 7 being

crucial for ﬂuorescence. Again, feasible explications for this beha-

viour are presented. The number of the substituents from the pyr-

rolo ring doesn’t seem to play an important role regarding

ﬂuorescence but, with the increase of the number of substituents

a certain hypsochromic shift in the absorption spectra was found.

to microwave for 5 min. Using MW irradiation, the best results

were obtained using a constant irradiation power (20% from the full

power of the magnetron, 800 W) and varying the temperature (the

so-called ‘power control’). The resulting mixture was ﬁltered hot to

remove triethylamine hydrobromide and the clear solution was

evaporated in vacuo to give the crude product, which was puriﬁed

by ﬂash chromatography (99/1 CH₂Cl₂/CH₃OH) to give 5,6,7-tri-

(methoxycarbonyl)pyrrolo[1,2-b]pyridazine 2a (0.44 g, 30% (under

classical heating) and 0.86 g, 59% (under microwaves)) as a white

solid, mp 168e169 ^ꢀC. Found: C, 53.32; H, 4.06; N, 9.48. C₁₃H₁₂N₂O₆

(292) requires C, 53.43; H, 4.14; N, 9.59%; R_f(99/1 CH₂Cl₂/CH₃OH)

0.21; IR (KBr, cm^ꢁ1): 3096 (CeH arom.), 2950 (CeH aliph.), 1725,

1722, 1709 (C]O est.), 1600, 1560, 1505, 1460 (C]C, C]N), 1230,

1130 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 3.92 (s, 3H: CH₃from

5 position), 3.96 (s, 3H: CH₃from 7 position), 4.02 (s, 3H: CH₃from 6

position), 7.16 (dd, J¼9.2, 4.4, 1H: H₃), 8.56 (dd, J¼4.4, 1.8, 1H: H₄),

4. Experimental section

4.1. General procedure

8.64 (dd, J¼9.2, 1.8, 1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 52.0

(CH₃from 5 position, COOMe), 52.3 (CH₃from 7 position, COOMe),

53.1 (CH₃from 6 position, COOMe), 102.8 (C_4a), 117.11 (C₅), 117.6

(C₃), 128.4 (C₂), 128.8 (C₆), 131.9 (C₇), 145.1 (C₄), 158.7 (CO from 7

position),162.7 (CO from 5 position),165.6 (CO from 6 position); MS

(EI, m/z): 292 (M^þ, 78%), 261 (P.B., 100%), 231 (10.71%), 203 (18%),

189 (9.5%), 144 (9.8%), 88 (4.9%).

All reagents and solvents employed were of the best grade avail-

able and were used without further puriﬁcation. The ¹H and ¹³C NMR

spectra and two-dimensional experiments 2D-COSY, 2D-HETCOR

(HMQC), long range 2D-HETCOR (HMBC) were recorded on a Bruker

Avance 400 DRX spectrometer at 400/100 MHz. Chemical shifts are

4.2.2. 7-Ethoxy-5,6-di-(methoxycarbonyl)pyrrolo[1,2-b]pyridazine

(2b). A mixture of cycloimmonium salt 1b (1.24 g, 5 mmol) and

dimethyl acetylenedicarboxylate (0.68 mL, 5.5 mmol) was sus-

pended in anhydrous benzene, 40 mL under classical heating or

10 mL under MW irradiation. Then, triethylamine (0.77 mL,

5.5 mmol) was added. Under classical conditions, the solution was

reﬂuxed (oil bath) for 2 h. Under microwave heating, the solution

was exposed to microwave for 5 min. Using MW irradiation, the

best results were obtained using a constant irradiation power (20%

from the full power of the magnetron, 800 W) and varying the

temperature (the so-called ‘power control’). The resulting mixture

was ﬁltered hot to remove triethylamine hydrobromide and the

clear solution was evaporated in vacuo to give the crude product,

which was puriﬁed by ﬂash chromatography (99/1 CH₂Cl₂/CH₃OH)

to give 7-ethoxy-5,6-di-(methoxycarbonyl)pyrrolo[1,2-b]pyridazine

2b (0.44 g, 29% (under classical heating) and 0.95 g, 62% (under

microwaves)) as a white solid, mp 137e138 ^ꢀC. Found: C, 54.78; H,

4.52; N, 9.01. C₁₄H₁₄N₂O₆(306) requires C, 54.90; H, 4.61; N, 9.15%;

R_f(99/1 CH₂Cl₂/CH₃OH) 0.18; IR (KBr, cm^ꢁ1): 3112 (CeH arom.),

2956 (CeH aliph.), 1751, 1712, 1677 (C]O est.), 1618, 1502, 1448,

given in parts per million (

downﬁeld shift from internal tetramethylsilane (

-scale), coupling constants (J) in hertz and

0.00 ppm). The IR

spectra were recorded on an FT-IR Shimadzu Prestige 8400s spec-

trophotometer in KBr. UVevis spectra were recorded on a Shimadzu

1800 PC spectrophotometer in ethanol, chloroform, cyclohexane

(spectroscopic grade) solution. Fluorescence measurements were

performed ona PerkineElmer LS 50 ﬂuorescence spectrophotometer,

in the same solvents as for the UVevis spectra. For the microwave

irradiation we used an 800 W STAR SYSTEM-2 monomode reactor

(CEM Corporation). Melting points were determined using an elec-

trothermal apparatus and are uncorrected. Flash chromatography

wasperformed withAldrich 230e400 mesh silicagel. TLC wascarried

out on Merck silica gel 60-F-254 plates. Compounds 2a, 2b and 2h,

were initially investigated by Wudl et al.;⁶here we obtained these

compounds classical by a modiﬁed pathway and also, using a new

method, under MW. All the remaining compounds are new being

synthetized by us. Some spectral data of compounds 3a,b and 5aed

were initially published by us in a Short Communication.^7a

4.2. Experimental procedure for [3D2] dipolar cycloaddition

1406 (C]C, C]N), 1284, 1127 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J,

under MW classical and heating

Hz): 1.36 (t, J¼6.8, 3H: CH₃from 7 position), 3.89 (s, 3H: CH₃from 5

position), 3.98 (s, 3H: CH₃from 6 position), 4.39 (q, J¼6.8, 2H: CH₂

from 7 position), 7.13 (dd, J¼8.8, 4.0, 1H: H₃), 8.54 (d, J¼8.8, 1H: H₄),

4.2.1. 5,6,7-Tri-(methoxycarbonyl)pyrrolo[1,2-b]pyridazine (2a). A

mixture of cycloimmonium salt 1a (1.17 g, 5 mmol) and dimethyl

acetylenedicarboxylate (0.68 mL, 5.5 mmol) was suspended in an-

hydrous benzene, 40 mL under classical heating or 10 mL under

MW irradiation. Then, triethylamine (0.77 mL, 5.5 mmol) was

added. Under classical conditions, the solution was reﬂuxed (oil

bath) for 2 h. Under microwave heating, the solution was exposed

8.60 (d, J¼4.0, 1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 14.0 (CH₃

from 7 position, COOEt), 51.9 (CH₃from 5 position, COOMe), 52.8

(CH₃from 6 position, COOMe), 61.2 (CH₂from 7 position, COOEt),

102.6 (C_4a), 117.1 (C₃), 117.5 (C₅), 128.3 (C₆), 128.8 (C₂), 131.7 (C₇),

145.0 (C₄), 158.0 (CO from 7 position), 162. 7 (CO from 5 position),

165.5 (CO from 6 position); MS (EI, m/z): 304 (M^þ, 90.8%), 275

4302

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

(24.6%), 261 (47%), 234 (P.B.; 100%), 203 (88.7%), 144 (19.7%), 117

(4.2%), 144 (9.8%), 76 (2.8%).

heating or 10 mL under MW irradiation. Then, triethylamine

(0.77 mL, 5.5 mmol) was added. Under classical conditions, the

solution was reﬂuxed (oil bath) for 2 h. Under microwave heating,

the solution was exposed to microwave for 5 min. Using MW ir-

radiation, the best results were obtained using a constant irradia-

tion power (20% from the full power of the magnetron, 800 W) and

varying the temperature (the so-called ‘power control’). The

resulting mixture was ﬁltered hot to remove triethylamine hydro-

bromide and the clear solution was evaporated in vacuo to give the

crude product, which was puriﬁed by ﬂash chromatography (99/1

CH₂Cl₂/CH₃OH) to give the dimethyl 7-(4-chlorobenzoyl)pyrrolo[1,2-

b]pyridazine-5,6-dicarboxylate 2e (0.19 g, 10% (under classical

heating) and 0.24 g, 13% (under microwaves)) as a white solid, mp

178e179 ^ꢀC. Found: C, 57.98; H, 3.47; N, 7.45. C₁₈H₁₃ClN₂O₅(372)

requires C, 58.00; H, 3.52; N, 7.52%; R_f(99/1 CH₂Cl₂/CH₃OH) 0.30; IR

(KBr, cm^ꢁ1): 3091 (CeH arom.), 2950 (CeH aliph.), 1744, 1707 (C]O

est.), 1648 (C]O keto), 1588, 1500, 1452, 1389 (C]C, C]N), 1242,

4.2.3. Diethyl 7-carbamoylpyrrolo[1,2-b]pyridazine-5,6-dicarboxylate

(2c). A mixture of cycloimmonium salt 1c (1.09 g, 5 mmol) and

diethyl acetylenedicarboxylate (0.88 mL, 5.5 mmol) was suspended

in anhydrous benzene, 40 mL under classical heating or 10 mL under

MW irradiation. Then, triethylamine (0.77 mL, 5.5 mmol) was added.

Under classical conditions, the solutionwas reﬂuxed (oil bath) for 2 h.

Under microwave heating, the solutionwasexposedtomicrowave for

5 min. Using MW irradiation, the best results were obtained using

a constant irradiation power (20% from the full power of the mag-

netron, 800 W) and varying the temperature (the so-called ‘power

control’). The resulting mixture was ﬁltered hot to remove triethyl-

amine hydrobromide and the clear solution was evaporated in vacuo

to give the crude product, which was puriﬁed by ﬂash chromatog-

raphy (99/1 CH₂Cl₂/CH₃OH) to give the diethyl 7-carbamoylpyrrolo

[1,2-b]pyridazine-5,6-dicarboxylate 2c (0.49 g, 32% (under classical

heating) and 0.78 g, 51% (under microwaves)) as a white solid, mp

196e197 ^ꢀC. Found: C, 55.07; H, 4.91; N, 13.71. C₁₄H₁₅N₃O₅(305)

requires C, 55.08; H, 4.95; N, 13.76%; R_f(99/1 CH₂Cl₂/CH₃OH) 0.17; IR

(KBr, cm^ꢁ1): 3446 (NeH amide), 3068 (CeH arom.), 2943 (CeH

aliph.),1721,1717(C]Oest.),1703(C]O amide),1598,1578, 1527 (C]

1106 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 3.66 (s, 3H: CH₃from

5 position), 3.92 (s, 3H: CH₃from 6 position), 7.10 (dd, J¼3.2, 8.8,1H:

H₃), 7.43 (d, J¼8.4, 2H: H₁₁), 7.73 (d, J¼8.4, 2H: H₁₀), 8.33 (d, J¼3.2,

1H: H₄), 8.61 (d, J¼8.8, 1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 52.0

(CH₃from 5 position), 52.7 (CH₃from 6 position), 103.4 (C₅), 117.0

(C₃), 126.2 (C₆), 126.3 (C₇), 128.7 (C₁₁), 128.8 (C₄), 130.8 (C₁₀), 131.0

(C_4a), 136.2 (C₁₂), 139.7 (C₉), 144.7 (C₂), 162.7 (CO from 5 position),

164.5 (CO from 6 position), 184.2 (C₈, keto).

Carom.); ¹H NMR (CDCl₃,

, ppm, J, Hz):1.41e1.37 (m, 6H: 2ꢂCH₃from

5 and 6 position), 4.36 (q, J¼7.2, 2H: CH₂from 5 position), 4.42 (q,

J¼7.2, 2H: CH₂from 6 position), 7.12 (br s,1H: NH), 7.42 (q, J¼4.8, 9.2,

1H:H₃), 8.50(brs,1H:NH), 8.73(dd,J¼1.6, 4.8,1H:H₄), 8.76 (dd, J¼1.6,

4.2.6. Dimethyl 7-(4-methylbenzoyl)pyrrolo[1,2-b]pyridazine-5,6-di-

carboxylate (2f). A mixture of cycloimmonium salt 1f (1.47 g,

5 mmol) and dimethyl acetylenedicarboxylate (0.68 mL, 5.5 mmol)

was suspended in anhydrous benzene, 40 mL under classical heating

or 10 mL under MW irradiation. Then, triethylamine (0.77 mL,

5.5 mmol) was added. Under classical conditions, the solution was

reﬂuxed (oil bath) for 2 h. Under microwave heating, the solutionwas

exposed to microwave for 5 min. Using MW irradiation, the best

results were obtained using a constant irradiation power (20% from

thefull powerof themagnetron, 800 W) and varying the temperature

(the so-called ‘power control’). The resulting mixture was ﬁltered hot

to remove triethylamine hydrobromide and the clear solution was

evaporated in vacuo to give the crude product, which was puriﬁed by

ﬂash chromatography (99/1 CH₂Cl₂/CH₃OH) to give the dimethyl 7-(4-

methylbenzoyl)pyrrolo[1,2-b]pyridazine-5,6-dicarboxylate 2f (0.21 g,

12% (under classical heating) and 0.21 g, 12% (under microwaves)) as

a yellow solid, mp 177e178 ^ꢀC. Found: C, 64.76; H, 4.57; N, 7.89.

C₁₉H₁₆N₂O₅(352) requires C, 64.77; H, 4.58; N, 7.95%; R_f(99/1 CH₂Cl₂/

CH₃OH) 0.27; IR (KBr, cm^ꢁ1): 3079 (CeH arom.), 2953 (CeH aliph.),

1739,1708 (C]O est.),1635 (C]O keto),1604,1537,1504,1452 (C]C,

9.2,1H: H₂);¹³C NMR (TMS, CDCl₃,

d, ppm): 15.1 (CH₃from 6 position),

15.3 (CH₃from 5 position), 61.8 (CH₂from 6 position), 62.4 (CH₂from

5 position),104.3 (C₅),106.3 (C₆),118.7 (C₃),124.3 (C₇),130.7(C₄),130.7

(C_4a),146.3 (C₂),159.2 (CO from 7 position),161.9(CO from 5 position),

166.8 (CO from 6 position).

4.2.4. Dimethyl 7-(4-ﬂuorobenzoyl)pyrrolo[1,2-b]pyridazine-5,6-di-

carboxylate (2d). A mixture of cycloimmonium salt 1d (1.49 g,

5 mmol) and dimethyl acetylenedicarboxylate (0.68 mL, 5.5 mmol)

was suspended in anhydrous benzene, 40 mL under classical heating

or 10 mL under MW irradiation. Then, triethylamine (0.77 mL,

5.5 mmol) was added. Under classical conditions, the solution was

reﬂuxed (oil bath) for 2 h. Under microwave heating, the solutionwas

exposed to microwave for 5 min. Using MW irradiation, the best

results were obtained using a constant irradiation power (20% from

the fullpowerof the magnetron, 800 W) and varyingthetemperature

(the so-called ‘power control’). The resulting mixture was ﬁltered hot

to remove triethylamine hydrobromide and the clear solution was

evaporated in vacuo to give the crude product, which was puriﬁed by

ﬂash chromatography (99/1 CH₂Cl₂/CH₃OH) to give the dimethyl 7-(4-

ﬂuorobenzoyl)pyrrolo[1,2-b]pyridazine -5,6-dicarboxylate 2d (0.18 g,

10% (under classical heating) and 0.25 g, 14% (under microwaves)) as

a white solid, mp 156e158 ^ꢀC. Found: C, 60.66; H, 3.61; N, 7.77.

C₁₈H₁₃FN₂O₅(356) requires C, 60.68; H, 3.68; N, 7.86%; R_f(99/1

CH₂Cl₂/CH₃OH) 0.32; IR (KBr, cm^ꢁ1): 3070 (CeH arom.), 2956 (CeH

aliph.),1739,1704 (C]O est.),1643 (C]O keto),1604,1537,1504,1452

C]N),1271,1105 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 2.42 (s, 3H:

CH₃from 12 position), 3.59 (s, 3H: CH₃from 5 position), 3.92 (s, 3H:

CH₃from 6 position), 7.05 (dd, J¼4.4, 9.2, 1H: H₃), 7.25 (d, J¼8.0, 2H:

H₁₁), 7.71 (d, J¼8.0, 2H: H₁₀), 8.32 (d, J¼4.4,1H: H₄), 8.60 (d, J¼9.2,1H:

H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 21.8 (CH₃from 12 position), 51.9

(CH₃from 5 position), 52.5 (CH₃from 6 position),103.2 (C₅),117.1 (C₃),

125.3 (C₆), 127.1 (C₇), 128.7 (C₄), 129.2 (C₁₁), 129.6 (C₁₀), 130.8 (C_4a),

135.2 (C₁₂),144.3 (C₉),144.6 (C₂),163.0 (CO from 5 position),164.5 (CO

from 6 position), 185.3 (C₈, keto).

(C]C, C]N),1247,1132 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 3.65

(s, 3H:CH₃from5 position), 3.92(s, 3H:CH₃from6 position), 7.08 (dd,

J¼4.8,9.2,1H:H₃), 7.13(dd,J¼8.4,8.8,2H:H₁₁), 7.82(dd,J¼8.4,5.2,2H:

H₁₀), 8.32 (dd, J¼4.8,1H: H₄), 8.62 (dd, J¼9.2,1H: H₂); ¹³C NMR (TMS,

4.2.7. Dimethyl

3-carbamoyl-1,10b-dihydropyrrolo[2,1-a]phthala-

CDCl₃,

d, ppm): 51.9 (CH₃from 5 position), 52.6 (CH₃from 6 position),

zine-1,2-dicarboxylate (2g). A mixture of cycloimmonium salt 1i

(1.34 g, 5 mmol) and dimethyl acetylenedicarboxylate (0.68 mL,

5.5 mmol) was suspended in anhydrous benzene, 40 mL under

classical heating or 10 mL under MW irradiation. Then, triethyl-

amine (0.77 mL, 5.5 mmol) was added. Under classical conditions,

the solution was reﬂuxed (oil bath) for 2 h. Under microwave

heating, the solution was exposed to microwave for 5 min. Using

MW irradiation, the best results were obtained using a constant

irradiation power (20% from the full power of the magnetron,

103.2 (C₅), 115.7, 115.5 (d, J¼22, C₁₁), 117.3 (C₃), 126.0 (C₆), 128.8 (C₄),

130.9 (C₇), 132.1, 132.0 (d, J¼10, C₁₀),132.1 (C_4a),138.4 (C₁₂),144.7 (C₂),

162.9(CO from 5 position),164.5 (CO from 6 position),184.0(C₈, keto).

4.2.5. Dimethyl 7-(4-chlorobenzoyl)pyrrolo[1,2-b]pyridazine-5,6-di-

carboxylate (2e). A mixture of cycloimmonium salt 1e (1.57 g,

5 mmol) and dimethyl acetylenedicarboxylate (0.68 mL, 5.5 mmol)

was suspended in anhydrous benzene, 40 mL under classical

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

4303

800 W) and varying the temperature (the so-called ‘power con-

trol’). The resulting mixture was ﬁltered hot to remove triethyl-

amine hydrobromide and the clear solution was evaporated in

vacuo to give the crude product, which was puriﬁed by ﬂash

chromatography (99/1 CH₂Cl₂/CH₃OH) to give the dimethyl 3-car-

bamoyl-1,10b-dihydropyrrolo[2,1-a]phthalazine-1,2-dicarboxylate 2g

(0.64 g, 39% (under classical heating) and 1.05 g, 64% (under mi-

crowaves)) as a white solid, mp 192e193 ^ꢀC. Found: C, 58.32; H,

4.53; N, 12.69. C₁₆H₁₅N₃O₅(329) requires C, 58.36; H, 4.59; N,

12.76%; R_f(99/1 CH₂Cl₂/CH₃OH) 0.23; IR (KBr, cm^ꢁ1): 3454 (NeH

amide), 3074 (CeH arom.), 2958 (CeH aliph.), 1721 (C]O est.), 1704

pyridazine 3b (0.40 g, 32% (under classical heating) and 0.76 g, 61%

(under microwaves)) asawhite solid, mp 111e112 ^ꢀC. Found: C, 57.96;

H, 4.84; N, 11.15. C₁₂H₁₂N₂O₄(248) requires C, 58.06; H, 4.87; N,

11.29%; R_f(99/1 CH₂Cl₂/CH₃OH) 0.26; IR (KBr, cm^ꢁ1): 3106 (CeH

arom.), 2958(CeHaliph.),1718,1711(C]Oest.),1601,1561,1502,1464

(C]C, C]N),1229,1132 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 1.42

(t, J¼7.2, 3H: CH₃from 7 position), 3.93 (s, 3H: CH₃from 5 position),

4.43 (q, J¼6.8, 2H: CH₂from 7 position), 7.09 (dd, J¼9.24.4, 1H: H₃),

8.06 (s,1H: H₆), 8.53 (d, J¼3.2,1H: H₄), 8.63 (dd, J¼9.2,1.6,1H: H₂); ¹³

NMR (TMS, CDCl₃, d, ppm): 14.4 (CH₃from 7 position, COOEt), 51.5

(CH₃from 5 position, COOMe), 60.7 (CH₂from 7 position, COOEt),

104.9 (C₅),116.5 (C₃),119.7 (C_4a),122.4 (C₆),128.0 (C₂),133.1 (C₇),144.2

(C₄), 159.2 (CO from 7 position), 164.0 (CO from 5 position); MS (EI,

m/z): 250 (Mþ2; 2.1%), 249 (Mþ1; 13.5), 248 (M^þ,100%), 217 (23.4%),

203 (90.1%), 189 (41.1%), 176 (73%), 145 (66.7%), 117 (9.9%), 70 (3%).

(C]O amide), 1601, 1569, 1558 (C]C arom.); ¹H NMR (CDCl₃,

ppm, J, Hz): 3.72 (s, 3H: CH₃from 1 position), 3.86 (s, 3H: CH₃from

2 position), 4.35 (d, J¼13.2, 1H: H₁), 5.04 (d, J¼13.2, 1H: H_10b), 6.18

(br s, 1H: NH), 6.41 (br s, 1H: NH), 7.27 (dd, J¼1.2, 6.4, 1H: H₁₀), 7.39

(m, overlapped peaks, 2H: H₈, H₉), 7.48 (d, J¼7.6, 1H: H₇), 7.59 (s,

1H: H₆); ¹³C NMR (TMS, CDCl₃,

, ppm): 51.7 (CH₃from 1 position),

4.2.10. Ethyl 7-carbamoylpyrrolo[1,2-b]pyridazine-5-carboxylate (3c).

A mixture of cycloimmonium salt 1c (1.09 g, 5 mmol) and ethyl

propiolate (0.56 mL, 5.5 mmol) was suspended in anhydrous ben-

zene, 40 mL under classical heating or 10 mL under MW irradiation.

Then, triethylamine (0.77 mL, 5.5 mmol) was added. Under classical

conditions, the solution was reﬂuxed (oil bath) for 2 h. Under mi-

crowave heating, the solution was exposed to microwave for 5 min.

Using MW irradiation, the best results were obtained using a con-

stant irradiation power (20% from the full power of the magnetron,

800 W) and varying the temperature (the so-called ‘power con-

trol’). The resulting mixture was ﬁltered hot to remove triethyl-

amine hydrobromide and the clear solution was evaporated in

vacuo to give the crude product, which was puriﬁed by ﬂash

chromatography (99/1 CH₂Cl₂/CH₃OH) to give the ethyl 7-carba-

moylpyrrolo[1,2-b]pyridazine-5-carboxylate 3c (0.33 g, 28% (under

classical heating) and 0.66 g, 57% (under microwaves)) as a white

solid, mp 207e208 ^ꢀC. Found: C, 56.64; H, 4.70; N, 17.96.

C₁₁H₁₁N₃O₃(233) requires C, 56.65; H, 4.75; N, 18.02%; R_f(99/1

CH₂Cl₂/CH₃OH) 0.20; IR (KBr, cm^ꢁ1): 3439 (NeH amide), 3084

(CeH arom.), 2947 (CeH aliph.), 1717 (C]O est.), 1703 (C]O am-

52.1 (C₁), 53.0 (CH₃from 2 position), 61.3 (C_10b), 123.3 (C₈), 125.0

(C₂), 125.8 (C₁₀), 128.8 (C₉), 131.0 (C_7a), 131.7 (C₇), 142.5 (C₆), 150.0

(C₃), 161.6 (CO from 3 position), 164.5 (CO from 2 position), 173.1

(CO from 1 position).

4.2.8. 5,7-Di-(methoxycarbonyl)-pyrrolo[1,2-b]pyridazine (3a). A mix-

ture of cycloimmonium salt 1a (1.17 g, 5 mmol) and methyl pro-

piolate (0.51 mL, 5.5 mmol) was suspended in anhydrous benzene,

40 mL under classical heating or 10 mL under MW irradiation.

Then, triethylamine (0.77 mL, 5.5 mmol) was added. Under classical

conditions, the solution was reﬂuxed (oil bath) for 2 h. Under

microwave heating, the solution was exposed to microwave for

5 min. Using MW irradiation, the best results were obtained using

a constant irradiation power (20% from the full power of the

magnetron, 800 W) and varying the temperature (the so-called

‘power control’). The resulting mixture was ﬁltered hot to remove

triethylamine hydrobromide and the clear solution was evaporated

in vacuo to give the crude product, which was puriﬁed by ﬂash

chromatography (99/1 CH₂Cl₂/CH₃OH) to give 5,7-di-(methox-

ycarbonyl)-pyrrolo[1,2-b]pyridazine 3a (0.35 g, 30% (under classical

heating) and 0.68 g, 58% (under microwaves)) as a brown light

solid, mp 147e148 ^ꢀC. Found: C, 56.36; H, 4.24; N,11.89. C₁₁H₁₀N₂O₄

(234) requires C, 56.41; H, 4.30; N, 11.96%; R_f(99/1 CH₂Cl₂/CH₃OH)

0.25; IR (KBr, cm^ꢁ1): 3101 (CeH arom.), 2960 (CeH aliph.), 1728,

1678 (C]O est.), 1599, 1561, 1490, 1444 (C]C, C]N), 1234, 1114

ide), 1600, 1569, 1522 (C]C arom.); ¹H NMR (CDCl₃,

d, ppm, J, Hz):

1.36 (t, J¼7.2, 3H: CH₃from 5 position), 4.33 (q, J¼7.2, 2H: CH₂from

5 position), 7.33 (dd, J¼4.8, 9.2, 1H: H₃), 7.79 (s, 1H: H₆), 7.95 (br s,

1H: NH), 8.21 (br s, 1H: NH), 8.61 (dd, J¼1.6, 9.2, 1H: H₄), 8.68 (dd,

J¼1.6, 4.8, 1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 14.3 (CH₃from 5

position), 59.9 (CH₂from 5 position), 104.1 (C₅), 116.6 (C₃), 119.6

(C₆), 123.3 (C₇), 128.3 (C₄), 131.0 (C_4a), 144.3 (C₂), 159.5 (CO from 7

position), 162.8 (CO from 5 position).

(CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 3.92 (s, 3H: CH₃from 5

position), 3.96 (s, 3H: CH₃from 7 position), 7.09 (dd, J¼9.2, 4.4, 1H:

H₃), 8.00 (s, 1H: H₆), 8.52 (dd, J¼4.4, 1.6, 1H: H₄), 8.63 (dd, J¼9.2, 1.6,

1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 51.5 (CH₃from 5 position,

4.2.11. Ethyl 7-(4-ﬂuorobenzoyl)pyrrolo[1,2-b]pyridazine-5-carboxy-

late (3d). A mixture of cycloimmonium salt 1d (1.49 g, 5 mmol) and

ethyl propiolate (0.56 mL, 5.5 mmol) was suspended in anhydrous

benzene, 40 mL under classical heating or 10 mL under MW irra-

diation. Then, triethylamine (0.77 mL, 5.5 mmol) was added. Under

classical conditions, the solution was reﬂuxed (oil bath) for 2 h.

Under microwave heating, the solution was exposed to microwave

for 5 min. Using MW irradiation, the best results were obtained

using a constant irradiation power (20% from the full power of the

magnetron, 800 W) and varying the temperature (the so-called

‘power control’). The resulting mixture was ﬁltered hot to remove

triethylamine hydrobromide and the clear solution was evaporated

in vacuo to give the crude product, which was puriﬁed by ﬂash

chromatography (99/1 CH₂Cl₂/CH₃OH) to give the ethyl 7-(4-ﬂuo-

robenzoyl)pyrrolo[1,2-b]pyridazine-5-carboxylate 3d (0.39 g, 25%

(under classical heating) and 0.31 g, 20% (under microwaves)) as

a white solid, mp 120e122 ^ꢀC. Found: C, 65.35; H, 4.13; N, 8.89.

C₁₇H₁₃FN₂O₃(312) requires C, 65.38; H, 4.20; N, 8.97%; R_f(99/1

CH₂Cl₂/CH₃OH) 0.28; IR (KBr, cm^ꢁ1): 3098 (CeH arom.), 2962 (CeH

aliph.), 1708 (C]O est.), 1647 (C]O keto), 1600, 1506, 1471 (C]C,

COOMe), 51.8 (CH₃from 7 position, COOMe), 105.0 (C₅), 116.6 (C₃),

119.5 (C_4a), 122.5 (C₆), 128.0 (C₂), 133.1 (C₇), 144.2 (C₄), 159.6 (CO

from 7 position), 163.9 (CO from 5 position); MS (EI, m/z): 236

(Mþ2; 2%), 235 (Mþ1; 18%), 234 (M^þ, 99.9%), 203 (P.B.; 100%), 176

(18.4%), 145 (21%), 116 (5%), 88 (10.52%).

4.2.9. 7-Ethoxy-5-methoxycarbonylpyrrolo[1,2-b]pyridazine (3b). A

mixture of cycloimmonium salt 1b (1.24 g, 5 mmol) and methyl

propiolate (0.51 mL, 5.5 mmol) was suspended in anhydrous ben-

zene, 40 mL under classical heating or 10 mL under MW irradiation.

Then, triethylamine (0.77 mL, 5.5 mmol) was added. Under classical

conditions, the solution was reﬂuxed (oil bath) for 2 h. Under

microwave heating, thesolutionwasexposedtomicrowave for5 min.

Using MWirradiation, the bestresults were obtained using a constant

irradiation power (20% from the full power of the magnetron, 800 W)

and varying the temperature (the so-called ‘power control’). The

resulting mixture was ﬁltered hot to remove triethylamine hydro-

bromide and the clear solution was evaporated in vacuo to give the

crude product, which was puriﬁed by ﬂash chromatography (99/1

CH₂Cl₂/CH₃OH) to give 7-ethoxy-5-methoxycarbonylpyrrolo[1,2-b]

C]N), 1255, 1097 (CeOeC); ¹H NMR (CDCl₃,

d, ppm, J, Hz): 1.41 (t,

4304

G.N. Zbancioc et al. / Tetrahedron 66 (2010) 4298e4306

J¼7.2, 3H: CH₃from 5 position), 4.40 (q, J¼7.2, 2H: CH₂from 5

position), 7.18 (dd, J¼4.4, 9.2, 1H: H₃), 7.19 (d, J¼8.4, 8.8, 2H: H₁₁),

7.73 (s, 1H: H₆), 7.95 (dd, J¼5.6, 8.4, 2H: H₁₀), 8.32 (dd, J¼4.4, 1H:

133.3 (C_4a), 136.3 (C₁₂), 143.1 (C₉), 144.2 (C₂), 163.6 (CO from 5

position), 184.1 (C₈, keto).

H₄), 8.68 (dd, J¼9.2, 1H: H₂); ¹³C NMR (TMS, CDCl₃,

d, ppm): 14.5

4.2.14. Pyrrolo[2,1-a]phthalazine-1,3-dicarboxylic acid dimethyl ester

(3g). A mixture of cycloimmonium salt 1g (1.42 g, 5 mmol) and

methyl propiolate (0.51 mL, 5.5 mmol) was suspended in anhy-

drous benzene, 40 mL under classical heating or 10 mL under MW

irradiation. Then, triethylamine (0.77 mL, 5.5 mmol) was added.

Under classical conditions, the solution was reﬂuxed (oil bath) for

2 h. Under microwave heating, the solution was exposed to mi-

crowave for 5 min. Using MW irradiation, the best results were

obtained using a constant irradiation power (20% from the full

power of the magnetron, 800 W) and varying the temperature (the

so-called ‘power control’). The resulting mixture was ﬁltered hot to

remove triethylamine hydrobromide and the clear solution was

evaporated in vacuo to give the crude product, which was puriﬁed

by ﬂash chromatography (99/1 CH₂Cl₂/CH₃OH) to give the pyrrolo

[2,1-a]phthalazine-1,3-dicarboxylic acid dimethyl ester 3g (0.58 g,

41% (under classical heating) and 0.94 g, 66% (under microwaves))

as a white solid, mp 224e225 ^ꢀC. Found: C, 63.32; H, 4.19; N, 9.72.

C₁₅H₁₂N₂O₄(284) requires C, 63.38; H, 4.25; N, 9.85%; R_f(99/1

CH₂Cl₂/CH₃OH) 0.34; IR (KBr, cm^ꢁ1): 3082 (CeH arom.), 2951 (CeH

aliph.), 1720, 1709 (C]O est.), 1600, 1564, 1519, 1464 (C]C, C]N),

(CH₃from 5 position), 60.5 (CH₂from 5 position), 105.5 (C₅), 115.7,

115.5 (d, J¼21, C₁₁), 117.7 (C₃), 124.6 (C₆), 126.5 (C₇), 128.1 (C₄), 132.1,

132.0 (d, J¼9, C₁₀), 133.5 (C_4a), 135.2 (C₁₂), 144.3 (C₂), 163.5 (C₉),

164.1 (CO from 5 position), 182.9 (C₈, keto).

4.2.12. Ethyl 7-(4-chlorobenzoyl)pyrrolo[1,2-b]pyridazine-5-carboxy-

late (3e). A mixture of cycloimmonium salt 1e (1.57 g, 5 mmol) and

ethyl propiolate (0.56 mL, 5.5 mmol) was suspended in anhydrous

benzene, 40 mL under classical heating or 10 mL under MW irradi-

ation. Then, triethylamine (0.77 mL, 5.5 mmol) was added. Under