IMINE CHEMISTRY-11-t

A NEW ROUTE TO CYCLIC ENAMINONES FROM IMINES AND /i-

PROPIOLACTONE OR r,l-UNSATURATED ACIDS. THE PREPARATION OF ENAMINO-THIONES

R. SHARAN,L* .I. R. ~~~~~~~~~~~~ S. 0. OI.FSF~\ and S.-O. L.AWI.SSO\

Department of Organic Chem~strq. Unlverslty of .Aarhua. DK-8000 Aarhus <‘. Denmark

Aktract-- Immes, formed from cyclohexanone and primary aromatic and ahphatlc ammes. wcrc rcactcd with /I-propiolactone. acrylic, cro1omc. and methacrylic acids 10 gwe as main products hicyclic lactams. 3.4.5.6.7.Shexahydro-2-quinolinone. 2. and enaminones. 2.3.5.6.7.8-hexahjdro-4-quinolinone. 3. The enaminones 3 and a scrics of noncyclic cnaminoncs I I u’crc reacted wth 2.4-bls (4-melhox~phcn~l)-1.3.2.4- dilhladlphohphetanc-2.4-dlsullide. 9. a new thlatlon reagent. gnmg rhc corrcspondlnp cnamlno-thrones IO

and 12. rcspcctwly. Compound 2a wa:, also reacted with 9 giving N-phenyl-3.4.5.6.7.X-hexahydro-2- qumolmthione. 139. 360 MHz ‘H NMR and 90.25 MHz ‘.‘CNMR data arc reported for the compounds 2a. 3a and IOa.

Enamincs, derived from cyclohexanones, undergo smooth reactions with /I-propiolactone and Z./I- unsaturated acids to give as main products 1% oxocarboxylic amides’ in reasonable yields:

or -a 0 /

CH, -CH, -k!-N \

CH,=CH-COOH 0

Scheme I.

No acylation of the enamines was observed. Also certain enaminones were found to react in the same way to give N-heterocycles.’ As it is well known that imincs are in tautomeric equilibrium with their respective enamines. and thus can react as cnamines. we felt prompted to study the reaction ofimines with /I- propiolactonc and r.b-unsalurated acids.

This paper reports a new synthesis ofenaminones as well as enamino-thiones, There are known methods. using P,S,,,,’ ” for the transformation of enaminones into cnamino-thiones. but unfortunately the yields arc low. Another method. the reaction of dithiolium salts’ A with amines, also gives low to medium yields. Howcvcr. by using a new thiation reagent. 2.4-bis-(4- methouyphenyl)- 1.3.2.4-dithladiphosphetanc-2.4-di- sulfide.-9. the cnammones were smoothly transformed into the corresponding vinologous thioamides. enamino-thiones, which are useful for the preparation of thiopyrans’ ” and thiophcnes.”

The reaction between imines and /I-proplolactone gave as major products enaminones. 3. but also blcyclic Iactams. 2, were formed. The formation of 2 -- ---- ----- - ___-

+Part I see Ref. 12. *On lcave from The NatIonal Research Ccntre of Egypt.

Dokki. Cairo.

and 3 can best be rationalized b) a pathway Involving the enamine. which is known to be in equilibrium with the imme. As /I-propiolactone.‘3 4. can undergo both alkyl-oxygen and acyl-oxygen fissions. the blcyclic lactams. 2. and enaminones. 3. can be formed under elimination of water as shown in Scheme 2.

When imines were reacted with acrylic. crotonic, or 2-methacrylic acid. the major products were bicyclic lactams. 2. A protonation of the imine. which will exist as a “tight Ionpair” with the deprotonatcd acid in low- polar solvents (i.e. chlorobcnzene). IS expected. The “tight ionpair” may collapse giving an activated r./I- unsaturated ester. which can react with another imine in a Michael addition followed by intramolecular acyl-ouygen fission giving bicyclic lactam\ 2 and enaminoneh 3.

The reaction between N-(cyclohexylidine)-aniline. la and /3-propiolactone. 4. or acrylic acid. 5. gave N- phenyl-3,4.5,6.7.X-hexahydro-2-quinolinonc. Za. and N-phenyl-2.3.5.6.7.X-heyahydro-4-quinollnonc. 3a.

Compound la was also reacted with crotomc acid, 6. giving 4-methyl-N-phenyl-3,4.5.6.7.X-hcxahydro-2- quinolinone. 2b. and 2-methyl-N-phcnyl-2.3.5.6,7,X- hexahydro-4-quinolinone. 3b. and with 2mcthacrylic acid. 7. giving only 3-methyl-N-phcnyl-3.4.5.6.7.8- hexahydro-2-quinolinone,2c. IIue tosteric hindrance6 and 7 were expected IO give lower yields of products. This was only observed with 7. In the reaction between N-(cyclohexylidine)-4-chloro-aniline. Id. and /G propiolactone. 4. or acrylic acid. 5. the mam products were I\j-(4-chlorophenyl)-2.3,5.6.7.X-hcxahydro-4- qulnolinone. .3d, or N-(4-chlorophcnyl)-3.4.5.6.7.X- hexahydro-2-qumohnone. 2d. rcspcctivcly, but in addition, 2-(4-chloroanilino)-propionic acid. 8.” was isolated.

The formatlon of 8 is due to the reaction of4 or 5 with 4-chloroaniline. a hydrolysis product from the iminc, Id. which is more easily hydrolysed” than la. Finally. N-(cyclohcxylidinc)-propylamine. le. wa5 reacted with both 4 and 5 giving onlj r\;-(propyI)- 3.4.5.6.7.X-hcxahydro-2-quinollnonc.

3047

R. SHARANA cl al.

Scheme 2.

R

a: R=Ph d*: R=- -Cl e: R = n-propyl

*HesIdes 2d and 3d also 2-(4-chloroanilino)_proplonic acid. 8. was wlated

T;rblc I. Results of the reactlon between I and 4.56 or 7

I -H, 0

1 2 1 I: P-propiolactone, 1: acrylic acid, 6: crotonic acid, 1: 2-methacryllc acid

R R1 Ra R= Heaction Reaction Yield Yield compound time/h of 2 of

(%T (SC 3

a Ph H H H !! 6 12 60

a Ph H H H 1 6 65 10

b Ph H He He 6 22 40 30

c Ph ne H He 2 20 20 -0

de p-Cl-Ph H H H 4 3 0 50

d** p-Cl-Ph H H H 1 3 50 0

. II-PI. H H H 4 3 30 0

m II-PX. H H H 5. 3 35 0

. 18s of g w.r. isolated.

.* 40% of 8 we=. isolated

[mine chcmlstry II 3049

Tl~ic~ior~ o/ e~~umi~~~~~.s. It has been found that 2.4- bis(4-methoxyphenyl)-l,3,2.4-dithiadiphosphetane- 2.4-disulfide. 9. is a most effective thiation reagent for ketones,lh carboxamides,” -” eslers.22.23 S- substituted thionesters.” lactones,L’ lactams” and imides.2’

S

9 -

Because of the vinylogous effect enaminones show great similarities with carboxamides and lactams. The reaction of 9 with enaminones at room temperature was finished in less than 1 hr giving high yields of enaminothiones in most cases (Table 2 and 3). At elevated temperatures the yields are low probably due to polymerisation.’

Srr~rc~~rre md .spwrro.scop~~. All compounds were characterized by the means of MS, IR, ‘HNMR.

Table 2. Thiatlon of cyclic enaminones

R I?’ Yield ($)

l Ph H 95

b Ph ne 80

c p-Cl-Ph H 70

’ 3C NMR and elementary analyses. Compound 2a is known.‘” but no proofofstructure has been given. The compounds 3a and IOa are unknown. As illustrative examples the ‘H NMR and 13C NMR data of these three compounds are collected in the Tables 4 and 5. The assignments are made by selective decoupling technique.

It is surprising that only four allylic protons are observed. As seen from the ‘H NMR data the protons at C-S are shifted up-field. This is due to the

neighbouring phenyl group.

On prolonged standing in CDCI, solution a recorded 360MHz ‘H NMR spectrum of 2a also showed a resonance of the C-8 proton at 4.56ppm demonstrating that the following equilibrium exists:

A similar equilibrium is not observed for 13a.

IM’ERIMMTAL

The ‘H NMR spectra were recorded at 6OMHz on a Varlan A-60 spectrometer and the “CNMR spectra on a Varian UT-20 spectrometer. except for 2a, 3a, IOa and 1311 which were recorded at 360MHz and 90.25 MHz. respectively, on a Bruker HX36O spectrometer. TMS was used as internal reference and chemical shifts in a-values. CDCI, was used as solvent. IR spectra were recorded on a Beckmann IR-18A spectrometer. Elementary analyses were carried out by NOVO-mlcroanalytical Laboratory. NOVO

Industry AS. NOVO All& DK-2880 Bagsvzrd. supervised by Dr. R. F.. Amsler. SIlicagel 60 (Merck) was used for column chromatography. M.ps are uncorrected.

Srtrrrirlf mofc~ritrls. The imines la and I h were prepared by the condcnsatlon of the aromatIc amlne with cyclohexanone

Table 3. Thlation of non-qcllc enaminonclr

i? 3 2 n’-C-CH.C(Re)_N;“* ___, s R’-C-CkC(R’)_h”

HJ

R ’ II*

R' R' RJ R' Yield of 11 (96) lit.

H.P. a(C=S)/ppm

a no Ma H H 20.’ oil** 209.3

b ne Ma Ph H 63' 64 207.4

c Ph H -CH.(CH.),CH,- 580 128 213.0

d Ph H -CHa(Cll,),CHp- 92' 146 210.3

l Optimal eeparation procedure not yet found.

l * B.P. 0.8

12oY.

Imine chemistry II 305 I

Table 6. Physical and analytical data of bicyclic lactams.2, enaminones.3. and the correspondmg enammo- thrones

b/pm Analyses (%)

Comp. HPPC ‘Sc(c=o) Calc. (Found)

C H N Cl s

za 118 170.2 Known. lit .‘I

2i 101

zb oil

2 '35

c oil

d ‘31

24 97

ze 011

1 oa* 12: -

1Ob* 146 -

loco - '57

191.2 79.29 (79.12

7.49 7.50

6.17 6.13)

179.9 79.67 7.88 5.81 (79.44 7.80 5.69)

191.1 79.67 7.88 5.81

(79.27 7.90 5.69)

179.5 79.67 7.88 5.81 (78.45 7.88 5.58)

170.1 68.83 6.12 5.35 13.58 (68.48 6.16 5.60 13.58)

191.0 68.83 6.12 5.35 13.58 (68.87 6.11 5.39 13.48)

l;o.o 74.57 9.91 i.25

(73.60 ?.92 7.40)

210.7 74.07 7.00 5.76 t-3.1-

(73.26 6.99 5.67 l?.L?Hl

2~8.8 74.66 7.44 5.44 12.ir,

(73.86 7.52 5.32 12.29)

211.8 64.85 5.80 12 .;6 11.54

(63.43 5.91 11.97 1l.W)

l b/ppm “c(c=s)

Rt:FFHt.\(‘t:S

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