Iodo analogues

Substituents are sometimes displaced thus chloroimidazoles are nitrated normally, but iodo analogues suffer nitro-deiodination. 

Bromo-3-methyl-4-nitroisothiazole can be converted into the 5-iodo analogue by reaction with sodium iodide in acetone (65AHC(4)107). Halogen exchange also takes place when 4-bromo-3-methylisothiazole-5-diazonium chloride is treated with methyl methacrylate and hydrolyzed, giving the chloro compound (150) (72AHC(14)l). 

Sandmeyer reactions used have included the preparation of the 5-iodo compound from the diazonium salt of 5-amino-8-isoquinolinol further reaction with iodine monochloride gave 5,7-diiodo-8-isoquinolinol (66JMC46). Treatment of 1-chloroisoquinoline with iodide gave the 1-iodo analogue (47%) (67YZ1342). 

Early work by Strassner and co-workers showed that the chelating bis-NHC Pd complexes 32a and 32c were capable of promoting the oxidation of methane, whilst the iodo-analogues 32b and 32d were inactive under the same reaction condition [45], Indeed, in a mixture of TEA and TFAA, in the presence of potassium peroxodisulfate under 20-30 bar of methane, trifluoroactic acid methyl ester is produced, using 32a or 32c as catalyst (Scheme 10.14). hi a more recent work, the authors disclosed the use of pyrimidine-NHC Pd complexes for the same reaction. A shghtly better catalytic activity was obtained with the unexpected cationic complex 34 [46],... 

The tendency to hydrolyse increases from the chloro to the iodo analogues. Oxohalide technetates are often used as precursors for oxotechnetium complexes, thus making use of their reactivity and good solubility of their tetraalkyl ammonium salts in various organic solvents. Particularly, salts of tetrachloro-oxotechnetate(V) have proven to be such effective starting materials. 

This is more shock sensitive than the iodo-analogue, which explodes both on melting and impact. The chloro-compound is not known. 

The reaction with HI at 25 °C gave the iodo analogue. However, if the reaction was run at a higher temperature, a mixture of 2-iodo-3-propenoic acid and 2-iodo-2-propenoic acid was formed [252],... 

Similar studies with the bromo- and iodo-analogues showed the reactivity order I > Cl > Unlike corresponding Rh and Pt" complexes, K2[Pd-... 

Fuller reported that A/-phenacyl-cyclopropylamine hydrochloride (48) displayed a slight preference for MAO B inhibition, and that analogues with various substituents on the phenyl ring were inhibitors of MAO A [117]. Subsequent research revealed that A/-[2-(o-chlorophenoxy)-ethyl]-cyclopropylamine (Lilly 51641) (42) had selectivity toward MAO A [118]. The iodo analogue of compound 42, A/-[2-(o-iodophenoxy)-ethyl]-cyclopropylamine (LY121768) (49), also proved to be a MAO A-selective irreversible inhibitor [119]. Silverman and coworkers reported that 1-phenylcyclopropylamine (50) and A/-cyclopropyl-a-methylbenzyla-mine (51) are 50 times more potent irreversible inhibitors for MAO B than MAO A, while 1-benzylcyclopropylamine (52) showed some selectivity for MAO A [120]. A/-Cyclopropyl-indolylmethylamine (53), A/-cyclopropylbenzylamine (54), and A/-(1-methylcyclopropyl)benzylamine (55) were also shown to be good inhibitors, but the selectivities were not reported [121]. 

The iodo analogue has been prepared by thermal1 7 and photochemical8 reactions of Mn2(CO)10 with I2. The former method, which is simple to perform, is described in Section D. The reaction of MnH(CO)s and I2 also has been reported to give MnI(CO)s.10 Another procedure utilizes the nucleophilic character of the anion Mn(CO)s. This reaction, which forms the basis of the procedure in Section C, was mentioned briefly some years ago,11 but no experimental detail was provided. Advantages of the method are speed, high yield, and absence of product contamination by unreacted Mn2(CO)10. 

When heated with potassium iodide in dimethylformamide, l-alkyl-4-chloro- (or bromo)-5-nitroimidazoles were converted into the 4-iodo analogues (79JGU1251). One would expect the 5-chloro-4-nitro isomers to be even more susceptible to this replacement (87AJC1399). 

Probably the best known monomeric Mov form is the green chloro complex, which can be isolated as the solid (NH4)2[MoOCls], and is retained in solution at >7 M HC1. The closely related [MoOCU]- and [MoOCLJr O]- ions are also known, and chloro and iodo analogues... 

The use of triphenylphosphine-carbon tetrachloride to convert lincomycin 2 into clindamycin 3 has already been mentioned the 7-bromo aud 7-iodo analogues of 3 were also prepared by treatment of lincomycin hydrochloride with triphenylphosphine and carbon tetrabromide or carbon tetraiodide, with acetonitrile as the solvent [6]. 

The vibrational spectra,79,155 160 197Au Mossbauer spectra75,74,78 and NQR spectra78,79 of [AuC12]- and the bromo and iodo analogues have been studied. The NQR study indicated that the AuCl bonds in [AuC121- have —68% ionic character,78,79 but theoretical studies indicate greater covalent character., 64... 

The iodo analogue in this series of compounds, GR 190028a (pKi = 8.2), was shown to be equipotent in vitro with GR 175737 [20], This compound was labelled by an isotopic exchange reaction (scheme 6) and evaluated for its potential use as a SPECT ligand for the H3 receptor. 

In a nucleophilic substitution procedure a number of chloropyridazines were converted by sodium iodide into the iodo analogues (77AJC2319). 

A somewhat simpler procedure was followed to prepare 3-astatotamoxifen (24) since in this case the acid and base treatment is not needed. Isolation and identification of astati-nated products—together with their iodinated carriers—are performed by HPLC or TLC. The HPLC radiochromatogram of 24 and the chromatogram of its inactive iodo analogue can be seen in Figure 3. In the presence of iodine, radiochemical yields of 80% and 60% could be achieved for / -astatobenzoic acid and astatotamoxifen, respectively. Without using an iodinated carrier, however, the yield did not exceed 0.5-1%. 

Inductive effects can sometimes influence product orientation. Whereas 3-methyl-6-methoxypyridazine methylates only at N-2, the 6-chloro- and 6-iodo analogues gave 21 and 22%, respectively, of the N-l product (67ACS1067). 

The facility with which the bromo, chloro and iodo analogues undergo reduction, with maintenance of the 5,6-double bond and replacement of the halogen by hydrogen, has been exploited for the electrochemical synthesis of 5-(3H)-uracil by conducting the reaction in tritiated water121). This procedure should be equally effective for the synthesis of labelled uracil nucleosides and nucleotides. 

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