New 1-oxa-2-oxo-3-R-3-aza- 5-Z-cyclopentane derivatives, wherein PA1 R is alkyl or hydroxyalkyl having in each case 1-6 C atoms, cycloalkyl having 3-8 C atoms, unsubstituted aryl or aralkyl or aryl or aralkyl each of which has a total of 6-15 C atoms and, in the aryl radical, is monosubstituted to trisubstituted by alkyl, alkoxy, OH and/or Cl or monosubstituted by methylenedioxy, PA1 Z is --(CHOH).sub.n --H and PA1 n is 2, 3, 4 or 5, can be used as intermediate products for the preparation of active compounds for medicaments, such as toloxatone.

BACKGROUND OF THE INVENTION 
This invention relates to new 1-oxa-2-oxo-3-R-3-aza-5-Z-cyclopentane 
derivatives (I). Similar compounds are described in U.S. Pat. No. 
3,120,510. 
SUMMARY OF THE INVENTION 
It is an object of this invention to provide such compounds. 
Upon further study of the specification and appended claims, further 
objects and advantages of this invention will become apparent to those 
skilled in the art. 
These objects have been achieved by providing new 
1-oxa-2-oxo-3-R-3-aza-5-Z-cyclopentane derivatives (I) wherein: 
R is alkyl or hydroxyalkyl having in each case 1-6 C atoms, cycloalkyl 
having 3-8 total C atoms (optionally substituted by alkyl), unsubstituted 
aryl or aralkyl each of 6-15 C atoms in total or aryl or aralkyl each of 
which has a total of 6-15 C atoms and, in the aryl radical, is 
monosubstituted to trisubstituted by alkyl (e.g., of 1-6 C atoms), alkoxy 
(e.g., of 1-6 C atoms), OH and/or Cl or monosubstituted by methylenedioxy, 
Z is -(CHOH).sub.n -H and 
n is 2, 3, 4 or 5. 
DETAILED DESCRIPTION 
The compounds I can be prepared by reacting a compound of the formula 
R--NH--CH.sub.2 --CHOH--Z (II) with a reactive derivative of carbonic 
acid. 
Compounds of the formula II are in part known and all can be conventionally 
obtained, for example, by reacting amines of the formula R--NH.sub.2 with 
aldehydes of the formula Z--CHOH--CHO and by subsequently or 
simultaneously reducing the resulting Schiff's bases or half-aminals of 
the formlae 
##STR1## 
Suitable examples of amines of the formula R--NH.sub.2 are methylamine, 
ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, 
sec.-butylamine, tert.-butylamine, pentylamine, 1-ethylpropylamine, 
1-methylbutylamine, isopentylamine, neopentylamine, tert.-pentylamine, 
hexylamine, isohexylamine, 1,1-dimethylbutylamine, 1-methylpentylamine, 
2-hydroxyethylamine, 2-hydroxypropylamine, 3-hydroxypropylamine, 
2-hydroxy-1-methylethylamine, 2-, 3- or 4-hydroxybutylamine, 
5-hydroxypentylamine, 6-hydroxyhexylamine, cyclopropylamine, 
cyclobutylamine, cyclopentylamine, cyclohexylamine, 1-, 2- or 
3-methylcyclopentylamine, 1-, 2-, 3- or 4-methylcyclohexylamine, 
cycloheptylamine, cyclooctylamine, 2-phenylethylamine, 
1-methyl-2-phenylethylamine, 1,1-dimethyl-2-phenylethylamine, 
2phenylpropylamine, 3-phenylpropylamine, 1-methyl-3-phenylpropylamine, 2-, 
3- or 4-phenylbutylamine, 2-(1-naphthyl)ethylamine, 
2-(2-naphthyl)-ethylamine, 2-, 3- or 1-p-methoxyphenylethylamine, 
2-(3,4-dimethoxyphenyl)-ethylamine, 
2-(3,4-methylenedioxyphenyl)-ethylamine, aniline, o-, m- or p-toluidine, 
o-, m- or p-anisidine, o-, m- or p-aminophenol, o-, m- or p-chloroaniline, 
3,4-dimethoxyaniline or 3,4-methxlenedioxyaniline. All alkyl portions in 
the R groups can correspondingly be selected from those mentioned above. 
Examples of suitable aldehydes of the formula Z--CHOH--CHO are 
2,3,4-trihydroxybutanals, such as the DL-, D- or L-forms of erythrose or 
threose, 2,3,4,5-tetrahydroxypentanals, such as the DL-, D- or L-forms of 
ribose, arabinose, xylose or lyxose, or 2,3,4,5,6-pentahydroxyhexanals, 
such as the DL-, D- or L-forms of allose, altrose, glucose, mannose, 
gulose, idose, galactose or talose. Examples of typical compounds of the 
formula II are N-R-2,3,4-trihydroxybutylamines, such as 
N-methyl-2,3,4-trihydroxybutylamines, 
N-R-2,3,4,5-tetrahydroxypentylamines, such as 
N-phenyl-2,3,4,5-tetrahydroxypentylamines, 
2N-R-2,3,4,5,6-pentahydroxyhexylamines, such as 
N-phenyl2,3,4,5,6-pentahydroxyhexylamines, 
N-m-tolyl-2,3,4,5,6-pentahydroxyhexylamines, or N-methyl-, N-ethyl-, 
N-isopropyl- or N-tert.-butyl-2,3,4,5,6-pentahydroxyhexylamines, for 
example the N-R-glucamines derived from D-glucose 
(N-R-2S,3R,4R,5R,6-pentahydroxyhexylamines). 
Examples of suitable carbonic acid derivatives are phosgene, dialkyl 
carbonates, such as dimethyl or diethyl carbonate, urea or 
carbonyldiimidazole. 
The reaction of II with the carbonic acid derivative can be carried out in 
the absence or presence of an inert solvent, such as dimethylformamide 
(DMF), methanol or ethanol, at temperatures between about 0 and about 
200.degree.. Thus the reaction is preferably carried out with 
carbonyldiimidazole at about 0.degree.-30.degree. in DMF, or, with the 
other carbonic acid derivatives mentioned, at about 80.degree.-150.degree. 
without a solvent, but the addition of a base, such as NaOH, KOH, 
triethylamine or pyridine can be advantageous. 
In some cases it is also possible to react further OH groups in II with the 
carbonic acid derivative, particularly if the latter is employed in 
excess. The carbonates thus formed can, however, be saponified readily 
under alkaline conditions with the formation of the desired compounds I. 
Oxidative cleavage of the compounds (I), for example using HIO.sub.4 or 
salts thereof, KMnO.sub.4 or lead tetraacetate, and subsequent reduction 
of the 1-oxa-2-oxo-3-R-3-aza-5-formylcyclopentanes formed as intermediates 
leads to the corresponding 
1-oxa-2-oxo-3-R-3-aza-5-hydroxymethylcyclopentanes (III), for example to 
toloxatone (R=m-tolyl). If compounds (I) wherein the C(5) atom has the 
S-configuration are used, the corresponding 
1-oxa-2-oxo-3-R-3-aza5S-hydroxymethylcyclopentanes are obtained. The 
conversion of the 3-isopropyl compound into S-propranolol is known. The 
corresponding 5-chloromethyl, 5-bromomethyl, 5-acyloxymethyl (for example 
also 5-methanesulphonyloxymethyl or 5-p-toluenesulphonyloxymethyl), 
5-alkoxymethyl or 5-aryloxymethyl derivatives can be prepared from the 
compounds III by reaction with SOCl.sub.2 or PBr.sub.3 or by 
esterification or etherification. 
The compounds I can be used as intermediate products for the preparation of 
active compounds for medicaments, such as toloxatone or certain beta 
receptor blockers. 
Without further elaboration, it is believed that one skilled in the art 
can, using the preceding description, utilize the present invention to its 
fullest extent. The following preferred specific embodiments are, 
therefore, to be construed as merely illustrative, and not limitative of 
the remainder of the disclosure in any way whatsoever. 
In the preceding text and the following examples, all temperatures are set 
forth uncorrected in degrees Celsius and all parts and percentages are by 
weight; unless otherwise indicated.

EXAMPLE 1 
1.62 g of carbonyldiimidazole are added to a solution of 2.71 g of 
N-m-tolyl-2S,3R,4R,5R,6-pentahydroxyhexylamine [IIa; m.p. 
111.degree.-114.degree., obtainable from D-glucose and m-toluidine/H.sub.2 
/Pd-C in methanol/water] in 30 ml of DMF, and the mixture is stirred for 3 
hours at 20.degree.. After the mixture has been concentrated, imidazole is 
removed by distillation at 130.degree./0.2 bar. This gives 
1-oxa-2-oxo-3-m-tolyl-3-aza-5S-(1R,2R,3R,4-tetrahydroxybutyl)-cyclopentane 
(Ia), which is purified by chromatography over silica gel. Rf 0.45 
(90:10:5 methylene dichloride/methanol/acetic acid). 
EXAMPLE 2 
A mixture of 2.71 g of IIa, 10 ml of diethyl carbonate and 0.5 ml of 
triethylamine is stirred for 23 hours at 110.degree.-120.degree.. The 
mixture is evaporated and the residue is chromatographed over silica gel 
to give Ia. 
EXAMPLE 3 
A mixture of 2.71 g of IIa, 0.72 g of urea and 0.1 g of KOH is heated at 
140.degree.-150.degree. for 2 hours. After cooling, the Ia obtained is 
chromatographed over silica gel. 
EXAMPLE 4 
A mixture of 2.71 g of IIa and 4 g of ethylene carbonate is heated at 
100.degree. for 3 hours. The mixture is evaporated and the residue is 
chromatographed over silica gel to give Ia. 
EXAMPLES 5 to 20 
The following 
1-oxa-2-oxo-3-aza-5S-(1R,2R,3R,4-tetrahydroxybutyl)-cyclopentanes are 
obtained, analogously to Example 1, 2, 3 or 4, from N-methylglucamine, 
N-ethyl-glucamine, N-propylglucamine, N-isopropylglucamine, 
N-butylglucamine, N-isobutylglucamine, N-sec.-butylglucamine, 
N-tert.-butylglucamine, N-(2-hydroxyethyl)-glucamine, 
N-cyclohexylglucamine, N-phenylglucamine, N-p-methoxyphenylglucamine, 
N-(2-phenylethyl)-glucamine, N-(1,1-dimethyl-2-phenylethyl)-glucamine, 
N-[2-(3,4-dimethoxyphenyl)-ethyl]-glucamine and 
N-[2-(3,4-methylenedioxyphenyl)-ethyl]-glucamine respectively: 
5. The 3-methyl derivative, m.p. 155.degree.. 
6. The 3-ethyl derivative. 
7. The 3-propyl derivative. 
8. The 3-isopropyl derivative, m.p. 163.degree.. 
9. The 3-butyl derivative. 
10. The 3-isobutyl derivative. 
11. The 3-sec.-butyl derivative. 
12. The 3-tert.-butyl derivative, m.p. 158.degree.. 
13. The 3-(2-hydroxyethyl) derivative. 
14. The 3-cyclohexyl derivative. 
15. The 3-phenyl derivative. 
16. The 3-p-methoxyphenyl derivative. 
17. The 3-(2-phenylethyl) derivative. 
18. The 3-(1,1-dimethyl-2-phenylethyl) derivative. 
19. The 3-[2-(3,4-dimethoxyphenyl)-ethyl] derivative. 
20. The 3-[2-(3,4-methylenedioxyphenyl)-ethyl] derivative. 
EXAMPLE 21 
1-oxa-2-oxo-3-isopropyl-3-aza-5R-(1R,2R,3R,4-tetrahydroxybutyl)-cyclopentan 
e is obtained, analogously to Example 2, from 
N-isopropyl-2R,3R,4R,5R,6-pentahydroxyhexylamine (m.p. 122.degree.; 
obtainable by treating a solution of D-mannose and isopropylamine in 
methanol/water with H.sub.2 over 5% Pd-on-C for 3 hours at 50.degree. and 
3 bar). 
EXAMPLE 22 
100 mg of KOH powder are added to a solution of 2.37 g of 
N-tert.-butyl-2S,3R,4R,5R,6-pentahydroxyhexylamine (m.p. 112.degree.; 
obtainable from D-glucose and tert.-butylamine/H.sub.2 /Pd-C) in 10 ml of 
diethyl carbonate, and the mixture is heated at 120.degree. for 4 hours. 
The mixture is concentrated, the residue is taken up in ethanol and the 
solution is filtered. After cooling, the crystals which have been 
precipitated are filtered off with suction; m.p. 212.degree.. The 
carbonate-ester groups which have been formed are saponified by warming 
the intermediate product briefly with a mixture of 3 ml of methanol, 3 ml 
of water and 0.5 g of KOH. After neutralization with hydrochloric acid; 
the solution is concentrated, the residue is extracted with methylene 
dichloride, and the extract is evaporated to give 
1-oxa-2-oxo-3-tert.-butyl-3-aza-5S-(1R,2R,3R,4-tetrahydroxybutyl)-cyclopen 
tane, m.p. 158.degree.. 
USE EXAMPLE 1 
7.2 g of NaIO.sub.4 are added at 20.degree. to a suspension of 2.97 g of Ia 
in 180 ml of water, and the mixture is stirred for 30 minutes. The pH is 
then adjusted to 8 and 0.2 g of NaBH.sub.4 are added in portions at 
20.degree.. After being stirred for a further 1.5 hours, the mixture is 
extracted with methylene dichloride, the extract is dried with Na.sub.2 
SO.sub.4 and evaporated and the residue is purified by chromatography. 
This gives 1-oxa-2-oxo-3-m-tolyl-3-aza-5S-hydroxymethylcyclopentane. 
USE EXAMPLES 2 to 17 
The following 1-oxa-2-oxo-3-aza-5S-hydroxymethylcyclopentanes are obtained, 
analogously to Use Example 1, by oxidative cleavage and subsequent 
reduction of the compounds mentioned in Examples 5 to 20: 
2. The 3-methyl derivative. 
3. The 3-ethyl derivative. 
4. The 3-propyl derivative. 
5. The 3-isopropyl derivative, m.p. 55.degree.-58.degree.. 
6. The 3-butyl derivative. 
7. The 3-isobutyl derivative. 
8. The 3-sec.-butyl derivative. 
9. The 3-tert.-butyl derivative. 
10. The 3-(2-hydroxyethyl) derivative. 
11. The 3-cyclohexyl derivative. 
12. The 3-phenyl derivative. 
13. The 3-p-methoxyphenyl derivative. 
14. The 3-(2-phenylethyl) derivative. 
15. The 3-(1,1-dimethyl-2-phenylethyl) derivative. 
16. The 3-[2-(3,4-dimethoxyphenyl)-ethyl] derivative. 
17. The 3-[2-(3,4-methylenedioxyphenyl)-ethyl]derivative. 
The preceding examples can be repeated with similar success by substituting 
the generically or specifically described reactants and/or operating 
conditions of this invention for those used in the preceding examples. 
From the foregoing description, one skilled in the art can easily ascertain 
the essential characteristics of this invention, and without departing 
from the spirit and scope thereof, can make various changes and 
modifications of the invention to adapt it to various usages and 
conditions.