You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via16.17.1.2.3 Method 3: Cyclization with Aldehydes
Please login to access the full content or check if you have access via
Seela, F.; Ramzaeva, N.; Rosemeyer, H., Science of Synthesis, (2004) 16, 974.
Condensation of a 5,6-diaminouracil with an aldehyde followed by ring closure of the 5-(alkylideneamino)-6-aminouracil intermediate (Schiff base) is the most commonly used route for the synthesis of 8-substituted xanthines. These preparations are frequently performed in one pot[174,212] (without addition of an oxidant), although in many cases the reaction conditions for the ring closure can be forcing. Commonly employed procedures for this step use an aqueous inorganic base at reflux temperature or oxidative cyclization [e.g., I2, DME, 50°C;[213] DEAD, DMF, 100°C;[214] DEAD, glyme, reflux;[215] DEAD (neat), heat;[216] SOCl2, reflux;[174,217] HgCl2, DMSO, rt;[218] FeCl3, EtOH, reflux;[174,185,219] FeCl3, AcOH;[220] NBS, CHCl3, reflux;[221] or MCPBA, MeCN, rt[222]]. An example is shown for the formation of xanthine 38 via ring closure of 6-amino-5-(ethylideneamino)uracil using 3-chloroperoxybenzoic acid in acetonitrile at room temperature (Scheme 30).[222]
Meeeee 88 8-Meeeeeeeeee Meeeeeeee ee Meeeeeeeeee ee 8-Meeee-8-(eeeeeeeeeeeeeee)eeeeeee[888]
M8 | M8 | Meeeee,e (%) | Mee |
---|---|---|---|
Me | 8-MM8M8 | 88 | [888] |
Me | 8-MMM8M8 | 88 | [888] |
Me | 8-Me8MM8M8 | 88 | [888] |
Me | MM=MMMe | 88 | [888] |
Me | 8-eeeee | 88 | [888] |
e M eeeeeee eeeeeee eee M8 = eeeeeeee, M8 = 8-MMM8M8 eee e eeeee ee 88%, eeeeeee ee ee eee eeeeee eeeee eeeeeeee eeeeee ee eeee.
8-Meeeeeeeeeee 88, eeeeeeeee eee 8-eeeeeeeeeee eeeeeeeeeee, eee eeeeeeee ee eee eeeeeeeeeeeeeee eeeeeeeeeee ee eeeee eeeeeeeeee, eeee ee eee Meeeee eeee 88 eeeee eeeeeee eeeeeeeeeeeeeeee (Meeeee 88).[888] Mee eeeeeeeeeeeeeee eeeeeeeeeee ee eeee Meeeee eeeee eeeeeeeeee e eeeeeeee ee ee eeeeeeeeeeeee eeeee eeeee eeeee eeeeeeeee eeeeee eeee ee eeee(MM) eeeeeee[888] ee eeeee eeeeeeeee.
Meeeee 88 8-Meeeeeeeeeeee ee Meeeeeeeeee ee 8-Meeeeeeeeee eeee Meeeeeeee[888]
M8 | M8 | M8 | Meeeeeeeeee | Meeeee (%) | Mee |
---|---|---|---|---|---|
MM | Me | M | eeeeeee, 88–88°M, 8 e | 88 | [888] |
MM | Me | Me | eeeeeee, 88–88°M, 8 e | 88 | [888] |
MM | Me | Me | MMM, 888°M, 8.8–8 e | 88 | [888] |
MMe | M | M | eeeeeee, 88–88°M, 8 e | 88 | [888] |
MMe | M | Me | eeeeeee, 88–88°M, 8 e | 88 | [888] |
MMe | M | Me | 888–888°M, 8–8 e | 88 | [888] |
e Mee eee eeeeeeeeee ee 88 eeee 88.
Meee eeeeeee eee eeeeeeeee eeeeeeeeeee eeee eeee eeeeeeeee eeeeeeeee eeeee eeeeeee eeeeeeeeeeeee. Mee eeeeeee, eeeeeee eeeeeeeeeeeeeeee ee ee eeeeeeeee eeeeeee, eee eee eee eeeeeeee eeeeeeeee eeeeeeee eee eeeee eeeeeeeeee; eeeeeee eeeeeeee ee e eeeeeeeee eeeeeeee, eeeeeeeee ee eeeeee ee eeeee-eeeee eeeeeeeeeeee eee eeeeeeee eeeeeeeee eeeeeeee eeeeeeeeee; eeeeeee(MM) eeeeeeee ee eeee eeeee eeee eeeeeeeeee eee ee eeeeeee eeee eeee. Meee eeeeeee eeeee eeee eeeeeeeee eeeeeeeeeee eee eee eeee eeeee eeeeeeeee ee eeeeeeeeeee eeee eeee eeeee eeeeeeeeee.
References
[174] | Meee, M. M.; Meeeeee, M.; Meeeee, M. M.; Meeee-Meee, M.; Meeeee, M., M. Mee. Meee., (8888) 88, 888. |
[185] | Müeeee, M. M.; Meee, M.; Meee, M.; Meeeeeee, M.; Meeeeeeee, M.; Meeeeeeee, M.; Meeeee, M.; Meeeeeee-Meeeeee, M., M. Mee. Meee., (8888) 88, 8888. |
[212] | Meeeeee, M.; Meeeee, M.; Meeeeee, M., Meeeee Meeeeee Mee. Meee., (8888) 888, 888. |
[213] | Meeeeeeeee, M., Meeee. Meeeee., (8888) 88, 8888. |
[214] | Meeeeeeee, M.; Meeeeeee, M.; Meeeee, M., Meeeeeeeeeee, (8888) 88, 888. |
[215] | Meeeee, M.; Meeeeeeee, M.; Meeeeee, M., M. Meee. Mee., Meee. Meeeee., (8888), 888. |
[216] | Meeeee, M.; Meeeeee, M.; Meee, M.; Meeee, M.; Meeeeeee, M.; Meeeeee, M.; Meeeeeeee, M., Meee. Meeee. Meee., (8888) 88, 8888. |
[217] | Meeee, M.; Meeeeee, M.; Meeeeeeee, M., Meee. Meeee. Meee., (8888) 88, 888. |
[218] | Meeee, M.; Meeeeeeee, M.; Meeeeee, M.; Meeee, M.; Meee, M., Meeeeeeeeeee, (8888) 88, 888. |
[219] | Meeeee, M. M.; Meeee, M.; Meeeeee, M. M.; Meee, M. M., M. Mee. Meee., (8888) 88, 8888. |
[220] | Meeeee, M.; Meeeeeee, M., Meee. Mee., (8888) 88, 888. |
[221] | Meeee, M.; Meee, M.; Meeeeee, M.; Meeeeeeee, M., Meeeeeeeeeee, (8888) 8, 8888. |
[222] | ee Meeeee, M. M.; Meeeee, M.; Meeeeee, M. M. M.; Meeeee, M. M., Meeeeeeeeeee, (8888) 88, 88. |
[223] | Meeee, M.; Mee eee Meee, M. M., Meee. Meeee. Meee., (8888) 88, 8888. |
Meeeeee Meeeeeeeeee
- 8.Meeeee-Meee, (8888) M 88-8, 8888.
- 8.Meeeee-Meee, (8888) M 8e8, 888.
- 8.Meeeee-Meee, (8888) M 8e8, 888.