Novel ring transformations of pyrazines by intramolecular diels-alder reactions

Temzhedron Vol. 44, No. 10,pp. 2977to 2983,1988 Printedin GreatBritain.

004MO20/88 $3.00+.oO 0 1988Pergamon Presspk

UapEL BIAG TBAMSFOBIUTI(RIS OFPTBAZIAKSBY IWEAKOLECXlLARDIELSALDERKEACTIOl'IS

D.A. DE BIE,a A. OSTROWICZ,b G. GEURTSENaAND H.C. VAN DER PLASa*

aLaboratory of Q-ganic aemistry, Agricultural Uoiverstty Wageniogen, De Dretjeo 5, 6703 BC Wageologeo, The Netherlands and bDepartment of Organic Chemistry, MedIcal Academy, Cruowaldzka 6, 60-780 Poznan, Poland (Received in UK 22 March 1988)

Pyrazioes carrying the w-alkyoe side-chain -XCH2CH2C-CB, Abstract. m,S,SO,SO ,C(CN)*) undergo on heating an intramolecular Diels-Alder Pyraz 1oes with the electron donating atom (0,N or S) in the reaction. side-chain afford [cl-fused pyridines as main products, whereas (3-butyand (3-butynylsulfonyl)pyrazioe are exclusively oylsulf foyl)pyrazine A [b]-fused pyrtdioe Is also the major converted into [b]-fused pyridioes. product in the reacttoo of 2,5-bis(l,l-dIcyaoo-4-peotyoyl)pyrazioe.

Inverse

electron

dtenophiles

have

demand Diels-Alder received

1,2,4,5-tetrazines react,

but less

dieoophtle

are

considerable

and 1,2,4-triazioes easily, placed

with

IO the

an appropriate

pyrtdioes side-chains.

side-chain

Erom the intermediate elimination Heterocyclic

of

diazadieoes

studies

dienophiles.

to stmilar

cyanide httherto

of

with

reacttons

of

Also

pyrtmidioes3

resulting

DIels-Alder

reactIons

the reactions

reactions

of of

these

from cycloaddftioo

two different invesclgated

annelated

pyridioes

have never

A

2 0.

X = NCIOICH,

b.

X=0 x=s

d.

X = SO

e.

X=50,

2977

pyrasioes

type

azadiene

Is

and

reacttons

pyridazines7

of

with

and pyrazioes4

oitropyrldines

carrying

and

carrytog

pyrimidtnes

and

S-membered w-alkyoe the posslbtllty

the C2 and C5 positIons

can be obtained

shown to yield

- I4+21

c.

of

across

this

Dfels-Alder

reactIons

pyrazines

electron-rich

reacttvlty,

1,2,4-triazines,5’6

cycloaddltioo

Scheme 1

1

azadienes

To enhance

on the intramolecular

feature

cycloadduct

hydrogen

Parttcularly,

documented. I”

1,2,4,5-tetrazines,5

our research

An toteresting

heterocycllc

as shown by the intramolecular

intramolecular 9 were observed.

to our current we extended

well

electron-rich

appropriately substituted g,9 pyrimtdioes. Recently, also

of

atteot1on.l are

same molecule

of

In addition

reactions

(see

two products.

that by

Scheme 1).

2978 In

D. A. this

paper

electronic course

of

the

we present

effect

of

the

initial

atom in

the intramolecular

DE BIE et al.

results

the

of

&de-chain

cyclization

our

study

directly

dIrected

attached

on

to

the

the

influence

pyrazine

of

ring

the

on the

reactions.

RESULTSAND DISCUSSION We first

examined

hetero

atom.

pyrazines

Heating of

aminobutyne

in

the

solvent

(X = NH). Prolongued material

took

quantitative

containing nitrobenzene

heating

place.

a side-chain

(3-butynylamino)pyrazine gave

at 210°C also

Fbwever,

intramolecular

electron

reaction

deficient bond of

Similar

ring

reactions

transformations

obtained

in good yield

were also

reacting (4b)

a mixture

(ratio

yield (4c)

the

involved.

lthe

in la more

rtng

intramolecular

of

of

lc,

(lc).

3-butyn-l-ol,

with

the

(3b)

prepared

thiopyraztne

of

pyrazines

1

and

4a (83)

3b (12),

4b (44)

lc

180

3

k

4~ (68)

(24),

Id

120

3

3d (57)

le

150

4.5

3e (88)

5

120

2

5

210

25

the

the time

cycltzation that

cyclires used. in

lc

is

of

The effects the

reactton

of

of

lc

in

50% at

p-bromotoluene of

the course

conversIon the

and pyrImIdine

for

the products solvent

7 (35)

(see

Table)

of

la,

lb and lc

we

X = NH < X = 0 < X = S < X = N C(O)CH3. This order

deffciency

reaction

Tne ratio

6 (53),

yield)

8 (60)

complete

converted

in nitrobenzene,

respecttvely. that

n-electron

and 2,3-

Reactlon

Reaction products Compounds (X isolated 3a (17),

the

(3~)

5.

4

of

we

and 4-iodo-

2,3-dihydrothieno[2,3+_]pyridtne

Reaction conditions Temp. (‘C) Time (h)

in the 1,2,4-triazlne

lb,

nitrobenzene

and 2.3-dthydrofuro[2,3-

from

4

found

CycloadditIon Cn heating

in

210

decrease

solvent

the

165

studied

may indicate

a

of

1:3).

time for

le

165’C

(4a)

to CycloaddItion

lb

We also

of

(ratio

In the order

that

mOre susceptible

sodturn salt

a mixture

increases

and 1.0,

at

a mixture

pyrazine

la

to those

1.7

making the

(3-butynylthio)pyrazine

compound

and reactIon

determining

the starting

gave on heating of

a

3 and 4

of

group on the amtno nitrogen

2,3-dihydrofuro[2,3+Jpyridtne

temperature the

(la)

the acetyl

Intramolecular Diels-Alder reactions conditions, products and yields

similar

found

the

the reactivity

reflects

decomposition

in the formation

when studying

and

Similarly

Pyrazines Starting compounds

that

via

and 4-

dihydropyrrolopyridines

only

Is decreased

obtained

with

of

1:3.5).

gave in excellent

Table

Comparing

of

therefore,

(lb)

chloropyrazine

dihydrothieno[2,3-L]pyridine

see

the

the heterocycle

and l-acetyl-2,3-dihydropyrrolo[2,3-c_jpyridine

the amino group

(3-butynyloxy)pyrazine

by

also

of

resulting

presence

than tn 1 (X = NH) and,

prepared

butyne,

of

the

to

from chloropyrazine

the side-chain.

of

clpyridine

(3a)

due to

character

no trace

(N-acetyl-3-butynylamino)pyrazine

Apparently,

donating

electron triple

1:5.

linked

X = NH) prepared

was not successful;

cycloaddition

acetyl-2,3-dihydropyrrolo[2,3-LJpyridine in a ratio

dienophile

(1,

solvents 180-C

less into

polar the

on varying

and pcymene

state

are with

than

products

X and ts

nitrobenzene. 3c and 4c,

with relative

3c and 4c (measured

on the rates

a transition

pyrazine ring 6b,8a

series.

small,

by glc) but

some ionic

rates is

tt of

By was 2.9,

tndependent

not negltgible character

and may be

Ring transformations of pyrazines We suggest

that

the triple

bond across

indicated as

in all

these the

in 2.4 (see

indicated

principle

in

reactions

cycloadduct

C2 and C5 positions

Scheme 2) leads

2B (Scheme

which determines

2)

that

to

2 is

in

intermediate,

the pyrazine

[b]-annelated

gives

the

of

being

ring.

pcoduct

[cl-annelated

the formation

2919

3, while

product

formed by addition

Loss of hydrogen loss

4.

of

hydrogen

What may be

4a, 4b and 4c is favored

to that of

of

cyanide

as

cyanide

the

leading

3a,

3b and

k.

We suppose develops to

the

that

in

electron

leading

from

which

the

a negative

is

transition

charge

donating

character

2B to 4 a positive

of course

a transition

favored

state

with

&e

to test

reactions

of

sulfinyl

be expected

to yield during

electronic

effect

distribution We also

obtained

aminopyrazine with

thermolysis

isomeric

we extended

by

following

Since

3.

of

X

both

5H_2-pyrindine

is

our

and

the

in the

C-C bond partly destabilized

transition

carbon

study

atom adjacent

by the slight

28’ to X,

solvent

to the intramolecular

an adjacent

has been found

of

depen-

indeed:

Id and le. to

These

the

Diels-Alder

results

pyrazine

reactions

ringtransformation

at

210-C

route

yields

given

ring

by TaylorI’

is

respectively, support

clearly

are

our

influences

observed It

(the

expected

to

be

that

the

the

product

when 2,5-bis(l,l-dicyano-

was found

that

preparation

described

in

of the

thermolysis this

intermediates

in

of

Experimental

Section) (8)

(6) the

5,

compound from

1,1,5,5-tetracyano-l,2,3,5,6,7-hexahydro-s-indacene be

a

exclusi-

view

3-(1,l-dicyano-4-pentyny1)-7,7-dicyano-6,7-dihydro-5~-pyrindine could

Since

Id and le can

pyrazines.

being

in nitrobenzene.

charge

1-oxo-2,3_dihydrothieno[2,3-

seem to

of

Diels-Alder (le).

positive

(3e),

2-bromo-5-nitropyrazine

reacting

(7)

due

state

N, 0 and S. Tne formation

(3-butynylsulfonyl)pyrazine

to stabilize

‘Ibis

attached

heated

the

of

seems to be supported

(ld)

on a “double”

(5)

5,5_dicyanopentyne,

Scheme 3).

further

products

atom

of

to X, which is

character

l,l-dioxo-2,3-dihydrothieno[2,3-L]pyridine of

breaking

on the bridgehead

donating

character

U’

On the contrary,

developed

group are not able

want to report

is

is

i.e.

atom adjacent

above).

in the intramolecular

4-pentynyl)pyrazine that

N, 0 and S.

charge

(see

mainly

or

U + 3,

carbon

(3-butynylsulfinyl)pyrazine

(M),

formed

from

to the electron

hypothesis

and a sulfonyl

l]pyridine vely

this

of

some ionic

dency as has been observed In order

state

on the bridgehead

formation

of

(see

and the 8,

we

D. A.

2980

DE

BIE et al.

Scheme 3

CN

NC

NC

NC CN 8

-

7

subjected

5 to

heating

in

both

isomers

6 and 7 was indeed formed

mixture

of

each of

them when heated

is

rmch closer

to

considerations the

(see

intermediate

intermediate

stage

temperature ctency

of

one

at than

above)

in

nitrobenzene

in case for

the formation

compared

to

of

the

loss

of

temperature (ratio

leads

la,

lb

of

and found

1.5:1).

or

lc

is

hydrogen

5. Attempts the formation

when carbon

of

la-lc

instead

is of

at

12O’C a

8. That the ratio with

to isolate of

in agreement

a hetero

already

the

from cycloadduct

6 and 7 from Ihat

of

In agreement

cyanide

that

Both compounds were isolated

to the formatton

failed.

the conversion

ring

lower

210-C exclusively

by NMR techniques

the pyrazine

at

atom is

6/7

with

9 or occurs

transition 9,

being

to

identify

and

of

supposed it

at a relative

the htgher

6:7

state

electron

as low

def i-

bound to the ring.

EXPERIMENTALSECTION Melting points are uncorrected. ’H NMR spectra were recorded on a Varian EM 390 spectrometer. Me4Si was used as internal standard (6 = 0 ppm). Mass spectral data were obtained on a ABI MS 902 spectrometer equipped with VG EAB console. Column chromatography was carried out over Merck silica gel 60 (70-230 mesh ASTM). GLC measurements were performed on a Varian Vista 6000 gas chromatograph equipped with a column: 200 x 2 mm t.d. filled with 3% SP 2250 on chromosorb W/HP loo-120 mesh. Starting

Materials

(N-acetyl-3-butynylamino)pyrazine (la). A mixture of chloropyraxine (4.60 g, 40 mmol), 4-aminobutyne (5.52 g, 80 mmol) and trtethylamine (8 mL) was heated at 13O’C for 24 h. After cooling the reaction mixture was purified by column chromatography (eluting first with dtchloromethane and then with 9:l dichloromethane/EtOH) to yield 1.26 g (21%) of (3-butynylamino)pyraxine: mp 73-74-C (water) ; ‘H NMR (CDCl,) 6 7.95 (m, 2H), 7.80 (d, J = 2.8 I-Ix, lH), 5.28 (br, 1H). 3.56 (q, 2.53 (dt, Jl = 6.2 lk, J2 = 2.7 ik, 2.05 2H)s JCH (t_2J-CH p2207J$H2-$= 6’2 Hxlz,2H)y Anal. 28.90.

.

&lcd.

.

ioi

.

‘(+%N~

(147.18):

c,

65.28;

H, 6.16;

N,

28.55.

Found:

C,

65.03;

H, 6.15;

N,

A mxture ot the latter compound (1.0 g. 6.8 nrmol), acetic anhydride (5 mL), acetic acid (2.5 mu) and sulfuric acid (3 drops) was heated at 90-C for 15 h. After cooling the excess of acetic anhydride and acetic acid were removed under reduced pressure. Tne residue was treated with water with sodium bicarbonate and extracted with dichloromethane. The organic (20 mL), neutralized layer was dried (anhydrous MgSO4) and evaporated under reduced pressure. Column chromatography of the residue (ether as eluent) yielded 0.92 g (72%) of la as an oil: ‘H NMR (CDCl,) 6 8.84 Jl = 7.0 AZ, J2 ~2.7 AZ, 2H). 2.20 (s, lH), 8.45 (s, 2H), 4.08 (t, J = 7.0 Hz, 2H), 2.55 (dt, (8, 3H). 1.95 (t, J = 2.7 Hz, 1H). MS Calcd. for C10H11N3 CM+): m/e 189.0902. Found: m/e 189.0902.

Ring transfonnations

of pyrazines

2981

of sodturn (0.31 g, 13.4 -1) In 3-butyn-l-01 (7 mu) (3-Butynyloxy)pyrazine (lb). To a solution was added chloropyrasine (1.54 g, 13.4 ms~l). The mfxture was stirred at 8O’C for 2 h and then washed with water (4 x 10 mL). The organic layer was taken up in ether (10 mL), dried (anhydrous MgS04) and evaporated under reduced pressure. ‘Ihe residual solid was plrIfted by crystallIzat1on mp 34-36’C; 1H NMR (cDCl3) 6 8.30 from petroleum ether 40-60 to yield 1.04 g (52%) of lb: (d. J = 1.2 Hz, lH), 8.13 (m, 2H), 4.50 (t, J = 7.2 Hz, 2H), 2.73 (dt, Jl = 7.2 Hz, J2 = 2.7 Hz, 2H). 2.10 (t, J = 2.7 Ha, 1H). Anal. Calcd. for C8H8N20 (148.16): C, 64.85; H, 5.44; N, 18.91. Found: C, 65.03; H, 5.52; N, 19.18. To a solution of thiopyrasfneIl (3-ButyHylthlo)pyrazine (lc). (1.12 g, 10 mmol) and 4-todobutyneLa (1.8 g, 10 -1) in water (25 mL) was added trtethylamine (4 mL). The mixture was heated and extracted with ether. at 7O’C for 3 h, then cooled Ihe organic layer was dried (anhydrou s MgS04) and evaporated under reduced pressure to afford a solid matertal which was plrIf ted by column c romatography (ether as eluent) to yield 0.73 g (44%) of lc: mp 43-44’C (petroleum ether ‘r 40-60) ; H NMR (CW13) 6 8.47 (d, J s 1.2 Hz, lH), 8.36 (dd, J = 2.8 Hz, J = 1.2 Hz, lH), 8.20 (d, J = 2.8 Hz, lH), 3.34 (t. J = 7.2 Hz, 2H), 2.63 (dt, Jl = j.2 Hz, J2 = 5.4 Hz, ZH), 2.09 (t, J = 2.4 Hz, 1H). C, 58.50; H, 4.91; N, 17.06. Found: C, 58.50; H, 4.90; N, Anal. Calcd. for C8H8N2S (164.23): 17.31. (2.07 g, 12.6 mmol) (3-Butynylsulf inyl)pyrasine (la). To a suspension of (3-butynylthlo)pyrazine In water (100 mL) was added sodium metaperiodate (2.70 g, 12.6 mmol). The mixture was stIrred at room temperature for 24 h and subsequently extracted wfth ether. The organic layer was dried (anhydrous MgSO4) and evaporated under reduced pressure. The residual solid material was plrif ied by column chromatography (ether as eluent) to yield 1.41 g (62%) of Id: mp 71-72’C; IR (CHC13) 3300, 1060 cm-‘; 1H NMR (CDC13) 6 9.19 (s, lH), 8.77 (d, J = 1.5 Ha, lH), 8.65 (d, J = 1.5 Hz, lH), 3.57-3.01 (m, 2H), 2.80-2.50 (m, 2H), 1.97 (t, J = 2.7 Hz, 1H). Anal. Calcd. for C8H8N20S (180.23): C, 53.30; H, 4.47; N, 15.54. Found: C, 53.30; H, 4.41; N, 15.47. To a stirred solution of (3-butynylthio)pyrazlne (0.82 g, (3-Butynylsulfonyl)pyrazine (le). 5.0 mmol) in drv dichloromethane (15 mL) at -15-C was added a solutfon of m-chlorooerbenzoIc acid (85X, 2.i g, lo:4 mmol) in dry dichloromethane (35 mL). This mtxture was stirred at room temperature for 16 h, cooled to 0°C and filtered. The filtrate was washed with a saturated solution of sodium sulfite (2 x 15 mL) and subsequently wtth a saturated solution of sodlum bicarbonate pressure. (2 x 25 mL). The organic layer was dried (anhydrous MgS04) and evaporated under reticed The residual oil was purified by column chromatogfaphyl (ether as eluent) to yfeld 0.62 g (63%) of IR (CHCl ) 3315, 1340, 1130 cm ; le as an oil: H NMR (cDC13) 6 9.33 (s, lH), 8.81 (d, 8.73 (d, J = 1.0 Ha, lH), J = 7.2 Hz, 2H), 2.75 (dt, J1 = 7.3 Hz, J /J 1.1 Hz, lH), 3.66 (t, = 2.7 Hz, 1H). J2 = 2.7 Hz, 2H), 1.81 (t,+J MS Cslcd. for C8H8N202S (M ): m/e 196.0307. Found: m/e 196.0312. To a 2,5-Bis(l,l-dicyano-4-pentynyl)pyraztne (5). a. Preparation of 2-bromo-5-nitropyrazine. solution of aminopyrazine (5.0 g, 52.6 mxol) in dry dIch1oromethan.e (300 mL), cooled to O’C, was added N-bromoeJccinlmide (9.4 g, 52.8 mmol). The mixture was stirred at O’C for 24 h and then washed with four 50 mL Fortions of a saturated solution of sodtum carbonate and water (50 mL). The organic layer was dried (anhydrous MgS04) and evaporated un@r reduced pressure to give 5.1 g (55%) of 2-amino-5-bromopyrazine: mp 112-114-C (EtOH/H 0) (Lit. 113’C). To a stirred solutfon of dimethyl sulfoxide (1.2 g, ;i 5.4 mmol) in dry dIchloromethane (40 mL), cooled to -75’C, was added trifluoromethanesulfonic anhydride (3.1 g, 10.7 mmol) at -70-C under of 2-amino-5-bromopyrazine (1.5 g, 8.6 mmol) In a nitrogen. After 30 min, at -7O’C a solution mixture of dichloromethane (30 mL) and dimethylsulfoxide (1 mL) was added. The reaction mfxture was stirred at -75-C for 3 h, and then at -40-C for 1 h. A 5% sodium hydroxtde solution (20 mL) and mbsequently dichloromethane (30 mL) were added maintaining the temperature below -1O’C. The aqueous layer was extracted with After stirring for 30 min the organic layer was separated. five 30 mL portions of dichloromethane. The combined dichloromethane extracts were washed with water (30 mt), dried over anhydrous MgS04 and evaporated under reduced pressure. The restdue was plrifted by column chromatography (ethyl acetate as eluens) to yield 1.7 g (85%) of N-(2-bromo-5pyrazinyl)-S,S-dimethylsulf ilimine: mp 122-123’C; ‘I-l NMR(CDC13) 6 7.93 (d, J = 1.2 Hz, lH), 7.80 (d, J = 1.2 Bs, lH), 3975 (s4 6H). MS Cslcd. for C H N S Br (M ): m/e 232.9623. Found: m/e 232.9630. acid (85X, 2.95 g, 14.6 mwl) In dry dichloromethane To a solution6 ,8f 3 m-chloroperbenaofc (130 mu), was added a solutton of N-(2-bromo-5-pyraz1nyl)-S,S-dimethylsulf illmine (1.08 g, 4.6 mmrpl) at -8’C over a period of 3.5 h. The mtxture was stfrred at -8-C to -5’C for 30 min and Ozone was bubbled through the clear orange filtrate at -5-C unttl subsequently filtered rapidly. It turned pale yellow. The mixture was washed with tW) 20 mL portIons of a saturated solution of The organtc layer was dried (anhydrous MgS04) and evaporated under reduced sodium bicarbonate. Column chromatography (eluting with I:1 dichloromethane/petroleum ether 40-60) yIelded pressure. 0.78 g (82%) of 2-bromo-5-nitropyrazine: mp 114’C; ‘H NMR (CDC13) 6 9.30 (d, J = 1.2 HZ, lH), 8.73 (d, J = 1.2 Hz, 174. MS Calcd. for C4H2N302 Br (M’): m/e 202.9331. Found: m/e 202.9336. Anal. Calcd. for C4H2N302Br (203.99): C, 23.55; H, 0.98; N, 20.60. Found: C, 23.62; H, 0.95; N, 20.43. b. Reactton of 2-bromo-5-nitropyrazfne with 5,5-dicyanopentyne. To a sttrred suspenston of sodium hydride (80% dlspersIon, 0.063 g, 2.1 mmol) In anh drous THF (15 mL) at room temperature 13 (0.25 g, 2.1 mmol) In anhydrous THF under nitrogen was added a solutton of 5,5-dicyanopentyne (15 mL) and the mtxture was then sttrred for 20 min. A solution of Z-bromo-5-nitropyrasine

2982

D. A. DE BIE et al.

(0.426 g, 2.1 mwl) in anhydrous THF (5 ml) was added and the mixture was stirred for 2 h. After addition of water (LOO ml) the mixture was extracted with ether (4 x 40 mL). The organic extracts dried (anhydrous MgS04) and evaporated under reduced pessure. The residue was were combined, as eluent) to afford 0.156 g (48%) of 5: mp (dichloromethane plrif ied by columy chromatography H NMR CDCl ) 6 9.18 (6, ZH), 2.90-2.50 (m, 8H), 1.96 (t, J = 2.7 Hz, 2H). 123-L24’C (EtOH); MS Calcd. for C18~12~6 (Mi ): m3e 312.1123. Found: m/e 312.1130. C, 69.22; H, 3.87; N, 26.91. Found: C, 69.42; H, 3.78; N, Anal. Calcd. for C18H12Ng (312.32): 26.75. General procedure for the intramolecular Diels-Alder reacttons of pyrasines 1 and 5. A stirred solution of the pyrazine derivative in nitrobenzene (100 mg solute/l ml., solvent) under The resultant nitrogen was heated under conditions depending on the substrate (see Table). with the appropriate solvent system yielded solution was chromatographed over silica gel; elution the reaction products 3, 4, 6, 7 and 8. Column chromatography (eluttng first with Cyclization of (N-acetyl-3-butynylamino)pyrazine (la). followed by 2:l dichloromethane/ether and finally 4:l dichloromethane to remOve nitrobenzene. ether/methanol) of the reaction mixture-obtained froiala (4.0 mmol) r ielded l-acetyl-2,3-dihydroH NMR (CDC13) identical with 122-123-C (lit. 123-124-C), pyrrolo [ 2,3-l]pyridine (3a, 17%).8fp and 1-acetyl-2,3-dihydropyrrolo[ 2,3-L]pyridine (4a, 83%)) mp that reported In the literature, LH NMR (CDCl,) 6 9.36 (s, lH), 8.23 (d, .I = 5.1 Hz, lH), 7.07 (d, 115-116’C (toluene); J = 5.2 HZ, lH), 4.01 (t, J = 8.6 Hz, 2H), 3.17 (t, J = 8.6 Hs, 2H), 2.20 (6, 3H). H, 6.21; N, 17.27. Found: C, 66.47; H, 6.18; N, C, 66.64; Anal. Calcd. for C9H10N20 (162.19): 17.34. Purification of the reaction mixture originating (lb). Cyclization of (3-butynyloxy)pyrazine from lb (3.4 mmol) by column chromatosraphv (eluting with dichloromethane) yielded 2,3-dihydro1H NMR (CDCi3) spectrum identical qith that reported in furo[2 3-b]pyrid ne (3b, 12%) as an oii, the li;er
Hs, 2H), 2.63 (br 8, 4H). Found: m/e 285.1015.

2.05

(t,

J = 2.7

HZ, 1~).

Cyclization of 5 at 21O’C. Column chromatography (eluting with dichloromethane) of the reaction mixture obtained from 5 (0.40 ml) yielded 1,1,5,5ytletrlacyano-l,2,3,5,6,7-hexahydro-s-indacene (ethanol). IR (CHC13) 2280 cm ; H NMR (CDC13) 6 7.63 (s, 2H), 3.31 (t, (8, 60X), mp 245-247’C J = 6.7 Hz, 4H), 3.00 (t, J = 6.8 Ha, 4H). MS Calcd. for C16HLON4(Me) m/e 258.0905. Found: m/e 258.0913. Anal. Calcd. for C16H1ON4 ( 258.27) : C, 74.40; H, 3.90; N, 21.69. Found: C, 74.65; H, 3.97; N, 21.97.

Ring transformations

ofpyrazines

2983

Cyclization of 6 and 7. Solutions of 6 (0.22 mmol) and 7 (0.15 mmol) in nitrobenzene (1 mu) were heated at 210-C for 25 h. Column chromatography (ether as eluent) of each of the reactton mlxtures gave 8 (65%).

ACKNOWLEDGEMENTS The authors are indebted to Mr. H. Jongejan for the microanalysis, Mr. C.J. TeunIs for mass spectroscopic data, Mr. A. van Veldhuizen for his advice on 'H NMR spectra and Mr. W.Ch. Melger for his advice on glc measurements.

REFERENCES 1. a. b. c. 2a. b. 3a. b. c. d. 4. 5a. b. 6a. b. 7:: b. c. 8a. b. 9. 10. 11. 12. 13. 14. 15.

For recent reviews see: D.L. Boger: Tetrahedron, 39, 2869 (1983). D.L. Boger: them. Rev., 86, 781 (1986). D.L. Boger and S.M. Weinreb, "Hetero Diels-Alder Methodology in Crganic Syntheses", Academic Press, New York, 1987, p. 300. A.T.M. Marcelis and H.C. van der Plas: Heterocycles, 23, 683 (1985). A.T.M. Marcelis and H.C. van der Plas: J. Heterocyclic Chem., 24, 545 (1987). H. Neunhoeffer and G. Werner: Ann. Chem., 1190 (1974). V.N. Charushin and H.C. van der Plas: Tetrahedron Lett., 23, 3965 (1982). A.T.M. Marcelis and H.C. van der Plas: J. (kg. Cbem., 51, 67 (1986). D.A. de Bie, G. Geurtsen and H.C. van der Plas: J. &g. Cbem., 51, 71 (1986). H. Neunhoeffer and G. Werner: Ann. C&em., 761, 39 (1972). G. Seitz, L. arge and S. DIetrtch: Tetrahedron Lett., 26, 4355 (1985). G. Seitz, S. Dietrich, L. Gb'rge and J. Richter: Tetrahedron Lett., 27, 2747 (1986). E.C. Taylor and L.G. French: Tetrahedron Lett., 27, 1967 (1986). E.C. Taylor and J.E. Macor: J. Org. Chem., 52, 4280 (1987). E.C. Taylor and J.L. Pont: J. Crg. &em., 52, 4287 (1987). D.L. Boger and R.S. Coleman: J. Org. Chem., 49, 2240 (1984). D.L. Boger and R.S. Coleman: J. Org. Cnem., 51, 3250 (1986). D.L. Boger and R.S. Coleman: J. Am. aem. Sot., 109, 2717 (1987). A.E. Frlssen, A.T.M. Marcel16 and H.C. van der Plas: Tetrahedron Lett., 28, 1589 (1987). T. bjima, H. Takeshiba and T. Ktnoto: Heterocycles, 12, 665 (1979). A.E. Frissen, A.T.M. Marcelis, G. Geurtsen, D.A. de Bte and H.C. van der Plas: Reel. Trav. Chim. Pays-Bas, 106, 547 (1987). E.C. Taylor, C.P. Tseng and J.B. Rampal: J. (kg. (hem., 47, 552 (1982). G.W.H. Cheeseman: J. Chem. Sot., 242 (1960). G. Eglinton and M.C. Whiting: J. aem. Sot., 3650 (1950). J.E. Macor: Ph.D. Thesis. Princeton Untversitv. 1986. 297. H. Sliwa: B_~ll. Sot. (II&. Fr., 646 (1970). *' ’ R.C. Ellingson and R.L. Henry: J. Am. Chem. Sot., 71, 2798 (1949).