Process of making naphthacene from a propargyl alcohol
View Patent ↗A process for synthesizing a single isomer of a naphthacene compound comprises the steps of: (a) reacting a symmetrically substituted 1,1-diarylpropargyl alcohol compound with a reagent capable of forming a leaving group to form a reaction mixture containing a intermediate; and then (b) heating the intermediate in the presence of a solvent and in the absence of any oxidizing agent to form a single naphthacene compound.
1. A process for synthesizing a single isomer of a naphthacene compound comprising the steps of:
(a) reacting a symmetrically substituted 1,1-diarylpropargyl alcohol compound with a reagent capable of forming a leaving group to form a reaction mixture containing a intermediate;
and then
(b) heating the intermediate in the presence of a solvent and in the absence of any oxidizing agent to form a single naphthacene compound.
2. A process of claim 1 wherein an acid scavenger is present in step (a).
3. A process of claim 2 wherein said acid scavenger is an amine.
4. A process of claim 2 wherein said acid scavenger is triethylamine.
5. A process of claim 2 wherein said acid scavenger is an inorganic base.
6. A process of claim 1 wherein a base is present in step (b).
7. A process of claim 6 wherein said base is an amine.
8. A process of claim 6 wherein said base is triethylamine.
9. A process of claim 6 wherein said base is an inorganic base.
10. A process of claim 9 wherein said inorganic base is the basic salt of a metal.
11. A process of claim 9 wherein said inorganic base is the basic salt of a metal from groups 1 and 2 of the periodic table.
12. A process of claim 9 wherein said inorganic base is a metal or non-metal carbonate.
13. A process of claim 9 wherein said inorganic base comprises one selected from Li 2 CO 3 , Na 2 CO 3 , K 2 CO 3 , Rb 2 CO 3 , Cs 2 CO 3 , MgCO 3 , CaCO 3 , BaCO 3 , sodium acetate(NaOAc), and (NH 4 ) 2 CO 3 .
14. A process of claim 1 wherein steps (a) and (b) employ solvents that are different.
15. A process of claim 14 wherein the solvent in step (a) is selected from diethyl ether, methylene chloride, ethyl acetate and tetrahydrofuran.
16. A process of claim 14 wherein the solvent in step (b) is selected from benzene, toluene, xylene and xylene mixtures.
17. A process of claim 1 wherein steps (a) and (b) employ solvents that are the same.
18. A process of claim 17 wherein the solvent is the same for both steps (a) and (b) and is selected from benzene, toluene and xylenes.
19. A process of claim 1 wherein the reaction temperature in step (a) is in the range from −30° C. to +30° C.
20. A process of claim 19 wherein the reaction temperature in step (a) is in the range from 0° C. to +20° C.
21. A process of claim 1 wherein the reaction temperature in step (b) is in the range from +30° C. to +180° C.
22. A process of claim 21 wherein the reaction temperature in step (b) is in the range from +70° C. to +120° C.
23. A process of claim 1 wherein the reagent capable of forming the leaving group comprises one selected from thionyl chloride, thionyl bromide, phosphorous pentachloride, phosphorous trichloride, phosphorous tribromide, phosphorous oxychloride, acetyl chloride, and alkanesulfonyl chlorides.
24. A process of claim 1 wherein the reagent capable of forming the leaving group comprises one from thionyl chloride, phosphorous trichloride, and methanesulfonyl chloride.
25. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (Ia):
wherein:
the R a groups are selected from hydrogen or substituent groups;
R b is hydrogen or a substituent group;
n is selected from 0-4;
X is a leaving group; and
provided that when n is 0 R b is not phenyl.
26. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (IIa):
wherein:
the R a and R c groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
m is selected from 0-5;
W represents the atoms necessary to complete a heterocyclic or carbocyclic ring group;
X is a leaving group; and
provided that when W forms a phenyl group the R a and R c are not all hydrogen.
27. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (IIIa):
wherein:
the R a groups are selected from hydrogen or substituent groups;
R c is hydrogen or a substituent group;
n is selected from 0-4;
m is selected from 0-5;
X is a leaving group; and
provided that R a and R c are not all hydrogen.
28. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (Ib):
wherein:
the R a and R b groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
X is a leaving group; and
provided that when R b is a phenyl group the R a groups are not hydrogen.
29. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (IIb):
wherein:
the R a and R c groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
m is selected from 0-5;
W represents the atoms necessary to complete a heterocyclic or carbocyclic ring group;
X is a leaving group; and
provided that when W forms a phenyl group the R a and R c are not all hydrogen.
30. A process of claim 1 wherein said intermediate of step (a) is represented by Formula (IIIb):
wherein:
the R a groups are selected from hydrogen or substituent groups;
R c is hydrogen or a substituent group;
n is selected from 0-4;
m is selected from 0-5;
X is a leaving group; and
provided that R a and R c are not all hydrogen.
31. A process of claim 1 wherein said naphthacene compound is represented by Formula (IVa):
wherein:
R a and R b are substituent groups;
n is selected from 0-4; and
provided that when n is 0 R b is not phenyl.
32. A process of claim 1 wherein said naphthacene compound is represented by Formula (IVb):
wherein:
the R a and R c groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
m is selected from 0-5;
W represents the atoms necessary to complete a heterocyclic or carbocyclic ring group; and
provided that when W forms a phenyl group the R a and R c are not all hydrogen.
33. A process of claim 1 wherein said naphthacene compound is represented by Formula (IVc):
wherein:
the R a groups are selected from hydrogen or substituent groups;
R c is hydrogen or a substituent group;
n is selected from 0-4;
m is selected from 0-5; and
provided that R a and R c are not all hydrogen.
34. A process of claim 1 wherein said symmetrically substituted 1,1-diarylpropargyl alcohol compound is represented by Formula (Va):
wherein:
R a and R b are substituent groups;
n is selected from 0-4; and
provided that when n is 0 R b is not phenyl.
35. A process of claim 1 wherein said symmetrically substituted 1,1-diarylpropargyl alcohol is represented by Formula (Vb):
wherein:
the R a and R c groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
m is selected from 0-5;
W represents the atoms necessary to complete a heterocyclic or carbocyclic ring group; and
provided that when W forms a phenyl group the R a and R c are not all hydrogen.
36. A process of claim 1 wherein said symmetrically substituted 1,1-diarylpropargyl alcohol is represented by Formula (Vc):
wherein:
the R a and R c groups are selected from hydrogen or substituent groups;
n is selected from 0-4;
m is selected from 0-5; and
provided that R a and R c are not all hydrogen.
37. A process of claim 25 wherein X is selected from Cl, Br, acetate(OAc), alkanesulfonate, and phosphate.
38. A process of claim 28 wherein X is selected from Cl, Br, acetate(OAc), alkanesulfonate, and phosphate.
39. A process of claim 25 wherein X is selected from Cl and methanesulfonate(CH 3 SO 3 ).
40. A process of claim 28 wherein X is selected from Cl and methanesulfonate(CH 3 SO 3 ).
41. A process of claim 27 wherein either of n or m is at least one, and R a and R c are individually selected from hydrogen, cyano, nitro, halogen, hydroxy, alkyl, alkenyl, alkoxy, aryl, aryloxy, acyl, oxysulfonyl, acyloxy, oxycarbonyl, carboxy, sulfoxide, thio, sulfamoyl, sulfonamido, sulfonyl, carbamoyl, carbonamido, ureido, and trifluoromethyl groups.
42. A process of claim 30 wherein either of n or m is at least one, and R a and R c are individually selected from hydrogen, cyano, nitro, halogen, hydroxy, alkyl, alkenyl, alkoxy, aryl, aryloxy, acyl, oxysulfonyl, acyloxy, oxycarbonyl, carboxy, sulfoxide, thio, sulfamoyl, sulfonamido, sulfonyl, carbamoyl, carbonamido, ureido, and trifluoromethyl groups.
43. A process of claim 27 wherein R a and R c individually can form a carbocyclic or heterocyclic ring.
44. A process of claim 27 wherein R a and R c individually can form an aryl ring.
45. A process of claim 27 wherein R a and R c individually can form a furyl, imidazolyl, pyrazolyl, pyridyl, pyrrolyl, thienyl, or triazolyl ring.
46. A process of claim 30 wherein R a and R c individually can form a carbocyclic or heterocyclic ring.
47. A process of claim 30 wherein R a and R c individually can form an aryl ring.
48. A process of claim 30 wherein R a and R c individually can form a furyl, imidazolyl, pyrazolyl, pyridyl, pyrrolyl, thienyl, or triazolyl ring.
49. A process of claim 33 wherein an acid scavenger is present in step (a).
50. A process of claim 49 wherein said acid scavenger is an amine.
51. A process of claim 33 wherein a base is present in step (b).
52. A process of claim 51 wherein said base is the basic salt of a metal from groups 1 and 2 of the periodic table.
53. A process of claim 51 wherein said base is a metal or non-metal carbonate.
54. A process of claim 33 wherein the solvents in steps (a) and (b) are different.
55. A process of claim 33 wherein the solvents in steps (a) and (b) are the same.
56. A process of claim 33 wherein the temperature in step (a) is in the range from −30° C. to +30° C.
57. A process of claim 33 wherein the temperature in step (b) is in the range from +30° C. to +180° C.
58. A process of claim 33 wherein the reagent capable of forming the leaving group comprises one selected from thionyl chloride, thionyl bromide, phosphorous pentachloride, phosphorous trichloride, phosphorous tribromide, phosphorous oxychloride, acetyl chloride, and alkanesulfonyl chlorides.
59. A process of claim 1 wherein step (b) is subjected to an inert atmosphere.
60. A process of claim 33 wherein step (b) is subjected to an inert atmosphere.
61. A process of claim 1 wherein the reaction time of step (a) is from 5 minutes to 3 hours.
62. A process of claim 1 wherein the reaction time of step (a) is from 10 minutes to 30 minutes.
63. A process of claim 1 wherein the reaction mixture of step (b) is heated from 1 to 48 hours.
64. A process of claim 1 wherein the reaction mixture of step (b) is heated from 1 to 8 hours.
65. A process of claim 1 wherein the reaction mixture of step (b) is heated from 4 to 5 hours.