Iodo analogs

The reaction has been extended (106) to the nucleoside field and provides a means for the direct iodination of suitably protected nucleosides. Thus treatment of 2,3-O-isopropylidene uridine (68) with tri-phenylphosphite methiodide in N,2V-dimethylformamide at room temperature afforded the corresponding crystalline 5-deoxy-5-iodo analog 69 in 77% yield. 

A recent reinvestigation of this reaction has substantiated the intermediacy of the 5-coordinate methylene complex 51. Thermally unstable 51 is formed when a THF solution of 46 is treated with CH2N2 at -60°C (56). The iodo analog Ir(=CH2)I(CO)(PPh3)2 has been similarly prepared and is somewhat more stable than 51, with iodide migrating less readily to the carbene carbon than chloride (56). 

In vitro studies have indicated that 5-astatouracil is chemically stable over the pH range 1-11.5 at room temperature, and 1-7 at 50°C over a period of 20 hours these results are similar to those for the iodo analog. Heating to 50°C at pH > 11.5 resulted in loss of 20-30% of bound astatine after 20 hours. This has been attributed to direct attack of OH on the 5-position of the pyrimidine nucleus, as in the case of 5-iodouracil, Both halouracils are stable in the presence of S03 and H2O2 (170). From distribution studies utilizing benzene and aqueous borax buffers, the pK, of 8.97 has been established for 5-astatouracil at 0 C (167). 

In contrast to the bromo and iodo analogs, organic chloro compounds are relatively inert toward organolithium reagents. There are only a few classes of chlorinated substrates, notably gm-dichlorocyclopropanes , l,l-dichloro-l-alkenes ° and doubly vicinal oligochlorobenzenes (1,2,3-trichlorobenzene , 1,2,3,4-tetrachlorobenzene , hexachlorobenzene etc.) that are capable of sustaining the halogen/lithium permutation mode. 

Monoamine oxidase catalyzes the deamination of primary amines and some secondary amines, with some notable exceptions. Aromatic amines with unsubstituted a-carbon atoms are preferred, but aromatic substituents influence the binding of these substrates. For example, m-iodobenzylamine is a good substrate, whereas the o-iodo analog is an inhibitor. The mechanism of deamination is as follows hydrolysis of the Schiff base that results from loss of a hydride ion on an a-proton yields an aldehyde, which is then normally oxidized to the carboxylic acid. Aromatic substrates are probably preferred because they can form a charge-transfer complex with the FAD at the active site, properly... 

The use of triphenylphosphine-carbon tetrachloride to convert lincomycin (1) into clindamycin (2) has already been mentioned (see Section I, p. 226) the 7-bromo and 7-iodo analogs of 2 were also prepared by treatment of lincomycin hydrochloride with triphenylphosphine and carbon tetrabromide or carbon tetraiodide, with acetonitrile as the solvent.3... 

While the reaction of MFA with cyanogen bromide (BrCN) in refluxing chloroform caused ring fission to yield 3 [Fig. (4)], under the same conditions cyanogen iodide did not provide the iodo analog 13. 

The first quantitative photochemical study of a Rh111 amine was reported by Moggi,8 who noted that both 254 nm (LMCT) and 365 nm (ligand field) excitation of [Rh(NH3)5Cl]2+ caused chloride labilization (equation 131). Other early reports include Basolo s study of the photoinduced stereo-retentive halide aquation from [M(en)2X2]+ (M = Rh, Ir X = Cl, Br, I), and Broomhead s observation of chloride aquation from [RhCl2(phen)2]+.726 While halide labilization dominates upon photolysis of [Rh(NH3)5Cl]2+, both bromo and ammine loss occur upon photolysis of the bromo analog (equation 132)685,707 and ammine is labilized from the iodo analog (equation 133).70 Biacetyl sensitization of the bromo complex quenches the biacetyl phosphorescence, but not the fluorescence,707 consistent with a photoreactive triplet state. 

Mercurioferrocenes (290) and (291) are separable by Soxhlet extraction and these may be used to prepare bromoferrocene or dibromoferrocene or the iodo analogs. Alternatively, these halogenated ferrocenes are prepared from the ferrocene boronic acids or from anions (322) or (323). Bromoferrocene is the starting material for cyanoferrocene, azidoferrocene, or aminoferrocenes, generally in the presence of a copper salt. Amtnoferrocene can be acylated to produce an amide, or converted to isocyanoferrocene by a formylation/dehydration sequence (Scheme 96). The 1,T-diisocyanoferrocene is available from the bis(acyl)azide, itself derived from ferrocene dicarboxylic acid. ... 

Steroid compounds (127) have been obtained (524) by condensing several iodo analogs of Reichstein s compound with N-alkyl (or aryl) thioureas in acetonic solution (Scheme 61), with X = or O, R = Et, Pr, iPr, n-Bu, s-Bu, Ph, p-MeOCgH4, p-EtOC6H4, p-MeCgH4, m-MeC H4, m-ClQH4, 3,5-Cl2C[Pg.129]

Reduction of acid (129) by lithium in ammonia furnished the spiro-fused bicyclic acid (130) as the major product (Scheme 22). Equally good results were obtained with calcium metal, but lower yields were obtained with sodium and potassium. The bromo and iodo analogs of (129), and the isomeric acid (131) failed to give any bicyclic products, however. " ... 

The most convenient dihaloborane reagent is the dibromoborane-dimethyl sulfide complex. It is commercially available as a neat liquid or is readily prepared by a redistribution reaction, of a type which is also applicable to chloro and iodo analogs (equation 43). Unlike the chloro analog, however, it reacts readily with alkenes ° " ° and alkynes in dichloromethane without need for a decomplexing agent such as trichloroborane. 

Bromosilane is a spontaneously flammable liquid with a freezing point of —94° and a boiling point of 1.9°. It is best stored in a stainless-steel cylinder with a stainless-steel needle valve, but alternatively, it may be stored as a liquid at —78° in a glass vessel. Bromosilane, unlike the iodo analog, does not attack mercury or stopcock grease. 

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