DE2012216A1 - Process for the preparation of 3,3-disubstituted beta-lactams - Google Patents

Description

Our reference: O.Zo26 666 WB / Be 6700 Ludwigshafen, 1.3. March 1970

Process for the preparation of 3,3-disubstituted β-lactams

This invention relates to a process for the preparation of 3,3-disubstituted β-lactams by dehydrohalogenation of ß-halocarboxamides in the presence of tertiary amines.

ß-lactams, the inner cyclic amides of ß-aminocarboxylic acids, cannot be prepared directly from the ß-amino carboxylic acids. The condensation of ß-aminocarboxylic acid esters with Grignard compounds (LiebigeAnnalen der Chemie, Volume 614 (1958), page 158) and the condensation of ß-aminocarboxylic acids with phosphorus pentachloride in the presence of acetyl chloride (German Auslegeschrift 1 181 710) are uneconomical because the ß -Aminocarboxylic acids, especially α, α-disubstituted, usually have to be obtained in a complex manner. 3,3-disubstituted β-lactams can also be obtained by adding chlorosulfonyl isocyanate to the process described in Angewandte Chemie 74 (1962) pages 523-524, Annalen, Volume 661 (1963), page 111 and Volume 722 (1969) page 11.0 ff Olefins not generally accessible »'A work in Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science, Volume 1960, pages 494 - 501, describes the dehydrobromination of the corresponding ß-bromocarboxamides with sodium amide in liquid ammonia and especially of ß- Aryl-ß-bromopropionic acid arylamides with potassium, sodium or lithium hydroxide or Triton B at O ⁰ C in aliphatic ketones as solvents. The cyclization of aja-diphenyl-β-bromocarboxamides by means of sodium ethylate, sodium isopropylate and the mentioned hydroxides in ethanol to form the 3) 3-diphenyl azetide ions is also cited. However, this method cannot be transferred with good success to other α, α-disubstituted β-bromocarboxamides (Liebigs Annalen der Chemie, Volume 673 (1964) »page 72), so that, according to the current state of the art, the technically only conditionally suitable Cyclization with sodium amide in liquid ammonia has priority.

481/69 - 2 -

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This is especially true for the manufacture of difficult to access 3,3-disubstituted 1-aryl and 1-alkyl azetidinones.

The ß-bromocarboxamides of the very weakly basic amines o-, m- and p-mtraniline are heated with pyridine (pK-g value 8.77) dehydrobrominated to the 1-nitrophenyl-azetidinones (Helvetia Chimica Acta 48 (1965), 1867). The disadvantage of this process is that it can only be used in special cases and requires high reaction temperatures and / or relatively long reaction times. In Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science, Volume 1960, pages 494 - 496 it is shown that the anilide of β-phenyl-β-bromopropionic acid not cyclized in the presence of triethylamine.

In US Pat. No. 3,297,754, hydrides, alkyl compounds and tertiary alcoholates of alkali and alkaline earth metals are used as condensation agents for β-halocarboxamides, the acidity of the basic compounds being less than or equal to that of tertiary alcohols (column 3, line 45 ), described in polar solvents. A conversion of β-bromopivaloylamide to pivalolactam does not take place in the presence of lithium carbonate and dimethylformamide (Table 1, Example 8).

It has now been found that 3,3-disubstituted β-lactams the general iormel

R-C-C = O

^ά ti

ι,

- «-" 4

-CHR ₄

in which R ₁ , R ₂ , R, and R. can be identical or different and each denotes an aliphatic, cycloaliphatic, araliphatic or heterocyclic radical, and also. R, and / or R, can each denote a hydrogen atom, R ₁ and R «together with the adjacent carbon atom or R ₁ and R, together with the two adjacent carbon atoms, also respective members of a cycloaliphatic

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- 3 - 0.Z.26 666

or heterocyclic ring, R ₁ , Rg and / or R. can also denote an aromatic radical,

R / also for an alkylsulfonyl radical, arylsulfonyl radical, the rest

^R 5. °

—Ή ^ , the rest -C-

6 6

0
or the radical -C-OR ₁ -,

in which the individual radicals R, - and Rg can be identical or different and each denote a hydrogen atom, an aliphatic, cycloaliphatic, araliphatic, aromatic radical, in addition Rg together with the neighboring nitrogen atom and the neighboring radical R ₁ - also members

of a heterocyclic ring, or Rg also denote a sulfonic acid group or an arylsulfonyl radical can,

R ₁
0 = C - C - R ₀

! I ^

the remainder - N - C - R, or the remainder

can stand, in which R ₁ , R ₂ and R, have the aforementioned meaning, η = 1 or an integer greater than 1, Ry means an aliphatic, cycloaliphatic or aromatic radical, can stand,

by dehydrohalogenation of ß-Balogencarboxamiden in The presence of basic compounds is advantageously obtained when using ß-halocarboxamides of the general formula

. ■■ '■' - - 4 -

10 9 8 3 9/18 2 2

- A - 0 "Z. 26 666

X-CH-C-C-N-Ro II,

R ₃ R ₂ 0 ^a

in which R _{Q has} the meaning of R. or the remainder

OR ₁ · / OR ₁

-NCC-CH-X or the radical -R ₇ -ZN -CC-CH-X

TJ I I '\ TJ I t

R ₂ R ₃ \ = R ₂ R ₃ / _n

tiezeic]] net, R ₁ , R ₂ and R, have the abovementioned meanings and X stands for a halogen atom, dehydrohalogenated in the presence of tertiary amines whose pK-n value is below 8.

The reaction can be represented by the following formulas for the case of using N-methyl-Brompivaloyl:

CH, CH,

Bv - CH ₉ -CC-IT-CH, j CH, -CC =

CH ₃ 0 ^{n Ά ΰΤ} H ₂ C -N-

In comparison with the known processes, the process yields according to the invention, a large number of 3,3-disubstituted β-lactars in a simpler way and in some cases in better yield and purity. In view of the prior art, it is surprising that using these advantageous results of the catalysts mentioned can be achieved. Bis- and poly-ß-lactams can also be produced in a simple way. By dehydrobrominating brompivaloylureld one obtains e.g. surprisingly not 5,5 ~ dimethyl-hexahydro-pyrimidin-dione (-2,4), but exclusively 1-carbamyl-3 »3-dimethyl-ß-lactam.

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BrCHo -

CC CH ₃ 0

- 5 -

-IT-C-

fl

0.Z.26 666

-C-NE

^, IT'-bisbromopivaloylhydrazide surprisingly provides a considerable proportion of 1,5-diaza-2,6-dioxo-3,3,7> 7-tetramethyl-bicycloJ3,0,3j-octane even at room temperature (21 <fo) ür, N'-bis- (3,3-dimethyl-azietidinone- (2)), which can be increased by increasing the temperature (for example at 90 ° 30 fo).

Br-CHo -

CH ₃

C- C ι π CH ₃ O

H γ - * -

If - Ii - C HHg

C - CHo-Br C]

Preferred starting materials II and correspondingly preferred end materials I are those in whose formulas R .., R «» R ₃ and R can be the same or different and in each case an alkyl radical with 1 to 7 carbon atoms, a cycloalkyl radical with 5 or 6 carbon atoms Aralkyl radical with 7 to 12 carbon atoms or a 5- or 6-membered, heterocyclic radical which can contain a nitrogen atom and / or an oxygen atom or another nitrogen atom, in addition, R and / or R can each denote a hydrogen atom , R ^ and R ₂ together with the adjacent carbon atom or R ^ and R, together with the two adjacent carbon atoms, are also members of a cycloalkyl ring with 4 to 8 carbon atoms or a 5- or 6-membered, heterocyclic radical containing a nitrogen atom and / or can contain an oxygen atom or a further nitrogen atom, R ^, R «and / or Ri can also mean an aryl radical with 6 to 12 carbon can denote substance atoms ,

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R, also for an alkylsulfonyl radical with 1 to 4 carbon atoms, a phenylsulfonyl radical, an acyl radical, in particular an alkylcarbonyl radical having 2 to 6 carbon atoms or an arylcarbonyl radical with 7 to 12 carbon atoms, the rest

Il

the remainder -C - N:

Il

or the remainder -C - OR,

in which the individual radicals R, - and Rg are identical or different can be and in each case a hydrogen atom, an alkyl radical with 1 to 6 carbon atoms, an acyl radical, in particular an alkylcarbonyl radical with 2 to 4 carbon atoms, a Cycloalkyl radical with 5 or 6 carbon atoms, an aralkyl radical with 7 to 12 carbon atoms, denote a phenyl radical, in addition Rg together with the adjacent nitrogen atom and its neighboring radical R ^ also members of a 5- or 6-membered, heterocyclic ring, which is next to the Nitrogen atom can also contain an oxygen atom or a further nitrogen atom, or Rg can also mean one Can denote a sulfonic acid group or a phenylsulfonyl radical,

the rest -N-

CR ₉

I ^

O - Iw I J

-R

or the rest

in which R ₁ , R ₂ and R, have the aforementioned meaning, η denotes the number 1, R ₇ denotes an alkylene radical having 2 to 6 carbon atoms, a cycloalkylene radical having 5 to 13 carbon atoms or a phenylene or biphenylene radical . - 7 -

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O = line 26 666

In the / preferred starting materials, X is a bromine atom and Rq has the meaning of R, or denotes the remainder

ti

C - CH - X or the radical - R ₇

it '

Itj Ά ·? '.

in which R .., Rp, R ,, X and η have the aforementioned preferred meanings. R _{Q denotes} the rest

O R ₁ CH dd I « I. N- C. - C - R, I. I. H

- X

so R. always designates the remainder in the end product

O =

C ι

C - R

stands

for the rest

so means

the rest in the end product

The radicals and rings mentioned can still be carried out under the reaction conditions inert groups and / or atoms, e.g. cyano, nitro, sulfonyl groups, chlorine, bromine or iodine atoms; Egg alkylamino groups with 2 to 6 carbon atoms, alkoxy groups,

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Alkyl groups each having 1 to 4 carbon atoms, carbalkoxy groups with 2 to 4 carbon atoms.

The starting materials II can easily be converted into halocarboxylic acid halides with ammonia or the corresponding amines, carboxamides, sulfonamides ^ ureas, Urethanes or hydrazines are produced. With di- or polyamino compounds, two or more are correspondingly obtained Starting materials II containing ß-halocarboxamide groups, their implementation by the process of the invention leads to the bis- or poly-ß-lactams. E.g. one obtains from α, α-disubstituted β-bromocarboxylic acid chlorides and alkylene or arylenediamines Alkylene- or arylene-bis-ß-bromocarboxamides and their Reaction in the presence of tertiary amines N, N'-alkylene or N, N'-arylene-bis-ß-lactams.

R.
ι

R t

BrCH-C-C-N-R'-N-C-C-CH-Br

1 t If I I It I I

R ³ R ² 0 HH 0 R ² R ⁵

- 2 HBr

In a preferred embodiment of the method according to In accordance with the invention, the starting material II thus formed is not separated off, but rather in the reaction mixture of the reaction of β-halocarboxylic acid halide and the aforementioned amino compound converted directly to the end product I. The tertiary amine is from Initially at least stoichiometric, advantageously in an excess, e.g. 2.2 to 10 mol of amine per mol of ß-halocarboxylic acid halide, added and serves at the same time in the production of the starting material II and the end product I each for binding of the hydrogen halide formed. The preferred embodiment can be in the case of β-bromo-α, α-dimethyl-propionic acid chloride and aniline can be represented by the following formulas:

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2012276

BrCH ₂ -

- HCl, -HBr

For example, the chlorides or bromides of the following ß-bromocarboxylic acids are used: α, α-dimethyl, a, a, diethyl, α, α-diisopropyl-, <x, a-dibutyl-, a-methyl-a-propyl, a-ethyl-abutyl-, a-methyl-a-cyclohexyl-, a, a-di (chloromethyl) -ß-bromopropionic acid, i-bromomethyl-cyclobutane, 1-bromomethyl-cyclopentane, 1-bromomethyl-cyclohexane, i-bromomethyl-cycloheptane-carboxylic acid, aMethyl-a-phenyl-, a, a-diphenyl-, a, a-di-p-tolyl-ß-bromopropionic acid, a, a-i) ibenzyl-bromopropionic acid, α, α-dimethyl-β-bromobutyric acid, 1-methyl-2-bromocyclohexanecarboxylic acid- (1); α-pyridyl-α-methyl, α, α-dimethyl-β-pyrrolidinyl, α, α-diethylβ-morpholinyl-β-bromopropionic acid; analogous ß-chloropropionic acids.

As amines for the production of starting material II come e.g. into consideration: methyl-, ethyl-, butylamine, 2-methylpentylamine, Benzylamine, 2-ethylhexylaniine, cyclohexylamine, ethylenediamine, Propylenediamine, hexamethylenediamine, bis (4-aminocyclohexyl) methane; Aniline, o-, m-, p-chloroaniline, 2,4-dichloroaniline, 3,4-dichloroaniline, 2,4,6-trichloroaniline, o-, m-, p-mtraniline, o-., m-, p-anisidine, phenetidine, p-aminO'-biphenyl, p-bromoaniline, p- (dimethylamino) -aniline, o-, m-, p-toluidine, p-aminobenzeo acid, α-, ß-lfaphthylamine, 9-aminoanthracene, 3-aminopyridine, 3-aminoquinoline, hydrazine, asymm. Dimethylhydrazine, acetic acid hydrazide, Acetamide, propionylamide, isobutyrylamide, urea, asymra. Dimethyl urea, O-ethyl urethane, O-phenyl urethane, Benzolsulfonsäureamid, Ä'thylsulfonsäureamid; Cyclohexyl, Benzylhydrazine, phenylhydrazine, piperidinecarboxamide, phenylenedlamine, Benzidine.

Correspondingly, the ^ -halocarboxamides obtained by reacting the abovementioned β-bromocarboxylic acid chlorides or bromides with ammonia or the abovementioned amines can be used as starting materials II. The dehydrohalogenation of the starting substance II is carried out in the homogeneous phase, as a rule, at a temperature between 0 and 30O ⁰ C, preferably between

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20 and 200 C, pressureless or under pressure, continuous or carried out discontinuously. In many cases, the tertiary amine also serves as a solvent, if appropriate if inert, organic, polar solvents are used under the reaction conditions, e.g. chlorinated hydrocarbons such as methylene chloride, Chloroform, carbon tetrachloride; Ethers such as tetrahydrofuran, dioxane; cyclic amines such as pyridine, quinoline; Ketones such as acetone, diethyl acetone, dibutyl ketone, methyl isobutyl ketone; Dimethyl sulfoxide; or corresponding mixtures. The preferred solvents include amides disubstituted on the nitrogen, such as dimethylformamide and N-methylpyrrolidone and hexamethyl phosphoric acid triamide. For reactions at normal pressure it is expedient to choose amines and solvents with a boiling point greater than or equal to the required reaction temperature. Conversions in pressure reactors, on the other hand, are common to all Cases can also be carried out with amines and solvents whose boiling points are below the reaction temperature of the amide in question lie.

The dehydrohalogenation is carried out in the presence of tertiary amines whose pK-g value is below 8, preferably between 3 and 5, carried out. The pK-g value is defined as described in S. Patai, "The Chemistry of the Amino Group" (Intersc. Publ., John Wiley & Sons, 1968), pp. 161-204. The amine can be used in a stoichiometric amount or in excess, based on the amount of hydrogen halide released; amounts of from 1 to 15 moles of amine per mole of starting material II are generally suitable. In many cases, the rate of dehydrohalogenation increases with the excess of amine; the amount of amine will therefore expediently be chosen depending on the desired reaction time and the effort required to distill the excess amine. The rate of reaction of the starting materials II increases with decreasing pE-g values of the tertiary amines and with increasing reaction temperature. Preferred tertiary amines are those of the aforementioned pK _ß - ¥ erts and the general formula

N — R ₉ III,

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in which the individual radicals Rq are identical or different can and each have an alkyl radical with 1 "to 6 carbon atoms, a cycloalkyl group with 5 to 12 carbon atoms, an aralkyl group with 7 to 12 carbon atoms, mean an aryl radical with 6 to 12 carbon atoms, in addition each two the residues Rg together with the neighboring nitrogen atom too Members of a 5- or 6-gelledrigen, · saturated heterocyclic Ring, which can also contain an oxygen atom, a sulfur atom or a further nitrogen atom. Such Rings come in the form of bicyclic compounds in which one or two nitrogen atoms and a radical Rg are common to both rings belong in question. Appropriately substituted polyamino compounds, for example ion exchange resins such as poly (dimethylaminoalkyl) styrene and poly (N-dimethylaminopropyl) acrylamide, can ~ can also be used advantageously. ™

For example, the following tertiary amines are suitable as catalysts: trimethylamine, triethylamine, tripropylamine, tributylamine, Dimethylethylamine, methyl-diisopropylamine, triisopropylamine, Dimethyl-benzylamine, dimethyl-cyclohexylamine, N-methylpiperidine, !! ", N'-dimethylpiperazine, N-methyl-morpholine, N-methylthiomorpholine, Quinuclidine, diaza-bicyclo-octane (2,2., 2), N, IT-diethylaniline, Ν, ΐί-dimethylaniline.

The reaction can be carried out as follows: A mixture of Starting material II and tertiary amine, optionally together with solvent, is for 5 minutes to 10 hours under good Jj Maintaining thorough mixing at the reaction temperature. The end product is then separated from the mixture in a conventional manner, e.g. by filtration of the tertiary ammonium salt, removal of excess Solvent and amine and fractional distillation of the residue. Before distillation, the residue can be removed by dissolving it in a suitable solvent, e.g. chloroform, and washing with water.

The starting material II can advantageously also be prepared first in the manner described, for example by reacting 0.9 to 1.2 mol of starting amine per 1 mol of β-halocarboxylic acid halide for 5 minutes to 4 hours at the reaction temperature in '

■ - 12 -.

109833/1822

° · ^Ζ

a mixture with the tertiary amine and optionally solvent. Parts of the starting material II formed begin to dehydrohalogenate as early as during production. Then cool the mixture is filtered off, the salt of the tertiary amine formed is filtered off and, if appropriate, the filtrate is kept for 5 min 5 hours again at the reaction temperature in order to implement remaining proportions of the starting material II formed. The other The mixture is then worked up in the aforementioned manner.

The compounds which can be produced by the process of the invention are valuable starting materials for the production of fibers, Textile auxiliaries, pesticides and plastics. With regard to their use, reference is made to the patent documents mentioned.

The parts given in the examples are parts by weight. They relate to parts by volume like the kilogram to the liter.

example 1

128 parts of bromopivaloylanilide (melting point 95 ° C.) are heated to boiling under reflux with stirring in a mixture of 300 parts by volume of dimethylformamide and 300 parts by volume of triethylamine. After the reaction mixture has cooled down, the precipitated triethylammonium bromide is filtered off and the dimethylformamide and triethylamine are distilled from the filtrate at from 20 to 200 torr. The residue is taken up in chloroform, washed with water, dried and fractionally distilled. This gives 80.6 parts of 1-phenyl-3,3-dimethylazetidinone of boiling point 115 to 117 ⁰ C at 2 Torr, corresponding to a yield of 91.6 $> of theory.

Example 2

131 parts Brompivaloyl-N-cyclohexylamide (melting point 99 to 100 ⁰ C) and 400 parts of triethylamine are mixed well for 8 hours at 200 ⁰ C in an autoclave. The precipitated triethylammonium bromide is filtered off and triethylamine is removed by distillation from the Fil . The residue is dissolved in chloroform

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taken ", washed with water, dried and fractionated,
This gives 75.2 parts of 1-cyclohexyl-3,3-dime-thyl-azetidinone (2) of boiling point 103 to 104 ⁰ C at 1 Torr, corresponding to 83 tf of theory. '

Example 3 to 12

Analogously to Examples 1 and 2, 0.5 mol of the amides of all common formula V in 400 parts by volume of the solvents mentioned in the table and 300 parts of triethylamine in the given reaction time to the ß-i-lactams of the general formula VI dehydrobrominated. The final product is cleaned by Crystallization from benzene / petroleum ether.

OH,

CH.

BrCH ₉ - CC
CH ₃ °

H H

CH,

- HBr

VI

10 9 8 3 9/1822

_0BlGlNAL

Amide 7 solution

Melting boiling point medium
point ⁰ C ⁰ C / Torr

React reaction. . End product temp. time (h) melting boiling yield ( ⁰ C) point ⁰ C ll% l _rx in * der

theory

36
82-84

119-120
112-114

145-146

114-115

187/1

195-196 / 1

Dimethyl formamide

Dimethylformamide

Dimethylformamide

Dimethylformamide

Dimethylformamide

Dimethylformamide

10 2

63-64 / 12 74.5

59-61 124-125 / 1 93.5

58-60 138-139 / 1

68-70 132-133 / 1

132-134 / 1 87.6

104-105 194-195 / 2 86.3

105-106

88.7 ν

Amid V solution

Melting boiling point middle point ⁰ C ° C / Torr

React reaction temp. tion ( ⁰ C) time (h)

End product VI

Melting boiling yield

in theory

point " ⁰ C

NO,

116-117

120-121

Dimethyl formamide

Dimethyl formamide

HCG1 "65

0.5 105-106

0.5 78-80

139-141

94.1

95.2

- 16 - O.Z. 26 666

Example 13

180 parts Brompivaloylamid (melting point 105 to 106 ⁰ C; boiling point 174 to 175 ^ ⁰ O), 500 parts of triethylamine, 200 parts by volume of dioxane and 300 parts by volume of chloroform are well durchmiecht 8 hours at 160 ⁰ C in an autoclave. The resulting triethylammonium bromide is filtered and the filtrate is fractionated. In the boiling range 94 A mixture of 32.5 parts of 3,3-dimethyl-azetidinone, a total yield of dehydrobromination of 88.3 is obtained to .100 ⁰ C at 13 Torr (2) and 47 parts of isomeric hydroxypivalic acid nitrile corresponding to $ the theory.

Example 14

386 parts of F, ff'-Ithy1en- (1,2) -bis-bromopivaloylamide (melting point 104 to 105 ° C) are in a mixture of 500 parts by volume of dimethylformamide and 800 parts of ΙΤ, Ν-dimethyl-cyclohexylamine for 15 hours reflux with stirring at 145 ⁰ C heated. Filter the reaction mixture and receives 182 parts of N, N'-ethylene-bis-3,3-dimethyl-azetidinone (2) of boiling point 165 to 170 ⁰ C at 4 Torr, and melting point 60 to 62 ⁰ C (from benzene / petroleum - ether), corresponding to 81 # of the theory.

Example 15

To a solution of 216 parts of p-phenylenediamine in 1,200 parts by volume of dimethylformamide, and 1000 parts of triethylamine are added with stirring at 40 to 50 ⁰ C in the course of 2 hours 1 800 parts Brompivaloylchlorid. The reaction mixture is heated under reflux for 4 hours to 105 to 110 ⁰ C, cooled to room temperature, filtered off from crystallizing Triäthylammoniumbromid and heated finally 4 hours at 110 ⁰ C. The solvent and triethylamine are removed by distillation under reduced pressure and the residue is washed with water until no more bromide can be detected in the washing machine. Recrystallization from benzene / petroleum ether gives 465 parts of N, N ^f -p-phenylene-bie-5,3-dimethyl-a-betidinone- (2) rom melting point 178 to 180 ⁰ , corresponding to 85 _f 5 I * of theory on p-phenylenediamine and bromopivaloylochloride.

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Example 16

To 188 parts of benzidine in 600 parts by volume of dimethylformamide and 500 parts of triethylamine are added with stirring at 40 ⁰ C over one hour 400 parts Brompivaloylehlorid and heated for 6 hours under reflux at 105 to 110 ⁰ C. The mixture is filtered and. removed the solvent from the mixture by distillation under reduced pressure. The residue is washed successively with water, hydrochloric acid and water and recrystallized from a mixture of acetone and water. This gives 206 parts of N, IT · -4,4'-biphenylene-bis-3., 3-dimethyl-azetidinone to 256 ⁰ C, corresponding to 59.2 i> of theory, relative (2) of melting point 253 to the Raw materials.

Example 17

To a solution of 137 parts-Phenetidiri p in 300 parts by volume of dimethylformamide and 500 parts of triethylamine are added at 40 to 50 ⁰ C, with stirring, 200 parts Brompivaloylehlorid and heated "5 hours" 105 to 110 ⁰ C. It is filtered, the Triäthylammoniumbromid, distilling the Solvent off, the residue washes successively with water, dilute hydrochloric acid and water and finally the residue is recrystallized from petroleum ether. This gives 134.5 parts of N- | p-ithoxyphenyl] -3,3-dimethyl-azetidinone (2) of melting point 62 to 64 ⁰ C, corresponding to 61.4 i> of theory, based on the starting materials. ■ ■ -

Example 18 - \

85 parts of 2-methyl-2-phenyl-3-bromopropionyl-N-methyl amide (melting point 96 to 98 ⁰ G), 300 parts of triethylamine and 100 parts by volume of dimethylformamide are well durohmischt 8 hours at 200 ⁰ C in an autoclave. It is filtered and the solvents are distilled off from the filtrate under reduced pressure. The residue ^{%:? Oil} is taken up in chloroform, washed with water and fractionated. 46 parts of 1-methyl-3-methyl-3-pnenyi ^ azeticli- ⁱ '\ ^K -non- (2) with a boiling point of 112 to 114 ⁰ O at 1 torr, corresponding to ^v ' ^: 76.2 $ ί ider ^ are obtained Theory, based on the starting material. ; ^ -v dc ^!

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Example 19

A solution of 100.5 parts Brompivaloyl-p-nitroanilide (m.p. 120-121 ⁰ C) in 300 parts by volume of dimethylformamide at 70 ⁰ C by 1000 parts by volume of the ion exchanger available under the name ® LEWATIT MP 62 commercially (poly- (dimethylamino -alkyl) -styrene). The exchanger is located in a vertical jacketed pipe the inside diameter of 5 cm and held by external heating with hot water at 70 ⁰ C. It is eluted with a further 200 parts by volume of dimethylformamide, the solvent is distilled off from the total eluate under reduced pressure and 70.4 parts of salt-free 1-p-nitrophenyl-3,3-dimethyl-azetidinone (2) with a melting point of 137 to 139 ^{0 are obtained as residue} C, corresponding to 96 $> of theory, based on the starting material.

Example 20

111.5 parts of bromopivaloyl ureide are refluxed for 15 hours in 400 parts by volume of triethylamine. The mixture is filtered the precipitating Triäthylammoniumbromid distilled from the filtrate the solvent off under reduced pressure and the residue kri from benzene / petroleum ether to crystallizes. This gives 5514 parts of 1-carbamoyl-3,3-dimethyl-azetidinone (2) melting point from 98 to 100 ⁰ C.

Example 21

A solution of 120 parts of Ν, Ν'-bis-brompivaloyl hydrazide (m.p. 186-188 ⁰ C) in 300 parts by volume of acetone and 300 parts of triethylamine is stirred for 4 hours in a stirred vessel. Triethylammonium bromide separates out and the temperature of the reaction mixture temporarily rises from 20 ° C. to 45 ° to 50 ^° C. It is filtered and the acetone and triethylamine are distilled off from the filtrate. The residue is taken up in benzene, after separating off an oily portion that remains undissolved, treated with a little animal charcoal and fractionally crystallized by adding petroleum ether while cooling with ice; Man

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initially holds 32 parts 1, S-Diaza ^ jö-ai-oxo-S, ^,?,? - tetramethylbicyclop, G, 3j -octane from melting point 148 to 150 C and finally. 28.5 parts of a mixed crystal of 56.2 fo 1,5-diaza-2,6-dioxo-3,3,7,7-tetramethylbicyclo- | 3, O, 3j-pctane and 43.8% N, N ' -Bis- (3,3-dimethyl-azetidinone- (2) .. By recrystallizing the mixed crystals from water, pure N ₁ N'-bis- (3,3-dimethyl-azetidinone - (2) with a melting point of 108 " up to 109 ⁰ C.

109839/1822

Claims (1)

- 20 - 0.Z.26 666 20122T6 Claim Process for the preparation of 3,3-disubstituted β-lactarns the general formula R ₂ - C - _? = O R-C-N-R may represent may be the same or different in R .., Rp, R * and R. and each is an aliphatic, cycloaliphatic, araliphatic or heterocyclic radical rule, in addition, also W Rz and / or R each represents a hydrogen atom denote off st , R ₁ and R ₂ ! Together with the adjacent carbon atom or RJ and R, together with the two adjacent carbon atoms, can also each denote members of a cycloaliphatic or heterocyclic ring, R 1, R ₂ and / or R. also denote an aromatic radical can, Usually also for an alkylsulfonyl radical, arylsulfonyl radical, the rest rest rest 0 ^R 6 R ₅ -C- \ ₀ the the Il
-C- 0R _c , or where the individual radicals R ₅ and Rg may be different or the same and each represents a hydrogen atom, an aliphatic _r cycloaliphatic, araliphatic, aromatic radical beseich NEN, moreover Rg together with the adjacent nitrogen - 21 109839/1822 - 21 - O. Z. 26 666 atom and the neighboring radical Rp- also members of a heterocyclic Can mean ring, or Rg also a .Sulfonic acid group or can denote an arylsulfonyl radical, O = C - C. - R _?
the remainder "" - Ä - 0 - R ~ or the rest can stand, in which R ₁ Y R 2 and R, have the abovementioned meaning, η = 1 or an integer greater than 1 W, R ₇ denotes an aliphatic, cycloaliphatic or aromatic radical., '■'. ---. - ■ · - .; ■, "· ■■■■ _"'■ ■ - · by dehydrohalogenation of -fl ^ ffalogencarbbrisatireamiden ^; in 'öegenwart of basic compounds, characterized in that ß-Halögencarbonsäureamide of the general formula χ - GH - G - C - F - Ro II * II Il - "tr ^{σ RR} 2 ° . - ■ in ä «r Eg has the meaning of R« or i ^ the remainder OR ₁ . I. O.Z. or the rest - R Il denotes, R .., R ^ and R, have the aforementioned meanings and X stands for a halogen atom, dehydrohalogenated in the presence of tertiary amines whose pK-g value is below 8. Badische Anilin- & Soda-Fabrik AG 109839/1822