Replacement of halogen by deuterium

When deuterated compounds were being first prepared, the reduction of aliphatic halogen compounds to the corresponding deuterium compounds was effected mainly by potassium or aluminum amalgam in D20 the preparation of acetic acid from potassium trichloroacetate53 and of methane from bromoform54 may be cited as examples. Later, reduction by zinc in an acid medium was preferred 4d 5 5 for instance, thymine was labelled in the methyl group by reduction of (chloromethyl)uracil with zinc and deuterium chloride 24 

Zinc powder (1.75 g) was added within 10 min to a stirred suspension of 5-(chloromethyl)-uracil (0.2 g) in 6n-DC1 (75 ml) at 60-75°C, and the mixture was stirred at that temperature for 2.5 h. The liquid was then decanted from the excess of metal powder, and the zinc was washed several times with water. After cooling, the aqueous solution was exactly neutralized with ammonia, freed from precipitated zinc hydroxide, and concentrated in a vacuum. The crystals that separated were collected. Recrystallization from water gave [oc-Di]thymine (0.04 g), m.p. 327-329°C (dec.). 

Reduction by lithium aluminum deuteride provides another method for direct replacement of halogen by deuterium, especially aliphatically bonded halogen for example, methylene dibromide is converted into deuterated methane in 93% yield.58 A mixture of LiD and LiAlD4, usually in tetrahydro-furan, is recommended59,60 especially for difficultly reducible compounds. This reduction is an SN 2 reaction, with the result that configuration is inverted at optically active centers, e.g., (R)-(+)-[2-D]butane is obtained from ( )-(+)-2-bromobutane in 82% yield 61 

A formally similar reaction of a-amino nitriles—whose CN group is bonded to a tertiary carbon atom—also leads to labeled compounds on replacement of the CN group by deuterium.62 

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Optical propagation loss for polymeric electro-optic materials is typically in the order of 1 dB/cm when care is taken to avoid scattering losses associated with processing and poling-induced damage [2, 3, 5, 63, 64, 257]. Lower loss values can be obtained by isotopic replacement of protons with deuterium and with halogens [211, 304, 305]. With effort, electro-optic material losses can be reduced to approximately 0.2 dB/cm for the telecommunication wavelengths of 1.3 and 1.55 microns. 

There are three methods which are commonly used in the steroid field to replace a halogen atom by deuterium. These methods involve treatment of the halides— generally chloride, bromide or iodide—(a) with lithium aluminum deuteride, (b) with deuterium gas and a surface catalyst or (c) with zinc in O-deuterated acids or alcohols. 

Furthermore, if an aldehyde or ketone is treated with D O. the acidic a hydrogens are replaced by deuterium. For a given ketone, the rate of deuterium exchange is identical to the rate of halogenation, implying that a common intermediate is involved in both processes. 

Displacement of aromatic halogen in 2,4-diiodo-estradiol with tritiated Raney nickel yields 2,4-ditritiated estradiol. Aromatic halogen can also be replaced by heating the substrate with zinc in acetic acid-OD or by deuteration with palladium-on-charcoal in a mixture of dioxane-deuterium oxide-triethylamine, but examples are lacking for the application of these reactions in the steroid field. Deuteration of the bridge-head position in norbornane is readily accomplished in high isotopic purity by treatment of the... 

When the silicon-transition-metal bond is reasonably strong, hydrogen attached to the metal may be replaced (mode 4b in Fig. 2) by halogens (entries 26,27, and 30) or deuterium (entry 29). In the case of the ruthenium example, halogenation can be followed by reductive elimination of RsSiH (226). 

Rather surprisingly, if the hydroxy group is replaced by a halogen atom, elimination of HX (X = Cl or Br) appears to prefer a five-membered transition state (Equation 2.53). Deuterium-labeling studies with n-butyl and -pentyl chloride demonstrate that abstraction of the hydrogen from the y-carbon is the favored process. There are also indications that cyclic chlorides and bromides eliminate HX by the 1,3-mechanism. 

Earlier, we saw how deuterium replaces all a hydrogens in acetaldehyde. Why doesn t the a-iodo compound react further to add more iodines The way to answer a question such as this one is to work through the mechanism of the hypothetical reaction and see if you can find a point at which it is disfavored. In this case, that point appears right away. It is enol formation itself that is slowed by the introduction of the first halogen. The introduced iodine inductively withdraws electrons and disfavors the first step in enol formation, protonation of the carbonyl group (Fig. 19.35). 

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