GB2143819A - Preparing monocyclic beta-lactams - Google Patents
Preparing monocyclic beta-lactams Download PDFInfo
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- GB2143819A GB2143819A GB08418094A GB8418094A GB2143819A GB 2143819 A GB2143819 A GB 2143819A GB 08418094 A GB08418094 A GB 08418094A GB 8418094 A GB8418094 A GB 8418094A GB 2143819 A GB2143819 A GB 2143819A
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- group
- process according
- formula
- beta
- aziridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Monocyclic beta-lactams are produced by reacting an aziridine with carbon monoxide in the presence of one or more metals of Group VIII of the Periodic Table in elemental or compound form as catalyst.
Description
SPECIFICATION
Process for the production of monocyclic beta-lactams
The present invention relates to a process for the production of monocyclic beta-lactams.
The production of bicyclic beta-lactams by reacting an azirine with carbon monoxide in the presence of a catalytic amount of tetrakis (triphenylphosphine) palladium (0) at 40"C and at 1 atmosphere is reported in J. Am. Chem. Soc, 1981, 103, 1289 by Alper H., Perera, C.P. and Ahmed F.R.
We have now found that aziridines can be catalytically converted by reaction with carbon monoxide to monocyclic beta-lactams.
Accordingly, the present invention provides a process for the production of a monocyclic beta-lactam having the formula:
wherein
R is a hydrocarbyl group or a substituted derivative thereof, Ri is a hydrocarbyl group other than a group containing an acidic hydrogen or acidic hydrogens on a carbon atom adjacent to the heterocyclic nitrogen atom, or a substituted derivative thereof, and
R2, R3 and R4 are independently either hydrogen atoms, hydrocarbyl groups or derivatives thereof by reacting an aziridine having the formula:
wherein R, Rt, R2, R3 and R4 are as defined above, with carbon monoxide in the presence of a catalyst comprising one or more metals of Group VIII of the Periodic Table in elemental or compound form.
The Periodic Table referred to throughout this specification is the Periodic Table as found in Advanced
Inorganic Chemistry by Cotton and Wilkinson, published by John Wiley & Sons, Fourth Edition.
As regards the aziridines of formula (II), these may be prepared by methods well known in the art. The group R in the beta-lactam of formula (I) and the aziridine of formula (II) may suitably be either alkyl, aryl, alkaryl or a substituted derivative thereof, of which aryl or alkaryl or substituted derivatives thereof are preferred. The hydrocarbyl groups may suitably be substituted by a halide group or groups, for example by a bromide group or groups, though other substituents may be employed. Examples of suitable
R groups include phenyl p-bromophenyl and p-phenylphenyl. The group Rq in the beta-lactam of formula (I) and the aziridine of formula (II) is a hydrocarbyl group other than a group containing an acidic hydrogen or acidic hydrogens on a carbon atom adjacent to the heterocyclic nitrogen atom or a substituted derivative thereof.The group R' may suitably be a tertiary alkyl group. Examples of suitable groups R' include tertiary-butyl and 1-adamantyl. R2, R3 and R4 in the formula (I) and the formula (II) may suitably be hydrogen.
Carbon monoxide may be employed over a wide range of pressures, typically in the range from 0 to 100 atmospheres.
The catalyst comprises one or more metals of Group VIII of the Periodic Table in elemental or compound form. Suitable metals of Group VIII include rhodium, palladium, cobalt, ruthenium, platinum or iridium. Preferably the metal or metals are employed in the form of solubie compounds thereof. Suitable compounds include salts of the metals and organo compounds of the metals. A preferred organo compound is a dienyl metal complex wherein the dienyl moiety may either linear or cyclic and either conjugated or non-conjugated. Examples of suitable catalysts include chlorodicarbonyl rhodium (I) dimer and 1,5-cyclooctadienerhodium (I) chloride dimer.
A solvent may be employed if so desired. Suitable solvents include hydocarbon sovents, such as for example, paraffinic and aromatic hydrocarbons. Examples of suitable solvents include n-hexane, heptane, toluene, benzene and xylenes.
The process may suitably be operated at a temperature in the range from 20 to 250"C. However, higher and lower temperatures may be employed if so desired. The reaction period under these conditions may suitably be up to 96 hours, though shorter reaction periods are preferred.
An advantage of the process of the invention is that it is highly regiospecific. The beta-lactam having the formula (I) can be produced in the substantial absence of the isomeric beta-lactam having the formula:
wherein R, RI, Ra, R3 and R4 have the same significance as for formulae (I) and (II).
The invention will now be illustrated by reference to the following Examples. In the Examples reference will be made to beta-lactams. Such reference will be to beta-lactams having the formula (I) where R2 = =R4=H.
Example I
A mixture of an aziridine of the fomula (II) wherein R is phenyl, Rq is tertiary-butyl and R, R3 and R4 are hydrogen [1.009; 5.71 mmol] and chlorodicarbonyl rhodium (I), [Rh(CO)2Cl]2, [0.11g; 0.28mmol] in dry benzene was stirred under carbon monoxide for 2 days at 20 atmospheres and 90 C. The solvent was removed by rotary evaporation and the analytically pure beta-lactam was obtained by silica gel chromatography using ethyi acetate/hexane as the eluant.
The beta-lactam of formula (I) wherein R is phenyl and R' is t-butyl and R2, R3 and R4 = H was obtained in quantitative yield. The beta-lactam was identified on the basis of analytical and calculated values for C,3H,7NO Calculated C = 76.81%
H= 8.43%
N= 6.89%
Found C = 77.08%
H= 8.44%
N= 6.95% and also on spectral data. In particular the infrared carbonyl stretching frequency occurred at 1740cm- and the proton magnetic resonance spectrum displayed a typical 12-line AMX spectrum for the three protons attached to the carbon atoms of the heterocyclic ring. Carbon-13 magnetic resonance (NMR) and mass spectral (MS) data are also in accord with the assigned structure. The pertinent NMR and MS data are given in the Table.
Example 2
Example 1 was repeated except that an aziridine of the formula (II) wherein R is phenyl, R is 1-adamantyl and R2, R3 and R4 are hydrogen was used in place of the aziridine of that Example.
The beta-lactam of formula (I) wherein R is phenyl, R is adamantyl and Ra, R3 and R4 are hydrogen was obtained in quantitative yield. The pertinent NMR and MS data are given in the Table.
Example 3
Example 1 was repeated except that an aziridine of the formula (II) wherein R is p-PhC6H4,R is t-butyi and Ra, Ra and R4 are hydrogen was used in place of the aziridine of that Example.
The beta-lactam of formula (I) wherein R is p-PhCEH4, RI is t-butyl and R,R and R4 are hydrogen was obtained in quantitative yield. The pertinent NMR and MS data are given in the following Table.
Example 4
Example 1 was repeated except that an aziridine of the formula (II) wherein R is p-PhC6H4, RI is 1-adamantyl and Ra, R3 and R4 are hydrogen was used in place of the aziridine of that Example.
The beta-lactam of formula (I) wherein R is PhC6H4, RI is 1-adamantyl and Ra, R3 and R4 are hydrogen was obtained in quantitative yield. The pertinent NMR and MS data are given in the following Table.
Example 5
Example 1 was repeated except that an aziridine of the formula (II) wherein R is p-BrC6H4, R' is t-butyl and R2, R3 and R4 are hydrogen was used in place of the aziridine of that Example.
The beta-lactam of formula (I) wherein R is p-BrC6H4, R' is t-butyl and R2, R3 and R4 are hydrogen was obtained in quantitative yield. The pertinent NMR and MS data are given in the following Table. TABLE
Example R R 'H-NMR, delta,ppm(i) C-NMR, delta,ppm (i) (ii) MS,m/e 1 Ph, C(CH3)3 1.36/s, 9H, C(CH3)3,3.07(dd,1H,Hb, 27.78(q,CH3), 44.70(t,CHz), 203[m]+
Jab=2H2,Jbc=6H2), 3.52(dd,1H,Hc, 52.28(s,C(CH3)3), 53.24(d,CHPh),
Jac=5Hz), 4.06(dd,1H,Ha) 7.23(s, 128.79, 127.26(d each, CH of Ph),
5H,Ph) 167.14(s,(0) 2 Ph, 1-adamantyl 1.68-2.05(m, 15H, adamantyl 29.06(d), 36.21(H), 40.83(t) 281[m]+
protons), 3.11(dd,1H,Hb,Jab=2Hz, (secondary and tertiary adamantyl
Jbc=5.5Hz), 3.55(dd, 1H,Hc, carbons), 43.75(t,CH2), 52.06
Jac=5.0Hz), 4.06(dd, 1H,Ha) (d,CHPh), 53.97(s, quaternary C of
7.23(s,5H, Ph) adamantane group), 127.29, 128.65 (d
each, CH of Ph), 136.45(s,quater
nary carbon of Ph), 167.12 (s.CO) 3 p-PhC6H4 C(CH3)3 1.33(s, 9H C(CH3)3, 3.13 (dd, 1H, 27.77 (q, CH3), 44.63 (t,CH2), 51.94 279[m]+
Hb, Jab=2Hz, Jbc=5.5Hz). 3.53 (dd, (d, CHPh), 53.28 (s,C(CH3)3 127.01,
1H, Hc=Jac=6Hz) 4.10 (dd, 1H, Ha), 127.26, 127.51, 127.66, 128.76
7.16-7.56 m,9H aromatic ring (d each, aromatic CH), 135.31,
protons) 140.26, 140.78 (s each, quaternary
carbons of p-PhC6H4), 167.05 (s,CO) 4 p-PhC6H4 1-adamantyl 1.70-2.05 (m, 15H, adamantyl 29.04 (d), 36.19(t), 40.82(t) 357[m]+
protons), 3.15 (dd, 1H, Hb, (secondary and tertiary adamantyl
Jab=2Hz, Jbc=5.5Hz), 3.56 (dd, 1H, carbons), 43.63(t,CH2), 51.72(d,
Hc), 7.15-7.65 (m, 9H, aromatic CHPh), 54.00(s, quaternary C of
ring protons) adamantane group), 127.01, 127.25,
127.50, 127.68, 128.75(d each,
aromatic CH), 135.44, 140.25
140.81 (s each, quaternary carbons of
p-PhC6H4), 167.03 5 p-BrC6H4 m(CH3)3 1.38(s, 9H,C(CH3)3), 3.06(dd, 1H,
Hb, Jab=2Hz, Jbc=5.5Hz), 3.53(dd,
1H, Hc, Jac=5.0Hz), 4.05(dd, 1H,
Ha), 7.00-7.60(m, 4H, aromatic
protons) (i) CDCl3 with tetramethyl silane as internal standard. (ii) Multiplicity of signals observed when C-13 spectra was recorded in the partially decouple mode.
Claims (12)
1. A process for the production of a monocyclic beta-lactam having the formula:
wherein
R is a hydrocarbyl group or a substituted derivative thereof, Ri is a hydrocarbyl group other than a group containing an acidic hydrogen or acidic hydrogens on a carbon atom adjacent to the heterocyclic nitrogen atom, or a substituted derivative thereof, and
R2, R3 and R4 are independently either hydrogen atoms, hydrocarbyl groups or derivatives thereof, by reacting an aziridine having the formula:
wherein R, R, R2, R3 and R4 are as defined above, with carbon monoxide in the presence of a catalyst comprising one or more metals of Group Villi of the Periodic Table in elemental or compound form.
2. A process according to claim 1 wherein the group R is either aryl, alkaryl or a substituted derivative thereof.
3. A process according to either claim 1 or claim 2 wherein the group R is either phenyl p-bromophenyl or p-phenylphenyl.
4. A process according to any one of the preceding claims wherein the group R is a tertiary alkyl group.
5. A process according to claim 4 wherein the group Ri is either tertiary-butyl or 1-adamantyl.
6. A process according to any one of the preceding claims wherein R2, R3 and R4 are hydrogen.
7. A process according to any one of the preceding claims wherein the metal of Group VIII is either rhodium, palladium, cobalt, ruthenium, platinum or iridium.
8. A process according to claim 7 wherein the Group VIII metal is in the form of a dienyl metal complex.
9. A process according to any one of the preceding claims wherein the catalyst is either chlorodicarbonyl rhodium (I) dimer or 1,5-cyclooctadiene rhodium (I) chloride dimer.
10. A process according to any one of the preceding claims wherein the aziridine is reacted with carbon monoxide at a temperature in the range from 20 to 250"C.
11. A process according to claim 1 substantially as hereinbefore described with reference to Examples 1 to 5.
12. Monocyclic beta-lactams whenever produced by a process as claimed in any one of claims 1 to 11.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB08418094A GB2143819A (en) | 1983-07-16 | 1984-07-16 | Preparing monocyclic beta-lactams |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB838319292A GB8319292D0 (en) | 1983-07-16 | 1983-07-16 | Production of mono-cyclic beta-lactams |
| GB08418094A GB2143819A (en) | 1983-07-16 | 1984-07-16 | Preparing monocyclic beta-lactams |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8418094D0 GB8418094D0 (en) | 1984-08-22 |
| GB2143819A true GB2143819A (en) | 1985-02-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08418094A Withdrawn GB2143819A (en) | 1983-07-16 | 1984-07-16 | Preparing monocyclic beta-lactams |
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| Country | Link |
|---|---|
| GB (1) | GB2143819A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010023931A1 (en) | 2008-08-29 | 2010-03-04 | 興和株式会社 | 1-adamantylazetidin-2-one derivative and pharmaceutical preparation comprising same |
-
1984
- 1984-07-16 GB GB08418094A patent/GB2143819A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010023931A1 (en) | 2008-08-29 | 2010-03-04 | 興和株式会社 | 1-adamantylazetidin-2-one derivative and pharmaceutical preparation comprising same |
| US8236789B2 (en) | 2008-08-29 | 2012-08-07 | Kowa Company, Ltd. | 1-adamantyl azetidin-2-one derivatives and drugs containing same |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8418094D0 (en) | 1984-08-22 |
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| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |