B U L L E T I N D E D ' A C A D É M I E P O L O N A I S E D E S S C I E N C E S S é r i e des sciences chimiques Vo lume X X V , No. 7, 1977

ORGANIC CHEMISTRY

I

Synthesis and Configuration of 1,3-Dibenzyl-2-phenyl-5-nitro-hexahydropyriinidine *)

by

Hanna PIOTROWSKA, Wojciech SAS, Tadeusz URBAŃSKI

Presi-nted by T. URBAŃSKI on February 19, 1977

Summary, cis-],3-Dibenzyl-2-phenyl-5-nitrohexahydropyrimidine (2) was obtained by reduction of l,3-dibenzyl-2-phenyl-5-nitro-l,2,3,4-tetrahydropyrimidine (1). Deuteration of cis-2 at C-5 proceeded without change of configuration. Isomer trans-2 was formed by equilibration of cis-2 in benzene.

Recently we have described the preparation of 2-substituted derivatives of 5-nitro-l,2,3,4-tetrahydropyrimidine [1]. In another paper we reported the reduction of 5-nitro-l,2,3,4-tetrahydropyrimidir.es (unsubstituted in position 2) with sodium borohydride to the corresponding 5-nitrohexahydropyrimidines [2]. Now we tried to reduce in a similar way the 2-substituted 5-nitrotetrahydropyrimidines. These attempts were successful only in the instance of l,3-dibenzyl-2-phenyl-5-nitro-l,2,3,4--tetrahydropyrimidine (1) which gave the corresponding hexahydro compound 2 in a good yield.

0 2 N C H 2 C 6 H 5 0 2 N C H 2 C P H 5

^ H '

f C 6 H 5 N C 6 H 5

с н 2 с 6 н 5 C H 2 C 6 H 5

cis-2

Scheme 1

1 H N M R spectrum of compound 2 (Fig. 1 ) indicates that the reduction gave only one isomer of 2 of the eiî configuration. The signal of H-5 proton is an almost regular quintet of the width W=14.3 c/s. The shape of this signal is very similar to that of H-4 observed in the spectrum of m-l-t-butyl-4-nitrocyclohexane in which the nitro group is axial [3]. The N M R spectrum of 2 lacks long-range coupling CV) of the proton H-2 with equatorial protons in positions 4 and б (protons H-2, H-4e and H-6e do not form planar W [4]). Such a long-range coupling was re­gistered by us in the spectra of the derivatives of 5-nitrohexahydropynrmdine

*) Part C X X I l l in the series: Chemistry of Nitroparaffins.

[519]

520 H . Piot rowska et al.

containing no substituent in position 2 ([2], spectrum 1). These facts indicate that compound 2 formed in the reduction reaction has the cis configuration, while the preferred conformation is that with the axial nitro and equatorial phenyl group.

( с н 2 ) с

Fig. 1. ' H N M R spectrum of trans-2 in ССЦ (a), and of 2-5-d in ССЦ (b)

с—isomer ш , /—isomer trans

The formation of small amounts of the trans isomer which could be lost by purification of the reaction product should not be excluded either. However, the exchange of H-5 into deuterium in compound 2 gave only isomer cis of unchanged

N 0 2

N ^ DME ,D20 ,N 'CC2H 5 ) 3 ^ D -N ^ C 6 H 5

\

cis -2

г ч | - Л / С 6 Н 5 \

cis - 2 - 5 - d

Scheme 2

configuration. The exchange reaction was carried out in a mixture of 1,2-dimethoxy-cthane (DME)-deuterium oxide. The structure of compound 2-5-d was confirmed by ' H N M R spectrum (Fig. 1).

l,3-Dibenzyl-2-phenyl-5-nitro-hexahydropyrimidine 521

We found that the trans isomer of compound 2 can be formed by heating cis-2 in benzene solution in the presence of triethylamine. The mixture of isomers thus obtained contained ca. 65% and 35% of isomers trans and cis, respectively. The isomer ratio was established by integration of the H-5 proton signals. However, we could not investigate the solvent dependence of the equilibrium because of low stability of compound 2 which partly decomposed during the equilibration process.

H

trans-2 65%

The N M R spectra of isomers cis and trans are shown in Fig. 2. The spectrum of isomer trans-2 shows the signal of H-5 proton of the width W =29.6 c/s (in the spectrum of //'o//.v-l-t-butyl-4-nitrocyclohexane the signal of H-4 proton is of the width of 30 + 0.5 c/s [3]). This indicates that in trans-2 the nitro group occupies an equatorial position.

Fig. 2. ' H N M R spectrum of 3 in C F 3 C O O H x

These results show that polar solvents able to form hydrogen bonds (eg. D M E - D 2 0 ) stabilize the isomer with the axial nitro group while in nonpolar solvents (benzeze) the isomer with the equatorial nitro group is preferred. This confirms our previous finding concerning the influence of the solvent on con­formational equilibrium of the derivatives of 5-nitrohexahydropynmidine unsub-stituted in position 2 [5].

c i s -2

35%

Scheme 3

522 H . Piotrowska et al.

Experimental

' H N M R spectra were measured on a Jeol spectrometer J N M M H 1 0 0 at 3 1 ± 1 °C using T M S as internal standard.

The preparation of compound 1 was described previously [1].

Preparation of cis-l,3-dibenzyl-2-phenyl-5-nitrohexahydropyrimidine (ci.s-2). To a solution of 1.95 g (0.005 m) of compound 1 in 40 ml of ethanol cooled to 0 °C 0.15 g (0.004 m) of sodium borohydride was added with stirring. The temperature of the reaction mixture was kept constant at — 5-0 °C. After ca. 0.5 h a white precipitate began to separate. After 2 h another 0.15 g of sodium borohydride was added and the stirring was continued for 2 h. Then the solution of 7 g of ammonium chloride in 30 ml of water was added, and the whole was stirred for 0.5 h. The white precipitate of cis-2 was washed with water, then with cold methanol, dried in vacuum over phosphorus pentoxide, and crystallized from carbon tetrachloride. Yield 60-70%, m.p. 147-149 °C.

Analysis: for C 2 4 H 2 5 N 3 0 2 calc: 74.4% C ; 6.5% H ; 10.9% N ; found: 74.4% C ; 6.4% H ; 11.0% N .

Deuteration of cis-2. 0.1 g of compound cis-2 was dissolved in 10 ml of dry 1,2-dimethoxy ethane (DME) , 3 ml of deuterium oxide and 3 drops of tricthylamine were added, and the solution was left at room temperature for 72 h. Then D M E was evaporated in vacuum, the precipitate filtered off, and dried in vacuum over phosphorus pentoxide.

Equilibration of cis-2. The solution of 0.8 g (0.002 m) of cis-2 in 15 ml of benzene and 0.1 ml of tricthylamine was refluxed for 1.5 h. After that time the solution became yellow. The solvent was evaporated in vacuum, and the residue crystallized from carbon tetrachloride.

INSTITUTE O F O R G A N I C C H E M I S T R Y A N D T E C H N O L O G Y , T E C H N I C A L UNIVERSITY. K O S Z Y ­K O W A 75, 00-661 W A R S A W

(INSTYTUT CHEMII I T E C H N O L O G I I O R G A N I C Z N E J , P O L I T E C H N I K A W A R S Z A W S K A )

R E F E R E N C E S

[1] H . P i o t r o w s k a , W.Sas , T . U r b a ń s k i , Roczniki Chem., 51, 483 (1977). [2] — , — , — , ibid., 47, 1233 (1973). [3] A . C . H u i t r i c , W. F .Trager , .1. Org. Chem., 27, 1926 (1962); H . F e l t k a m p , N . C . Frank­

l i n , J. A m . Chem. Soc, 87, 1616 (1965). [4] M . B a r f i e l d , B. C h a k r a b a r t i , Chem. Rev., 69, 757 (1969). [5] H . P i o t r o w s k a , W.Sas , T . U r b a ń s k i , Roczniki Chem. [in press].

Г. Пётровска, В. Сас, Т. Урабньски, Синтез н конфигурация 1,3-дибс1Пил-2-фенн.1-5-нн1ро-гексагидропиримидина

Со:ержание. Получен (/иг-1,3,-дибензоил-2-фенил-5-нитрогслсагидропнримид1ш (2) путем восстановления 1,3-дибензил-2-фенил-5-нитро-1,2,3,4-тетрагидропиримидина (1 ). Дсутери-рование цис-2 при С-5 происходило без изменения конфигурации. Изомер траис-2 путем эквилибрации изомера цис-2 в бензоле.