CH642370A5 - Process for the preparation of imidazo[2,1-a]isoindoles - Google Patents

Description

The present invention relates to a process for the preparation of imidazo (2, l-a) isoindoles of the formula (I):

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where X represents hydrogen, halogen and in particular fluorine, chlorine and bromine and lower alkoxy.

Imidazo (2, l-a) isoindoles of the formula (I) and processes for their preparation have already been described, for example in GB-PS 1 225 411.1 225 412 and 1 225 413.

In these patents such imidazo (2, l-a) isoin-doles are described as biologically active substances and are said to be used as psychological stimulants and anorectics. At present, the best known compound is probably the 5- (p-chlorophenyl) -2,3-dihydro-5-hydroxy-5H-imidazo (2, l-a) isoindole, commonly referred to as "mazindole".

The prior art knows several processes for the preparation of compounds of the formula (I), but all of these processes have disadvantages. For example, in the processes described in the above-mentioned patents, the reduction of an intermediate carbonyl compound is carried out, which is followed by a very difficult oxidation. The individual process steps and especially the latter are very time consuming. Although it is stated in the patents that the oxidation can be carried out by blowing air or oxygen in a relatively short period of time, it is emphasized at the same time and shown in all examples with only one exception that a very mild oxidation is carried out in which the reaction mixture is in contact with air for a period of several and usually six days. Because the simple process of blowing gas, and particularly air, into a reaction mixture generally presents few problems, the emphasis on the use of very long-term oxidation indicates that this type of oxidation is highly preferred. In the above methods, lithium aluminum hydride s is used as an agent for reducing the carbonyl intermediate. This agent is very expensive and also very flammable. This may be acceptable in small quantities, the use of this reagent in large quantities, i.e. On a commercial scale, however, it is very (I) dangerous, requires special precautionary measures and is associated with large expenses. It should also be pointed out that the above-mentioned patents only describe the process yield with general expressions and, for example, as “considerable”. No specific yield is given in any of the three cited patents, and although a much later reference [J. Med. Chem. 18, 177, (1975)] states that a yield of 65% is possible in the oxidation, the applicant of the present application could not even achieve a yield of 20% of the stated value by carrying out the same process .

The present invention is therefore based on the object of specifying an improved process for the preparation of compounds of the formula I, in which process less dangerous and cheaper reagents are used, in which the reaction is carried out in a substantially shorter period of time and the overall yield is increased can.

The method according to the invention has the features mentioned in claim 1.

30 The terms "lower alkyl" and "lower alkoxy" mean groups with at most 6, preferably at most 3, carbon atoms.

Preferred embodiments of the new process relate to imidazo- (2, l-a) isoindoles, in which the halogen 35 is preferably fluorine, chlorine or bromine.

Preferably, when reacting the compound of formula (II) with the alkylating agent and / or when reacting the salt of formula (III) with ethylenediamine under an inert gas atmosphere, such as nitrogen, and / or in the presence of a solvent, such as Methylene chloride. The hydrolysis of the intermediate of formula (IV) is preferably carried out in the presence of an acid. The reactions in methylene chloride can be carried out at temperatures up to the reflux temperature 45 of the solvent.

The dialkylaminolactams of the formula (IIa) given below which are suitable as starting materials for the process according to the invention are new compounds. These and the alkoxylactams of the formula (IIb) can simply be prepared from the corresponding benzoylbenzoic acid derivatives, for example according to the following scheme:

O SOCI;

* Cl

X

(VI)

H2NRi HO -

L>

NO

X

(VIi)

5

Scheme (continued)

642 370

SOCI.

NO

1, 5NR zR ■

RuO

(IIa)

(Till)

(Hb)

wherein Ri, R2, R3, R4 and X have the meaning given above.

The benzoyl-benzoic acid derivatives of the formula (V) are easy to prepare [for example according to W. Graf, E. Girod, E. Schmid and W. G. Stoll, Helv. Chim. Acta, 42, 1085 (1959)]. For example, the 2- (4'-chlorobenzoyl) benzoic acid required as a starting material for the production of mazindol can be obtained by reacting chlorobenzene with phthalic anhydride.

The invention is described below with the aid of a few preferred exemplary embodiments, without being restricted to these examples.

Examples 1 to 6 show the preparation of specific compounds of the formula (I) using the new compounds of the formula (IIa). Examples 1 to 5 provide the preferred compound mazindole.

example 1

Preparation of Mazindol from Dimethylaminolactam [Formula (IIa) with Ri = CH3: R2 = R3 = CHj: X = Cl],

60 g (0.20 mol) of crystalline dimethylaminolactam II were added to a solution of 48 g (0.25 mol) of triethyloxonium fluoroborate [the triethyloxonium fluoroborate was prepared in situ according to H. Meerwein, Org. Synthesis, Coli. Vol. V, 1080 (1973)] added to 80 ml of dry methylene chloride. The mixture was stirred at reflux temperature under nitrogen for 5 hours, cooled to 0 ° and for 30 minutes. an amount of 30.6 g (0.51 mol) of ethylenediamine was added. The mixture was then heated to reflux temperature for a further 5 hours under nitrogen, cooled to 5 ° and strongly acidified by carefully adding 200 ml of an aqueous solution of 4N hydrochloric acid. After a further 3 hours of heating to the reflux temperature of 40 °, the methylene chloride was removed by distillation and the mixture was made basic (pH 8.0 to 8.5) with 45 ml of 50% (w / v) sodium hydroxide. The resulting voluminous white precipitate was filtered off and washed twice with 100 ml of water. After drying at 25 °, 64 g of raw material were obtained. The recrystallization from methanol methylene chloride (1: 1) followed by

Slurry with reflux in the same solvent system gave a yield of 35.3 g (corresponding to 62% of theory based on (IIa) pure Mazin-dols with a melting point of 201 to 202 °, determined with a Thompson-Hoover capillary melting point determination apparatus with Setting 6.5.

35

Analysis:

Calcd: C 67.49%; H 4.60%; N9.84%; Cl 12.45%; 0 5.62% 40 found: C 67.25%; H 4.69%; N9.74%; Cl 12.42%; 0 5.62%

Example 2

4s Preparation of Mazindol from Pyrrolidinyllactam [Formula (IIa) with Ri = CH3; R2 with R3 = - (CH2) 4-; X = Cl].

2.0 g (6.1 mM) pyrrolidinyl lactam dissolved in 3 ml dry methylene chloride was added to 2.4 g (13 mM) triethyloxonium fluoroborate, prepared as described in Example 1 50 and dissolved in 3 ml methylene chloride and heated to reflux under nitrogen for 5 hours. After cooling to 0 °, 3.6 g (60 mM) of ethylenediamine were added, the mixture was heated to reflux 55 under nitrogen for 5 hours and then stirred at 25 ° for 18 hours. Then 10 ml of 4N hydrochloric acid were added until the solution was strongly acidic and the mixture obtained was heated to reflux for 3 hours. After cooling, 10 ml of 20% sodium hydroxide solution were added until the pH 60 was 7.5 to 8.5 and a large amount of a white one

Precipitation was observed. The mixture was then 30 min. stirred at 0 °, filtered off and the filtrate washed with cold water. The crude mazindol obtained in this way was dried at 60 ° for 18 hours and then recrystallized from 65% methanol, giving 0.8 g of pure mazindol, which corresponds to 46% of theory. The pure Mazindol had the same properties as the product of Example 1.

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Example 3

Preparation of Mazindol from Piperidinyllactam [Formula (IIa) with Ri = CHs; R2 with R3 ■ = - (CHîJs; X = Cl].

A solution of 1.0 g (2.9 mM) of the lactam dissolved in 5 ml of dry methylene chloride was added to 2.4 g (13 mM) of triethyloxonium fluoroborate (prepared according to Example 1 and dissolved in 2 ml of dry methylene chloride). The mixture was heated to reflux under nitrogen for 5 hours and then cooled in an ice bath. 3 g (50 mM) of ethylenediamine were then added dropwise over the course of 10 minutes and the mixture was heated to reflux under nitrogen for 18 hours. After the mixture had cooled to 25 °, 15 ml of 10% strength aqueous hydrochloric acid were added and the acidic mixture was heated to reflux with a pH 1 for 4 hours. After basification of the solution obtained in the manner described with 15 ml of 10% sodium hydroxide solution, a voluminous white precipitate separated off. The entire mixture was then stirred in an ice bath for 20 min, filtered and washed well with cold water. After air drying, the precipitate was slurried in cold ether, filtered off and washed with cold ether to give 250 mg (30% of theory) of crystalline mazindol, which had the same properties as the product of Example 1.

Example 4

Preparation of Mazindol from Dimethylaminolactam [Formula (IIa) with Ri = CH3; R2 = R3 = CH3; X = Cl] using dimethoxycarbenium fluoroborate [(CH30) 2C + H BFÏ],

5 g (31 mM) of dimethoxycarbenium fluoroborate [prepared in situ according to RF Borch, J. Org. Chem., 34, 627 (1969)] were slurried in 10 ml of methylene chloride under a nitrogen atmosphere and 3 g (10 mM) of the dimethylamino-lactam added. The mixture was stirred at room temperature for 18 hours. The resulting yellow solution was cooled to 0 ° and then 6.3 g (105 mM) ethylenediamine were added over 15 min. The mixture was heated to reflux for 5 hours and then cooled back to 0 °. 20 ml of 4N aqueous hydrochloric acid were then added and the mixture was heated to reflux again at 40 ° for 5 hours. After cooling, the mixture was separated and the organic fraction was washed with 10 ml of 2N aqueous hydrochloric acid. The washing liquid was combined with the previously separated aqueous fraction and the mixture was made basic with 10 ml of a 50% sodium hydroxide solution, after which the pH was about 9.0. A precipitate formed, which was collected by filtration and washed with 20 ml of water and then dried at 25 °. The crude product was slurried in ethyl acetate, filtered and washed with cold ethyl acetate, whereby 450 mg (corresponding to 16% of theory) of crystalline mazindol with the properties described above were obtained.

Example 5

Preparation of Mazindol from methoxylactam [Formula (IIb) with R4 = Ri = CH3; X = CI]. A solution containing 500 mg (1.7 mM) of methoxylactam in 5 ml of dry methylene chloride was added to a solution of 370 mg (1.9 mM) of triethyloxonium fluoroborate in 2 ml of dry methylene chloride, the latter of which was kept under a nitrogen atmosphere. The mixture was stirred at room temperature under nitrogen for 18 hours. The resulting yellow solution, which contained the corresponding methoxyimidate salt, was then added over 15 minutes to a solution of 2 g (33 mM) of ethylenediamine in 10 ml of methylene chloride kept at 0 °. The mixture was stirred at room temperature for 48 hours and then strongly acidified by adding 50 ml of 5% aqueous hydrochloric acid. The mixture was then heated to reflux at 40 ° for 5 hours and then partitioned. The layer of organic material was washed with 10 ml of a 5% aqueous hydrochloric acid and the combined aqueous phases by adding 5 ml of a 50% (w / v) sodium hydroxide solution to a pH of 8.0 up to 8.5 basic. The resulting precipitate was separated by filtration, washed 10 with 20 ml of water and dried at 60 °. The crude product was then slurried in cold ether, filtered, washed with cold ether and gave 85 mg (17% of theory) of crystalline mazindol with the properties described above.

15

Example 6

Preparation of 5-phenyl-2,3-dihydro-5-hydroxy-5H-imi-dazo- (2, l-a) isoindole from dimethylaminolactam [Formula (IIa) with Ri = C2H5; R2 = Rs = CHs; X = H]. 12 g (63 mM) of triethyl 20 oxonium fluoroborate, prepared as in Example 1, were dissolved in 7 ml of dry methylene chloride. A solution of 7.2 g (26 mM) of dimethylaminolactam in 10 ml of methylene chloride was added to this solution and the mixture was heated under reflux for 5 hours and stirred. After cooling to 0 ° C. for 25 minutes, 20 g (330 mM) ethylenediamine were added in 15 min and the mixture was stirred at room temperature under nitrogen for 18 h. The mixture was then cooled to 0 ° and strongly acidified by adding 80 ml of 4N aqueous hydrochloric acid. After reheating to reflux for 3 hours, the mixture was cooled again and made basic by adding a 10% aqueous sodium hydroxide solution. The resulting voluminous white precipitate was filtered and washed twice with cold water. The crude product was dried at 60 ° for 3 seconds and recrystallized from methanol, 4.4 g (corresponding to a theoretical yield of 68%) of pure target product with a melting point of 200 to 202 ° [Lit .: 202 to 203 °, P. Äberli et al, J. Med. Chem. 18, 177 (1975)]

were obtained.

40 The following examples describe the preparation of new lactams of the formula (IIa):

Example 7a

Preparation of pseudo acid chloride [formula (VI) with 45X = H],

100 g (0.44 mM) of o-benzoylbenzoic acid (V) were added to a solution of 55.3 g (0.47 mM) of thionyl chloride in 100 ml of chloroform and the mixture was heated to reflux for 2 hours. Excess thionyl chloride and solvent were then removed under reduced pressure; 108 g (100% of theory) of crude acid chloride (VI) were obtained. This material was used for the following reactions without additional purification.

55 Example 7b

Preparation of hydroxylactam [Formula (VII) with Ri = -C2H5; X = H].

A mixture of 110 ml of 70% aqueous ethylamine (corresponding to 1.7 mM amine) and 100 ml of dioxane 60 was prepared and cooled to 0 °. A solution of 24.5 g (0.10 mM) of the crude acid chloride (VI) prepared according to Example 7a in 50 ml of chloroform was added dropwise to this mixture in 30 minutes. The resulting mixture was stirred at room temperature for 30 minutes and then all of the solvent was removed by heating under reduced pressure. The solid raw material was recrystallized from benzene and gave 19.9 g (79% of theory) of white crystalline hydroxylactam (VII) with a melting point of 167 to 169 ° (Lit .: 168 to

170 °, W. Graf, E. Girod, E. Schmid & W. G. Stoli, Helv. Chim. Acta, 42, 1085 (1959)).

Example 7c

Preparation of dimethylaminolactam [Formula (lia) with Ri - -C2H5; R2 = R3 = CHa; X = H],

10 g (39.5 mM) of hydroxylactam (VII), prepared according to Example 7b, were added in portions to 15 ml of thionyl chloride over the course of 20 minutes. The solution was left to stand at room temperature for 30 minutes and then excess thionyl chloride was removed under reduced pressure. The obtained solid chlorolactam (VIII) was dissolved in 20 ml of chloroform and the solution was added to 30 ml of chloroform which had been saturated with dimethylamine gas beforehand. The mixture was left to stand for 10 minutes, then washed with water and the organic portion dried over sodium sulfate. The crystalline raw material obtained after removal of the solvent under reduced pressure was slurried in hexane and, after filtering, gave 7.8 g (70% of theory) of white crystalline dimethylaminolactam (IIa) with a melting point of 116 to 117 °.

Example 8a-b

Preparation of pseudo acid chloride [formula (VI) with X = Cl] and its conversion into the corresponding hydroxylactam [formula (VII) with Ri = CH3; X = Cl].

51.2 g (0.43 mol) of thionyl chloride were added to a suspension of 100 g (0.38 mol) of 2- (p-chlorobenzoyl) benzoic acid (V) and 2 g of dimethylformamide in 250 ml of methylene chloride within 15 min given. The mixture was slowly warmed, held at reflux temperature for 3 hours and stirred, a solution of the acid chloride (VI) used as an intermediate being formed. This solution was cooled to room temperature and added to 100 g of a 40% aqueous solution of methylamine (1.29 mol amine) over a period of 20 minutes at 0 °. The mixture was stirred at room temperature for one hour, then cooled to 0 ° and acidified with 150 ml of 6N aqueous hydrochloric acid. After that, most of the methylene chloride was evaporated, whereupon the product crystallized out. The crystals obtained in this way were filtered off, washed with cold water, dried at 60 ° and gave 102 g (97% of theory) of hydroxylactam (VII) with a melting point between 190 to 194 ° (Lit .: 196 to 199.5 ° , W. Graf, E. Girod, E. Schmid & WG Stoll, Helv. Chim, Acta, 42.1085 [1959]).

Example 8c (l)

Preparation of dimethylaminolactam [Formula (IIa) with Ri = CHs; R2 = R3 = CHs; X = Cl].

To a slurry of 46 g (0.17 mol) of hydroxylactam (VII), which was prepared according to Example 8b, in 140 ml of methylene chloride, 24 g (0.20 mol) of thionyl chloride were added at 0 ° and for 20 minutes. The solution obtained was warmed to 25 °, stirred for 1 hour and then cooled again to 10 °. Gaseous dimethylamine was introduced into this solution of chlorolactam (VIII) for 15 to 20 minutes. The resulting mixture was washed twice with 50 ml of water and the remaining organic portion was dried with sodium sulfate. The solvent and the excess amine were then removed under reduced pressure and an oily crude product was obtained. After trituration with cyclohexane, 45 g (89% of theory) of high-quality crystalline dimethylaminolactam (II) with a melting point of 111 to 112 ° were obtained.

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Example 8c (2)

Preparation of pyrrolidinyl lactam [Formula (IIa) with Ri = CH3; R2 with R3 = - (CH2>; X = C1],

2 g (7.3 mol) of solid hydroxylactam (VII), which had been prepared according to Example 8b, were added in portions to 10 ml of thionyl chloride and the mixture was left to stand at room temperature for 10 min. The excess thionyl chloride was then removed under reduced pressure and a crude solid chlorolactam (VIII) was obtained which was dissolved in 10 ml of chloroform. 1.3 g (18 mol) of pyrrolidine in 5 ml of chloroform were then added. The mixture thus obtained was stirred at room temperature for 10 minutes and then washed with 10 ml of water. The organic portion was then dried over sodium sulfate and the solvent removed under reduced pressure to give 2.2 g (92% of theory) of pyrrolidinyl lactam in the form of an oil. This material was used for the production of Mazindol without additional purification.

Example 8c (3)

Preparation of piperidinyl lactam [Formula (IIa) with Ri = CH3; R2 with R3 = - (CH2) s-; X = Cl].

1.0 g (3.7 mol) of solid hydroxylactam (VII), which had been prepared according to Example 8b, was carefully added to 6 ml of thionyl chloride. The mixture was left at room temperature for one hour and then the excess thionyl chloride was removed. This gave crude solid chlorolactam (VIII), which was dissolved in 5 ml of methylene chloride. 1.0 g (12 moles) of pipidine was then added to the solution. After 10 min at room temperature, the mixture was washed with 5 ml of water and the organic fraction was dried over sodium sulfate. After removal of the solvent under reduced pressure, 1.2 g (96% of theory) of oily piperidinyl lactam (II) remained. This material was used directly for the production of Mazindol without additional purification.

Example 9

Preparation of methoxylactam [Formula (IIb) with Ri = R4 = CH3; X = Cl].

10 g (36.5 mM) of solid hydroxylactam of the formula (VII), which had been prepared according to Example 8b, were added in portions over 15 minutes and with external cooling to 25 g (210 mM) of thionyl chloride. After the addition was complete, the mixture was stirred at room temperature for an additional 20 min. The excess thionyl chloride was then removed under reduced pressure, giving crude, solid chlorolactam of the formula (VIII) with Ri = CH3 and X = Cl. 50 ml of methanol were added to the solid material and the resulting solution was stirred at room temperature for one hour. The excess methanol was removed under reduced pressure and the residue was triturated with chloroform, which gave 9.6 g (91% of theory based on hydrolactam (VII)) crystalline methoxylactam (IIb) with a melting point of 83 to 85 ° [melting point 83 to 85 ° according to W. Graf, E. Girod, E. Schmid & WG

Stoll, Helv. Chim. Acta 42, 1085 (1959)]. This material was used for the production of Mazindol without additional purification (Example 5).

The following examples show the preparation of the preferred compounds mazindole using triethyloxonium hexachloroantimonate or triethyloxonium hexafluorophosphate as the alkylating agent and are only intended to show the possibility of using different alkylating agents, without having to optimize the working conditions and in particular the yield.

7

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

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8th

Example 10

Preparation of Mazindol from Dimethylaminolactam [Formula (IIa) with Ri = CH3; R2 = R3 = CHs; X = Cl].

using triethyloxonium hexachloroanti-month

KC2H5) 30 ~ SbCir]

6.4 g (21.4 mM) of crystalline dimethylaminolactam were dissolved in 12 ml of dry methylene chloride and added to a slurry of 11.9 g (27.2 mM) of triethyloxonium hexychloroantimonate (Aldrich) in 12 ml of dry methylene chloride at room temperature. The mixture was stirred at reflux temperature under nitrogen for 3 hours, then cooled to 5 °, and 3.3 g (55 mM) of ethylenediamine were added in the course of 5 minutes. This mixture was then heated under reflux under nitrogen for 5 hours, then cooled to 5 ° and strongly acidified by adding 20 ml of aqueous 4N hydrochloric acid. After heating for a further 2 hours at the reflux temperature, the mixture was cooled and made basic with 13 ml of 25% sodium hydroxide solution. The resulting slightly yellow solid was filtered off from the 2-phase system after cooling to 0 ° for 30 min. The crude Mazindol was dried at 60 ° and recrystallized from methanol methylene chloride (1: 1) to give white crystalline Mazindol, which corresponded to the product of Example 1.

Example 11

Preparation of Mazindol from Dimethylaminolactam [Formula (IIa) with Ri = CH3; R2 = R3 = CH3; X = Cl] using triethyloxonium hexyfluorophorphate

[(C2H5) 30 "PFr]

A solution of 9.3 g (31 mM) of dimethylaminolactam in 10 12 ml of dry methylene chloride was added at room temperature to a solution of 9.8 g (40 mM) of triethyloxonium hexafluorophosphate (Aldrich). The mixture was heated to reflux under nitrogen for 5 hours and then left at room temperature for 16 hours. 15 After cooling to 0 °, 4.8 g (80 mM) of ethylenediamine were added in 15 min. The mixture was then heated under reflux for 5 hours under nitrogen, then cooled to 5 ° and acidified by adding 34 ml of aqueous 4N hydrochloric acid. After heating to reflux 20 for a further 15 minutes, the mixture was stirred at room temperature for 16 hours. After basing with 25 ml of aqueous 25% sodium hydroxide solution, a voluminous white precipitate separated, which was filtered off after 30 min cooling to 5 °. The crude product was dried at 60 ° and then recrystallized from methanol (1: 1). The crystalline mazindol obtained had the properties given in Example 1.

B

Claims (16)

642370 2nd PATENT CLAIMS 1. Process for the preparation of imidazo (2, l-a) ision doles of formula (I) so (I) 20th (HD, x Reacting this salt with ethylenediamine to form one wherein X is hydrogen, halogen or lower alkoxy; 23 intermediate of formula (IV) characterized by reacting a compound of formula (II) and then hydrolyzing this intermediate of formula (IV) to obtain the compound of formula (I). 2. The method according to claim 1, characterized in that the compound of formula (II) is alkylated under an inert gas atmosphere. 3. The method according to claim 1 or 2, characterized in that the compound of formula (III) is reacted with ethylenediamine under an inert gas atmosphere. 4. The method according to claim 2 or 3, characterized in that the inert gas atmosphere contains nitrogen. 5. The method according to any one of the preceding claims, «O characterized in that X stands for fluorine, chlorine or bromine. 6. The method according to claim 5, characterized in that X represents chlorine. 7. The method according to any one of the preceding claims, 65, characterized in that the alkylation of the compound of formula II and / or the reaction of the compound of formula III with ethylenediamine is carried out in the presence of an inert organic solvent. X wherein Ri represents a lower alkyl and X has the meaning given above and Y represents NR2R3 or -O-R4, in which R2, R3 and R4 are individual lower alkyls or R2 and Rj together for an alkylene chain of the formula - (where n is 4.5 or 6, with an alkylating agent which is an oxonium salt of the formula (R> 0 + Z- (a) or a carbenium salt of the formula ^ O-R HC + <^ Z- (b) \ Q-R is in which formulas R stands for methyl or ethyl and Z ~ for fluoroborate, hexachloroantimonate or hexafluorophosphate ion to form a salt of formula (III) 3rd 642 370 8. The method according to claim 7, characterized in that methylene chloride is used as the inert organic solvent. 9. The method according to claim 8, characterized in that the reaction is carried out at the reflux temperature of the methylene chloride. 10. The method according to any one of the preceding claims, characterized in that triethyl oxonium fluoroborate is used as the alkylating agent. 11. The method according to any one of claims 1 to 9, characterized in that dimethoxycarbenium fluoroborate is used as the alkylating agent. 12. Application of the method according to claim 1 to compounds of formula (II) which are prepared by treating a compound of formula (VIII) 10th RuO (Hb) 2o 13. Compound of formula (I), prepared by the process according to claim 1. 14. A compound according to claim 13 in the form of 5- (p-chloro-rophenyl) -2,3-dihydro-5-hydroxy-5H-imidazole (2,1-a) - (V111) 7 isoindole, prepared by the process according to claim 6. 2s 15. Dialkylaminolactam compounds of the formula (IIa) as agents for carrying out the process according to claim 1 30th 35 wherein Ri is a lower alkyl and X represents hydrogen, halogen or lower alkoxy, with (a) an amine of the formula HNR2R3, in which R2 and R3 are 40 individual lower alkyls or together an alkylene chain of the formula - (CH2) n-, in which n = 4, 5 or 6, to form an aminolactam compound of the formula (IIa) N -Ri (IIa) NO, 45 wherein Ri is lower alkyl, R2 and R3 are individual lower alkyls or together represent an alkylene chain of the formula 50 - (CH2) n-, where n = 4,5 or 6 and X is hydrogen, halogen or lower alkoxy. 16. A compound according to claim 15, characterized in that X represents halogen. 17. A compound according to claim 16, characterized in that X is fluorine, chlorine or bromine. 18. A compound according to claim 17, characterized in that X represents chlorine. 60 or at 65 (b) an alcohol of the formula R4OH, in which R4 is lower alkyl, to form an alkoxylactam of the formula (Hb)