•cis-β-Bromostyrene derivatives are synthesized from cinnamic acids.•The reactions are stereospecific and only cis-β-bromostyrenes are formed.•β-Lactone intermediates are stable but do not need to be isolated.cis-β-Bromostyrene derivatives were synthesized stereospecifically from cinnamic acids through β-lactone intermediates. The synthetic sequence did not require the purification of the β-lactone intermediates although they were found to be stable and readily purified in most cases.Download high-res image (26KB)Download full-size image

•Reductive debrominations compete with dehydrobrominations.•C–H acidity of the substrates determines selectivity.•Triethylamine is not an efficient base for reductive debromination.The interaction of various 1,2-dibromides with NEt3 under various conditions (THF and DMF, respectively) at different temperatures was investigated. Our results from these reactions show that substrate dependent dehydrobrominations compete with reductive debrominations. A comprehensive discussion of these competitive pathways is offered.Download high-res image (34KB)Download full-size image

•cis-Stilbenes are synthesized from benzaldehydes and phenylacetic acids.•The synthesis involves sequential Perkin condensation and decarboxylation.•The method is convenient, efficient, and stereospecific.•The method allows the mix-and-match of substituents on either starting material.cis-Stilbenes were synthesized stereospecifically in high yields from the cuprous oxide-catalyzed decarboxylation of α-aryl-trans-cinnamic acids that were prepared from the Perkin condensation of benzaldehydes and phenylacetic acids.

•Phosphonohydrazines were prepared in good yields from corresponding arylamines.•The reaction involves nucleophilic addition of trialkyl phosphite to a diazo intermediate.•The trialkyl phosphite functions as reducing agent as well.Phosphonohydrazines were prepared in good yields from corresponding arylamines by a one-pot reaction through diazotization with an organic nitrite and treatment with a trialkyl phosphite. The trialkyl phosphite is postulated to function as a nucleophile as well as a reducing agent.

vic-Dibromides containing the α-bromocarbonyl or α-bromoaromatic moieties were reductively debrominated to furnish alkenes in high yields. o- and m-anisidines but not p-anisidine were found to be effective debrominating agents. The reductive debrominations were found to be trans-stereospecific.

The “element effect” in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, L = F > NO2 > Cl ≈ Br > I, in activated aryl substrates. A different leaving group order is observed in the substitution reactions of ring-substituted N-methylpyridinium compounds with piperidine in methanol: 2-CN ≥ 4-CN > 2-F ∼ 2-Cl ∼ 2-Br ∼ 2-I. The reactions are second-order in [piperidine], the mechanism involving rate determining hydrogen-bond formation between piperidine and the substrate-piperidine addition intermediate followed by deprotonation of this intermediate. Computational results indicate that deprotonation of the H-bonded complex is probably barrier free, and is accompanied by simultaneous loss of the leaving group (E2) for L = Cl, Br, and I, but with subsequent, rapid loss of the leaving group (E1cB-like) for the poorer leaving groups, CN and F. The approximately 50-fold greater reactivity of the 2- and 4-cyano substrates is attributed to the influence of the electron withdrawing cyano group in the deprotonation step. The results provide another example of β-elimination reactions poised near the E2-E1cB mechanistic borderline.

A convenient and efficient method for the synthesis of N1-substituted orotic acid derivatives is reported. The synthetic route utilizes substituted maleimide as synthetic intermediate and takes only four simple steps from readily available starting materials. As a result, orotic acid derivatives with various alkyl and aromatic groups at N1 can be readily synthesized.

An improved method for the synthesis of N1-substituted orotic acid derivatives is reported. The method involves sequential incorporation of nitrogen atoms to the pyrimidine structure from simple starting materials and thus allows the synthesis of N1-substituted orotic acid derivatives with single 15N label at either N-1 or N-3.

The “element effect” in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, F > NO2 > Cl ≈ Br > I, in activated aryl halides. Multiple causes for this result have been proposed. Experimental evidence shows that the element effect order in the reaction of piperidine with 2,4-dinitrophenyl halides in methanol is governed by the differences in enthalpies of activation. Computational studies of the reaction of piperidine and dimethylamine with the same aryl halides using the polarizable continuum model (PCM) for solvation indicate that polar, polarizability, solvation, and negative hyperconjugative effects are all of some importance in producing the element effect in methanol. In addition, a reversal of polarity of the C–X bond from reactant to transition state in the case of ArCl and ArBr compared to ArF also contributes to their differences in reactivity. The polarity reversal and hyperconjugative influences have received little or no attention in the past. Nor has differential solvation of the different transition states been strongly emphasized. An anionic nucleophile, thiolate, gives very early transition states and negative activation enthalpies with activated aryl halides. The element effect is not established for these reactions. We suggest that the leaving group order in the gas phase will be dependent on the exact combination of nucleophile, leaving group, and substrate framework. The geometry of the SNAr transition state permits useful, qualitative conceptual distinctions to be made between this reaction and other modes of nucleophilic attack.

The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5–C6 bond length as well as the H5–H6 coupling constants were probed. It was found that the bond length and coupling constants correlate well with the proton affinities at the carbonyl or thiocarbonyl groups at C4 but not C2. The possible implication in the tighter binding of thiouracil based nucleotides to orotidine-5′-monophosphate decarboxylase was discussed.

α-Halo and α-cyano pyridiniums were found to undergo facile hydrolysis, in contrast to the sluggish reactions of corresponding uracils. The greatly enhanced rates found with pyridinium compounds have indicated a possible source of the rate acceleration seen in the hydrolysis of 6-cyanouridine 5′-monophosphate catalyzed by orotidine 5′-monophosphate decarboxylase.α-Halo and α-cyano pyridiniums were found to undergo facile hydrolysis, in contrast to the sluggish reactions of corresponding uracils. The greatly enhanced rates found with pyridinium compounds have indicated a possible source of the rate acceleration seen in the hydrolysis of 6-cyanouridine 5′-monophosphate catalyzed by orotidine 5′-monophosphate decarboxylase.

trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the direct coupling of benzyl halides in the presence of silver oxide and DMSO under mild conditions.trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the direct coupling of benzyl halides in the presence of silver oxide and DMSO under mild conditions.

The gas phase stability of carbanions centered at various positions on pyridine N-oxide were investigated by computational and experimental methods. In addition, G3MP2 computations were completed on ring-deprotonated pyridine and N-methylpyridinium. With these species, the effect of a nitrogen-centered positive charge on carbanion stability was assessed. Introduction of the nitrogen-oxide group into the benzene ring decreases the ΔHacid by ∼20 kcal/mol, but surprisingly, the effect is nearly independent of the position of the group (ortho, meta, or para). The results indicate that the N-oxide offers a balance of field, resonance, and local effects that cancels out any positional preferences. G3MP2 calculations indicate that a similar lack of positional selectivity is seen in nitrobenzene and benzonitrile. Overall, the data suggest that π-effects are limited in phenyl anions, and as a result, ylide-like, rather than carbene-like, resonance structures are most important in the anions derived from ring deprotonation of arenes and heterocycles of these general types.

We have calculated the rate acceleration in decarboxylation reactions that can be accomplished by charge–charge repulsion between the substrate carboxylate and an adjacent negative charge in media of various dielectric constants. It has been shown that a full negative charge or surrounding partial negative charges will have the same effect. It is concluded that the rate of decarboxylation could be greatly accelerated by the presence of a negative charge nearby. For example, in media with dielectric constants from 5.62 to 20.7, a 108-fold rate acceleration could be achieved by a negative charge placed 3.77 Å away from the substrate carboxylate group. However, pKa perturbation on two carboxylate groups at close proximity may limit the extent of catalysis. It should also be noted that the extent of catalysis does not change much when the dielectric constant varies from 5.62 to 20.7.

•3-Benzyl-halouracil is prepared from N-benzylbarbituric acid with POX3.•The halogenation reaction is improved by the addition of water.•Coupling of 3-benzyl-halouracil to ribose is difficult.•N,O-bis(trimethylsilyl)acetamide is the only efficient silylating agent.•Trimethylsilyl trifluoromethanesulfonate is an efficient Lewis acid catalyst.6-Halouridine derivatives were synthesized regiospecifically through the coupling of N3-protected 6-halouracil to a ribose derivative. The combination of the silylating reagent N,O-bis(trimethylsilyl)acetamide and Lewis acid catalyst trimethylsilyl trifluoromethanesulfonate is unique in their ability to facilitate the coupling of sterically hindered pyrimidine bases to ribose to form nucleoside derivatives.

The “element effect” in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, L = F > NO2 > Cl ≈ Br > I, in activated aryl substrates. A different leaving group order is observed in the substitution reactions of ring-substituted N-methylpyridinium compounds with piperidine in methanol: 2-CN ≥ 4-CN > 2-F ∼ 2-Cl ∼ 2-Br ∼ 2-I. The reactions are second-order in [piperidine], the mechanism involving rate determining hydrogen-bond formation between piperidine and the substrate-piperidine addition intermediate followed by deprotonation of this intermediate. Computational results indicate that deprotonation of the H-bonded complex is probably barrier free, and is accompanied by simultaneous loss of the leaving group (E2) for L = Cl, Br, and I, but with subsequent, rapid loss of the leaving group (E1cB-like) for the poorer leaving groups, CN and F. The approximately 50-fold greater reactivity of the 2- and 4-cyano substrates is attributed to the influence of the electron withdrawing cyano group in the deprotonation step. The results provide another example of β-elimination reactions poised near the E2-E1cB mechanistic borderline.