Derivatives and reactions of glutaconaldehyde—IX

DERIVATIVES AND REACTIONS OF GLUTACONALDEHYDl&IX SUBSITI’WION REK’I’IONS IN THE GLUTACONALDEHYDE MSIGNh4ENT OF !9I’RUCTURE OF A PREE GLUTACONALDEHYDE

ANION.

Compound

X

R

Compound

X

II

J

-

v c,

J

III

VI c

a

Cl

-

Vd

Cl

111 b

Br

-

VO

Br

III

J

-

Vf

J

Br

-

VII

a

c

IV a

-

VII

b

Br

V a,

VI a

-ocIIzcI13

VII

c

Cl

V b.

VI b

Br

-oClltCl13

VII

d

Br

‘Notrumofa~~irwavmarar.~d-‘HNMRapectn ‘Tbc umc4 vakm afa v8:Vta=3.s:I: Vb:VIb-3J;l: vc:VIc-3.o:l.

-C6HS -C6H5

-OCH2C1i3

Cl

cldomfom8teinDAlw,andxtmsofthetwo~v~ vI~obt&alinachcase,withtbcr8tiuv:VI=3:1. i!mmemcouldnot mcaaumdby’HNMRlbemixtnmof besqmmtcdbyrepeotedaya-orbytic ~yercbromatog@ly,umstbc~~fortbc~ mixture of tbc 2- sod 4Me suktituted &tama@hydc bauoykstm. h4a&imltofthedl-tmJu~to~proQcts dewibaiinScbuncIfolbwedfromtbc’HNMR spcctm8ndtheuV~(lolc~oftbes8mclordet

-C6HS

-llC112C115

Cl

rcyLtionWUaniadOUtWithtbClCSSrwctiveOthyl

-oc112cI13

Cl

1V b

&&msuhsobginedprcviouaiy.‘Hm;tvsr,whentk

R

-C6H5 -C6H5

1525

Ih!htivesMd~of~yAeLn Tab&I. ‘HNMRpmmctcd

Yh-IVb JilllIz

on DMSOd,; II. V.-VIII in CDCI,

mcscvahn!fwexcmauun?4itromtbecomrpoodial peneyl cars (R = C&J.

A rclaively concdnd

sohltial

isstabkt for30mill

at -m. Howcvu, whmthiaexpciml!nthrepatedlvith 8V~dihlk8OhlthlatfOOlDtempaotun-iIletbrwl

O&

8

~2HSO+c
I

nlle sotll abwly d8lkcm.

“ovwo

of gtatscoar#ebyde MI wit!l1 A,=3osnm (455). tdeapluxbyaimpkpmmbonoftheutimduetothe lugcexcu8ofCo2,whmthefactilmhf~lbwdwith uvitiss4altlmtthcmctioainneiutyrcvaaibkwitb isobatk pointa ill tbc uv spectnm -nIlIs no iIltc!fllledieh~dthcA,-304am(459)1thcaune ~npatedbycir&lwn=far~dtkrnioa mtedwithbydrochbric8cid.-~ estenarnioar

VIII

arcmtplwentastheabso&mofthcknownd

Tabb.2

“C NMRchanhi shifts’

I

:m-

I

pound

c

I

C2

Carbon nusber cs IC4

0 CS

II

183.55

92.22

166.79

111~

195.69 106.69

17s.10

IIIb

195.69

98.56

IIIC

186.01

76.73

179.71

96.55

I -l-o-

I

Other

I

175.69

.

Nb

176.74 106.10 146.56 106.10 178.74

Vd

184.91 KU.26

VO

185.57 126.24 145.15 112.80 147.66 162.44 l'f;.;f$, 150.40 Co . m, 134.56 C I. I P

I 141.64 110.59 147.23 162.56 ;;;A; $, 130.47 Co ‘ m' 134.56 c* II

Vf

187.25 106.44 146.07 116.50 / VIIl _lIS.SJ 1311.96 139.11 112.60 143.46 151.13 ;;.f;-CH2-

I vrrb

I

l

-

3

185.63 125.01 144.50 100.64 144.50! 1,1.26! 1":;:M~; I

VIIC

185.23 lSO.40 lS9.37 llS.83

VIII

195.69 124.61 145.53 102.07 nm

L

d

0 0

0 =

DOD

00

~~ D Ii

spwing 88 wall 8s the p&s due to Iit 8t 5.14 disap pc8rs.t ‘C NMR unarms that we do have tbc same compom&~thrtshmadpakrucsl!eaat183.8ppm. (C-l and c-s), 162.4(C-3) and 114.0(C-2 ud Cd). The vduafdrc-1,c38adc-3ueidenwwitbtbc~ lqmrtaif5rths~“bat~~fromtivahlc0f l~~~f~C-2~C~.

0

0 -.==+

Hti

w

0

D D 0.

-I 0

e

D

s

0.1

'8

\

J.dL Dti:

CD0

HI

m.p. OC 88-90

70

d>lOO

369 23s 218

4.64 2.46

d>lOO

567.5 231.0

4.69

6,100

-Isa

Vf

I

4177 3.79

4.68 3.43

d,lOO

56

370,o 225.0

loge

372.0 237.5 222sh

--

vo

xmu

d>lOO

_ IIIb

IJV absorntion

in 96 t 1EiOll

T

(Jom-

Vd

:z vb,

i VIb

\ 55

4.55 3.38

379.0

4.62 3.57

126-128 b

20

91-94 8

370.0 2a5.5

3.2s 4.44

39

88. S-90

209.0 367.5

I 3.15

a

2

69

VIla

41

74-7a a

+

84-85 a

v11t

52

4

4.20

VIIC

66

370 292.5

4.15 3.95

I

2.61 4.28

78.5-7s

114-116 b

VIId

65.

98-100 b

Recrystallized

from,a:

b:

toluens

c:

mothylcyclohcxane

I

-I---! 307.5 287sh 250

a

131-141 e

OC 3.18 4.51 3.9’

127-128 b

W obsorptiwl

8.P.

36a.a 29a.a 238.0

3.70

379.0 237.0 221sh 237.5 215sh

iOld

pound

cyclohoxano

!

[

1529

Derivatives and reactionsof glutaconaldehyde-IX

~CHO 10%

-,e

x

H,S +---steam destill.

°VJJO. ,,\'

'I

\,..'\;,~l \~.,.' '. ,r.'

Ilia X=CI IIlb X= Sr

yield, and with some confusion concerning the structure of the starting material. The saIt IlIa have been described by Zincke," Ince" and Dieckmann." Dieckmann'? concludes that it is the sodium saIt of chloro glutaconaldehyde which give rise to thiophene - 2 - carboxaldehyde, and finally Dieckmann" prepared and reported the m.p. 127° for a benzoyl derivative of the saIt IlIa, this has been fully confirmed by us, compound Yd. The correct structure of some isomers described by Hantzsch have been assigned by Moye and Steinhell" and by Burgstahler et al." On the basis of our experiments it can be concluded that the correct reaction scheme for the preparation of thiophene - 2 - carboxaldehyde and the 3-halogeno pyridines is the one shown above. EXPERIMENTAL

Microanalyses were carried out at the microanalytical Department of the University of Copenhagen by Mr. P. Hansen. Instrumentation. IR: Perkin Elmer 457. UV: Beckman ACTA III. IH NMR: Jeol JNM-PMX 60, 13C NMR: Jeol FX 60. M.p. Buchi apparatus(uncorrected). The sodium salt of 2-chloro-5-hydroxy-trans-2, trans-4-pentadienal (IlIa). The Na salt of I, (3.11 g, 0.02 moles) was stirred inwater(100 ml,00). Liquid Ch collected ina freezing trap,(0.8ml) was allowed to evaporate inthe course of j min into the glutaconaldehyde soln. The orange-yellow mixture was stirred for 5 minuntil the smell of Ch disappeared and it was then extracted with ether (2 x 200 mI). The yellow ether phase was dried with Na2SO. and concentrated (100 ml) in vacuo. The ether phasethen '\vas cooled on an icebath and under vigorous stirring NaOH in MeOH was slowly added (16ml; 0.5M), the pH of the mixture rose from 3.5 to 9.6.The lightbrown Na-salt, which precipitated was collected and washed with dry ether, yield (0.81 g). The crude product was purified by reflux for 3 hr in MeOH with activated carbon (1g of salt/20ml of MeOH). The mixture was filtered hot and on addition of dry ether (200 mi/20 ml of filtrate) to the filtrate, the Na-saltprecipitated,t as the trihydrate. The sodium salt of 2 - bromo - 5 - hydroxy - trans - 2, trans - 4 - pentadienal (IlIb). The Na-salt of glutaconaldehyde (6.24 g0.04 moles) was dissolved in water (200 ml, 0°) and Br2 (1.7 ml0.033 moles) was added under vigorous stirring. The red-orange mixture was stirred for 5 min and then extracted with ether (4x 300 ml). The yellow ether phase was treated as described for IlIa. The brown crude product (dihydrate) which was pure enough for most purposescould be purified as described for IlIa. 2 - lodo - 5 - hydroxy - trans - 2, trans - 4 - pentadienal (II). The K-salt of glutaconaldehyde (1.36 g, 0.01 mole) was dissolved in icewater (25 mI). Under vigorous stirring a soln of h (2g) and KI (16g) in 25ml water was slowly added.The temp.was kept at 0° by occasional addition of crushed ice. The resulting orange suspension was quickly extracted with ether (2 x 125 mI). The cooledextract was treated withactivatedcarbon,dried (Na2S0.) and filtered. The yellow-orange filtrate was concentrated in vacuo with the temp. below 5°, this gave orange crystals m.p. 88-90°. Baumgarten' reported m.p.89". Unstable (1'1/2< 10min at 20°). tThese glutaconaldehyde salts usually contains small amounts of inorganic material.

(NH.),HPO. steam

deslill.

17-31%

The sodium salt of 2 - iodo - 5 - hydroxy. trans - 2, trans - 4 pentadienal (IlIc). A soln of II from 1.36 g glutaconaldeh yde potassium salt in ether was treated as described for IlIa. The browncrude product was dissolved in MeOH (25 ml/g) activated carbon was added and the mixture was stirred at 40° for 5 min and then filtered. On addition of dry ether to the yellow filtrate (100 ml ether/25 ml filtrate) the light yellow Na-salt precipitated, as the monohydrate yield 1.3 g. The sodium salt of 2,4- dibromo . 5 - hydroxy - trans - 2, trans ·4 - pentadienal (IVa). The Na-saltof glutaconaldehyde (3.12 g 0.02 moles) was stirred in 100 ml icewater and Br2 (1.8 ml) was added. The nearly colourless soln was stirred 30min at 0°, and then extracted with ether (3x 200mI). The combined lightyellow ether phase was dried with 1'1 a2S0. filtered and concentrated in vacuo (50ml). To the ether soln NaOH in MeOH (I M) was added under vigorous stirring and cooling in an icebath until the pH of the suspension remained at 9. The yellow Na-salt was collected and dried in vacuo at room temp. The almost pure compound could be further purified by heating under reflux in MeOH withactivatedcarbonfor 5 minfollowed by reprecipitation with dry ether. The sodiumsalt of 2,4- dichloro • 5 • hydroxy· trans - 2, trans - 4 • pentadienal (IVb). Ch (about 2 ml of fluid Cl2 at -34.6°)was slowly added to a well stirred soln of glutaconaldehyde sodium salt (3.12 g = 0.02 moles) in water (100 ml, 0°) until the colour of the soln turned pale yellow. After stirring for 2 min the soln was extracted withether (3 x 100 ml). The ether extract was treated as described for compound IVa.This gave the title compound as the dihydrate. General procedure for the preparation of the halogen substituted O-ethoxy carbonyl - 5 - hydroxy - trans - 2, trans - 4 pentadienal. Va,b, c, Via, b, c, VIla, b. 0.005 moles of chloroformic acid ethyl ester was mixed with 0.005 moles of the halogenated salt in 20ml of DMF under stirring and cooling. After 10min the mixture was added to 200ml icewater. A light brown ppt of the O-ethoxy carbonylcompound was isolated. Recrystallization of the crude product from cyclohexane gave unstable colourless needles. (Can be stored in the freezer at -20° for 2 weeks). Analyses: Va, Via (Found: C, 46.75: H, 4.52; CI, 17.25. C.H90.CI requires: 46.96: H, 4.43; CI, 17.33%). Vb, Vlb (Found: C, 38.85; H, 3.50; Br, 32.45. C.H90.Br requires: C, 38.58: H, 3.64; Br, 32.09%). Vc, Vic (Found: C, 32.45; H, 3.09; J, 42.85. C.H90.J requires: C, 32.45; H, 3.06: J, 42.86%). VIla (Found: C, 40.35; H, 3.38; CI, 29.92. C.H.0.CI 2 requires: C, 40.19; H, 3.37; CI, 29.65%). VIlb (Found: C, 29.35; H, 2.35; J, 48.60. C.H.0.Br2 requires: C, 29.30: H, 2.46; Br, 48.73%). r-

General procedure for the preparation of the 2- or 4-halogen substituted 0 - benzoxy - 5 • hydroxy - trans - 2, trans - 4 pentadienals. Vd, e, I, VIlc and VlId 0.005 moles of benzoyl chloride was added to 0.005 moles of the halogenated Na-salt in 20ml pyridine under vigorous stirring and cooling in an icebath. After 15min the mixture was poured into 200 ml icewater under stirring and after 0.5hr the resulting brown ppt was filtered off and dried in vacuo (CaCh). The crude product could be recrystallized from methylcyclohexane or toluene,or it could be sublimed in vacuo at temps near the m.p. Analyses: Vd(Found: C, 60.85; H, 3.65; CI, 14.78. C12H 90 3C1 requires: C, 60.90; H, 3.83; CI, 14.98%). Vf (Found: C, 43.90; H, 2.69; J, 38.80. C12H90J requires: C, 43.92: H, 2.77: J, 38.68%), VIlc (Found: C, 53.10; 2.93; J, 26.26. C12H.03C12 requires: C,