p-Toluenesulfonic acid → HCID 12449505, compound
Reaction equation
[NH2:1][C:2]1C=CC(Cl)=C(C(F)(F)F)C=1.[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][C:15]=1[C:22]([F:25])([F:24])[F:23].C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.[C-]#N.[K+]>>[Cl:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[C:2]#[N:1])=[CH:16][C:15]=1[C:22]([F:25])([F:24])[F:23]Participants
Procedure
According to the method in "Organic Syntheses", 5-amino-2-chlorobenzotrifluoride is converted to 4-chloro-3-(trifluoromethyl)benzaldehyde. As in Example 35, the following reactions are carried out. 4-Chloro-3-(trifluoromethyl)benzaldehyde (13.9 g.), 14.27 g. of p-toluenesulfonic acid, 13.01 g. of morpholine and 4.88 g. of potassium cyanide is reacted to give α-[4-chloro-3-(trifluoromethyl)phenyl]-4-morpholineacetonitrile as white crystals, m.p. 73°-74° C. This compound (14.0g.) is reacted with ethyl acrylate to give ethyl γ-cyano-γ-[4-chloro-3-(trifluoromethyl)phenyl]-4-morpholinebutyrate as a yellow oil (16.5 g.). This compound (16.5 g.) is reacted with 2.11 g. of hydrazine in 100 ml. of ethanol to give 6-[4-chloro-3-(trifluoromethyl)phenyl]-4,5-dihydro-3(2H)-pyridazinone (4.2 g.) as white crystals, m.p. 195°-198° C. This intermediate is heated with bromine in acetic acid to give 6-[4-chloro-3-(trifluoromethyl)phenyl]-3-(2 H)-pyridazinone as white crystlas, m.p. 249°-251° C. A mixture of this compound (5 g.) and 60 ml. of phosphoric oxychloride is refluxed 18 hours to give 3-chloro-6-[4-chloro--3-(trifluoromethyl)phenyl]pyridazine as cream colored crystals, m.p. 145°-147° C. A mixture of 2.2 g. of the preceding compound, 0.9 g. of formylhydrazine, and 50 ml. of n-butanol is refluxed for 48 hours to give 2.1 g. of product, m.p. 211°-214° C. Recrystallization from n-propanol gives cream colored crystals, m.p. 217°-218° C.
Sources & evidence
- ORD record
- ord-6797e30a4f2d4ee3b29ce244eb225313
- Source dataset
- uspto-grants-1978_09
- Patent number
- US04112095
Reaction notes
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