5- Chloro-4- -1,3-dimethylpyrazole

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

Cross-coupling of 5-ethynyl-4-chloro-l,3-dimethylpyrazole with 3-iodo-4-chloronitrobenzene was carried out in the presence of (PPh3)2PdCl2, Cul, and EtjN (66%) (96MC98) (Scheme 69). 

From 4-chloroethynyl-l,3-dimethylpyrazole 80% of 4-ethynyl-5-chloro-l,3-dimethylpyrazole was obtained. There is simultaneous formation of about 10% of 4-ethynyl-l,3-dimethylpyrazole (76IZV2148 77IZV2306) (Scheme 106). 

Chloro-2-hydrazinoquinoxaline 4-oxide and acetylacetone gave 6-chloro-2-(3,5-dimethylpyrazol-l-yl)quinoxaline 4-oxide (249) (EtOH, reflux, 2 h 68%) analogs likewise. ... 

The other possible isomer, 1,4-dimethylpyrazole (and its other N-alkyl and -aryl analogues), reacted with chlorine in dichloroethane at 25-35°C to produce 5-chloro derivatives in around 70% yields (90EUP366329). 5-Aryl-3-methylpyrazoles were chlorinated by NCS at C-4 (86JHC459), as were a range of pyrazoles by chloroperoxidase in the presence of hydrogen peroxide and potassium chloride at pH 2.9. Yields of 68-83% make this latter process an improvement over some traditional chemical methods (87JHC1313). 

A-Chloro- and A/ -bromo-pyrazoles are unstable compounds, whilst iV-iodopyrazoles are stable (Section 4.04.2.1.3(xii)). These last compounds readily yield the lodonium ion, which in turn acts as an iodinatlng agent. Thus, the formation of 3-iodo-4,5-dlmethylpyrazole from l-iodo-4,5-dimethylpyrazole (B-76MI40402) is explained. The different steps in the chlorination of 3,5-diphenylpyrazole have been characterized (Scheme 45). The (V-chloro derivative (533) was fairly stable when stored at low temperatures, but it was converted into the isopyrazole (534) on standing for several hours at room temperature (80JOC76, 82S844). 

One of the examples shown by Kline and Cheatham compares the correlations observed in a GNHMBC experiment with those from a N-optimized CIGAR-HMBC experiment performed on 5-chloro-l,3-dimethylpyrazole (2). When conventional, statically optimized GNHMBC data were acquired, then only a correlation from the H4 resonance to the NMe N1 resonance at 196.7 ppm was observed. In contrast, when a 3-10 Hz optimized CIGAR-HMBC spectrum was recorded, a correlation was also observed to the N2 resonance at 309.5 ppm. 

When trying to prepare the 4-chloro derivative of l-adamantyl-3,5-dimethylpyrazole (179 Ad =... 

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