DEZ0003614MA - - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

Registration date: August 7, 1953. Advertised on November 10, 1955

GERMAN PATENT OFFICE

. All previously known processes for the production of the hydrocarbon called "azulene" the following formula

and its substitution products lead through intermediate stages, which are already characteristic

ίο bicyclic ring system of the azulene, namely one • Five-membered ring condensed with a seven-membered ring, but not yet containing the full number of five double bonds. To convert these partially hydrogenated intermediates into the azulenes themselves, is on At the end of all known syntheses dehydrated, z. B. by heating with palladium high temperature. The yields are usually unsatisfactory, often even pronounced bad. The final yields of azulenes, calculated on the basis of those required for the synthesis of the first precursors Starting materials "amount to" at most a few percent, often only a fraction of a percent. So give E. A. Braude and W. F. Forbes (Nature, Vol. 168, 1951, p. 874) for the eight-stage described by them Azulene synthesis from cycloheptanone in contrast to the yields of the precursors for the dehydrogenation of the alkylbicyclodecadiene to the alkylazulene no yield. H. Pommer (Liebigs Annalen der Chemie, Vol. 579, 1953, p. 47 ff.) Describes a multi-stage synthesis of alkylated Azulenes with yields in the dehydrogenation stage of at most 10 to 15%. Anderson's too and Nelson (Journ. of Am. Chem. Soc, Vol. 73, 1951, P. 232 ff.) Carried out six-stage azulene synthesis

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only proceeds with a yield of 5.8%, based on the decahydro-2-naphthol used as the starting material. See also: H. Pommer, »On the state of research in the field of azulenes, -, - (Angew. Chemie, Hd. (> 2, 1950, pp. 281 to 289) and M. Ciordon. "The Azulenes" · (Chem. Review, 1951, Pp. 127 to 200).

The present invention relates to a process which allows azulene derivatives to be prepared directly, without the need for dehydration at all. The yields are much better

CH CH

XH

' ^H a OCH-CH

(III)

CH CH

CH

OCH-CH ₂

(IV

! as well as dimethylfulvene by splitting off water can arise from cyclopentadiene and acetone (VII), should azulene by intramolecular dehydration arise from the aldehyde (III). A tautomeric The form of compound (III) again with a true fulvic structure is compound (IV). It's a Fulven from cyclopentadiene and (llutacondialdehyde (VI).

A consideration of the azulene formula thus results from a fairly simple consideration the task of (llutacondialdehyde (VI) and cyclopentadiene (V) by splitting off water twice to condense to a / .ulen.

The solution to this problem is described below. The conditions under which the very sensitive (llutacondialdehyde itself gives azuleii directly with cyclopentadiene have not yet been determined. On the other hand, it is very easy to identify certain derivatives of this aldehyde, which can be identified by methods known to date. For example, in the Synthesis of the unsubstituted azulene (C ₁₀ H ₈ ) according to the present invention achieves a yield of 60% and more in the final stage, and the intermediates are also quite easily accessible by simple reactions.

The new method goes back to the idea that azulene has a structure similar to that of the fulvene. This can be easily understood by comparing the formulas for azule (I) and dimethylfulvene (II).

(Π)

H ₂

, CH ₃

CH ₃

o = c;

XH,

XH,

(VII)

(V)

OCH --CH

V /

OCH-CH ₂
(VI)

CH

Characterized by an increased shelf life to condense with cyclopentadiene, so that an azulene derivative arises.

A particularly easily accessible and excellently suitable modification product of glutacondialdehyde is the compound (X), the methyl anilide of the enol form of glutacondialdehyde

can be understood. This compound can be prepared from pyridine in various ways, e.g. B. according to Th. Zincke and W. Würkcr (Licbigs Annalcn der Chemie, Vol. 338, 1905, p. 127) from the adduct of dinitrochlorobenzene on pyridine (VIII) by treatment with methylaniline (VIII-> IX) and subsequent partial hydrolysis to give the compound (X).

C. II
X \
C.
Il II IK Il
C. II IK

(NO ₂ ) X _n Il,

HC

HC CH

CH

CH

Cl

(VIII)

Cl - N-CH ₃ N-CH ₃

C ₀ H ₅ C ₆ H ₅

HC

(X)

CH CH ₃ CH 5 N - C ₀ H

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This 5-N-methylanilido-pentadienal (X) is combined very easily and almost quantitatively turns into a deep red color in the presence of alkali with cyclopentadiene Fulven, and this gives when distilling,

C ₆ H ₅ -N-CH ₃

CH = CH
OCH-CH

μ r τι

CH = CH

best in a vacuum, or even when transferring of superheated steam in addition to methylanuiri very smooth azulene (compounds XI, XII and XIII).

CH = CH 7ο

jJCH + C, H _B -NH-CH ₈

CH-CH

(XI)

(XII)

The conversion can easily be transferred to substituted cyclopentadienes. However, these must contain at least two adjacent unsubstituted carbon atoms. So isopropylcyclopentadiene similarly gives a deep blue colored, otherwise oily product which can easily be purified in a known manner via the molecular compounds with trinitrobenzene. The light absorption of isopropyllazulene, which among other things has strong maxima at 608, 665 and 738 μμ , suggests that largely or exclusively i-isopropyllazuien

Vs previous year JTXo -Π. Vv -tig

is present.

One can of course also use others for these syntheses. derivable from glutacondialdehyde by substitution Use connections. This is how these azulene syritheses also work with monoanilides of glutacondialdehyde, z. B. that of Th. Zincke and Schreyer (Liebigs Annagen der Chemie, Vol. 353, 1907,

S. 384) described p-chloroanilide of the formula

OCH-CH = CH-CH = CH-NH-C ₆ H ₄ Ci.

In addition, the Th. Zincke reaction of the splitting with dinitrochlorobenzene can be carried out without any particular Difficulties also transferred to / 3-picoline, whereby Derivatives of methylglutacondialdehyde arise, which then after condensation with cyclopentadiene or its homologues lead to azulenes which also contain methyl in the seven-membered ring. It is there it goes without saying that to represent the derivatives of glutacondialdehyde used instead the reaction according to Th. Zincke with dinitrochlorobenzene-pyridine also other similar cleavage reactions of the pyridine can be used,

z. B. the splitting with cyanogen bromide according to W. König, J. pr. Chem. [2], Vol. 69, 1904, p. 105, or those with Chlorosulfonic acid ester according to P. Baumgarten, Ber. of the German Chemical Society, Vol. 57, 1924, P. 1622.

Instead of the cyclopentadiene, benzocyclopentadiene, i.e. indene, can also be used. The benzofulven from indene and 5-N-methylanilido-pentadienal (XIV) gives quite CH-CH when heated in a high vacuum

(XIII)

CH ₃ -NC _R H _S

CH

smooth the 1,2-benzazulen (XV) with those of Plättner, Fürst, Chopin and Winteler (Helvetica Chimicä Acta, Vol. 31, 1948, p. 501) described properties:

(XIV) (XV)

The implementation of the present procedure is very easy. The Fulvenbilduhg in the first stage is in the usual way by alcoholic alkali or Alkali alcoholate causes. In individual cases, however, metal compounds (ζ. Β. Na-, Cl-Mg or Ca substitution products) of the cyclopentadienes, in particular with N-methylanilido-pentadienal be condensed.

The 2nd stage of the synthesis, the ring closure, is already when the intermediate stage is heated Fulvene detectable in the test tube by the appearing blue color. It works better, as above indicated by heating in vacuo or by distilling with superheated steam. The Ring closure also by catalysts, e.g. B. small amounts of alkali, acids, metals in the form of powders or salts, basic solvents, are accelerated. The yield of azulenes is often better, when working in the presence of solvents. You can z. B. the fulvene, instead of them as such Heat, also boil in a high-boiling solvent and the azulenes formed either with the Vapors of the solvents themselves or by means of passed vapors of other solvents or also discharge by a gas stream. In these cases, the azulene from the distillate must be one of the separate known processes from possibly existing accompanying substances, e.g. B. by shaking with Acids or via the trinitrobenzolates.

example 1

[IO ) i- [N-Methyianilido] -pentadien-1,3-al-5, presented by Th. Zincke, (Liebigs Annalen der Chemie, Vol. 333, 1904, p. 296) and Th. Zincke and W. Würker, (Liebigs Annalen der Chemie, Vol. 338, 1905, pp. 121 to 127) are absolute in 50 ecm

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Ethanol dissolved in the heat and ^{poured together with 6.6 g (1} Z ₁₀ mol) of cyclopentadiene into a solution of 2.3 g of sodium in 30 ecm of absolute ethanol. The mixture, which heats up strongly, is cooled with ice. The solution turns dark red. The crystal pulp that separates out on cooling is filtered off with suction, washed well with very dilute acetic acid and, after drying, crystallized from cyclohexane or ethyl alcohol. 23 g (98 ⁰ Z ₀ of theory) 5- [N-methylanilido] pentadienylidenecelopentadiene are obtained in deep red crystals with a melting point of up to 112 °, this fulvene is ^{heated to 150 to 200 0} in a high vacuum, methylaniline and azulene distill into a trap cooled to -80 ". After about 5 hours the contents of the trap are taken up in ether and the blue-green ethereal solution is washed several times with normal hydrochloric acid. The neutral washed, now pure blue ethereal azulene solution is

ao dried and the ether is distilled off on a small column. 340 mg remain as residue -63 "/" Theoretically crystallized azulene with a melting point of 96 to 98 ". Melting point of Trinitrobenzolates 165 to 166 °.

The fulvine can also be converted into azulene by passing water vapor overheated to about 300 " Methylaniline are broken down. The azulene then swims in the distillate in blue flakes and is made from it separated with ether and freed from methylaniline with hydrochloric acid, as described above. The yield of pure azulene corresponds to the yield of azulene obtained by decomposition in a high vacuum.

Example 2

Kino solution of 10.8 g ( ¹ Z ₁₀ mol) isopropylcyclopentadiene (prepared from dimethylfulvene with lithium aluminum hydride), 18.7 g ( ¹ Z _1n mol) i- [N-methylanilido] -pentadiene-i, 3-al-5 in 50 ecm of absolute ethyl alcohol are dissolved in a solution of 2.3 g of sodium

C / i (| mol) is poured into 30 ecm of absolute ethanol, and the solution, which turns deep dark red, is heated very briefly. After 1 hour, the solution is poured into very dilute acetic acid and the oil which separates out on the surface is taken up in ether. The ethereal solution is washed neutral, dried and then the ether is distilled off. A dark red, viscous oil remains as a residue, which solidifies in crystalline form when rubbed with cyclohexane. The recrystallized 5 -N--Metliylanilido pentadienylidene from cyclohexane - isopropy cyclopentadiene melts at 98 ^0!.

1 g of the dark red oil is heated to 180 to 190 "in a high vacuum. Isopropylazulene and methylaniline distill into a deep-frozen trap (acetone-carbonic acid). After about 5 to 8 hours, no more isopropylazulene distills over. The contents of the trap are taken up in ether, several times Washed with n / 10-III Cl and, after washing neutral, dried over calcium chloride; the ether is then distilled off. A blue, viscous oil remains, the trinitrobenzolate of which has a melting point of 112 to 113 ^0. Yield of isopropyllazulene 350 mg - 56% of theory .

Example 3

^χ & · 7 g ( ¹ Ii ₀ mol) i- (N-methylaniliclo) -pentadieni, 3-al-5 are dissolved in 50 ecm absolute ethanol in the heat and together with 8 g ( ¹ Z ₁₀ mol) methylcyclopentadiene in a Solution of 2.3 g of sodium poured into 30 ecm of absolute ethanol. The solution instantly turns dark red. It is warmed gently and then left to stand for 5 hours at room temperature. The reaction mixture is then poured into very dilute acetic acid and the oil of 5-N-methylanilido-pentadicnylidenemethylcyclopentadiene which separates out on the surface is taken up in ether. The ethereal solution is dried, and after the ether has been suctioned off, a viscous, oily residue remains, ι g of this residue is heated to 200 ° in a high vacuum. During this process, N-methylaniline and methylazulene are distilled into a frozen trap. After the distillation has ended, the contents of the trap are taken up in ether, the N-methylaniline is removed from the ethereal solution with normal hydrochloric acid, this is washed neutral and the now pure blue ethereal solution of methylazulcine is dried. After the ether has been distilled off on a small column, 400 mg (= 67 ° / ₀ of theory) of methylazulene remain as a blue oil. The well-crystallized trinitrobenzolate melts at 157 to 159 ^0. The light absorption of the methylazulene shows strong maxima at 608, 670 and 740 //// and indicates, like the melting point of the trinitrobenzolate, that largely or exclusively i- Mcthylazulen is present.

Example 4

93 g (1 mol) of pure /? - picoline are refluxed for 2 hours in 200 ecm of ethyl alcohol with 202.5 S ( ^J mol) of 2,4-dinitro-i-chlorobenzene. After cooling, the violet-colored crystal brci is filtered off with suction and recrystallized from absolute ethanol. There are 266 g (= 90% of theory) of 2, 4-dinitro - that melt picolinium pale gray colored in the form of needles at 200 ⁰ receive - /.

29.6 g ( ¹ Z _1n mol) of 2,4-dinitrobenzene - /? - picolinium chloride are heated with 10.7 g ( ¹ Z ₁₀ mol) of freshly distilled N-methylaniline in 100 ecm of ethanol for 4 hours on a water bath. The red-colored solution is then poured into very dilute hydrochloric acid, the 2,4-dinitroaniline separating out in crystalline form, while the i- (N-methylanilido) methylpentadiene-1,3-al-5-anilchloromethylate that is formed remains in solution. A solution of 30 g of soda in 50 ecm of water is added to the red-colored solution and warmed awake for a short time. The solution turns yellow and cloudy. After cooling, the yellow solution is weakly acidified with dilute acetic acid and extracted several times with ether. The combined ether extracts are dried and the ether is distilled off. The remaining red-brown colored oil (14 g - 70% of theory) is the crude product of i- (N-methylanilido) -methylpentadicni, 3-al-5.

¹⁰ S ( ¹ im mol) of the aldehyde are mixed with 3.3 g ( ¹ Z ₂₀ mol) of cyclopentadiene in a solution of 1.5 g

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Sodium given in 20 ecm of absolute ethanol; the Solution immediately turns dark red and warms up slightly. The reaction mixture becomes after 2 hours given in very dilute acetic acid, the i-N-Methylanüido-methylpentadienylidene-cyclopentadiene which separates out as a red oil taken up in ether and dried the ethereal solution. After distilling off of the ether, the residue is distilled in a high vacuum at 150 to 180 °. It goes methyl

azulene as a blue oil with N-methylaniline in the deep-frozen Template over. After the distillation has ended, the contents of the trap are absorbed in ether and the N-methylaniline removed with normal hydrochloric acid. The pure blue colored one ethereal methylazulene solution is

dried. After. When the ether is distilled off, a deep blue colored oil remains.

Example 5

A solution of 11.6 g ( ^x / ₁₀ mol) of freshly distilled indene and 18.7 g ( ¹ Z ₁₀ mol) of 5- (N-methylanilido) pentadienal in 30 ecm of absolute ethyl alcohol becomes a solution of 2.3 g Sodium given in 30 ecm absolute ethanol. The mixture instantly turns deep red. After brief warming, it is left to stand at room temperature for 24 hours, then the reaction mixture is poured into very dilute acetic acid and the dark red, oily layer of iN-methylanilido-pentadiene-aldehyde indene is taken up in ether. After the ethereal has dried

Dissolving and distilling off the ether leaves a viscous, deep red colored oil. Part of this oil is heated ^{to 250 to 300 0 in a high vacuum.} N-methylaniline and 1,2-benzazulene are distilled in a frozen trap. After the distillation has ended, the contents of the trap are taken up in ether, the green-blue ethereal solution shaken out several times with normal hydrochloric acid and dried after washing neutral. When the ether is distilled off, dark blue to violet colored crystals with a melting point of 175 ^{° are obtained} . The trinitrobenzolate has a melting point of 154 to 155 ^° .

Example 6

93 g (1 mol) of beta-picoline (o, 8 _^0/0 solution) together with 107 g (1 mol) of N-methylaniline under ice-cooling to a solution of 116 g of cyanogen bromide in 300 cc of ether (prepared according to F. tree, Reports of the German Chemical Society, Vol. 41, 1908, p. 523).

After a vigorous reaction, an orange-red crystal sludge precipitates, which is immediately filtered off with suction and recrystallized from ethanol. There are 191g (= 85% of theory) of 1 - N - Methylanilido-methyl pentadiene-1, 3 - al-5-cyanamide in the form of orange-red needles melting at 146-147 ^0th

22.5 g ( ¹ ZiO mol) of this decomposition product of / 3-picoline are dissolved in 100 ecm of methanol and shaken with 500 ecm of 20 ° / _O aqueous sodium hydroxide solution at room temperature for about 15 minutes. The orange-red color changes to yellow. Then it is diluted with water, neutralized with dilute acetic acid and the yellow-brown oil which has separated out is taken up in ether. After drying the ethereal solution, and evaporation of the ether remains behind a brown crystal which, recrystallized from hexane, the in-Methylanilido-methyl pentadiene-i, 3-al (5) in the form of yellow crystals of melting point 93 to 95 ⁰ in a yield of 148 g (= 74% of theory) results.

10 g ( ¹ Z ₂₀ mol) of this aldehyde are added with 3.3 g ( ¹ Z ₂₀ mol) of cyclopentadiene to a solution of 1.5 g of sodium in 20 ecm of absolute ethanol. The solution immediately turns dark red with slight warming. After 2 hours, the reaction mixture is poured into very dilute acetic acid and the iN-methylanilidomethylpentadienylidene-cyclopentadiene which separates out as a red oil is taken up in ether. After the ethereal solution has been dried and the ether has been distilled off, the residue is heated to 150 to 180 ° in a high vacuum. The azulene formed is transferred to the deep-frozen receiver as a blue oil with N-methylaniline. After the distillation has ended, the contents of the trap are taken up in ether and the N-methylaniline is removed with nZio hydrochloric acid. The pure blue colored ethereal methylazulene solution is dried. After the ether has been removed, a deep blue-colored oil remains, which has the properties and physical constants described in the literature for 5-methylazulene.

Example 7

ι g of 5- (N-methyl-anilido) -pentadienylidencyclopentadien is mixed with 50 g of benzidine and subjected to distillation at 300 ⁰ superheated steam. The azulene formed is carried away with part of the benzidine by the steam from the reaction vessel. The azulene is extracted from the distillate with hexane and the benzidine is washed out of the hexane with dilute hydrochloric acid. The hexane solution is dried and the hexane is distilled off on a small column. The residue remaining (380 mg = 70 ° / ₀ of theory) crystallized azulene.

Example 8

ι g of 5- (N-methyl-anilido) pentadienylidenecyclopentadiene is mixed well with 20 g of Cu powder and heated to 100 ° in a high vacuum. Methyl aniline and azulene distill into a cooled trap. After 3 to 4 hours the contents of the trap are taken up in hexane and the blue-green hexane solution is washed with dilute hydrochloric acid. The blue-colored hexane is washed neutral, dried and the hexane is distilled off on a small column. The residue obtained is 360 mg (= 66.7% of theory) of crystallized azulene with a melting point of 96 to 98 ^° .

Example g

^{r y}

2.2 g ( ¹ cubic centimeter) of secondary undecylcyclopentadiene (prepared from methylnonyl ketone and cyclopentadiene and partial hydrogenation of the fulvene formed with lithium aluminum hydride) are mixed with 1.87g ( ¹ cubic centimeter) of iN-methylanilidopentadiene-i, 3-al-5. dissolved in 10 ecm of absolute alcohol and a

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of 0.3 g of Na in 5 ecm of absolute alcohol. In the process, slight warming occurs and the reaction solution turns deep dark red. After 2 hours of sieving, the alcohol is stripped off in vacuo and the residue, a dark red-colored viscous oil, is mixed with 50 g of benzidine and subjected to distillation with steam superheated to 300 ". The azulene formed passes over with the steam and is after the distillation shaken out of the distillate with hexane; the benzidine distilled over is washed out with dilute hydrochloric acid. After the deep blue colored hexane has been dried, the hexane is distilled off. A dark blue oil leaves behind with a yield of 1.4 g (5% ^u / _{u of} theory) , which on the basis of the elemental analysis, molecular weight and absorption spectrum turned out to be i-secondary undecylazulene.

Example 10

2.32 g 1 cm of absolute alcohol and a solution of 0.3 g of Na in 5 cm of absolute alcohol is added. It is warmed slightly for a short time, during which the reaction solution turns dark red. After standing ßstündigem the alcohol is removed by suction and the residue treated with 50 g of benzidine were mixed and subjected to distillation to 300 with ⁰ superheated steam. The azulene formed passes over with the steam and, after the distillation has ended, is shaken out of the distillate with ether, and the benzidine which has passed over is washed out with dilute hydrochloric acid. The ethereal light blue solution is dried. Then the ether is distilled off, and the azulene that has formed remains in Eonn blue crystals. They show a melting point of 90 to ο, τ "and a molecular weight of 289 (calculated 294). 1.3 g of I-Heiizhydrilazulen were obtained.

Example 11

j, 79 g ('/ ion MoI) 2-diethylamino-isopropylcyclopentadiene (prepared from diethylaminoacetone and cyclopentadiene and partial hydrogenation of the resulting fulvene with lithium aluminum hydride) are mixed with 1.87 g ( ¹ _{l 100} mol) IN-methylanilidopentadiene-i, 3- al-5 dissolved in 10 ecm absolute ethanol and a solution of 0.3 g Na in 5 ecm absolute ethanol added. The reaction solution turns deep red and is freed from alcohol after standing for one hour in vacuo. The remaining red oil is mixed with g benzidine and subjected to distillation with superheated steam. The resulting azulene distills over with the steam and is extracted from the distillate with hexane. The deep blue colored hexane is dried. After the hexane has been distilled off, a deep blue oil remains which is easily soluble in dilute hydrochloric acid. 1.3 g of 1- (2-diethylaminoisopropyl) -azulene are obtained.

Claims (3)

PATENT CLAIMS: 1. A process for the preparation of azulenes, characterized in that optionally substituted cyclopentadienes containing at least 2 adjacent unsubstituted carbon atoms own, or indene with derivatives of glutacondialdehyde, those in α and / or in / {position can be alkylated and in which the enolized aldehyde group is optionally substituted by N-alkyl Arylidgruppe can be exchanged in a known manner to the corresponding FuI veins condensed and this then by heating, optionally in the presence of inert organic Solvents, converted into the corresponding azulenes. 2. The method according to claim 1, characterized in that that the heating of the fulvenes in vacuo or in the presence of catalysts such as alkalis, acids, metals or metal salts, carries out or completes the ring closure by distillation. 3. The method according to claim 1 or 2, characterized in that the azulenes formed with the vapors of the solvent or suspension medium or with gases being blown through or Steaming is removed and the azulene is obtained from the distillate in a known manner. Referred publications: Angewandte Chemie, Vol. 62, 1950, pp. 281 to 289; Nature, Vol. 16S, 1951, p. 874; Liebigs Annalen der Chemie, Vol. 579, 1953, pp. 47ff .; Journal of Am. Chem. Soc, Vol. 73, 1951, pp. 232ft. © 509 579/34 11.55