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US 2005/0033090 A1Published application
Process for the preparation of cinnamaldehyde compounds
AssigneeLymphoSign Inc.
InventorsThomas Osswald, Olivier Ruha
Life of this patent
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Abstract
A process for the preparation of cinnamaldehyde, α,β-unsaturated cyanoester, and cyanoamide compounds using a Heck reaction is described. Methods for further elaboration of these aldehydes are also provided.
Claims37
A process for the preparation of cinnamaldehyde compounds of the general formula (I)
- in which X is O or —NH—,
- wherein a compound of the general formula (II):
- wherein
- R1 is a leaving group which is able to react in a Heck reaction as complex-forming leaving group,
- X is O or —NH—;
- and
- when X is O:
- R2 and R3, independently of one another, are trialkylsilyl, (C1-4)-allyl, (C1-4)-alkenyl, aryl;
- or R2 and R3 together are —C(CH3)2—, —CH2—, —CH2—CH2—, —C(O)—C(O)—, or dialkylsilyl, thereby forming a ring;
- and
- when X is —NH—, R2 and R3, independently of one another, are trialkylsilyl or
- alkyloxycarbonyl or phenyloxycarbonyl, or R2 and R3 together are —C(O)—C(O)—;
- is reacted with a compound of the general formula (III):
- wherein
- R4 and R5, independently of one another, are C1-8-alkyl or trialkylsilyl;
- or R4 and R5 together are —CH2—, —CH2—CH2— or —C(O)—C(O)—, thereby forming a ring
- in a Heck reaction, and then the protective groups are removed.
14 more elements
A process for the preparation of cinnamaldehyde compounds of the general formula (IV)
- wherein
- R1 is selected from H, OH, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C1-6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, CF3, OCF3, and halo, or R1 and R2 together represent O-C1-6alkyl-O, thereby forming a ring;
- R3 is selected from H, OH, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C1-6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, halo, and CH2—S—(CH2)n Ar;
- Ar is an aromatic or heteroaromatic group, unsubstituted or substituted with 1-4 substituents, independently selected from OH, C1-6alkyl, C1-6alkoxy, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), SH, S-C1-6alkyl, NO2, CF3, OCF3, and halo
- n is 0 to 4;
- and
- the process comprising reacting a compound of the general formula (V)
- wherein
- R1 and R2 are independently selected from H, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), NH(C1-6alkyloxycarbonyl), NH(phenyloxycarbonyl), NH(C1-6trialkylsilyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C1-6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, CF3, OCF3 and halo, or R1 and R2 together represent O—C6alkyl-O, thereby forming a ring;
- R3 is selected from H, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C1-6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, halo, and CH2—S—(CH2)n Ar;
- L is a leaving group which is able to react in a Heck reaction as complex-forming leaving group;
- and
- Ar is an aromatic or heteroaromatic group, unsubstituted or substituted with 14 substituents, independently selected from OH, C1-6alkyl, C1-6alkoxy, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), SH, S-C1-6alkyl, NO2, CF3, OCF3, and halo
- n is 0 to 4;
- with a compound of the general formula (III)
- wherein
- R4 and R5, independently of one another, are C1-8-alkyl or trialkylsilyl;
- or R4 and R5 together are —CH2—, or —CH2—CH2— or —C(O)—C(O)—, thereby forming a ring,
- in a Heck reaction, and then the protective groups are removed.
16 more elements
A process for the preparation of α,β-unsaturated cyanoester and cyanoamide compounds of the general formula (VIII)
- wherein
- R1 and R2 are independently selected from H, OH, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C1-6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, CF3, OCF3, and halo, or R1 and R2 together represent O-C1-6alkyl-O, thereby forming a ring;
- R3 is selected from H, OH, C1-6alkyl, C1-6alkoxy, C1-6alkylCO2, NH2, NH—C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C1-6alkyl(C═O)NH, C1-6alkyl(C═O)N(C1-6alkyl), SH, S-C6alkyl, O—Si(C1-6alkyl)(C1-6alkyl)(C1-6alkyl), NO2, halo, and CH2—S—(CH2), Ar;
- and
- R4 represents C(X)R5, SO3Ar, SO2Ar, SO2(C1-6alkyl), NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), P(O)(OH)2, P(O)(OC1-6alkyl)2, and C(NH2)═C(CN)2;
- X is selected from O, S, NH, and N-C1-6alkyl;
- R5 is selected from NH2, OH, NH(CH2)pAr, NH(CH2)pOH, (CH2)pOC1-6alkyl, C1-6alkyl, C1-6alkoxy, (OCH2CH2)pOCH3, NHNH2, NHC(O)NH2, NHC(O)C1-6alkoxy, N-morpholino, and N-pyrrolidino;
- Ar is an aromatic or heteroaromatic group, unsubstituted or substituted with 1-4 substituents, independently selected from OH, C1-6alkyl, C1-6alkoxy, NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), SH, S-C1-6alkyl, NO2, CF3, OCF3, and halo;
- n is 0 to 4;
- p is 1 to 4;
- and
- the process is wherein a compound of the general formula (VIII) is reacted in accordance with Knoevenagel with a compound of the general formula (IX)
- wherein
- R4 represents C(X)R5, SO3Ar, SO2Ar, SO2(C1-6alkyl), NH2, NH-C1-6alkyl, N(C1-6alkyl)(C1-6alkyl), P(O)(OH)2, P(O)(OC1-6alkyl)2, and C(NH2)═C(CN)2;
- X is selected from O, S, NH, and N-C1-6alkyl;
- R5 is selected from NH2, OH, NH(CH2)pAr, NH(CH2)pOH, (CH2)pOC1-6alkyl, C1-6alkyl, C1-6alkoxy, (OCH2CH2)pOCH3, NHNH2, NHC(O)NH2, NHC(O)C1-6alkoxy, N-morpholino, and N-pyrrolidino;
- Ar is an aromatic or heteroaromatic group, unsubstituted or substituted with 1-4 substituents, independently selected from OH, C1-6alkyl, C1-6alkoxy, NH2, NH-C1-6-alkyl, N(C1-6alkyl)(C1-6alkyl), SH, S-C1-6alkyl, NO2, CF3, OCF3, and halo;
- n is 0 to 4;
- and
- p is 1 to 4.
17 more elements
Dependencies are inferred from the claim text.