Preparation of polyenecarbonyl compounds having a high content of the all-E isomer, and of their acetals or ketals

A process for preparing polyenecarbonyl compounds having a high all-E content and their acetals or ketals by aldol condensation or Horner-Emmons reaction comprises carrying out the reaction, for the purposes of the preferred formation of a double bond of E configuration and in order to maintain the E configuration of the double bonds in the stating compounds as completely as possible, in the presence of oxygen or an oxygen-inert gas mixture or nitric oxide or a nitric oxide-inert gas mixture and/or in the presence of specific stable radicals and/or in the presence of quinones or quinone derivatives.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The invention relates to an improved process for preparing poly-encarbonyl 
compounds having a high all-E content, and their acetals or ketals, in 
particular carotenoids, such as .beta.-apo-8'-caro-tenic acid esters, 
citranaxanthin and neurosporaxanthin esters. 
Polyenes are very generally understood as meaning unsaturated aliphatic 
hydrocarbons having three or more conjugated double bonds in the molecule, 
ie. compounds containing numerous alternating single and double bonds. 
Polyenecarbonyl compounds are defined as polyenes which have a carbonyl 
group conjugated to the polyene chain. 
Many polyenes and polyenecarbonyl compounds have gained interest as 
biologically active medicinal compounds or as food colorants and feed 
additives. 
2. Description of the Related Art 
According to their importance, numerous methods for preparing polyenes and 
polyenecarbonyl compounds have been developed (for survey cf. O. Isler in 
Carotenoids, Birkhauser-Verlag, 1971). 
Known methods for preparing polyenes are, for example, the Horner-Emmons 
reaction, ie. the coupling of aldehydes and ketones to appropriate 
phosphonic acid esters in the presence of bases (cf. Houben-Weyl, Methoden 
der Organischen Chemie Methods of Organic Chemistry! 5/ld (1972) pages 
127 to 129 or Pure & Appl. Chem. Vol. 63 (1991), No. 1, pages 45-48) and 
the aldol condensation, ie. the base-catalyzed coupling of ketones and/or 
aldehydes to CH-acidic compounds to give .beta.-hydroxycarbonyl compounds 
and subsequent elimination of water with formation of a system of 
conjugated double bonds (cf. Houben-Weyl 5/ld (1972) pages 142-144 or J. 
Org. Chem. 30 (1965) page 2481). C-C couplings of this type with formation 
of a double bond can lead to double bonds of Z or E configuration. In the 
processes known until now, products were in general obtained which only 
consisted of all-E isomers to an unsatisfactory extent. As most of the 
desired natural polyenecarbonyl compounds have the all-E configuration, it 
is expedient to start from all-E polyene building blocks and to carry out 
the C-C coupling under reaction conditions which preferably lead to a 
double bond of E configuration, and to prevent isomerization of the 
polyene building blocks to Z isomers as completely as possible. 
It was therefore the object of the invention to find reaction conditions 
under which the coupling of polyene building blocks to polyenecarbonyl 
compounds preferably proceeds with formation of a double bond of E 
configuration and with retention of the E configuration of the double 
bonds in the starting material. 
SUMMARY OF THE INVENTION 
It has now surprisingly been found that in said olefin coupling reactions a 
coupling in the E configuration with retention of the E configuration in 
the starting compounds is preferably obtained if the reaction is carried 
out in the presence of oxygen, nitric oxide, certain sizable radicals or 
radical scavengers and/or in the presence of certain quinones, quinone 
derivatives or coenzyme Q10 hydroxyquinone. 
DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present invention accordingly relates to a process for preparing 
polyenecarbonyl compounds having a high all-E content or their acetals or 
ketals by a Horner-Emmons reaction or an aldol condensation of a suitable 
carbonyl compound with a suitable dialkyl phosphonate or of a suitable 
CH-acidic compound, which comprises carrying out the reaction, for the 
purposes of the preferred formation of a double bond having E 
configuration and in order to maintain the E configuration of the double 
bonds in the starting compounds as completely as possible, in the presence 
of oxygen or an oxygen-inert gas mixture, or in the presence of nitric 
oxide or a nitric oxide-inert gas mixture and/or in the presence of a 
stable radical of the formula I 
##STR1## 
where R.sup.6 and R.sup.7 are a C.sub.1 - to C.sub.4 -alkyl group or else 
R.sup.6 and R.sup.7 are an ethylene group, propylene group, vinylene group 
or propenylene group, which can be substituted by alkyl, aryl, hydroxyl, 
alkoxy, silyloxy, oxo, amino, mercapto, alkylmercapto, cyano, carboxyl or 
aminocarbonyl (carbamoyl), heteroaryl or alkylcarbonyloxy groups; 
and/or in the presence of a stable radical of the formula II 
##STR2## 
where R.sup.8, R.sup.9 and R.sup.10 can have the meanings indicated above 
for R.sup.6 and R.sup.7 ; 
and/or in the presence of the stable radical 
2,2-diphenyl-1-pic-rylhydrazyl, or a hydrogen peroxide-urea adduct and/or 
in the presence of quinones, quinone derivatives or coenzyme Q10 
hydroquinone, the oxygen, the nitric oxide, said stable radicals or the 
hydrogen peroxide-urea adduct, the quinones, quinone derivatives or 
coenzyme Q10 hydroquinone being used in amounts from 0.3 to 10 mol %, 
preferably 0.5-6 mol %, in particular 1.0 to 5 mol %, based on the 
carbonyl compound employed. 
For example, polyenecarbonyl compounds of the formula III, their acetals or 
ketals can be prepared by the process according to the invention. 
##STR3## 
In this formula, R.sup.1 to R.sup.4 are hydrogen or organic radicals; n is 
an integer from 0 to 20, in particular 3-10; m is an integer from 0 to 20, 
in particular 0 to 10, m+n being at least 2; X and Y are a C.sub.1 - to 
C.sub.4 -alkoxy group, in particular a methoxy or ethoxy group, or else X 
and Y together are oxygen or a radical --O--CH.sub.2 --CH.sub.2 --O--, 
--O--CH.sub.2 --C(CH.sub.3).sub.2 --CH.sub.2 --O--, --O--CH.dbd.CH--O-- or 
--O--CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- which may be substituted by one 
or more methyl groups. The hydrogen atoms in the brackets can be partly 
substituted by organic radicals, preferably alkyl groups, in particular a 
methyl group. 
Suitable polyene building blocks are accordingly, for example, carbonyl 
compounds of the formula IV 
##STR4## 
where R.sup.1 and R.sup.2 are hydrogen or organic radicals, n is an 
integer from 0 to 20, in particular 3 to 10, and the hydrogen atoms on the 
double bonds within the brackets can also be replaced by organic radicals. 
The carbonyl compounds of the general formula IV used as starting compounds 
are generally known compounds. Suitable polyene building blocks are eg. 
compounds of the formula IV where R.sup.1 and R.sup.2 are hydrogen, alkyl, 
alkoxy, cycloalkyl, cycloalkenyl or phenyl groups, it being possible for 
the cycloalkyl, cycloalkenyl and phenyl groups to be additionally 
substituted, for example by alkyl, hydroxyl, oxo, amino, carboxyl, 
carbamoyl, alkylcarbonyloxy or cyano groups or alternatively by halogen. 
R.sup.1 is preferably the following cycloalkenyl groups 
##STR5## 
or else a formyl group while R.sup.2 is preferably hydrogen or alkyl. 
The number of double bonds in the compounds of the formula IV (termed n) is 
preferably from 2 to 15, in particular from 3 to 10. The double bonds 
within the brackets can in particular carry C.sub.1 - to C.sub.4 -alkyl 
groups, preferably methyl groups, as organic radicals. Suitable carbonyl 
compounds which may be mentioned are, for example: 
.beta.-apo-12'-carotenal (C.sub.25 -aldehyde), .beta.-apo-8'-carotenal 
(C.sub.30 -aldehyde), retinal (C.sub.20 -aldehyde), 
2,7-dimethyl-2,4,6-octa-trienedial (C.sub.10 -dialdehyde), 
crocetindialdehyde (C.sub.20 -dialdehyde) and .beta.-apo-4'-carotenal 
(C.sub.35 -aldehyde). 
When using dialdehydes, compounds of the formula IX 
##STR6## 
can also be formed by reaction with 2 mol of the compounds of the formula 
V. 
To prepare polyenecarbonyl compounds of the formula III preferably having 
the all-E configuration, the compounds of the formula IV must also 
preferably have the all-E configuration. 
The carbonyl compounds and their acetals or ketals of the formula V are 
also generally known compounds. Suitable compounds are especially those of 
the formula V 
##STR7## 
where R.sup.3 and R.sup.4 are organic radicals, m is an integer from 0 to 
20, preferably 0 to 10, 
X and Y are a C.sub.1 -C.sub.4 -alkyl group, in particular a methyl group 
or ethyl group, 
or else X and Y together are oxygen or a radical --O--CH.sub.2 --CH.sub.2 
--O--, --O--CH.sub.2 --C(CH.sub.3).sub.2 --CH.sub.2 --O--, 
--O--CH.dbd.CH--O-- or --O--CH.sub.2 --CH.sub.2 --CH.sub.2 --O-- which may 
be substituted by one or more methyl groups and Z is hydrogen or a 
dialkylphosphono group, in particular --PO(OCH.sub.3).sub.2 or 
--PO(OC.sub.2 H.sub.5).sub.2. The number of double bonds (termed m) can be 
0 (as in acetone), but also up to 20, preferably from 0 to 10. R.sup.3 is 
hydrogen, or an alkyl, alkoxy, cycloalkyl, cycloalkenyl or phenyl group 
which can also be substituted by other radicals, such as C.sub.1 -C.sub.4 
-alkyl, hydroxyl, alkoxy, silyloxy, oxo, amino, cyano, carboxyl, carbamoyl 
or alkylcarbonyloxy groups. 
R.sup.4, and also R.sup.3, is preferably hydrogen, C.sub.1 -to C.sub.4 
-alkyl or C.sub.1 to C.sub.4 -alkoxy groups. 
When carrying out a Horner-Emmons reaction, polyene compounds of the 
formula III, however, can also be obtained by using polyene building 
blocks which in each case contain the reacting groups on the other 
building block, ie. compounds of the general formula IV where, instead of 
the group 
##STR8## 
a group 
##STR9## 
is contained, are reacted with compounds of the formula V where, instead 
of the group 
##STR10## 
the group 
##STR11## 
is contained. 
Carbonyl compounds of the general formula V which may be mentioned are, for 
example: 
acetone, ethyl 4-dimethylphosphono-2-methyl-2-butenoate, ethyl 
4-diethylphosphono-2-methylbutenoate, 
4-diethylphosphono-3-methyl-2-butenoic acid esters, methyl 
2-diethylphosphonoacetate, ethyl 2-diethylphosphonoacetate, 
4-diethylphosphono-2- or 4-diethylphosphono-3-methyl-2-butenal acetals. 
To prepare polyenecarbonyl compounds of the formula III mainly having the 
all-E configuration, the higher carbonyl compounds of the formula IV or V 
must also mainly have the all-E configuration. When using compounds having 
only one double bond, isomerizations in favor of an all-E configuration 
additionally occur in alkaline medium during the reaction according to the 
invention, such that, for example, in the Horner-Emmons reaction of 
C.sub.25 -aldehyde or C.sub.30 -aldehyde with alkyl 
4-dialkylphosphono-2-methyl-2-butenoates the C.sub.5 - building block can 
be employed in an E/Z ratio from 2:1 to 100:1 and in spite of this all-E 
selectivities from 85 to 95% are obtained. 
For safety reasons, the oxygen is in general not used in pure form, but 
preferably as an oxygen-inert gas mixture. Nitrogen is suggested as an 
inert gas. Preferably, oxygen is used in a mixture with nitrogen in the 
ratio of N.sub.2 to O.sub.2 of from 1 to 1-100:1, preferably approximately 
95 to 5% by volume (lean air). The oxygen or the oxygen-containing gas 
mixture can be passed over the stirred reaction mixture or else passed 
into the reaction mixture. The action of the oxygen is dependent on its 
solubility, or on its partial pressure in the reaction mixture. For these 
reasons, it is also more advantageous to pass the oxygen into the reaction 
mixture instead of only over it. 
It was very surprising that the oxygen in the process according to the 
invention exerts such an advantageous effect. In general, it is advisable 
when handling polyenes to work with exclusion of oxygen (cf. Houben-Weyl 
5/ld page 13), as the polyenes frequently contain oxidation-sensitive 
double bonds. 
Surprisingly, nitric oxide or a nitric oxide-inert gas mixture also exerts 
a catalytic effect favoring the formation of a double bond of E 
configuration in aldol or Horner-Emmons reactions. The nitric oxide, 
preferably in a mixture with an inert gas such as N.sub.2, can be passed 
into the reaction mixture continuously. In the batchwise procedure it is 
sufficient if the nitric oxide needed is passed into the reaction vessel 
before the reaction and ensures that it cannot escape during the reaction. 
The mechanism of action of the process according to the invention is still 
not known. Besides oxygen and NO, catalysts which can be employed are 
stable radicals in which a nitrogen radical or an N-oxyl are present in 
the molecule. When using stable radicals, the reaction can be carried out 
under inert gas protection. Preferably, stable radicals of the general 
formula I used are di-tert-butylamine-N-oxyl of the formula Ia; 
2,2,6,6-tetramethyl-piperidine-N-oxyls of the formula Ib 
##STR12## 
where R.sup.11 is hydrogen and R.sup.12 is hydrogen, or a hydroxyl, 
alkoxy, acetoxy, amino, cyano or carboxyl group, oder else R.sup.11 and 
R.sup.12 together are an oxo group; 
2,2,5,5-tetramethylpyrrolidine-N-oxyls of the formula Ic 
##STR13## 
where R.sup.13 is hydrogen or one of the groups indicated above for 
R.sup.12 or 
2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrole-N-oxyls of the formula Id 
##STR14## 
where R.sup.13 is hydrogen or one of the groups indicated above for 
R.sup.12. 
Particularly suitable stable radicals which may be mentioned, for example, 
are: 
2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), 
4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (4--OH--TEMPO), or esters 
with mono- or dibasic carboxylic acids thereof, such as the commercially 
available bis(1-oxyl-2,2,6,6-tetramethyl-piperidin-4-yl) sebacate, 
4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl, 
3-carboxy-2,2,5,5-tetramethylpyrroline-N-oxyl, 
3-aminocarbonyl-2,5-dihydro-2,2,5,5-tetramethyl-1H-pyrrole-N-oxyl, 
di-tert-butylamine-N-oxyl or 2,2-diphenyl-1-picrylhydrazyl. 
In general, the stable radicals are also used in amounts from 0.3 to 10 mol 
%, preferably 0.5 to 6 mol %, in particular 1 to 5 mol %, based on the 
polycarbonyl compound of the formula IV or V. 
Depending on the nature of the reaction and of the reaction components, the 
reaction times are very different. For example, in the reaction of 
.beta.-apo-12'-carotenal (C.sub.25 -aldehyde) or .beta.-apo-8'-carotenal 
(C.sub.30 -aldehyde) with ethyl 4-diethylphosphono-2-meth-yl-2E-butenoate, 
ie. in a Horner-Emmons reaction with a C.sub.5 -phosphonate, they are in 
general from 1 to 20 hours, preferably 2 to 5 hours. When using the stable 
radicals in amount of less than 1 mol %, however, the reaction times are 
very much longer if it is wished to achieve optimum all-E selectivities. 
Suitable catalysts for carrying out all-E selective Horner-Emmons reactions 
are very generally compounds which act themselves as oxidants and can 
easily be converted into the reduced form or into the hydro derivatives, 
but do not cause any oxidations or additions to the polyene building 
block. This also applies to quinones and quinone imines. Quinones and 
quinone imines are generally known, frequently physiologically active 
compounds. The biologically active quinones are derived essentially from 3 
quinone nuclei, 1,4-naphthoquinone, methyl-substituted 1,4-benzoquinone 
and methyl- and methoxy-substituted 1,4-benzoquinone. They can contain a 
phytyl or derived phytyl group or a multiisoprenyl group. Mention may also 
be made of tocoquinones, such as vitamin E.sub.2 (50), which is derived 
from 2,3,5-trimethyl-1,4-benzoquin-one; plastoquinones, which are derived 
from 2,3-dimethyl-1,4-benzoquinone; ubiquinones, such as coenzyme Q10, 
coenzyme Q6 or coenzyme Q0, which are derived from 2,3-dimethoxy-5-methyl- 
1,4-benzoquinone, menaquinones, such as vitamin K.sub.2 (50) and vitamin 
K.sub.2 (30), which are derived from 2-methylnaphtho-1,4-quinone and 
phylloquinones, such as vitamin K.sub.1, which are derived from a 
phytyl-substituted 2-methylnaphtho-1,4-quinone. With respect to more 
detailed information about the structure of biologically active quinones, 
refer to the "Handbuch zur Anwendung der Nomenklatur organisch-chemischer 
Verbindungen" Handbook on the use of the nomenclature of organic chemical 
compounds! by W. Liebscher, Akademie-Verlag, Berlin 1979, pages 838 to 
847. 
Particularly suitable quinones or quinone imines are those of the general 
formula X or XI 
##STR15## 
where A is =O, =NH or =N--R.sup.5, in which R.sup.5 is an alkyl group or 
else R.sup.5, together with one of the adjacent radicals R.sup.14 to 
R.sup.17, forms an alkylene radical or alkenylene radical having 2 or 3 C 
atoms, which can be substituted by halogen, C.sub.1 - to C.sub.4 -alkyl 
groups or C.sub.1 - to C.sub.4 -alkoxy groups; R.sup.14 to R.sup.17 are 
hydrogen, halogen or an alkyl, alkenyl, cycloalkyl, alkoxy, 
alkoxycarbonyl, cyano, acyloxy, aryl or heteroaryl group, it being 
possible for R.sup.2 additionally to be a phytyl group, a group derived 
from the phytyl group, an isoprenyl group or a multiisoprenyl group. 
Both electron-rich quinones or quinone derivatives of the formula I or II, 
such as coenzyme Q0, coenzyme Q10 or tocoquinones, and also 
electron-deficient quinones or quinone derivatives, such as 
tetrachloro-1,4-benzoquinone or dichlorodicyano-1,4-benzoquinones are 
suitable for the process according to the invention. 
It was particularly surprising to find that even strong oxidants, such as 
chloranil (tetrachloro-1,4-benzoquinone) or dichloro-dicyanobenzoquinones 
(DDQ) have a high activity and selectivity, ie. have an all-E selective 
action without causing side reactions. 
Advantageously, quinolones of the general formula Xa according to the 
invention are used 
##STR16## 
where R.sup.14, R.sup.16 and R.sup.17 have the meanings indicated above 
and R.sup.18 to R.sup.21 are C.sub.1 - to C.sub.4 -alkyl or alkoxy groups 
or halogen, 
in particular the quinolone of the formula Xb 
##STR17## 
which can be derived from the known antioxidative stabilizer ethoxyquin 
and is known as a metabolite of ethoxyquin (cf. Xenobiotica 9 (1979), 
pages 649 to 57). Ethoxyquin itself only causes a moderate improvement in 
the all-E selectivity, while the quinolone Ib is to be included in the 
most active catalysts. 
Further active derivatives of ethoxyquin are the dimers of the formulae 
XIIa and XIIb 
##STR18## 
and N-oxides of the general formula X 
##STR19## 
where R.sup.14 and R.sup.16 to R.sup.21 have the meanings indicated above, 
but in particular are C.sub.1 - to C.sub.4 -alkyl or alkoxy groups or 
halogen. 
Besides the para-quinones, however, ortho-quinones can also be employed 
according to the invention, as these too have very high redox potentials. 
With respect to further details about ortho-quinones refer to Houben-Weyl 
Vol. 7/3b, pages 3 to 6. 
Surprisingly, individual hydroquinones, such as coenzyme Q10 hydroquinone, 
also have a higher activity. Possibly, these are those quinones which can 
be converted particularly easily to quinones. 
Suitable quinoid compounds which may be mentioned in particular are: 
1,4-benzoquinone, dimethyl-1,4-benzoquinone, trimethyl-1,4-benzoquinone, 
naphthoquinone, tetrachloro-1,4-benzo- quinone, tocoquinone acetate, 
phytyltrimethyl-1,4-benzoquinone, quinones of the vitamin K series and 
coenzyme Q10, coenzyme Q0 or 2,2,4-trimethyl-6(H)-quinolone. 
The quinones and quinone imines are also in general employed in amounts 
from 0.3 to 10 mol %, preferably 0.5 to 6 mol %, in particular 1.0 to 5 
mol %, based on the carbonyl compound employed. 
Depending on the nature of the reaction and the reaction components, the 
reaction times are very different. For example, in the reaction of 
.beta.-apo-12'-carotenal (C.sub.25 -aldehyde) or .beta.-apo-8'carotenal 
(C.sub.30 -aldeyhde) with ethyl 4-diethylphosphono-2-methyl-2E-butenoate, 
ie. in a Horner-Emmons reaction with C.sub.5 -phosphonate, they are in 
general 1 to 20 hours, preferably 2 to 5 hours. When using the quinones or 
quinone derivatives in amounts of less than 0.5 mol %, however, the 
reaction times are longer if it is wished to achieve optimum all-E 
selectivities. 
Both oxygen and NO, stable free radicals, quinones, quinone derivatives and 
coenzyme Q10 hydroquinone are suitable as catalysts for carrying out 
Horner-Emmons reactions. On the other hand, O.sub.2 and NO are preferred 
for carrying out aldol condensations. 
To carry out the reaction according to the invention, in general a 
procedure is used which is known and customary for the aldol condensation 
or the Horner-Emmons reaction, only during the reaction oxygen or an 
oxygen-inert gas mixture or nitric oxide or a nitric oxide-inert gas 
mixture is passed over the reaction mixture or into the reaction mixture 
and/or the reaction is carried out in the presence of the claimed stable 
radicals, quin-ones, quinone derivatives or coenzyme Q10 hydroquinone. 
When using stable radicals, quinones, quinone derivatives or coenzyme Q10 
hydroquinone, the reaction is in general carried out with inert gas 
protection. 
An aldol condensation is understood in the context of the present invention 
as meaning the coupling of the carbonyl compound of the formula IV with a 
compound of the general formula V, where Z is hydrogen, as a CH-active 
compound in the presence of a strong base. Strong bases which can be used 
are, in particular, alkali metal hydroxides, alkali metal alkoxides, 
alkali hydrides or alkali metal hexaalkylbissilazides. In isolated cases 
the use of a weak base, such as sodium carbonate, is also sufficient. 
The reaction is in general carried out in a solvent, but also takes place 
in some cases without solvent. In many cases an excess of the more stable 
starting compound can also be used as a solvent. Suitable solvents are: 
acyclic, cyclic or aromatic hydrocarbons or halohydrocarbons, such as 
dichloroethylene, alkanols, such as methanol, ethanol or isopropanol, or 
mixtures of the solvents mentioned or else polar aprotic solvents, such as 
tetrahydrofuran, dimethylformamide or diethoxyethane. 
To carry out the reaction, a procedure is in general used in which a 
solution of approximately equimolar amounts of the base is slowly added to 
the mixture of the starting compounds in a solvent in the presence of 
O.sub.2, NO or one of the claimed catalysts and the reaction mixture is 
worked up in a manner known per se. However, in many cases it is also 
possible to initially introduce one reactant with the base and to slowly 
add the second reactant. 
The reaction temperatures during the reaction should be from approximately 
-70 to 100.degree. C., preferably -20.degree. to 70.degree. C. 
Depending on the nature of the reactions, the reaction temperatures and the 
amount of catalyst, the reaction times are from 0.5 to 24 hours, 
preferably 1 to 10 hours. With respect to further details about aldol 
condensations, refer to Houben-Weyl, Vol. 5/1 (1972) page 142 to 144. 
A Horner-Emmons reaction is understood in the context of the present 
invention as meaning the reaction of a carbonyl compound of the formula IV 
with a compound of the formula V, where Z is a dialkylphosphono group, in 
the presence of a base. 
Suitable strong bases which may be mentioned in this case are also all 
alkali metal hydroxides, alkali metal alkoxides, alkali metal hydrides and 
alkali metal hexaalkylbissilazides and also LiNH.sub.2 and NaNH.sub.2, and 
in the isolated case also alkali metal carbonates. The reaction is in 
general carried out in a solvent, but also takes place in some cases 
without solvent. The solvent employed can in general be the solvent 
mentioned above for the aldol condensation. The reaction is particularly 
advantageously carried out in hydrocarbons or in mixtures of hydrocarbons 
and alkanols. 
In this case, too, a procedure is in general used in which a solution of 
approximately equimolar amounts of the strong base is slowly added to the 
mixture of the starting compounds in a suitable solvent in the presence of 
O.sub.2, NO and/or in the presence of one of the compounds claimed as a 
catalyst and, after complete reaction of the reaction mixture, worked up 
in a manner known per se for Horner-Emmons reactions. In this case, too, 
it is, however, possible in many cases for the more alkali-stable 
reactants to be initially introduced with the base and the other reactants 
to be slowly added to the mixture. 
The process according to the invention is of particular importance for the 
preparation of a .beta.-apo-8'carotenic acid ester of the formula VI 
##STR20## 
having an all-E content of greater than 85% by reaction of 
.beta.-apo-12'-carotenal (C.sub.25 -aldehyde) having an all-E content of 
greater than 85% with an alkyl 4-dialkylphosphono-2-methyl-2-butenoate in 
a Horner-Emmons reaction, 
for the preparation of neurosporaxanthic acid esters of the formula VII 
(C.sub.35 -esters) 
##STR21## 
having an all-E content of greater than 85% by reaction of 
.beta.-apo-8'-carotenal (C.sub.30 -aldehyde) having an all-E content of 
greater than 85% with an alkyl 4-dialkylphosphono-2-methyl-2-butenoate in 
a Horner-Emmons reaction and the preparation of citranaxanthin having an 
all-E content of greater than 85% by reaction of .beta.-apo-8'-carotenal 
having an all-E content of greater than 85% with acetone in an aldol 
condensation. 
As the all-E isomers crystallize significantly better and more easily in 
suitable solvents in the case of said long-chain polyenecarbonyl compounds 
of the general formula III, higher yields of the desired polyenecarbonyl 
compound in crystalline form are in general also obtained. When using 
stable radicals, quin-ones, quinone derivatives or coenzyme Q10 
hydroquinone as a catalyst, during working up these in general remain 
virtually quantitatively in the wash liquor or in the mother liquor. 
Using the process according to the invention, polyenecarbonyl compounds of 
the general formula III can be obtained, such as the 
.beta.-apo-8'-carotenic acid esters, neurosporaxanthin acid esters and 
citranaxanthin having an all-E content of up to 95% which are all very 
much desired as foodstuff colorants, if the longer-chain starting products 
are mainly present in the all-E configuration.

EXAMPLE 1 
Preparation of ethyl .beta.-apo-8'-carotinate (C.sub.30 -ethyl ester) by 
Horner-Emmons reaction 
##STR22## 
Variant A (use of 1 mol % 4--OH--TEMPO (reaction time: 5 hours) 
1.72 g (10 mmol) of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl 
(4-OH-TEMPO) in 5 ml of ethanol were added at 25.degree. C. under a 
nitrogen atmosphere to a mash of 350.5 g (1 mol) of crystalline 
.beta.-apo-12'carotenal (C.sub.25 -aldehyde) in 1200 ml of technical 
heptane. 289 g (1.05 mol of a 96% ethyl 
4-diethylphosphono-2-methyl-2E-butenoate (C.sub.5 -ester phosphonate) were 
then added. 500 ml of a 20% strength sodium ethoxide solution (1.28 mol; 
density 0.873 kg/l) were then metered in at 25.degree.-30.degree. C. in 
the course of 4 hours (h) with good N.sub.2 gassing (about 8 l/h). The 
mixture was then stirred at 25.degree. C. for 1 h. The all-E content in 
the C.sub.30 -ester was 92.2% according to HPLC. 
The organic phase was then washed with dilute aqueous sulfuric acid and 60% 
strength aqueous methanol. 
After addition of methanol, the ethyl .beta.-apo-8'-carotenate obtained was 
filtered off and washed twice with methanol. Drying to constant weight was 
carried out under N.sub.2 at 50.degree. C. 
Yield: 390.2 g (84.7%); all-E content: 99.7%. 
Variant B (use of 0.5 mol % TEMPO; reaction time 76 h) 
0.79 g (5 mmol) of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) in 5 ml of 
ethanol was added at 25.degree. C. under a nitrogen atmosphere to a mash 
of 350.5 g (1 mol) of crystalline C.sub.25 -aldehyde in 1200 ml of 
technical heptane. 289 g (1.05 mol) of a 96% C.sub.5 -ester phosphonate 
were then added. 
500 ml of a 20% strength NaOEt solution (1.28 mol; density 0.873 kg/l) were 
metered in at 25.degree. C. in the course of 76 h with good N.sub.2 
gassing. The all-E content in the C.sub.30 -ester was 92.3% according to 
HPLC. Working up was carried out in a similar manner to variant A. 
Yield: 380.4 g (82.6%); all-E content: 99.3%. 
To determine the effect of the amount of TEMPO or 4-hydroxy-TEMPO 
(4--OH--TEMPO) employed, the C.sub.25 -aldehyde .beta.-apo-12'-carotenal 
was reacted with the C.sub.5 -ester phosphonate in a similar manner to 
Example 1, variants A and B in the presence of the amounts of TEMPO or 
4-hydroxy-TEMPO evident from Table 1 or Table 2 and the all-E content in 
the C.sub.30 -ester was determined by means of HPLC in the reaction 
mixture obtained. The results are compiled in Tables 1 and 2. 
TABLE 1 
__________________________________________________________________________ 
As the all-E isomers crystallize significantly better and more easily in 
suitable solvents in the case 
of said long-chain polyenecarbonyl compounds of the general formula III, 
high yields of the desired 
polyenecarbonyl compound in crystalline form are in general also 
obtained. When using stable free rad- 
icals, quin-ones, quinone derivatives or coenzyme Q10 hydroquinone as a 
catalyst, during working up 
these in general remain virtually quantitatively in the wash liquor or in 
the mother liquor. 
Effects of the amount of TEMPO on the E/Z ratio in the Horner-Emmons 
reaction described 
C.sub.5 -Ester all-E all-E- 
phosphonate: 
TEMPO mol % 
content of 
content of 
Example 
Variant purity based on C.sub.25 
C.sub.25 
the C.sub.30 
1 (reaction time) 
Procedure 
(E/Z ratio) 
aldehyde! 
aldehyde 
ester 
__________________________________________________________________________ 
a A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 99.0% 94.6% 
b A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 99.0% 94.3% 
c A (5 h) under N.sub.2 
97% (7/1) 
5 mol % 99.0% 94.9% 
d A (5 h) under N.sub.2 
96% (18/1) 
3 mol % 99.0% 93.5% 
e A (5 h) under N.sub.2 
96% (18/1) 
1 mol % 99.0% 88.5% 
f A (5 h) under N.sub.2 
96% (18/1) 
0.5 mol % 
99.0% 77.5% 
g B (76 h) 
under N.sub.2 
96% (18/1) 
0.5 mol % 
98.6% 92.3% 
__________________________________________________________________________ 
TABLE 2 
__________________________________________________________________________ 
Effect of the amount of 4-OH-TEMPO on the E/Z ratio in the Horner-Emmons 
reaction described 
C.sub.5 -Ester 
4-OH-TEMPO 
all-E all-E 
phosphonate: 
mol % based 
content of 
content of 
Example 
Variant purity on C.sub.25 
C.sub.25 
C.sub.30 
1 (reaction time) 
Procedure 
(E/Z ratio) 
aldehyde! 
aldehyde 
ester 
__________________________________________________________________________ 
h A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 99.0% 95.0% 
i A (5 h) under N.sub.2 
96% (18/1) 
3 mol % 99.0% 94.7% 
j A (5 h) under N.sub.2 
96% (18/1) 
1 mol % 99.0% 92.2% 
k A (5 h) under N.sub.2 
96% (18/1) 
0.5 mol % 
99.0% 77.4% 
__________________________________________________________________________ 
In a similar manner to Example 1, variant A, the C.sub.25 -aldehyde was 
reacted with the C.sub.5 -ester phosphonate without addition of oxygen or 
stable radicals (comparison experiments) or in the presence of various 
stable radicals or radical scavengers and the all-E content in the 
C.sub.30 -ester was determined by means of HPLC in the reaction mixture 
obtained. The results are compiled in Table 3. Experiments with inactive 
stable radicals or radical scavengers or antioxidants are comparison 
experiments and are given an asterisk *. The oxygen was used in all 
experiments in the form of lean air (95% N.sub.2 +5% O.sub.2). In the case 
of the use of NO gas, 120 ml of NO were passed in in 5 to 10 min, care 
being taken that the NO can leave the reaction space during the addition 
of base. 
The name 3-carboxyproxyl or 3-carbamoylproxyl in this case stands for 
3-carboxy- or 3-carbamoyloxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl and the 
name 3-carbamoyldoxyl for 
3-carbamoyl-2,5-dihydro-2,2,5,5-tetramethyl-pyrrole-N-oxyl. 
TABLE 3 
__________________________________________________________________________ 
Effect of free radicals or of radical scavengers on the E/Z ratio in the 
Horner-Emmons reaction described 
C.sub.5 -ester C.sub.25 - 
phosphonate: aldehyde 
C.sub.30 -ester 
Example 
Variant purity Additive all-E 
all-E 
1 (reaction time) 
Procedure 
(E/Z ratio) 
mol % based on C.sub.25 -ald.! 
content! 
content! 
__________________________________________________________________________ 
l A (5 h) under N.sub.2 
96% (18/1) 
--* 99.0% 72.4% 
(comparison experiment) 
m A (5 h) under N.sub.2 
96% (18/1) 
2 mol %* 99.0% 72.4% 
tocopherol 
n A (5 h) under N.sub.2 
96% (18/1) 
5 mol %* 99.0% 76.5% 
N-methylmorpholine-N-oxide 
o A (5 h) under N.sub.2 
96% (18/1) 
5 mol %* 99.0% 76.7% 
dipotassium nitroso- 
disulfonate (Fremy's salt) 
p A (5 h) under N.sub.2 
96% (18/1) 
5 mol %* 99.0% 76.8% 
triacetoneaminoalcohol 
q A (5 h) under N.sub.2 
96% (18/1) 
5 mol %* 99.0% 78.5% 
galvinoxyl 
r A (5 h) under N.sub.2 
96% (18/1) 
5 mol %* 99.0% 79.6% 
nitrosobenzene 
s A (5 h) under N.sub.2 
96% (18/1) 
1.8 mol % O.sub.2 
99.0% 86.6% 
t A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 3-carboxyproxyl 
99.0% 90.5% 
u A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 2,2-diphenyl-1- 
99.0% 92.9% 
picrylhydrazyl 
v A (5 h) under N.sub.2 
96% (18/1) 
7.2 mol % O.sub.2 
99.0% 93.8% 
w A (5 h) under N.sub.2 
96% (18/1) 
5 mol % TEMPO 99.0% 94.6% 
x A (5 h) under N.sub.2 
97% (7/1) 
5 mol % TEMPO 99.0% 94.9% 
y A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 4-OH-TEMPO 
99.0% 95.0% 
z A (5 h) under N.sub.2 
96% (18/1) 
5 mol % H.sub.2 O.sub.2 -urea 
99.0%ts 
84.1% 
aa A (5 h) under N.sub.2 
96% (18/1) 
5 mol % NO 99.0% 89.6% 
ab A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 99.0% 93.9% 
di-tert-butylnitroxyl 
ac A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 3-carbamoylproxyl 
99.0% 92.2% 
ad A (5 h) under N.sub.2 
96% (18/1) 
5 mol % 3-carbamoyldoxyl 
99.0% 92.8% 
__________________________________________________________________________ 
* = comparison experiments 
EXAMPLE 2 
Preparation of ethyl .beta.-apo-8'-carotenate 
a) in the presence of O.sub.2 
70 g of .beta.-apo-12'-carotenal (E content 98%) were suspended in 300 ml 
of heptane and treated with 60 g of a 96% ethyl 
4-diethylphosphono-2-methyl-2E-butenoate. 110 ml of a 20% strength sodium 
ethoxide solution were added dropwise at 20.degree.-25.degree. C. in the 
course of 4 h while stirring and passing in 10 l/h of lean air (mixture of 
N.sub.2 and air in the ratio 3:1). The organic phase was then washed with 
dilute sulfuric acid and with 60% strength aqueous methanol. The all-E 
content in the ethyl .beta.-apo-8'-carotenate obtained was 94.7% and the Z 
content 5.3% according to HPLC. 
After cooling to 0.degree. C., filtering off with suction and drying the 
crystals in a stream of N.sub.2, 79.7 g of pure crystalline ethyl 
all-E-.beta.-apo-8'-carotenate were obtained (all-E content: &gt;98%). This 
corresponds to a yield of 86.6% of theory, based on 
.beta.-apo-12'-carotenal. 
b) Comparison example (under an N.sub.2 atmosphere) 
The procedure was carried out as described above under a), only instead of 
lean air 10 l/h of nitrogen were passed into the reaction mixture. The 
all-E content in the ethyl .beta.-apo-8'-carotenate obtained was 77.4% and 
the content of ethyl Z-.beta.-apo-8'-carotenate isomers was 22.6% 
according to HPLC. 
Under identical crystallization conditions, it was possible to obtain only 
63 g of a pure crystalline ethyl all-E-.beta.-apo-8'-carotenate. This 
corresponds to a yield of only 68.5%, based on .beta.-apo-12'-carotenal 
employed. 
EXAMPLE 3 
Preparation of ethyl .beta.-apo-4'-carotenate (C.sub.35 -ester) by 
Horner-Emmons reaction 
##STR23## 
7.8 g (50 mmol) of TEMPO were added at 25.degree. C. under a nitrogen 
atmosphere to a mash of 419.6 g (1 mol) of a 99.3% pure crystalline 
C.sub.30 -aldehyde in 1200 ml of technical heptane. 289 g (1.05 mol) of a 
96% C.sub.5 -ester phosphonate were then added. 500 ml of a 20% strength 
NaOEt solution (1.28 mol; density 0.873 kg/l) were then metered in at 
25.degree.-30.degree. C. in the course of 4 h with good N.sub.2 gassing 
(about 8 l/h). A very substantial crystal mash formed during the reaction. 
The all-E content in the C.sub.35 -ester after the end of the addition of 
base was 94.0% according to HPLC. 
The separated organic phase was then washed with dilute aqueous sulfuric 
acid and with a mixture of methanol and dilute aqueous sulfuric acid. 
After addition of heptane and methanol, the product was filtered off and 
washed with water. Drying: under N.sub.2 at 50.degree. C./1 mbar to 
constant weight. 
Yield: 495.2 g (94.0%) of crystallizate; all-E content: 97.5%; m.p. 
140.degree.-141.degree. C. 
E.sup.1 (1%, 1 cm): 2656 (cyclohexane; 479 nm); content 98.4% caic. with 
E.sup.1 =2700 
An approximately identical result was obtained when using 5 liters (1) of 
lean air per hour and mol instead of TEMPO. 
EXAMPLE 4 
Preparation of citranaxanthin by aldol condensation 
##STR24## 
41.67 g (0.1 mol) of C.sub.30 -aldehyde in each case were suspended in a 
mixture of 417 ml of acetone and 208 ml of heptane at room temperature 
(RT) under lean air or nitrogen gassing (10 liters/h) according to the 
data in the following table. The suspension was warmed to 40.degree. C. 
and 63 ml of a 1% strength solution of the base in methanol which is 
apparent from the table were added dropwise in the course of 6 h under 
lean air or N.sub.2 gassing. Samples were taken hourly to determine the 
course of the reaction by means of HPLC. 
The crystallized citranaxanthin was filtered off with suction and washed 
with methanol. Drying was carried out in an N.sub.2 stream at 50.degree. 
C./1 mbar. The yields were only determined in the reaction mixtures which 
proceeded without appreciable isomerization. 
TABLE 4 
__________________________________________________________________________ 
C.sub.30 - Base mol % all-E 
Example 
aldehyde based on C.sub.30 
Reaction 
isomers 
Z isomers 
Yield 
4 % all-E-! 
Gassing 
aldehyde! 
time h! 
%! %! %! 
__________________________________________________________________________ 
a 99% lean air 
1% strength 
6 97 2.5 90% 
(10 l/h) 
NaOCH.sub.3 ; 
9.2 mol % 
b* 99% N.sub.2 
1% strength 
2 62.2 37.8 61% 
NaOCH.sub.3 ; 
9.2 mol % 
c* 93.2 (6.8% 
N.sub.2 
1% strength 
4 63.6 4.9% 9-Z-, 31.8% 
62% 
9-Z) NaOH; other isomers 
12.3 mol % 
d 93.2 (6.8% 
lean air 
1% strength 
6 92.2 6% 9-Z, 1.8% 
80-85% 
9-Z) (10 l/h) 
NaOH; other Z isomers 
12.5 mol % 
e* 93.2 (6.8% 
N.sub.2 
1% strength 
6 61.9 5.9% 9-Z-, 32.2% 
60% 
9-Z) KOH; other Z isomers 
7.6 mol % 
f 93.2 (6.8% 
lean air 
1% strength 
15 92 6.4% 9-Z-, 1.6% 
75% 
9-Z) (10 l/h) 
KOH; other Z isomers 
7.6 mol % 
g 93.2 (6.8% 
lean air 
1% strength 
4 92 6.2% 9-Z-, 1.8% 
80-85% 
9-Z) (10 l/h) 
NaOH; other Z isomers 
12.5 mol % 
__________________________________________________________________________ 
* = comparison example 
EXAMPLE 5 
Preparation of Citranaxanthin 
33 g (0.08 mol) of C.sub.30 -aldehyde (all-E content 98%) in each case were 
suspended in 575 ml of acetone, 2 g of BHT (butylated hydroxytoluene as an 
antioxidant) and the amount of TEMPO apparent from Table 5 which follows 
were added if desired and the reaction mixture obtained was warmed to 
43.degree. C. 5.2 g of a 50% strength by weight aqueous NaOH (0.07 mmol) 
were added dropwise at this temperature in the course of the reaction time 
indicated in Table 5 which follows. 
The reaction mixture was then cooled to 20.degree. C. in the course of 30 
min and stirred at 20.degree. C. for a further 30 min. The content of the 
reaction mixture of all-E-citranaxanthin and the content of other 
citranaxanthin isomers was determined by means of HPLC and is indicated in 
Table 5 which follows. 
The mixture was then filtered through a suction filter. The filter cake was 
washed with methanol and dried at about 50.degree. C. in a drying oven. 
TABLE 5 
__________________________________________________________________________ 
Example 
"TEMPO" Reaction time 
all-E isomer 
Other isomers 
4 mol %! Gassing 
Base h (.degree.C.)! 
%! %! 
__________________________________________________________________________ 
a* -- (+2 g BHT) 
N.sub.2 
NaOH 3 (43.degree. C.) 
51.4 47.9 
b 5 (+2 g BHT) 
N.sub.2 
NaOH 3 (43.degree. C.) 
71.7 26.9 
c* -- N.sub.2 
NaOH 1 (43.degree. C.) 
50.7 48.5 
d 5 N.sub.2 
NaOH 3 62.9 35.5 
e 30 N.sub.2 
NaOH 3 67.0 31.3 
f 100 N.sub.2 
NaOH 3 73.5 24.7 
__________________________________________________________________________ 
* = Comparison example 
EXAMPLE 6 
Preparation of ethyl .beta.-apo-8'-carotenate by Horner-Emmons reaction in 
the presence of bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) sebacate 
1.28 g (2.5 mmol) of bis(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl) in 5 ml 
of ethanol were added at 25.degree. C. under a nitrogen atmosphere to a 
mash of 25.05 g (100 mmol) of crystalline .beta.-apo-12'-carotenal in 120 
ml of technical heptane. 30.3 g (110 mmol) of a 96% strength C.sub.5 
-ester phosphonate were then added. 50 ml of 20% strength sodium ethoxide 
solution (128 mmol) were metered in at 25.degree.-30.degree. C. in the 
course of 4 h with N.sub.2 gassing. The mixture was then stirred at 
25.degree. C. for 1 h. The all-E content in the C.sub.30 -ester was 94.9% 
according to HPLC. 
The organic phase was then washed with dilute aqueous sulfuric acid and 60% 
strength methanol. 
After addition of methanol, the ethyl .beta.-apo-8'-carotenate obtained was 
filtered off and washed twice with methanol. Drying was carried out to 
constant weight. 
Yield: 39.5 g (85.8%); all-E content: 99.8%. 
EXAMPLE 7 
Preparation of ethyl .beta.-apo-8'-carotenate (C.sub.30 -ethyl ester) by 
Horner-Emmons reaction in the presence of 2,2,4-trimethyl-6(H)-quinolone 
1.96 g (10 mmol) of 2,2,4-trimethyl-6(H)-quinolone in 5 ml of ethanol were 
added at 25.degree. C. under an argon atmosphere to a mash of 350.5 g (1 
mol) of crystalline .beta.-apo-12'-carotenal (C.sub.25 -aldehyde) in 1200 
ml of technical heptane. 320.8 g (1.1 mol) of a 96% ethyl 
4-diethylphosphono-2-methyl-2E-butenate (C.sub.5 -ester phosphonate) were 
then added. 500 ml of a 20% strength sodium ethoxide solution (1.28 mol) 
were then metered in at 25.degree.-30.degree. C. in the course of 4 hours 
(h) with argon gassing. The mixture was then heated to 55.degree. C. The 
all-E content in the C.sub.30 -ester was 94.8% according to HPLC. 
The organic phase was then washed at 55.degree. C. with dilute aqueous 
sulfuric acid and 60% strength aqueous methanol. 
After addition of 1 1 of methanol, the mixture was cooled to -5.degree. C. 
and the ethyl .beta.-apo-8'-carotenal was filtered off and washed with 
ethanol. Drying was carried out under N.sub.2 at 50.degree. C. to constant 
eight. 
Yield: 401.3 g (87.1%); all-E content: 98.9%. 
EXAMPLE 8 
Preparation of ethyl .beta.-apo-8'-carotenate (C.sub.30 -ethyl ester) by 
Horner-Emmons reaction in the presence of quinones, quinone derivatives 
and coenzyme Q10 hydroquinone 
The amounts apparent from Table 1 of the additive apparent from the table 
in 2 ml of ethanol were added at 25.degree. C. under an argon atmosphere 
to a mash of 35.05 g (0.1 mol) of C.sub.25 -aldehyde in 120 ml of 
technical heptane. 30.3 g (110 mol) of a 96% C.sub.5 -ester phosphonate 
having the E/Z isomer ratio apparent from Table 6 were then added. 50 ml 
of a 20% strength sodium ethoxide solution (128 mmol) were metered in at 
25.degree.-30.degree. C. in the course of 4 h under argon gassing. The 
mixture was then stirred at 25.degree. C. for 1 h. The all-E content in 
the C.sub.30 -ester was determined in each case by means of HPLC. The 
results are shown in Table 6. 
TABLE 6 
__________________________________________________________________________ 
Effect of quinones, quinone imines and coenzyme Q10 hydroquinone on the 
E/Z ratio 
in the Horner-Emmons-reaction described 
C.sub.25 - 
C.sub.5 -ester phosphonate: 
aldehyde 
C.sub.30 -ester 
purity Additive all-E 
all-E 
Example 
Procedure 
(E/Z ratio) 
mol % based on C.sub.25 -aldehyde! 
content! 
content! 
__________________________________________________________________________ 
2a under argon 
96% (25/1) --* 99.0% 76% 
(comparison experiment) 
2b under argon 
96% (25/1) 5 mol % 99.0% 90.2% 
trimethyl-1,4-benzoquinone 
(TMC) 
2c under argon 
96% (25/1) 5 mol % coenzyme Q10 
99.0% 91.7% 
2d under argon 
96% (25/1) 5 mol % 99.0% 91.6% 
tetrachloro-1,4-benzoquinone 
2e under argon 
96% (25/1) 5 mol % tocoquinone acetate 
99.0% 90.3% 
2f under argon 
96% (25/1) 5 mol % coenzyme Q0 
99.0% 88% 
2g under argon 
96% (25/1) 5 mol % 99.0% 88% 
2-methyl-1,4-naphthoquinone 
2h under argon 
96% (25/1) 1 mol % 2,2,4-trimethyl- 
99.0% 94.8% 
6(H)-quinolone 
2i under argon 
96% (18/1) 6 mol % 2,2,4-trimethyl- 
98.7% 93.7% 
6(H)-quinolone 
2k under argon 
96% (25/1) 5 mol % coenzyme Q10 
99.0% 88.4% 
hydroquinone 
__________________________________________________________________________ 
EXAMPLE 9 
Preparation of ethyl .beta.-apo-4'-carotenate (C35-ester) by Horner-Emmons 
reaction in the presence of quinones, quinone derivatives and coenzyme Q10 
hydroquinone 
41.67 g (100 mmol) of C.sub.30 -aldehyde were suspended in 400 ml of 
technical heptane and treated at room temperature (RT) under an argon 
atmosphere with 30.3 g (110 mmol) of 96% C.sub.5 -ester phosphonate and 5 
mmol of the additives indicated in Table 7. 50 ml of a 20% strength 
sodiumethoxide solution were metered in in the course of 4 h. The mixture 
was stirred at RT for 16 h. The all-E contents in the product were 
determined by HPLC and compiled in Table 7. 
TABLE 7 
__________________________________________________________________________ 
Effect of quinones, hydroquinones and quinone imines on the E/Z ratio in 
the 
Horner-Emmons reaction described 
C.sub.30 - E/Z selectivity 
C.sub.5 -ester phosphonate: 
aldehyde 
C.sub.35 -ester 
of the reaction 
purity Additive all-E 
all-E 
based on 
Example 
Procedure 
(E/Z ratio) 
mol % based on C.sub.30 -aldehyde! 
content! 
content! 
C.sub.30 -aldehyde 
__________________________________________________________________________ 
3a under argon 
96% (25/1) --* 95.8% 70% 73% 
(comparison experiment) 
3b under argon 
96% (25/1) 5 mol % coenzyme Q10 
95.8% 83.5% 87% 
3c under argon 
96% (25/1) 5 mol % 2,2,4-trimethyl- 
95.8% 88.6% 92.5% 
6(H)-quinolone 
3d under argon 
96% (25/1) 5 mol % coenzyme Q10 
95.8% 82.6% 86% 
hydroquinone 
__________________________________________________________________________