2.6- dichlorophenyl substituents

Liu et al., reported the synthesis of ethyl 5-(2,6-dichlorophenyl)-7-methyl-2-(1 -naphthylmethylene)-3 -oxo-2,3 -dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate 37 (Scheme 15). The reaction of ethyl 2-mercapto-4-methyl-6-(2,6-dichlorophenyl)-l,6-dihydro-pyrimidine-5-carboxylate, ethyl chloroacetate and naphaldehyde in acetic acid and acetic anhydride afforded the target molecule 37. In the molecular, the thiazolo[3,2-a]pyrimidine and naphthalene systems are essentially coplanar, with a dihedral angle between the combined plane and the mean plane of the benzene ring of the 2,6-dichlorophenyl substituent of 94.7(4)° [39]. 

In addition, one of the most relevant interactions resulting from the molecular dynamics calculations was found to be an aromatic contact between the 2,5-dichlorophenyl substituent and a Phe residue of the a -AR model. It is described in our pharmacophore as a more generic hydrophobic interaction involving the substituted phenyl ring attached to the piperazine nucleus. All these considerations prompted us to retrace the steps performed to build the pharmacophore model for a -AR inhibitors and check for any possibility of improving it. 

Makriyannis and co-workers designed and synthesized a series of pyrazole derivatives to aid in the characterization of the CB receptor binding sites and also to serve as potentially useful pharmacological probes. Structural requirements for potent and selective brain cannabinoid CBi receptor antagonistic activity included (1) a para-substituted phenyl ring at the 5-position, (2) a carboxamido group at the 3-position, and (3) a 2,4-dichlorophenyl substituent at the 1-position of the pyrazole ring (Lan et al. 1999). 

It is worth mentioning that under the conditions applied the silanediols 15d,g could not be obtained the final products of the acid hydrolysis of 9d,g were the 1-hydroxyalkylsilanols 14d,g. Similarly, 9d and 9g were reluctant to take part in a Cl/OSiMes exchange and the formation of lld,g and their resultant products. We suppose that the tert-butyl group in 9d prevents the molecule from adopting a suitable conformation for the replacement of the respective substituents, and the isomerisation of 9g fails as the result of the electronic effect of the dichlorophenyl substituent, destabilizing a necessary carbenium ion transition state. Interestingly, also in case of the related equally substituted 1-hydroxyalkyl tris(trimethylsilyl)silanes 1 (R = H, = tert-butyl R = H, R = 2,6-dichlorophenyl, respectively) no acid-induced isomerization could be performed. 

Carbon-centered radicals have been shown to undergo addition reactions with azirine-3-carboxylates. Methyl 2-(2,6-dichlorophenyl)azirine-2-carboxylate thus reacts with alkyl and aryl iodides in the presence of triethylborane to give aziridines in good yields. The radical approaches from the opposite face to the aryl substituent, giving the cis products as single diastereoisomers (Scheme 4.43) [63],... 

Optically active 2-allylpiperidines and -pyrrolidines arc obtained by treating hydroxylactams containing the l-[(S)-l-arylethyl]substituent as an auxiliary (see Appendix) with tin(IV) chloride and trimethyl(2-propenyl)silane46. Interestingly, the moderate diastereoselection when the aryl group is phenyl decreases when 2-chlorophenyl is used, whereas the sense of the stereoselectivity reverses for 2,6-dichlorophenyl or pentachlorophcnyl. These results are rationalized by application of molecular orbital theory and substrate conformational preferences46. 

Substituents in the aryl ring, too, can exert their own directional effects a p-nitro group deactivates the benzene ring and directs further attack into the heterocyclic ring in 4-(3, 4-dichlorophenyl)imidazole nitration is mainly at C-5 in 4-(p-methoxyphenyl)imidazole (195) subsequent nitration takes place adjacent to the methoxy function and then at C-5 (Scheme 104) (77CHE1110). The nitration of 2-(p-fluorophenyl)imidazole has been discussed earlier (Section 4.07.1.4.2). 

There are few examples of enantioselective reductions of imines bearing chiral substituents. According to Polniaszek and Dillard [139], reduction ofimmin-ium salts 6.23 by NaBHLj, followed by hydrogenolysis, leads to nonracemic-substituted tetrahydroquinolines. To observe a high asymmetric induction, it is necessary to introduce a 2,6-dichlorophenyl group on the chiral substituent (Figure 6.19). 

Elansch C, Silipo C, Steller EE. Formulation of de novo substituent constants in correlation analysis inhibition of dihydrofolate reductase by 2,4-diamino-5-(3,4-dichlorophenyl)-6-substituted pyrimidines. J Pharm Sci 1975 64 1186-1191. 

By varying the aryl substituent and the 1-substituents of 3-aryl ureas several effective herbicides have been prepared, such as neburon, l-butyl-3-(3,4-dichlorophenyl)-l-ntethylurea (27) trimeturon, 3-(4-chlorophenyl)-0,l,l-trimethylisourea (28) buturon, 3-(4-chlorophenyl)-l-methyl-1-(1-methylprop-2-ynyl)urea (29) and Proban , 3-(3,4-dichlorophenyl)-l-isopropyl-l-(2-propynyl)-urea (30). Hiose containing unsaturated side-chains include siduron, l-(2-niethyicyclohexyl)-3-phenylurea (31), and methazole, 2-(3,4-dichlorophenyI)-4-methyl-1,2,4-oxa azolidine-2,S-dione (32). 

One might expect that a phosphorus reagent having for R an aryl group activated for bimolecular nucleophilic substitution (68) by electron- withdrawing substituents might participate in a Michaelis-Arbuzov reaction. Kamai and Koshkina (159), who prepared a number of chloro-and nitro-substituted derivatives of triphenyl phosphite, found this to be the case for both ortho and para isomers of tris(monochlorophenyl) phosphite, which reacted with alkyl halides to furnish phosphonates. On the other hand, tris(2,4,6-trichlorophenyl) phosphite and tris(2,4-dichlorophenyl) phosphite (155) gave only complexes with methyl iodide however, lower reaction temperatures were employed. 

The changes in potency in the inhibition of the 5-HT transporter caused by different substituents on the phenylgroup often correspond qualitatively in both series. The series differ in potency, the indanamines in general being significantly more potent than the tetralins. Compare for instance ds ( )-3-(3,4-dichlorophenyl)-... 

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