Deuterium oxide amides

Unlike the parent system, 5-methyl-5//-dibenz[c,e]azepine (1, R1 = Me R2 = H) on treatment with lithium diisopropyl amide fails to yield the tautomeric phenanthridine-imine (see Section 3.2.1.5.4.2.), but forms the 5-carbanion, which on quenching with deuterium oxide furnishes 5-methyl-[5-2H,]-5//-dibenz[e,e]azepine (l).83 5,7-Diphenyl-5//-dibenz[r,e]azepine (1. R1 = R2 = Ph) behaves similarly. In contrast, however, 5,7-dimethyl-5//-dibcnz[c,e]azepine (1, R1 = R2 = Me) yields theazaallyl anion 3, which on addition of deuterium oxide deuterates regiospecifically at the 7-methyl group to give derivative 4. 

Deprotonation of a dihydrothiazine ring, followed by a reaction with an electrophile, is most straightforward in benzothiazin-3-ones (general structure 35), which are deprotonated at the 2-position by lithium diisopropyl amide (LDA). The enolate can then react with a variety of electrophiles including deuterium oxide, methyl iodide, and aldehydes <1982T3059>. Compound 70 was prepared in this manner from 2,4-dimethyldihydro-l,4-benzothiazin-3-one (Equation 27) <1985T569>. 

The usefulness of infrared spectroscopy of proteins and membranes is increased when spectra of dry films are compared with those taken in deuterium oxide. Exchange of protons for deuterons can affect both the amide I and amide II bands. For randomly coiled proteins in D20 the amide I band is shifted down by about 10 cm."1 but for many proteins D20 does not affect the frequency of the carbonyl stretch of either the ft structure or the a-helix. In addition, upon complete exchange the amide... 

Replacement of water in gelatin by deuterium oxide, which replaces the )N-H group by >N-D decreases the conductivity by a factor of l/j/2. While this does suggest that the amide protons are involved in conduction, the method of replacing the hydrogen atom does not rule out the possibility that conduction takes place through the water contained in the material (20, 138). 

To supplement the data on prolyl isomerization, I will draw on the literature describing rotation about the C-N bond in secondary amides. Early studies in this field were described by Stewart and Siddall in an excellent 1970 review. As we will see, these reactions are related to prolyl isomerization and support the mechanism to be proposed for prolyl isomerization. The mechanism is based on results from a variety of experimental approaches. In all cases, experiments employing kinetic-based probes will be used to obtain an accurate picture of the activated complex in the rate-limiting transition state. The experiments that will be described include thermodynamics, in which activation parameters (i.e., AG, AHt, and ASt) will be described solvent effects, in which the influence of organic solvents and deuterium oxide will be reviewed acid-base catalysis substituent effects and secondary deuterium isotope effects. 

Bonm-alabilized earbanions. Ordinarily bases coordinate with the boron atom of organoboranes. However, Rathke and Row report that a highly hindered lithium amide such as lithio-2,2,6,6-tetramcthylpiperidine or lithio-t-butylneopentylamine can remove the a-proton from an organoborane to generate earbanions. Thus treatment of the boron compound B-tnethyl-9-borabicyclononane (1) in benzene with the former base for 12 hr. at room temperature followed by quenching with deuterium oxide results in deuterium incorporation of 50% (equation I). 

PMR spectra cannot indicate the presence of amide hydrogen because of rapid exchange of the proton with deuterium oxide solvent. We have found that nitrogen-cobalt bonded complexes with infrared absorptions at 1575 cm. may be formed when N-bromo primary amides react with pentacyanocobaltate(II). Comparison with the spectrum of a complex formed from an N-bromo secondary amide, in which no acidic hydrogen would be present, should help resolve this problem. 

Hydroxypyridine protonates on nitrogen, with a typical pyridine p of 5.2, the pyridones however are much less basic, and both, like amides, protonate on oxygen. Electrophilic substitution at carbon can be effected more readily with the three oxy-pyridines than with pyridine itself, and it occurs ortho and para to the oxygen function, acid catalysed exchange of 4-pyridone in deuterium oxide, for example, giving 3,5-dideuterio-4-pyridone, via C-protonation of the neutral pyridone. ... 

The influence of the protein component of cytochrome c on the haem has also been investigated with the new technique of Raman difference spectroscopy. The basis of the method is similar to conventional difference spectroscopy and the resolution of the haem resonance has been increased S-fold. The method has also been used to study structural changes in methaemoglobin. Williams et a/. have used numerical methods to produce and interpret Raman difference spectra. These workers subtracted solvent spectra from protein spectra and showed that the amide I Raman scattering intensity could be used to define helix, sheet, and reverse turns with unparalleled accuracy. The method depends on computing reference spectra for each variety of secondary structure and fitting these in linear combination to the observed spectrum. The same technique has also been successfully applied to the amide III spectrum of proteins in deuterium oxide. ... 

Barrett and Adlington have shown that allenic dianions (96), prepared from a-keto-amides via the Shapiro reaction, react at C-2 with aldehydes, acetone, and deuterium oxide to form a variety of substituted acrylamide derivatives. ... 

Beyer synthesis, 2, 474 electrolytic oxidation, 2, 325 7r-electron density calculations, 2, 316 1-electron reduction, 2, 282, 283 electrophilic halogenation, 2, 49 electrophilic substitution, 2, 49 Emmert reaction, 2, 276 food preservative, 1,411 free radical acylation, 2, 298 free radical alkylation, 2, 45, 295 free radical amidation, 2, 299 free radical arylation, 2, 295 Friedel-Crafts reactions, 2, 208 Friedlander synthesis, 2, 70, 443 fluorination, 2, 199 halogenation, 2, 40 hydrogenation, 2, 45, 284-285, 327 hydrogen-deuterium exchange, 2, 196, 286 hydroxylation, 2, 325 iodination, 2, 202, 320 ionization constants, 2, 172 IR spectra, 2, 18 lithiation, 2, 267... 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

A kinetics study has been performed on the aqueous iodine oxidation of the thiolactam (78). The rate of oxidation of (78) was found to be approximately 100 times that of a simple cyclic thioether, and this enhancement was ascribed to transannular anchimeric assistance provided by the nitrogen of the amide group <87JOC258i>. The thermal decomposition of the fused dioxetane (79) has been monitored by chemiluminescence decay, and this has been shown to follow first-order kinetics. The activation parameters have been calculated <83CL431>. Second-order rate constants for the quatemization of octahydro-lfl-azonine (9) and other azacycloalkanes with iodomethane in acetonitrile and methanol have been measured <68CCC1429>. The kinetics of the hydrogen-deuterium... 

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