Transformation of compounds containing C-N bonds on heterogeneous catalysis

Journal of Molecular Catalyszs, 49 (1988) 103 - 111

103

TRANSFORMATION OF COMPOUNDS CONTAINING C-N BONDS ON HETEROGENEOUS CATALYSIS PART IV*. HYDROGENOLYSIS OF /3-LACTAMS ON RANEY NX A NEW METHOD FOR THE PREPARATION OF 1,3-AMINOALCOHOLS MIHALY BART6K, Department

LAJOS GERA, GYORGY

GONDOS and WRPAD MOLNAR

of Orgamc Chemzstry, J&sef Attda Unrverslty, Steged (Hungary)

(Recewed January 18,1988,

accepted March 18,1988)

The transformations of the condensed-skeleton fl-lactams (azetldin-2ones) 1 - 4 were studied under various reductive condltlons. On the action of a complex metal hydride, selective formation of azetldmes occurs. A new heterogeneous catalytic method 1s reported, which 1s suitable for the preparation of cychc 1,3ammoalcohols m the presence of Raney Nl m hquldphase hydrogenation On a Nl on Cab-O-S@ catalyst m a flow reactor, 1 ISconverted to the carboxyhc acid amide 9 with high selectmlty.

Introduction The unportance of /3-lactams (azetldmones) 1sconfirmed by the reviews that have appeared on thev synthesis and chemistry [2 - 71. The theoretical and practical sgmflcance of /3-lactams 1s well illustrated by consldermg the pubhcatlons m a narrow field (their synthesis and hydrogenation), e g m 1985 [8 - 121. The reduction of p-lactams with hydmde reagents has been studied widely [8 - 211. Dependmg on the reagent and on the posltlons of the substltuents on the /3-lactam ring, 1,3-ammoalcohols and azetldmes may be prepared As concerns catalytic rmg hydrogenolysls of p-lactams containing a substltuent on the N, acid amides are formed as a result of cleavage of the l-4 bond on Pd/C [22 - 251 and on Raney Nl [26,27] (Scheme 1). Surpmsmgly, m spite of this, a number of literature reports [ 19,20,28, 291, mcludmg recent pubhcatlons, describe hydrogenolysls m the presence of Raney Nl as mvolvmg cleavage of the l-2 bond with formation of ammoalcohols, whereas the reports to which they refer [25,26] clearly mention acid amide formation. On this bass, and smce we found no literature reports concemmg experunental observations on the metal-catalysed hydrogenolysls of N*For Part III, see [ 1 ]

0304-5102/88/$3

50

@ Elsevler Sequola/Prmted m The Netherlands

104

R3

-c

b

M/H

a

R3 CHzOH NHR

Scheme 1

unsubstltuted /3-lactams, we have studied the transformations of ahcychc condensed @-lactams under various reductive condltlons. The auJl of our studies was to develop a stereospeck syntheses for the 1,3ammoalcohols 5 -8. Results and discussion We mvestlgated the transformations of the p-lactams 1 -4 by means of three drfferent reductive procedures. The observed expenmental results and reaction dvectlons are shown m Table 1 and Scheme 2. (1) In the presence of the complex metal hydnde m the liquid phase, the reaction results m the selective formation of the correspondmg cycloalkane condensed azetldmes, 1 e ammoalcohols are not formed from the condensed Nunsubstituted p-lactams 1 -4 m the same way as from the similar, but not condensed p-lactams.

H a R-N/EtOH

ether,reflux

Scheme 2

(CH2)n x

NH H

13-16

1 2 3 4

fl-lactam

55 57 68 64

Yield of azetldme

Method (I) LIAlHa/ether

52 51 40 20

89 75 88 75

Ammoalcohol

11 25 12 25

Carboxamide

Method (II) Raney Nl/ethanol, 150 “C, 70 atm ~ Conversion Selectivity

Transformations of P-lactams 1 - 4

TABLE 1

80 50 90 88

Conversion

95 70 30 15

Carboxamide

Selectivity

NI on Cab-O-&l@

70 85

Carbonitrile 35 30 52 57

Conversion

Raney N1

Method (III), flow reactor, 300 “C, 1 atm

95 65 19 17

Carboxamide

Selectivity

81 83

Carbonitrlle

106

(11)Of the various metals (Pd/C, PtOz, Raney Ni) applied under hydrogenation conditions at elevated temperature m a high-pressure autoclave (150 “C, 70 atm, 12 h), only Raney Ni proved active. Hydrogenolysis of the l-2 bond (cleavage a) leads to ammoalcohols as the mam product, while cleavage of the l-4 bond (cleavage b) results m the formation of acid amides. The tabulated expelvnental data reveal that the conversion decreases as zz mcreases; the selectivity of ammoalcohol formation lies m the range 75 - 89% In spite of the forcmg conditions of the catalytic hydrogenolysis, eplmerlzation did not occur, z e the correspondmg czs-ammoalcohols can be obtamed from the czs-/3-lactams. (m) On supported Pd and Ni catalysts and on Raney Ni m a flow reactor at atmospheric pressure and at high temperature (250 - 350 “C), the transformation agam occurred only on the Ni catalysts Under the experimental conditions apphed, Ni/Cab-O-S@ proved more active. 1 is transformed with hzgh selectivity to carboxyhc acid amide 9, while nitriles are formed m the reactions of 3 and 4. The catalytic hydrogenolyses occurrmg under the two different reaction conditions ((11) and (in)) suggest a mechamsm mvolvmg parallel reactions. The stoichiometric formation of the ammoalcohol and of the acid amide requires the uptake of 2 and 1 mol hydrogen, respectively. Atmospheric pressure of hydrogen and the elevated temperature applied m the flow reactor ensure a lower surface hydrogen coverage that is sufficient for only the latter process to take place. The higher temperature favours cleavage of the less polarized l-4 bond, z e the occurrence of the process requlrmg the higher activation energy. Clear-cut data concernmg nitrlle formation cannot be obtamed, and a parallel formation of the acid amide and the rutrile cannot be excluded, as opposed to a consecutive reaction, m spite of the fact that the acid amides may be converted to mtrlles m low amounts under expelvnental conditions identical to those of thezr formation.

Conclusions Condensed-skeleton /3-lactams, which can be prepared from olefins through simple (2 + 2) cycloaddition with chlorosulphonyl isocyanate [7,8], may be utilized m many ways as starting compounds for the synthesis of various types of compounds through different reductive methods: (1) L1A1H4 reduction of the correspondmg cycloalkane-condensed /3-lactams 1s a selective method suitable for the preparation of condensedskeleton azetidmes. (2) A new heterogeneous catalytic procedure has been discovered for the preparation of 1,3ammoalcohols via hydrogenolysis of p-lactams not contammg a substituent on the N (azetidmones) on Raney Ni under high pressure; the selectivity is 75 - 89%. Although the method demands vigorous

107

expervnental condrtrons and selectwrty 1s not lOO%, the procedure 1s consrdered to be of apprecrable importance Stereospecrfrc syntheses of the ahcyclic 1,3ammoalcohols by known methods can be attained only through 10 - 12 reaction steps [ 30 - 321, while the syntheses of 8, for instance, was unsuccessful. With the method described m the present paper, startmg from cycloalkenes, cu-1,3aminoalcohols can be obtained m merely 2 steps. Further, although a small amount of acid amrde may also be formed m the procedure, this can be separated m a very simple way (see Experunental section). The srgmficance of the method 1s mcreased by the fact that metal hydride reduction does not lead to ammoalcohols with /3-lactams of thus type. (3) Under drfferent expenmental condrtlons, Nl catalyses the selective transformatron of 1 to the acid anude 9, while the reactions of 3 and 4 lead to the correspondmg mtnles

Experimental section The fl-lactams were prepared m accordance with literature methods [ 33,341. The products were rdentlfred on the basis of therr NMR spectra TABLE

2

Physlcal data of fl-lactams azetldmes (13 - 16) Compounds

1 2 3 4 5 6 7 8 9 10 11 12 13e 14e 15e 16e

(1 - 4),

ammoalcohols

(5 - 8),

carboxamldes

Bodmg pomt

Meltmg pomt

(“C (mmHg))

(“C)

106 151118 145 -

108/2 (81. 15313 12012 14812 9512 87 - 9213 96 - 10013 106 - 11113

60 - 65130 76 - 77130 97 - 102130 114 - 116130d

(9 - 12) and

8412) [ 351

80 - 82*, (82 - 83) [31], 125 - 127b 134 - 135c, (133 - 134) [ 301,148 - 150b 150c, (149 - 150) [32], 167b hygroscoplcC 198 - 201b 174, (177 - 178) [36] 187 - 189, (185 - 186) [37] 200, (195) [38] 201- 203, (192 - 196) [39] 166 - 167b 131b 135 - 136b 165 - 166b

aHydrobronude bRcrate CHydrochlor~de dNew compound, anal (C15H~cN407) C, H, N eThe results of MS mvestlgatlons of azetldmes can be found m 1401

108 TABLE 3 Gas chromatographlc

data (column

Compound

1 2 m 15% OV-17, Chromosorb W) Retention time (s)

Temperature (“Q/flow rate of carrier gas (ml mm-‘)

1 5 9

200 105 170

200130

2 6 10

350 125 265

200130

3 7 11 Cycloheptane carbomtrlle

480 265 400 115

4 8 12 Cyclooctane carbomtrlle

560 260 420 110

200150

200/100

(JEOL C 60-HL mstrument, tetramethylsllane as internal standard), with a GC method, with the use of reference substances (Carlo Erba Fractovap Mod. G instrument), and m the form of derlvatlves The physrcal data on the compounds are given m Table 2, the GC retention data m Table 3, and the NMR data m Table 4. Reductzon wzth complex metal hydrzde (Method (i)) A solution of 0.05 mol azetldmone m 100 ml absolute ether was added dropwlse durmg 0.5 h to a refluxmg solution of 0.125 mol LiARI, m 400 ml absolute ether. The reaction mixture was refluxed for 50 h during strrrmg, and then decomposed with the calculated quantity (15 ml) of water durmg cooling with icewater. The precipitated alummmm hydroxide was filtered off, the solution was extracted with ether, the combmed ether solutions were dned with sodium sulphate and evaporated to dryness, and the residue was d&&d at reduced pressure.

Transformatwn on Raney Nz zn a hzgh-pressure autoclave (Method (zz)) Ten mmol /3-lactam was dissolved m 30 ml ethanol, and 8 mmol Raney Nl was added as catalyst. The reaction mrxture was shaken for 12 h m a stamless steel autoclave at 150 “C and an mitral hydrogen pressure of 70 atm. After completion of the reaction, the catalyst was filtered off and the solution was evaporated to dryness; 25 ml absolute ether was added to the resultmg oily product. The acid amrdes 9 - 12 separated out as white crystals msoluble m ether, and were filtered off; the filtrate was evaporated to

3 69(dd),3 3 72(d) 3 55(dd)

CH~(A.B)

76(dd)

2 85(b) 280(b) 6 70(b)

3 63(t)

NH2

3 64(t) 3 75(b)

OH

(6 - 8)a* b

41 05

c2

53 78 43 74 52 70 4204

50 41

Cl

13C NMR

67 50 6458

65 95

CH20H

JLX, =41 Jw, = 8 3 JU, = 8 2

J1,2 = 4 1 J1,2 = 4 05 J1,2 = 5 05

JI,xa=41

(Hz)

JI,x, = 4 05 J1,x, = 5 1

Couplmg const

n=2

n=3

n=4

6

7

8

iLn2$l

aThe free ammoalcohols were obtamed from their plcrates, and the NMR data on the bases are given bAll spectra were taken m CDC13, chemical shifts are given m ppm with external tetramethylsdane as reference d, doublet, dd, double doublet, t, tnplet, dt, double tnplet, b, broad The spectra were recorded on a Varlan XL-400 MHz instrument CThe czs-assignment of compound 8 was based on the spectral data These mdlcate that the ammo group IS pseudo-axml, and hence proton HI 1s pseudo-equatonal Thus, It displays an eclipsed equatorial-equatorml couplmg w&h the X-protons of 8 2 Hz, and an equatorlal-axial couphng of 5 1 Hz The 5 05 Hz couplmg constant of the HI and proton H2 also mdlcate equatorial-axial couplmg, because the proton Hz I axial, and consequently the CH20H group can only be equatorud Therefore, the ammoalcohol (8) has CIS conflguratlon As concerns the posltlons of the substltuents, the 8-membered rmg IS probably m a twisted boat conformatlon

3 25(dt)

3 34(dt) 2 95(dt)

7 8c

Hl

‘H NMR

6

Ammoalcohols

‘H and 13C NMR data of cychc 1,3-ammoalcohols

TABLE 4

110

dryness. The oily residue was a mixture of the startmg azetldmone and the ammoalcohol formed, and did not contam acid amide, as proved by GC. Various methods were used to determine the azetldmone/ammoalcohol ratio and to separate the two compounds: (a) A stock solution was prepared from the dry residue with ethanol, and the content of ammoalcohol 5 - 8 m this was determmed by titration agamst a tltrant of glacial acetic acid and HC104 (b) The ammoalcohol was separated from the unchanged /3-lactam by fractional dlstlllatlon. (c) Separation could also be achieved through crystalhzation m dlisopropyl ether. The ammoalcohol remams m solution, while the startmg azetldmone crystallizes out. Cls-2-(hydroxymethyl)cyclooctylamme (8) The new compound separated by fractional distillation as m method (b) is a colourless liquid; on standmg, crystalhzatlon occurs at room temperature, and the carbonate is rapidly formed m air. ‘H NMR (CDCl,): &.rA 33.7, 6nz 3.5, jsnl 3 05, 6nn,on 6.7, 6n2 1.8. Plcrate ‘H NMR (pyrrdme-d,). 6n~ 3.88, 6Hz 3.88, 6n1 3.55, 6~n.o~ 5.48, 6n2 2.1; JAB = 9 HZ; JAH~= = 20 Hz. Anal. (Ci5HZ2N40s) C, H, N. 3.8 HZ; JBH* = 5.3 HZ; ACIH~ Transformation m a flow reactor (Method (au)) The reactions were carried out on 50 mg Ni on Cab-O-S@ catalyst or on 50 mg Raney Ni m a flow reactor. The catalysts were activated for 2 h at 400 “C or at 300 “C, respectively, m a stream of hydrogen (25 ml mm-l), and a 1 mol dmw3 solution of /3-la&am 1 - 4 m absolute dloxan was then added at a rate of 1 ml h-’ at 300 “C m a hydrogen flow rate of 10 ml mm-’ The reaction products were analysed by GC

Acknowledgements We acknowledge the support provided for this research by the Hungarian Academy of Sciences (Grant 320/1986). We thank the Central Research Institute for Chemistry of the Hungarian Academy of Sciences for the NMR spectra, and Dr. Gy. Dombl for his aid m their evaluation.

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