The invention discloses a method for the preparation of 3,3-dialkxoy-l-methylenepropyl arenes from crotonaldehyde and aryldiazonium salts, and intermediates for the preparation of perfumes.

Aromatic aldehydes are widely used as flavors and fragrances in cosmetics, perfumes, and numerous household products. Alpha, beta-unsaturated aromatic aldehydes, such as substituted cinnamic aldehydes, are known to have distinct fragrance and are therefore used in the perfume industry

WO 98/45237 A discloses certain aromatic aldehydes, a method for producing them starting from acetophenone acetals, their use as perfumes and their use as intermediates for the preparation of 3-arylpropanals. They have a musky fragrance.

Aldehydes of general formula (100)

are usually prepared by Heck reaction of an aryl iodide or an aryl bromide with

crotonaldehyde using a Pd catalyst.

Stadler et al. in Synlett 2008, 4, 597-599 disclose the reaction of aryl bromide with crotonaldehyde in NMP as solvent in the presence of one mol equivalent of

tetrabutylammonium chloride, 2 mol% of Pd(OAc) ₂ and a molar excess of NaOAc. 2- bromotoluene as aryl bromide provides 46% yield; 2,2'-Me ₂ C6H ₃ as substrate provides no yield.

Kjell et al, J. Org. Chem. 1999, 64, 5722 to 5724, discloses a method for the preparation of compound of formula (100), which starts from 4-iodo benzoic acid methyl esters and 3-buten- l-ol. The desired product can be separated from isomeric byproducts via a bisulfit adduct. G. Schiemann et al, Organic Syntheses, Coll. Vol. 2, p.299 (1943); Vol. 13, p.52 (1933) discloses diazotization reactions.

Ohno et al, J. Org. Chem. 2003, 68, 7722 to7732, discloses the preparation of certain 4,4- alkoxy-l-buten-l-ylarenes using expensive starting materials and by a long multistep synthesis from substituted benzaldehydes by Wittig olefmation using large amounts of triphenylphosphines, further the hydrogenation of such unsaturated acetals to the

corresponding saturated acetals is disclosed, which then are hydro lyzed with water in the presence of acid to provide the respective aldehydes.

The perfume and household product industry has a constant need for new perfumes with interesting, new and not yet available fragrances in order to increase the available choice of fragrances and to adapt the fragrances to the ever changing demand of fashion. Furthermore the respective substances need to be synthesized economically and with consistent quality. High purity and strong fragrances are desired. The present invention provides precursors of alpha, beta-unsaturated aromatic aldehydes, which have strong and interesting, aldehydic fragrances, intensely spicy and sweet, and an improved process for the production thereof. These precursors have hithereto been difficult to synthesize and can also be used as intermediates for other chemical substances.

The present invention provides for example the precursor for the alpha, beta-unsaturated aromatic aldehyde 3-(2,3-dimethylphenyl)-2-butenal, which has strong and interesting, aldehydic fragrance, intensely spicy and sweet.

The costs of the required bromo or iodoarenes are high. These are prepared from the corresponding anilines via diazotization and reaction with respective halogen derivatives of copper. These copper compounds are usually used in stoechio metric amounts.

Wittig olefmations generate large amounts of triphenylphosphine derived waste.

There was a need for a method for preparation of precursors of compound of formula (100) and its analogues with lower costs and less process steps.

Unexpectedly, it was found, that diazonium salts of anilines can be used in Heck reaction with crotonaldehyde.

The following abbreviations are used, if not otherwise stated: halogen means F, CI, Br or I, preferably F, CI or Br;

alkyl means linear and branched alkyl and cycloalkyl.

Subject of the invention is a method (A) for the preparation of a compound of formula (I),

wherein

Rl, R2 and R3 are identical or different and independently from each other selected from the group consisting of H, Ci_ ₄ alkyl, Ci_ ₄ alkoxy, halogen, CF ₃ , N0 ₂ , S0 ₂ Me, OCF ₃ , OCHF ₂ , C(0)OR5, CN, C(0)N(R7)R8, C(O)R10 and phenyl, the phenyl being unsubstituted or substituted by 1 , 2 or 3 identical or different substituents selected from the group consisting of Ci_ ₄ alkyl, halogen, N0 ₂ , CF ₃ , OCF ₃ , OCHF ₂ , CN and C(0)R11;

R5 is Ci_8 alkyl, CH ₂ CF ₃ or CH(CF ₃ ) ₂ ;

R7 and R8 are identical or different and independently from each other Ci_io alkyl;

RIO is selected from the group consisting of Ci_io alkyl, CF ₃ and phenyl, the phenyl being unsubstituted or substituted by 1 , 2 or 3 identical or different substituents selected from the group consisting of Ci_ ₄ alkyl, halogen, N0 ₂ , CF ₃ , OCF ₃ , OCHF ₂ and CN;

Rl 1 is selected from the group consisting of Ci_io alkyl and CF ₃ ;

R4 is selected from the group consisting of Ci_ ₄ alkyl and (CH ₂ ) ₂ -OMe; method (A) comprises a reaction (A) of a compound of formula (II) with a compound of formula (III) in the presence of a palladium source (Aa) and of a compound of formula

(IV);

R4 (IV)

HO wherein

in formula (II), the Rl, R2 and R3 are defined as above, i.e. they are identical with the Rl, R2 and R3 in formula (I);

X is selected from the group consisting of BF ₄ , PF ₆ , CI , Br , H ₂ P0 ₄ and HS0 ₄ ; palladium source (Aa) is selected from the group consisting of Pd(0) on a support, Pd(0) complex, Pd(II) complex and mixtures thereof.

Preferably,

R4 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl and (CH ₂ ) ₂ -OMe;

more preferably,

R4 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl and (CH ₂ ) ₂ -OMe;

even more preferably,

R4 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl

(CH ₂ ) ₂ -OMe;

especially,

R4 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe;

more especially,

R4 is methyl or (CH ₂ ) ₂ -OMe;

even more especially,

R4 is methyl. Preferably,

R5 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl or tert-butyl;

more preferably,

R5 is methyl or ethyl;

even more preferably,

R5 is methyl.

Especially, R4 and R5 are methyl. Preferably,

R7 and R8 are identical or different and independently from each other Ci_ ₆ alkyl;

more preferably,

R7 and R8 are identical and or different and independently from each other methyl, ethyl, n-propyl, iso-propyl, n-butyl or cyclohexyl.

Preferably,

RIO is selected from the group consisting of Ci_ ₆ alkyl, CF ₃ and phenyl, the phenyl being unsubstituted or substituted by 1 , 2 or 3 identical or different substituents selected from the group consisting of Ci_ ₄ alkyl, halogen, N0 ₂ , CF ₃ , OCF ₃ , OCHF ₂ and CN; and

Rl 1 is selected from the group consisting of Ci_ ₆ alkyl and CF ₃ ;

more preferably,

RIO is selected from the group consisting of methyl, ethyl, CF ₃ , propyl, cyclopropyl,

cyclopentyl, cyclohexyl and phenyl, the phenyl being unsubstituted or substituted by 1 , 2 or 3 identical or different substituents selected from the group consisting of Ci_ ₄ alkyl, halogen, N0 ₂ , CF ₃ , or CN; and

Rl 1 is selected from the group consisting of methyl, ethyl, CF ₃ , propyl, cyclopropyl,

cyclopentyl and cyclohexyl.

Preferably,

Rl , R2 and R3 are identical or different and independently from each other selected from the group consisting of is H, Ci_ ₄ alkyl, Ci_ ₄ alkoxy, F, CI, Br, N0 ₂ , CF ₃ , S0 ₂ Me, OCF ₃ , OCHF ₂ , C(0)OR5, CN, C(O)R10, C(0)N(R7)R8 and phenyl, the phenyl being un substituted or substituted by 1 substituent selected from the group consisting of Ci_ ₄ alkyl, halogen, N0 ₂ CF ₃ , OCF ₃ , OCHF ₂ and CN;

more preferably,

Rl , R2 and R3 are identical or different and independently from each other selected from the group consisting of is H, Ci_ ₄ alkyl, Ci_ ₄ alkoxy, F, CI, Br, N0 ₂ , C(0)OR5, CN,

C(O)R10, C(0)N(R7)R8 and phenyl;

even more preferably,

Rl , R2 and R3 are identical or different and independently from each other selected from the group consisting of is H, Ci_ ₄ alkyl, Ci_ ₄ alkoxy, F, CI, Br, N0 ₂ , C(0)OMe, C(0)OEt, C(0)CH ₃ , C(0)Ph and CN;

especially,

Rl , R2 and R3 are identical or different and independently from each other selected from the group consisting of is H, methyl, ethyl, methoxy, ethoxy, F, CI, Br, N0 ₂ , C(0)OMe, C(0)CH ₃ and C(0)Ph;

with R4, R5, R7, R8 and RIO as defined above, also with their preferred embodiments;

preferably R4 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe.

In case of Rl not being H, and R2 and R3 being H,

Rl is preferably selected from the group consisting of methyl, ethyl, F, CI, Br, N0 ₂ and C(0)OMe; with R4 as defined above, also with its preferred embodiments; preferably R4 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe.

In case of Rl and R2 not being H and R3 being H,

preferably Rl and R2 are identical and selected from the group consisting of methyl, F, CI, Br and C(0)OMe; with R4 as defined above, also with its preferred embodiments; preferably R4 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe.

In case of Rl , R2 and R3 not being H,

preferably Rl , R2 and R3 are identical and selected from the group consisting of is F and CI; with R4 as defined above, also with its preferred embodiments; preferably R4 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe.

Preferably,

X is BF ₄ ^" . Especially, R4 and R5 are methyl and X is BF ₄

If Pd(0) on a support is used as a palladium source (Aa), the support is preferably BaS04 or charcoal.

Preferably the palladium source (Aa) is selected from the group consisting of PdCl ₂ ,

Pd(OAc) ₂ , Pd(dba) ₂ , Pd ₂ (dba) ₃ , PdCl ₂ (PhCN) ₂ , PdCl ₂ (MeCN) ₂ , PdCl ₂ (PPh ₃ ) ₂ , Pd(P(tBu) ₃ ) ₂ , Pd ₂ (P(tBu) ₃ ) ₃ , Pd(P(l-adamantyl) ₃ ) ₂ , Pd ₂ (P(l-adamantyl) ₃ ) ₃ , Pd(PPh ₃ ) ₄ , Pd on charcoal or on BaS0 ₄ , and mixtures thereof;

more preferably from the group consisting of PdCl ₂ , Pd(OAc) ₂ , Pd(dba) ₂ , Pd ₂ (dba) ₃ ,

PdCl ₂ (PhCN) ₂ , PdCl ₂ (MeCN) ₂ , Pd on charcoal or on BaS0 ₄ , and mixtures thereof; even more preferably from the group consisting of PdCl ₂ , Pd(OAc) ₂ , Pd(dba) ₂ , Pd ₂ (dba) ₃ , PdCl ₂ (MeCN) ₂ and mixtures thereof;

especially the palladium source (Aa) is PdCl ₂ , Pd(OAc) ₂ or Pd ₂ (dba) ₃ ;

more especially the palladium source (Aa) is PdCl ₂ or Pd(OAc) ₂ .

In one embodiment, reaction (A) is done or carried out without a solvent (Ad).

In another embodiment, reaction (A) is done or carried out in the presence of a solvent (Ad); solvent (Ad) is selected from the group consisting of acetone, methylethylketone,

dichloromethane, CCI ₄ , chloroform, benzene, fluorobenzene, benzonitrile, acetonitrile, propionitrile, ethyl acetate, butyl acetate, THF, methyl-THF, dioxane, toluene, xylene and mixtures thereof.

Preferably the solvent (Ad) is selected from the group consisting of benzonitrile, acetonitrile, dichloromethane, chloroform and propionitrile;

more preferably from the group consisting of benzonitrile, acetonitrile and propionitrile; especially the solvent (Ad) is acetonitrile or propionitrile.

Preferably, the compound of formula (IV) serves also as solvent.

Preferably, the compound of formula (IV) serves also as solvent and no further solvent (Ad) is used. In one embodiment, reaction (A) is done or carried out without the addition of a salt (Ae) or an acid (Ab).

In another embodiment, reaction (A) is done or carried out in the presence of a salt (Ae); salt (Ae) is selected from the group consisting of MgS0 ₄ , CaCl ₂ , A1 ₂ 0 ₃ , Na ₂ S0 ₄ and

molecular sieves derived from alumosilicates or zeolites.

Salt (Ae) is added to the reaction mixture, so that the reaction mixture comprises the

palladium source (Aa), compound of formula (IV) and the salt (Ae). Salt (Ae), compound of formula (IV) and palladium source (Aa) can be added in any sequence.

In another embodiment, reaction (A) is done or carried out in the presence of an acid (Ab); acid (Ab) is selected from the group consisting of HBF ₄ , HPF ₆ , HCl, HBr, H ₃ P0 ₄ , CF ₃ S0 ₃ H,

MeS0 ₃ H, 4-toluenesulfonic acid and sulfuric acid,

preferably acid (Ab) is selected from the group consisting of HBF ₄ , CF ₃ S0 ₃ H, MeS0 ₃ H,

4-toluenesulfonic acid and sulfuric acid.

Acid (Ab) is added to the reaction mixture, so that the reaction mixture comprises the

palladium source (Aa), compound of formula (IV) and the acid (Ab). Acid (Ab), compound of formula (IV) and palladium source (Aa) can be added in any sequence.

In another embodiment, reaction (A) is done or carried in the presence of salt (Ae) and of acid (Ab). In this case, salt (Ae) and acid (Ab) are added to the reaction mixture, so that the reaction mixture comprises the palladium source (Aa), compound of formula (IV), the salt (Ae) and the acid (Ab). Salt (Ae), acid (Ab), compound of formula (IV) and palladium source (Aa) can be added in any sequence.

Preferably, the reaction temperature of reaction (A) is from -25 to 150°C, more preferably from -10 to 100°C, even more preferably from -5 to 75°C.

Preferably, after mixing the components, the temperature is shortly elevated to initiate

reaction; more preferably, after the reaction has started, the temperature is kept below

40°C, preferably below 30°C. Preferably, the reaction (A) is done at a pressure of from atmospheric pressure to 10 bar, more preferably of from atmospheric pressure to 5 bar, even more preferably of from atmospheric pressure to 4 bar. Preferably, the progress of the reaction is monitored by measuring the amount of nitrogen evolved, or by standard techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), high performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LCMS), or thin layer chromatography (TLC), and workup of the reaction mixture can start, when the conversion of the starting material exceeds 95%, or when no more starting material can be detected. The time required for this to occur will depend on the precise reaction temperature and the precise concentrations of all reagents and catalysts, and will vary from batch to batch.

Preferably, the reaction time of reaction (A) is from 15 min to 48 h, more preferably from 30 min to 36 h, even more preferably from 1 h to 24 h.

Preferably, the amount of palladium source (Aa) is from 0.01 to 25 mol%, more preferably from 0.1 to 15 mol%, even more preferably from 1 to 10 mol%, especially from 2 to 10 mol%, the mol% based on the molar amount of compound of formula (II).

Preferably, the molar amount of compound of formula (III) is from 1 to 10 fold, more preferably from 1 to 5 fold, and even more preferably from 1 to 3 fold, of the molar amount of compound of formula (II). Preferably, the molar amount of compound of formula (IV) is from 2 to 200 fold, more preferably from 2 to 150 fold, and even more preferably from 2 to 120 fold, of the molar amount of compound of formula (II).

If the compound of formula (IV) serves also as solvent, the preferably the molar amount of compound of formula (IV) is from 2 to 200 fold, more preferably from 10 to 150 fold, even more preferably from 20 to 120 fold, especially from 50 to 120 fold of the molar amount of compound of formula (II).

Preferably, if acid (Ab) is present in the reaction (A), the amount of palladium source (Aa) is from 0.01 to 25 mol%, more preferably from 0.1 to 15 mol%, even more preferably from 1 to 10 mol%, especially from 2 to 10 mol%, the mol% based on the molar amount of compound of formula (II).

Preferably, the amount of solvent (Ad) is from 0.5 to 50 fold, more preferably from 2 to 40 fold, even more preferably from 5 to 35 fold, especially from 10 to 25 fold, of the weight of compound of formula (II).

Preferably, the molar amount of solvent (Ad) is from 1 to 400 fold, more preferably from 2 to 200 fold, even more preferably from 5 to 150 fold, of the molar amount of compound of formula (II).

Preferably, if salt (Ae) is present in the reaction (A), the amount of salt (Ae) is from 0.5 to 5 fold, more preferably from 0.75 to 2.5 fold, even more preferably from 0.75 to 2 fold, of the weight of compound of formula (II).

In a further embodiment, the diazonium salt (II) is dosed during the reaction at a rate similar to its consumption, preferably at such a rate, that stationary amount of diazonium salt (II) during the reaction is at least 5 mol%, but does not exceed 25 mol%, the mol% based on the initial molar amount of compound of formula (III).

The stationary amount of diazonium salt (II) in the reaction mixture can be monitored during the reaction by standard techniques, preferably it is monitored online or by taking samples by infrared spectroscopy (IR), UV spectroscopy (UV-VIS) or nuclear magnetic resonance spectroscopy (NMR). Preferably, the reaction (A) is done under inert atmosphere in a closed vessel, and the evolution of nitrogen is monitored qualitatively or quantitatively.

After the reaction (A), the compound of formula (I) can be isolated from the reaction mixture resulting from reaction (A) by standard methods known to the skilled person such as evaporation of volatile components from the reaction mixture, dilution of the reaction mixture with water, addition of base, extraction, washing, drying, concentration, crystallization, distillation and any combination thereof. Preferably, addition of base is done by the addition of a base (A-basify), preferably of an aqueous solution of the base (A-basify).

Base (A-basify) is an base commonly used in the isolation of organic reaction products from a reaction mixture.

Preferably, base (A-basify) is selected from the group consisting NaOH, NaHC0 ₃ , KOH, KHC0 ₃ , Na ₂ C0 ₃ and K ₂ C0 ₃ .

Preferably, the base (A-basify) is added in such an amount, that the pH of the resulting mixture is from 14 to 7, more preferably from 12 to 8, even more preferably from 1 1 to 9. The palladium source (Aa) can optionally be recovered by adding to the reaction mixture after reaction (A) an insoluble substance, which binds palladium, such as charcoal or BaS0 ₄ , or a commercial scavenger for noble metals, which are known to the skilled person, and filtering said insoluble substance, loaded with the palladium source (Aa), off. Preferably, the volatile components of the reaction mixture are removed by evaporation under reduced pressure.

Any extraction of an aqueous mixture containing compound of formula (I) is preferably done with a solvent (A-extr), solvent (A-extr) is selected from the group consisting of toluene, benzene, dichloromethane, chloroform, acetic acid Ci_8 alkyl esters and mixtures thereof. Preferably, the acetic acid Ci_8 alkyl ester is an acetic acid Ci_ ₄ alkyl ester, more preferably ethyl acetate, isopropyl acetate or butyl acetate.

Preferably, solvent (A-extract) is toluene, ethyl acetate or isopropyl acetate. The compound of formula (I) can be isolated by dilution of the reaction mixture with aqueous base, followed by extraction with a solvent (A-extr) and followed by concentration and optional distillation of the extract.

Preferably, the optional washing of any organic phase after the reaction during isolation is done with water or with brine.

Even more preferably, the reaction mixture is first poured into aqueous NaHC0 ₃ and then extracted with ethyl acetate. Optionally, any organic phase can be dried, preferably with magnesium sulfate or sodium sulfate.

Any concentration is preferably done by distillation, preferably under reduced pressure.

The compound of formula (I) can be purified, preferably by chromatography, crystallization or distillation under reduced pressure.

Separation of compound of formula (I) from a compound of formula (I-iso),

wherein in formula (I-iso), Rl, R2, R3 and R4 are as defined above, also with all their preferred embodiments,

which can be formed as byproduct, can also be accomplished by column chromatography on silica gel. Suitable eluents are for example mixtures of pentane, hexane, heptane,

cyclohexane, methy Icy clo hexane or dichloromethane with a more polar solvent, such as ethyl acetate, ethanol or methanol. Small amounts of a tertiary amine can be added to the silica gel or the eluent in order to prevent hydrolysis of the acetals. Purification of organic compounds by column chromatography on silica gel is a well-established technique and is known to the skilled in the art.

Further subject of the invention is the method (A) for the preparation of a compound of formula (I);

with the method (A) being as defined above, also with all its preferred embodiments, wherein

the compound of formula (II) has been prepared by a reaction (B), the reaction (B) is a Rl

wherein

in formula (V), Rl, R2 andR3 are defined as above, i.e. they are identical with the Rl, R2 and

R3 in formula (II);

compound (Ba) is R12-ONO, KN0 ₂ or NaN0 ₂ ;

R12 is CLIO alkyl; acid (Bb) is selected from the group consisting of HBF ₄ , HPF ₆ , HC1, HBr, H ₃ P0 ₄ and

H ₂ S0 ₄ .

Reaction (B) is a common diazotization reaction, which can be done with known parameters, conditions and reagents, as e.g. disclosed in G. Schiemann et al, see citation above. Preferably,

acid (Bb) is HBF ₄ .

Reaction (B) can be done or carried out without a solvent (Bd).

Preferably, reaction (B) is done or carried out in a solvent (Bd).

The solvent (Bd) is selected from the group consisting of water, compound of formula (B-IV), solvent (B-Ad) and mixtures thereof; wherein

R40 is selected from the group consisting of Ci_ ₄ alkyl and (CH ₂ ) ₂ -OMe; the solvent (B-Ad) is selected from the group consisting of acetone, methylethylketone,

dichloromethane, CC , chloroform, benzene, fluorobenzene, benzonitrile, acetonitrile, propionitrile, ethyl acetate, butyl acetate, THF, methyl-THF, dioxane, toluene, xylene and mixtures thereof.

Preferably the solvent (B-Ad) is selected from the group consisting of benzonitrile,

acetonitrile, dichloromethane, chloroform and propionitrile;

more preferably from the group consisting of benzonitrile, acetonitrile and propionitrile; especially the solvent (B-Ad) is acetonitrile or propionitrile.

Preferably,

R40 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl and (CH ₂ )2-OMe;

more preferably,

R40 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl and (CH ₂ ) ₂ -OMe;

even more preferably,

R40 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl and

(CH ₂ ) ₂ -OMe;

especially,

R40 is selected from the group consisting of methyl, ethyl and (CH ₂ ) ₂ -OMe;

more especially,

R40 is methyl or (CH ₂ ) ₂ -OMe;

even more especially,

R40 is methyl. Preferably, solvent (Bd) is water, methanol, acetonitrile or mixtures thereof.

Compound of formula (II) is preferably present in the reaction mixture, which results from the reaction (B), as a solution or as a suspension, in a solvent (Bd). Preferably, the reaction temperature of reaction (B) is from -20 to 50 °C, more preferably from -10 to 20°C, even more preferably from 0 to 10 °C. Preferably, the reaction (B) is done at a pressure of from atmospheric pressure to 10 bar, more preferably of from atmospheric pressure to 5 bar, even more preferably of from atmospheric pressure to 2 bar. Preferably, the reaction time of reaction (B) is from 1 min to 10 h, more preferably from 5 min to 5 h, even more preferably from 10 min to 1 h.

Preferably, the molar amount of compound (Ba) is from 1 to 5 fold, more preferably from 1 to 3 fold, and even more preferably from 1.05 to 1.5 fold , of the molar amount of compound of formula (V).

Preferably, the molar amount of acid (Bb) is from 1 to 10 fold, more preferably from 1 to 5 fold, and even more preferably from 1 to 3 fold, of the molar amount of compound of formula (V).

In the case, that compound (Ba) is not R12-ONO, then preferably the molar amount of acid (Bb) is from 2 to 10 fold, more preferably from 2 to 5 fold, and even more preferably from 2 to 3 fold, of the molar amount of compound of formula (V). Preferably, the amount of solvent (Bd) is from 2 to 100 fold, more preferably from 5 to 50 fold, even more preferably from 10 to 30 fold, of the weight of compound of formula (V).

Preferably, the reaction (B) is done under inert atmosphere. After the reaction (B), the compound of formula (II) can be isolated from the reaction mixture resulting from reaction (B) by standard methods known to the skilled person such as precipitation, for example by addition of an ether or by cooling, filtration, washing with an inert solvent, and drying under reduced pressure. Preferably, the compound of formula (II) is first washed with, preferably cold, dilute acid (Bb), then with, preferably cold, water, then with, preferably cold, MeOH or EtOH, then with, preferably cold, diethylether or, preferably cold, methyl(tert-butyl)ether. "Cold" in this paragraph means preferably 0 to 10°C.

The compound of formula (II) can be purified, preferably by crystallization. In one embodiment, compound of formula (II) is isolated, before it is used in reaction (A).

In another embodiment, compound of formula (II) is used in reaction (A) without isolation after reaction (B).

In another embodiment, the reaction (B) is done in the presence of compound of formula (III), palladium source (Aa) and compound of formula (IV).

Preferably, if a solvent (Bd) is used in reaction (B) and a solvent (Ad) is used in reaction (A), solvent (Ad) and solvent (Bd) are identical.

Preferably, solvent (Ad) and solvent (Bd) are methanol or acetonitrile or mixtures thereof, compound of formula (II) is used in reaction (A) without isolation after reaction (B), and compound (Ba) is R12-ONO.

More preferably, solvent (Ad) and solvent (Bd) are methanol or acetonitrile or mixtures

thereof, preferably methanol, and compound of formula (II) is used in reaction (A) without isolation after reaction (B), and compound (Ba) is R12-ONO, and the compound of formula (III) and the palladium source (Aa) is added to the reaction mixture after reaction (B).

Further subject of the invention is a compound of formula (I), with the compound of formula (I) being as defined above, also with all its preferred embodiments; especially with R4 being methyl; more especially with R4 being methyl and with at least one of the substituents Rl, R2 and R3 not being H.

Further subject of the invention are the compounds of formulae (I-l-iso), (I-2-iso), (I-3-iso), (I-4-iso), (I-5-iso), (I-6-iso), (I-7-iso), (I-8-iso) and (I-9-iso).

10

Further subject of the invention is the use of compound of formula (I) as a precursor for the preparation of a compound of formula (X);

(X) wherein Rl, R2 and R3 are defined as above, also with all their preferred embodiments;

preferably the use of compound of formula (I) as a precursor for the preparation of a compound of formula (X) by hydrolysis of compound of formula (I) in water with acid. Compound of formula (X) can be used as a fragrance, preferably in perfumes or house hold products.

The method of the present invention makes it possible to use anilines as starting materials, which are less expensive than the respective bromo or iodo aryls. The respective bromo aryls, are usually prepared from the amino aryls by diazotization and Sandmeyer reaction of the diazonium salt with CuBr. In the method of the present invention, the use of CuBr no longer is required and can therefore be avoided. It was surprising and unexpected, that diazonium salts of anilines can be used in Heck reaction with crotonaldehyde. Compound of formula (I) and compound of formula (I-iso) are unsaturated acetals and can be separated by known methods. For example, the unsaturated acetals can be hydro lysed in water in the presence of acid, providing the respective alpha,beta unsaturated aldehydes, for example in analogy to Ohne et al, see citation above. The aldehydes can for example be separated via bisulfit adducts, in analogy to Kjell et al., see citation above. Alternatively, compound of formula (I) and compound of formula (I-iso) can be separated by column chromatography on silica gel or reversed-phase silica gel, or by preparative gas

chromatography, or by another chromatographic method, well known to those skilled in the art.

Examples

Methods, raw materials and diazonium salts

The yield was determined by NMR using as internal reference the compound 4-nitro- benzaldehyde, if not otherwise stated. The delta (δ) is given in ppm, if not otherwise stated.

4-Nitrobenzenediazonium tetrafluoroborate (compound of formula (Π-3), see below) and 4- bromobenzenediazonium tetrafluoroborate (compound of formula (Π-4), see below) were commerically available (Aldrich), and used as purchased.

All the remaining diazonium salts were prepared according to the following, representative procedure for 4-(methoxycarbonyl)benzenediazonium tetrafluoroborate (compound of formula (Π-2), see below):

To a suspension of methyl 4-aminobenzoate (1.50 g, 9.92 mmol) in water (24 ml) at 0 °C was added HBF ₄ (48% (w/w) in water, 3.89 ml, 30 mmol). Then, while stirring, sodium nitrite (5.8 M in water, 1.88 ml, 10.9 mmol) was added dropwise. When the addition was finished, stirring at 0 °C was continued for 15 min. The resulting suspension was filtered, and the solid was washed with cold HBF ₄ (24% (w/w) in water, 6 ml), with cold water (8 ml), with cold MeOH (6 ml), and then with cold tBuOMe (2 times 8 ml). "Cold" in this paragraph means preferably 0 to 10°C. The solid was dried under reduced pressure, to provide the diazonium tetrafluoroborate (compound of formula (Π-2), see below) as colorless solid (1.66 g, 67%> yield), which was used without further purification. The yield iwas determined

gravimetrically.

By this procedure the following diazonium salts were prepared by using the respective molar amount of the respective aniline:

2-(methoxycarbonyl)benzenediazonium tetrafluoroborate (compound of formula (II- 1), see below): yield: 89%

2-chlorobenzenediazonium tetrafluoroborate (compound of formula (Π-5), see below): yield: 71%

3-fluorobenzenediazonium tetrafluoroborate (compound of formula (Π-6), see below): yield: 65%

2,3-dimethylbenzenediazonium tetrafluoroborate (compound of formula (Π-7), see below): yield: not determined 2-fluorobenzenediazonium tetrafluoroborate (compound of formula (Π-8), see below): yield: 71%

2-ethylbenzenediazonium tetrafluoroborate (compound of formula (Π-9), see below): yield: 64%

Example la

To a mixture of Pd(OAc) ₂ (18 mg, 0.080 mmol), MgS0 ₄ (0.46 g), and methanol (8.0 ml) at room temperature was added crotonaldehyde (0.29 ml, 3.53 mmol). Then compound of formula (II- 1) (439 mg, 1.76 mmol), prepared according to the representative procedure described above in 'Methods',

was added, the mixture was stirred for 1 min at 50 °C and then for 5.5 h at room temperature. The resulting mixture was poured into an aqueous solution of NaHCC"3 (150 ml), extracted with AcOEt (2 x 30 ml), the combined organic extracts were washed with brine, dried over MgS0 ₄ , and concentrated under reduced pressure, to provide 0.36 g of a dark oil. The yield of compound of formula (I-l) was 80 % based on compound of formula (II-l).

Compounds of formula (I-l) and of formula (I-l-iso) were provided (peak area ratio 97:3).

Bulb-to-bulb distillation of 0.328 g of the crude product (200 °C at 4 mbar) yielded 250 mg of compound of formula (I-l) as an oil. 1H NMR (400 MHz, CDC1 ₃ ): δ 2.59 (t, J = 6 Hz, 2H), 3.37 (s, 6H), 3.89 (s, 3H), 4.50 (t, J = 6 Hz, 1H), 6.09 (dt, J = 16, 8 Hz, 1H), 7.25 (m, 2H), 7.44 (br t, J = 8 Hz, 1H), 7.55 (br d, J = 8 Hz, 1H), 7.84 (br d, J = 8 Hz). ¹³ C NMR (125 MHz, CDC1 ₃ ): δ 36.78, 52.00, 52.97, 104.08, 126.82, 127.34, 127.67, 128.26, 130.31 , 131.19, 131.96, 139.23, 167.94.

MS (EI) m/z (%) 250 (M ⁺ , 0.1), 218 (M ⁺ - MeOH, 6), 75 (100). Anal. Calcd for Ci ₄ Hi ₈ 0 ₄ : C, 67.18%; H, 7.25%. Found: C, 67.00%; H, 7.20%. Example lb

A mixture of compound of formula (I-l) (0.30 g, 1.20 mmol), prepared according to example la, methanol (100 ml), and 10% (w/w) Pd on charcoal (33 mg) was stirred at room temperature and atmospheric pressure under hydrogen for 14 h. The catalyst was filtered off and the solvent evaporated under reduced pressure to provide compound of formula (I-lb) (0.30 g, 99% yield).

1H NMR (400 MHz, CDC1 ₃ ): δ 1.60-1.75 (m, 4H), 2.98 (m, 2H), 3.30 (s, 6H), 3.89 (s, 3H), 4.38 (m, 1H), 7.20-7.30 (m, 2H), 7.41 (t, J = 7 Hz, 1H), 7.86 (d, J = 7 Hz, 1H).

¹³ C NMR (125 MHz, CDC1 ₃ ): δ 26.68, 32.45, 34.07, 51.88, 52.67, 104.46, 125.87, 129.51 , 130.66, 130.92, 131.88, 144.10, 168.09.

MS (EI) m/z (%) 252 (M ⁺ , 0.1), 220 (M ⁺ - MeOH, 10), 75 (100).

Example lc

A mixture of compound of formula (I-lb) (140 mg, 0.56 mmol), prepared according to example lb, trifluoroacetic acid (2.0 ml) and water (0.15 ml) was stirred at room temperature for 4.5 h. The mixture was concentrated under reduced pressure, the residue mixed with brine (4 ml) and extracted with AcOEt (4 ml), the extract was dried with MgS0 ₄ and concentrated under reduced pressure to provide 164 mg of compound of formula (I-lc) as an oil, slightly contaminated with AcOEt.

1H NMR (400 MHz, CDC1 ₃ ): δ 1.97 (quint, J = 7 Hz, 2H), 2.57 (t, J = 7 Hz, 2H), 2.99 (t, J = 7 Hz, 2H), 3.91 (s, 3H), 7.20-7.30 (m, 2H), 7.45 (m, 1H), 7.89 (m, 1H), 9.76 (s, 1H).

¹³ C NMR (125 MHz, CDC1 ₃ ): δ 23.94, 33.54, 43.36, 52.35, 126.41, 129.10, 131.01, 131.14, 132.47, 143.23, 168.81, 205.34.

MS (EI) m/z (%) 206 (M ⁺ , 1), 174 (M ⁺ - MeOH, 28), 163 (100).

These spectral data correspond to those published by Ohno et al.

Example 2

To a mixture of Pd(OAc) ₂ (30 mg, 0.134 mmol), MgS0 ₄ (0.68 g), and methanol (7.0 ml) at room temperature was added crotonaldehyde (0.263 ml, 3.20 mmol). Then compound of formula (Π-2) (395 mg, 1.58 mmol), prepared according to the representative procedure described in 'Methods',

was added, the mixture was heated to 30°C and stirred for 1 min at 30°C, and then stirred at room temperature for 1 h.

The resulting mixture was poured into an aqueous solution of NaHC0 ₃ (200 ml), extracted with AcOEt (2 x 30 ml), the combined organic extracts were washed with brine, dried over MgS0 ₄ , and concentrated under reduced pressure, to provide 0.351 g of a dark oil. The yield of compound of formula (1-2) was 59%, that of compound of formula (I-2-iso) was 13%, the yield based on compound of formula (Π-2).

1H NMR (compound of formula (1-2); 400 MHz, CDC1 ₃ ): δ 2.57 (t, J = 6 Hz, 2H), 3.38 (s, 6H), 3.91 (s, 3H), 4.48 (t, J = 6 Hz, 1H), 6.31 (dt, J = 16, 8 Hz, 1H), 6.51 (d, J = 16 Hz, 1H), 7.41 (d, J = 8 Hz, 2H), 7.96 (d, J = 8 Hz, 2H). ¹³ C NMR ((1-2), 125 MHz, CDC1 ₃ ) δ 36.81, 52.00, 53.13, 103.94, 126.00, 127.77, 129.69, 129.88, 131.78, 141.92, 166.93.

MS ((1-2), EI) m/z (%) 250 (M ⁺ , 0.03), 218 (M ⁺ - MeOH, 4), 75 (100). 1H NMR (compound of formula (I-2-iso), 400 MHz, CDC1 ₃ ) δ 2.83 (d, J= 6 Hz, 2H), 3.29 (s, 6H), 3.91 (s, 3H), 4.44 (t, J= 6 Hz, 1H), 5.28 (s, 1H), 5.45 (s, 1H), 7.48 (d, J = 8 Hz, 2H), 8.00 (d, J = 8 Hz, 2H).

Example 3

To a mixture of Pd(OAc) ₂ (16 mg, 0.071 mmol), MgS0 ₄ (0.80 g), and methanol (8.5 ml) at room temperature was added crotonaldehyde (0.347 ml, 4.22 mmol). The mixture was cooled to 0 °C, and compound of formula (Π-3) (511 mg, 2.16 mmol) was added. The mixture was heated to 30°C and stirred for 1 min at 30°C, then stirred at room temperature for 1.5 h.

The mixture was poured into a saturated aqueous solution of NaHC0 ₃ (50 ml), extracted with AcOEt (2 x 25 ml), the combined organic extracts were washed with brine, dried over MgS0 ₄ , and concentrated under reduced pressure. The yield of compound of formula (1-3) was 61%, that of compound of formula (I-3-iso) was 15%, the yield based on compound of formula (Π-3).

1H NMR (compound of formula (1-3); 400 MHz, CDC1 ₃ ): δ 2.60 (t, J = 6 Hz, 2H), 3.39 (s, 6H), 4.50 (t, J = 6 Hz, 1H), 6.38 (dt, J = 16, 8 Hz, 1H), 6.54 (d, J = 16 Hz, 1H), 7.48 (d, J = 8 Hz, 2H), 8.16 (d, J = 8 Hz, 2H).

¹³ C NMR ((1-3), 125 MHz, CDC1 ₃ ) δ 36.85, 53.25, 103.73, 123.94, 126.61, 130.22, 130.75, 143.89, 146.72. MS ((1-3), EI) m/z (%) 206 (M ⁺ - MeOH, 1.2), 75 (100).

1H NMR ( compound of formula (I-3-iso), 400 MHz, CDC1 ₃ ) δ 2.85 (d, J= 6 Hz, 2H), 3.31 (s, 6H), 4.44 (t, J= 6 Hz, 1H), 5.37 (br s, 1H), 5.51 (br s, 1H), 7.57 (d, J= 8 Hz, 2H), 8.19 (d, J= 8 Hz, 1H).

Example 4 To a mixture of Pd(OAc) ₂ (11 mg, 0.049 mmol), MgS0 ₄ (0.70 g), and methanol (7.5 ml) at 0°C was added crotonaldehyde (0.303 ml, 3.69 mmol) and then compound of formula (Π-4) (520 mg, 1.92 mmol).

The mixture was allowed to warm to room temperature, and kept at 15 to 25°C by occasional cooling with a water bath.

After stirring for 5 h, the mixture was poured into a saturated aqueous solution of NaHC0 ₃ (50 ml), extracted with AcOEt (2 x 25 ml), the combined organic extracts were washed with brine, dried over MgS04, and concentrated under reduced pressure to provide 465 mg of an oil. The yield of compound of formula (1-4) was 74%, that of compound of formula (I-4-iso) was 10%), the yield based on compound of formula (Π-4).

1H NMR (compound of formula (1-4); 400 MHz, CDC1 ₃ ): δ 2.52 (t, J = 6 Hz, 2H), 3.37 (s, 6H), 4.46 (t, J = 6 Hz, 1H), 6.17 (dt, J = 16, 8 Hz, 1H), 6.40 (d, J = 16 Hz, 1H), 7.21 (d, J = 8 Hz, 2H), 7.41 (d, J = 8 Hz, 2H).

¹³ C NMR ((1-4), 125 MHz, CDC1 ₃ ) δ 36.68, 53.09, 104.00, 120.84, 125.69, 127.66, 131.40, 131.55, 136.38.

MS ((1-4), EI) m/z (%) 241 (M ⁺ - MeOH, 0.5), 75 (100).

1H NMR (compound of formula (I-4-iso), 400 MHz, CDC1 ₃ ) δ 2.78 (d, J= 6 Hz, 2H), 3.29 (s, 6H), 4.43 (t, J= 6 Hz, 1H), 5.19 (br s, 1H), 5.35 (br s, 1H), 7.28 (d, J= 8 Hz, 2H), 7.44 (d, J = 8 Hz, 1H). Example 5

To a mixture of Pd(OAc) ₂ (17 mg, 0.076 mmol), MgS0 ₄ (0.83 g), and methanol (9.0 ml) at room temperature were added crotonaldehyde (0.408 ml, 4.97 mmol) and then compound of formula (Π-5) (461 mg, 2.10 mmol), prepared according to the representative procedure described in 'Methods'.

The mixture was kept at 20 to 30°C by occasional cooling with a water bath.

After stirring for 1.5 h, the mixture was poured into a mixture of brine (50 ml) and saturated aqueous solution of NaHC0 ₃ (100 ml), extracted with AcOEt (2 x 25 ml), the combined organic extracts were washed with brine, dried over MgS0 ₄ , and concentrated under reduced pressure to yield 423 mg of an oil. The yield of compound of formula (1-5) was 63%, that of compound of formula (I-5-iso) was 9%, the yield based on compound of formula (Π-5).

1H NMR (compound of formula (1-5); 400 MHz, CDC1 ₃ ): δ 2.59 (t, J = 6 Hz, 2H), 3.38 (s, 6H), 4.50 (t, J = 6 Hz, 1H), 6.18 (dt, J = 16, 8 Hz, 1H), 6.85 (d, J = 16 Hz, 1H), 7.10 to 7.25 (m, 2H), 7.32 (dd, J = 8 Hz, 1 Hz, 1H), 7.52 (dd, J = 8 Hz, 1 Hz, 1H). i ₃

C NMR ((I-5),125 MHz, CDC1 ₃ ) δ 36.82, 53.06, 104.04, 126.75, 127.75, 128.19, 128.76, 129.59, 130.64, 132.68, 135.51.

MS ((1-5), EI) m/z (%) 194 (M ⁺ - MeOH, 2), 75 (100).

1H NMR (compound of formula (I-5-iso), 400 MHz, CDC1 ₃ ) δ 2.81 (d, J= 6 Hz, 2H), 3.26 (s, 6H), 4.35 (t, J= 6 Hz, 1H), 5.09 (br s, 1H), 5.35 (br s, 1H), 7.15 to 7.40 (m, 4H). Example 6

To a mixture of Pd(OAc) ₂ (47 mg, 0.21 mmol), MgS0 ₄ (1.55 g), and methanol (21.4 ml) at room temperature were added crotonaldehyde (0.783 ml, 9.53 mmol) and then compound of formula (Π-6) (1.07 g, 5.10 mmol), prepared according to the representative procedure described in 'Methods'.

The mixture was kept at 21 to 25°C by occasional cooling with a water bath.

After stirring for 1.5 h, the mixture was poured into saturated aqueous solution of NaHC0 ₃ (150 ml), extracted with AcOEt (2 x 50 ml), the combined organic extracts were washed with brine, dried over MgS0 ₄ , and concentrated under reduced pressure to yield 848 mg of an oil. The yield of compound of formula (1-6) was 59%, that of compound of formula (I-6-iso) was 11 ), the yield based on compound of formula (Π-6).

1H NMR (compound of formula (1-6); 400 MHz, CDC1 ₃ ): δ 2.54 (t, J = 6 Hz, 2H), 3.37 (s, 6H), 4.47 (t, J = 6 Hz, 1H), 6.19 (dt, J = 16, 8 Hz, 1H), 6.43 (d, J = 16 Hz, 1H), 6.88 (m, 1H), 7.05 (d, J = 8 Hz, 1H), 7.09 (d, J = 4 Hz, 1H), 7.24 (m, 1H).

¹³ C NMR ((1-6), 125 MHz, CDC1 ₃ ): δ 36.61, 53.04, 103.99, 112.53 (d, J = 21 Hz), 113.88 (d, J = 21 Hz), 121.99, 126.32, 129.85 (d, J = 9 Hz), 131.49, 139.82 (d, J = 8 Hz), 163.11 (d, J = 244 Hz).

MS ((1-6), EI) m/z (%) 179 (M ⁺ - MeOH, 1), 75 (100). 1H NMR (compound of formula (I-6-iso), 400 MHz, CDC1 ₃ ) δ 2.79 (d, J = 6 Hz, 2H), 3.30 (s, 6H), 4.45 (t, J= 6 Hz, 1H), 5.22 (br s, 1H), 5.38 (br s, 1H), 6.90 to 7.40 (m, 4H).

Example 7

To a mixture of Pd(OAc) ₂ (6 mg, 0.027 mmol) and methanol (3.0 ml) at room temperature was added crotonaldehyde (0.136 ml, 1.65 mmol) and then compound of formula (Π-7) (154 mg, 0.70 mmol), prepared according to the representative procedure described in 'Methods'.

After stirring for 1.5 h at room temperature, a sample (1 ml) of the reaction mixture was diluted with brine (5 ml) and extracted once with AcOEt (2 ml). The extract was concentrated under reduced pressure, and the residue analyzed by 1H NMR. Compounds of formula (1-7) and of formula (I-7-iso) were provided (peak area ratio 8:2).

1H NMR (compound of formula (1-7); 400 MHz, CDC1 ₃ ): δ 2.23 (s, 3H), 2.28 (s, 3H, 2.56 (t, J = 6 Hz, 2H), 3.37 (s, 6H), 4.47 (t, J = 6 Hz, 1H), 5.97 (dt, j = 16, 8 Hz, 1H), 6.74 (d, J = 16 Hz, 1H), 7.00 to 7.30 (m, 3H).

1H NMR (compound of formula (I-7-iso), 400 MHz, CDC1 ₃ ) δ 2.14 (s, 3H), 2.20 (s, 3H), 2.66 (d, J= 6 Hz, 2H), 3.27 (s, 6H), 4.34 (t, J= 6 Hz, 1H), 4.95 (br s, 1H), 5.28 (br s, 1H), 6.90 to 7.30 (m, 3H).

Example 8 To a mixture of Pd(OAc) ₂ (6 mg, 0.027 mmol) and methanol (3.0 ml) at 0 °C was added crotonaldehyde (95.6 mg, 1.36 mmol) and then compound of formula (Π-8) (117 mg, 0.56 mmol), prepared according to the representative procedure described in 'Methods'.

The stirred mixture was allowed to warm to room temperature.

After stirring for 4 h at room temperature, a sample (1 ml) of the reaction mixture was diluted with brine (5 ml) and extracted once with AcOEt (2 ml). The extract was concentrated under reduced pressure, and the residue analyzed by 1H NMR. Compounds of formula (1-8) and of formula (I-8-iso) were provided (peak area ratio 77:23).

1H NMR (compound of formula (1-8); 400 MHz, CDC13): δ 2.57 (t, J = 6 Hz, 2H), 3.37 (s, 6H), 4.48 (t, J = 6 Hz, 1H), 6.26 (dt, J = 16, 8 Hz, 1H), 6.63 (d, J = 16 Hz, 1H), 6.95 to 7.30 (m, 3H), 7.45 (m, 1H).

1H NMR ( compound of formula (I-8-iso), 400 MHz, CDC1 ₃ ) δ 2.81 (d, J= 6 Hz, 2H), 3.32 (s, 6H), 4.48 (t, J= 6 Hz, 1H), 5.24 (br s, 1H), 5.32 (br s, 1H), 6.95 to 7.45 (m, 4H).

Example 9

To a mixture of Pd(OAc) ₂ (76 mg, 0.34 mmol), MgS0 ₄ (1.61 g), and methanol (20.4 ml) at room temperature were added crotonaldehyde (0.747 ml, 9.09 mmol) and then compound of formula (Π-9) (1.06 g, 4.82 mmol), prepared according to the representative procedure described in 'Methods'.

The mixture was kept at 21 to 25°C by occasional cooling with a water bath.

After stirring for 1 h, the mixture was poured into saturated aqueous solution of NaHC0 ₃ (120 ml), extracted with AcOEt (2 times 30 ml), the combined organic extracts were washed with brine, dried over MgSC^, and concentrated under reduced pressure to provide 767 mg of an oil. The yield of compound of formula (1-9) was 50%, that of compound of formula (I-9-iso) was 10%), the yield based on compound of formula (Π-9). Moreover, 16%> of 2-ethylanisole was formed as byproduct.

1H NMR (compound of formula (1-9); 400 MHz, CDC1 ₃ ): δ 1.20 (t, J = 7 Hz, 3H), 2.56 (t, J ^■ 6 Hz, 2H), 2.69 (quart, J = 7 Hz, 2H), 3.37 (s, 6H), 4.47 (t, J = 6 Hz, 1H), 6.05 (dt, J = 16, 8 Hz, 1H), 6.72 (d, J = 16 Hz, 1H), 7.10 to 7.25 (m, 3H), 7.42 (d, J = 7 Hz, 1H).

¹³ C NMR ((I-)), 125 MHz, CDC1 ₃ ): δ 15.25, 26.38, 36.97, 52.99, 104.26, 125.95, 126.26, 127.33, 128.57, 130.21, 136.01, 141.15.

MS ((1-9), EI) m/z (%) 188 (M ⁺ - MeOH, 0.4), 75 (100).

1H NMR (compound of formula (I-9-iso), 400 MHz, CDC1 ₃ ) δ 1.21 (t, J = 7 Hz, 3H), 2.65 (quart, J = 7 Hz, 2H), 2.67 (d, J= 6 Hz, 2H), 3.27 (s, 6H), 4.36 (t, J= 6 Hz, 1H), 4.97 (br s, 1H), 5.29 (br s, 1H), 7.05 to 7.30 (m, 4H).