Labeling reactions nucleophilic substitution

One after the other, step through the sequence of structures corresponding to the three nucleophile substitution reactions shown above (reaction 1, reaction 2, reaction 3). Decide whether loss of Br occurs with or without the assistance of RO /ROH. The nucleophile-assisted and unassisted mechanisms are called Sn2 and SnI mechanisms respectively. Label each reaction as Sn2 or SnI as appropriate. 

Imagine that you are in a research group that measures the relative rates of nucleophilic substitution (5 2) reactions. The reactions that you have investigated are listed below. Prepare a table, like Table 1 in exercise 4.16, to summarize these reactions. Include the following equation at the top of the table R-Br + Nu —> R-Nu + Br". Use compound labels to link the equation and table entries. 

Aliphatic and aromatic nucleophilic substitutions with p Fjfluoride are usually performed either on an immediate precursor of the target molecule (direct labelling using a one-step process) or on an indirect precursor followed by one or more chemical steps leading to the target radiotracer. The first approach, if highly desirable, is in fact rarely practicable. The reaction conditions are often not compatible with the structure or with the various chemical functions borne by the radiopharmaceutical. It is therefore common that the radiosynthesis comprises at least two chemical steps first the introduction of fluorine-18 followed by what is often a (multi)deprotection step. It is not unusual either that fluorine-18 is first incorporated into a much simpler and chemically more robust molecule which is then coupled to a more sensitive entity under milder conditions, possibly still followed by a final deprotection step. Suchlike multi-step procedures are possible thanks to the favourable half-life of fluorine-18. However, the more complicated the process, the more chance of side reactions and complicated final purifications (see also Section 2.3), which may seriously hamper the automation of the process. 

C.Y. Shiue, L.Q. Bai, R. Teng, A.P. Wolf, Application of the nucleophilic substitution reactions to the synthesis of NCA F-labeled radioligands, J. Label. Compds Radiopharm. 23 (1986) 1038-1039. 

For further reactions including displacement of the sulfonyl group with a labelled fluorine atom, see refs 191-193. The next homolog, tetraethylammonium fluoride has been also used for nucleophilic substitution of sulfonates. 3 /f-(Tosyloxy)-5 a//-androstan-l 7-one (7) on refluxing with tetraethylammonium fluoride in acetone yields 3a-fluoro-5a//-androstan-l 7-one (8) in 78% yield.194... 

Methylation reactions with [3H]-, [14C]- or [nC]methyliodide or [ CJmethyltriflate are widely used for the introduction of a labelled methyl group through nucleophilic substitution reactions. [3H]- and [14C]methyliodide are commercially available or can be produced as has... 

The labels 7a and 7d are used to denote mechanisms which approach, but fail to reach, the extremes of A and D character respectively. In the case 7d, the E-Y bond is perceptibly weakened prior to any significant bonding of Z to E, but EX is never present as a free entity. The label 7a is appropriate where there is evidence of incipient E-Z bond formation while the E-Y bond remains more or less intact. It is often impossible to decide whether a mechanism should be labelled A, 7or 7a, on the strength of the experimental evidence alone. If the intermediate Y—EX —Z is a plausible species, having a right to exist , we may tend to favour A as opposed to 7. If, on the other hand, the intermediate offends our notions about bonding and stability, we are inclined to postulate an 7 mechanism. Thus the well-known nucleophilic substitution reaction at a saturated carbon atom ... 

The photochemical reactions of some a-arylvinyl bromides (31), in acetic acid in the presence of sodium acetate and tetraethylammonium bromide (labeled with 8zBr) give nucleophilic substitution, reductive debromination, cis-stilbene photocyclization, and oxidation as the primary pathways to product... 

The first step, which is rate-determining, is an ionization to a carbocation intermediate that reacts with the nucleophile in the second step. Because the transition state for the rds includes R-X but not Y, the reaction is unimolecular and is labeled S l (substitution nucleophilic unimolecular). First-order kinetics are observed, with the rate being independent of the nucleophilic identity and concentration. 

Originally the difference between unimolecular and bimolecular substitution reactions was deduced from kinetic studies on a wide range of reagents. It was observed that for some reactions the overall rate of substitution depended only upon the concentration of the substrate, i.e. the species undergoing substitution, and that the rate was independent of the concentration of the attacking species, i.e. the nucleophile. The reaction, therefore, is a first order reaction that is, the sum of the indices of the concentration of the reagents in the rate equation equals one. These reactions are called unimolecular nucleophilic substitution reactions, and are given the label SN1. 

The other major type of nucleophilic substitution reaction is bimolecular, and is given the label SN2. In this case, the rate of the reaction is observed to be... 

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