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A tandem mass spectrometric study of a series of secondary amides of acetylglycine and hippuric acid utilizing electrospray ionization (ESI) was conducted. Among the fragment ions observed was an unusual one, which we have determined to be a nitrilium ion having the structure CH3-C≡N⊕-Ph or Ph-C≡N⊕-Ph by loss of the full mass of glycine as a neutral fragment. A mechanism that we propose involves an initial protonation of the oxygen atom at the N-terminus, followed by cyclization to a five-membered imidazolium ring, and its subsequent collapse to the nitrilium ion. This mechanism is supported by extensive isotopic labels and considerable variation of substituents. A similar study of the amides of acyl β-alanine and acyl γ-aminobutyric acid revealed that the former furnishes the same nitrilium ion, but not the latter. Thus, a six-membered intermediate is also possible and capable of losing the full mass of β-alanine as a neutral fragment. When the size of the ring is forced to be seven-membered, this pathway is blocked. When this study was expanded to include a variety of N-acylproline amides, the nitrilium ion was observed in 100% abundance only when the acyl group was acetyl. Thus a proline effect (involvement of a strained bicyclic [3.3.0] structure) is being observed.

The treatment of a 1,2,5-thiadiazolidine 1,1-dioxide-derived phenylthiomethyl ether with sulfuryl chloride yielded an unexpected dimeric product whose structure was determined using X-ray crystallography. A plausible mechanism for the formation of this product is proposed. J. Heterocyclic Chem. (2009).

The presence and position of a single beta-alanine (betaA), gamma-aminobutyric acid (gammaABu) or epsilon-aminocaproic acid (Cap) residue has been shown to have a significant influence on the formation of b(n)+ and y(n)+ product ions from a series of model, protonated peptides. In this study, we examined the effect of the same residues on the formation of analogous [b3 - 1 + cat]+ products from metal (Li+, Na+ and Ag+)-cationized peptides. The larger amino acids suppress formation of b3+ from protonated peptides with general sequence AAXG (where X = beta-alanine, gamma-aminobutyric acid or epsilon-aminocaproic acid), presumably because of the prohibitive effect of larger cyclic intermediates in the 'oxazolone' pathway. However, abundant [b3 - 1 + cat]+ products are generated from metal-cationized versions of AAXG. Using a group of deuterium-labeled and exchanged peptides, we found that formation of [b3 - 1 + cat]+ involves transfer of either amide or alpha-carbon position H atoms, and the tendency to transfer the atom from the alpha-carbon position increases with the size of the amino acid in position X. To account for the transfer of the H atom, a mechanism involving formation of a ketene product as [b3 - 1 + cat]+ is proposed.

Formation of [bn+17+cat]+ is a prominent collision-induced dissociation (CID) pathway for Li+- and Na+-cationized peptides. Dissociation of protonated and Ag+-cationized peptides instead favors formation of the rival bn+/[bn-1+cat]+ species. In this study the influence of a 4-aminomethylbenzoic acid (4AMBz) residue on the relative intensities of [b(3)-1+cat]+ and [b(3)+17+cat]+ fragment ions was investigated using several model tetrapeptides including those with the general formula A(4AMBz)AX and A(4AMBz)GX (where X=G, A, V). For Li+- and Na+-cationized versions of the peptides there was a significant increase in the intensity of [b(3)-1+cat]+ for the peptides that contain the 4AMBz residue, and in some cases the complete elimination of the [b(3)+17+cat]+ pathway. The influence of the 4AMBz residue may be attributed to the fact that [b(3)-1+cat]+ would be a highly conjugated species containing an aromatic ring substituent. Comparison of CID profiles generated from Na+-cationized AAGV and A(4AMBz)GV suggests an apparent decrease in the critical energy for generation of [b(3)-1+Na]+ relative to that of [b(3)+17+Na]+ when the aromatic amino acid occupies a position such that it leads to the formation of the highly conjugated oxazolinone, thus leading to an increase in formation rate for the former compared to the latter.

In a previous study we found that a dominant fragmentation pathway observed for collision-induced dissociation (CID) of b derived from peptides with sequence AXAG, where X is γ-aminobutyric acid (γAbu) or e-aminocaproic acid (Cap), involved the loss of 89 mass units (u). A neutral loss of 89 u corresponded to the free acid mass of an alanine (A) residue. This specific pathway was studied in greater detail here using a series of A(γAbu)AG peptides with strategic positioning of 15N, 13C and 2H isotope labels. Based on the extensive labeling, several possible routes to the net elimination of 89 u are proposed. One is based on initial elimination of either aziridinone or imine and CO, followed by opening of an oxazolinone, tautomerization and elimination of H2O. Another involves formation of an aziridinone by cleavage of the N-terminal amide bond, and transfer of O and H atoms to this fragment via an H-bonded ion-molecule complex to complete the loss of 89 u. Both types of pathway include the transfer/migration of H atoms from the α-carbon position of γAbu or A residues. Copyright © 2007 John Wiley & Sons, Ltd.

We report a new fragmentation pathway for the CID of (b3 - 1 + Cat)+ product ions derived from the model peptide AXAG, where X = beta-alanine, gamma-aminobutyric acid, epsilon-amino-n-caproic acid, or 4-aminomethylbenzoic acid. By changing the amino acid to the C-terminal side of the amino acid X, and incorporating 15N and 13C labeled residues at the same position, we conclude that the dissociation pathway most likely leads to a metal cationized nitrile. With respect to the various amino acids at position X, the putative nitrile product becomes more prominent, relative to the conventional (a3 - 1 + Cat)+ species, in the order beta-alanine < gamma-aminobutyric acid < epsilon-aminocaproic acid < 4-aminomethylbenzoic acid. The pathway is not observed for peptides with alpha-amino acids at position X. The product ion is observed most prominently during the CID of Li+ and Na+ cationized peptides, only to a small extent for Ag+ cationized peptides, and not at all from protonated analogues.

The Raman and infrared spectra of a series of 1-alkyl-3-methylimidazolium hexafluorophosphate ([C2-4MIM]PF6) ionic liquids have been recorded and analyzed using density functional theory (DFT) and RHF methods at the 6-311+G(2d,p) computational level. The DFT calculations reproduce the vibrational spectra of 1-ethyl-3-methyl imidazolium hexafluorophosphate [EMIM]PF6, 1-propyl-3-methyl imidazolium hexafluorophosphate [PMIM]PF6, and 1-butyl-3-methyl imidazolium hexafluorophosphate [BMIM]PF6 using correction factors of 0.964−0.967 with correlation coefficients R2 of 0.999. The vibrational spectra calculated at the RHF/6-311+G(2d,p) level require a correction factor of 0.89 and a correlation coefficient R2 of 0.999 using the fully optimized structures. The 1-alkyl-3-methyl hexafluorophosphate ionic liquids have common Raman C−H stretching frequencies that may serve as possible probes in studies of ionic liquid interactions. The DFT (B3LYP) and RHF gas-phase molecular structures of the [C2-4MIM]PF6 ion pairs in...

The aim of this study was to investigate the dissociation patterns, and in particular the relative abundance of [b(3) + 17 + Cat](+), for peptides with C-termini designed to allow transfer of the -OH required to generate the product ion, but not necessarily as the most favored pathway. Working with the hypothesis that formation of a five-membered ring intermediate, including intramolecular nucleophilic attack by a carbonyl oxygen atom, is an important mechanistic step, several model peptides with general sequence AcFGGX were synthesized, metal cationized by electrospray ionization and subjected to collision-induced dissociation (CID). The amino acid at position X was one that either required a larger ring intermediate (beta-alanine, gamma-aminobutyric acid and epsilon-amino-n-caproic acid to generate six-, seven- or nine- membered rings, respectively) to transfer -OH, lacked a structural element required for nucleophilic attack (aminoethanol) or prohibited cyclization because of the inclusion of a rigid ring (p- and m-aminobenzoic acid). For Ag(+), Li(+) and Na(+) cationized peptides, our results show that amino acids requiring the adoption of larger ring intermediates suppressed the formation of [b(3) + 17 + Cat](+), while amino acids that prohibit cyclization eliminated the reaction pathway completely. Formation of [b(3) - 1 + Cat](+) from the alkali metal cationized versions was not a favorable process upon suppression or elimination of the [b(3) + 17 + Cat](+) pathway: the loss of H(2)O to form [M - H(2)O + Cat](+) was instead the dominant dissociation reaction observed. Multiple-stage dissociation experiments suggest that [M - H(2)O + Cat](+) is not [b(4) - 1 + Cat](+) arising from the loss of H(2)O from the C-terminus, but may instead be a species that forms via a mechanism involving the elimination of an oxygen atom from an amide group.

In a previous report we showed that certain binary Ag+–amino acid complexes formed adduct ions by the attachment of a single water and methanol molecule when stored in an ion trap mass spectrometer: complexes with aliphatic amino acids and with 4-fluorophenylalanine formed the adduct ions whereas complexes with phenylalanine and tryptophan did not. In this study we compared the tendency of the Ag+ complexes derived from phenylalanine, 4-fluorophenylalanine, 4-hydroxyphenylalanine (tyrosine), 4-bromophenylalanine, 4-nitrophenylalanine and aminocyclohexanepropionic acid to form water adducts when stored, without further activation, in the ion trap for times ranging from 1 to 500 ms. Because the donation of π electron density to the Ag+ ion is a likely determining factor in complex reactivity, our aim in the present study was to determine qualitatively the influence of para-position substituents on the aromatic ring on the formation of the water adducts. Our results show that the reactivity of the complexes is influenced significantly by the presence of the various substituents. Decreases in [M + Ag]+ ion abundance, and increases in adduct ion abundance, both measured as a function of storage time, follow the trend —NO2 > —Br > —F > —OH > —H. The complex of Ag+ with 4-nitrophenylalanine was nearly as reactive towards water as the Ag+ complex with aminocyclohexanepropionic acid, the last being an amino acid devoid of π character in the ring system. Collision induced dissociation of the [M + Ag]+ species derived from the amino acids produces, among other products, Ag+ complexes with a para-substituted phenylacetaldehyde: complexes that also form adduct species when stored in the ion trap. The trends in adduct ion formation exhibited by the aldehyde–Ag+ complex ions were similar to those observed for the precursor complexes of Ag+ and the amino acids, confirming the influence of the ring substituent. Copyright © 2002 John Wiley & Sons, Ltd.

During our ongoing investigation of the formation and reactivity of gas-phase complex ions composed of Ag(I) and various α-amino acids, we discovered that the mass-to-charge ratio for the major collision-induced dissociation (CID) product generated from a binary Ag+ complex with phenylalanine was consistent with the formation of an Ag+ complex with an aldehyde. In this study we investigated and compared the fragmentation pathways for complexes of Ag+ with phenylalanine, phenylalanine with exchangeable protium replaced with deuterium, phenylalanine with the carboxylic acid group labeled with 13C, and phenylalanine with the benzylic group labeled with deuterium. The reaction pathways were determined using multidimensional dissociation steps in an ion-trap mass spectrometer. The dissociation experiments provide clear evidence for the formation of several novel product species, including the Ag+ complex with phenylacetaldehyde, as well as the formation of an Ag+ complex with either a benzyl carbene or styrene...

Electrospray ionization was used to generate gas phase complexes of Ag+ with selected alpha-amino acids. Following storage (isolation without collisional activation) in an ion trap mass spectrometer, the mass spectra produced from the complexes of Ag+ with alpha-amino acids such as alanine, valine and tert-leucine contained peaks consistent with the formation of water or methanol molecule adduct ions. The same adduct ions were not present, however, in the mass spectra generated from the Ag+ complexes with phenylalanine, tyrosine and tryptophan following isolation and storage under similar conditions. For those complexes that showed reactivity, the uptake of water and methanol increased with longer storage times in the ion trap. A preliminary molecular modeling study using phenylalanine demonstrated that the aromatic ring coordinates the Ag+ ion, and the interaction between the metal ion and pi-system, in part, is assumed to prohibit the binding of water or methanol during isolation in the gas phase. This conclusion is supported by a comparison of the adduct formation by the Ag+ complexes with phenylalanine, 4-fluorophenylalanine and alpha-aminocyclohexanepropionic acid. In addition, collision induced dissociation experiments involving the Ag+ complexes of phenylalanine, tyrosine and tryptophan suggest that limiting the coordination of the Ag ion by the complexing molecule (i.e. by loss of a coordinating functional group and/or change in structure due to dissociation) results in the binding of a water or methanol molecule during storage in the ion trap. Surprisingly, the bare Ag+ ion, when trapped and stored under identical experimental conditions, formed neither adduct species, suggesting that the attachment of water or methanol may be due to interactions with a molecular orbital within the Ag+/molecule complex.

The crystal and molecular structure of (RS)-N-Tert-butyl-2-anilino-3,3-dimethylbutanamide, a derivative of an amino acid that was obtained by highly selective cleavage of 1,3-di-tert-butylaziridinone by aniline, is described. The racemic mixture of the amide crystallizes in the space groupP 21/n with four molecules per unit cell. Crystal Data:a=10.483(2) A,b=6.206(1) A,c=24.767(5) A,β=90.39(3),V=1611.5(6) A3,R(F)[I>2σ(I)]=0.0679.wR(F 2) [I>2σ(I)]=0.1148.

Reaction of 1,3-di-t,'rt-bu~.laziridinonc (la) and similar aziridinones with thiosemicarbazide affords, as one of the products, a compound devoid of sulfur, vie., a substituted N- aminoimidazolidinone (3a) by selective cleavage of the acyl-nitrogcn bond. Compound 3a undergoes a novel, acid-catalyzed rearrangement to a 3-imino-hexahydro-1,2,4-tri~in-6-one (7a), which can also be obtained ~' treatment of la with hydrazinc followed by BrCN. involving again selective cleavage of the acyl-nitrogen bond.

A tandem mass spectrometric study of a series of secondary amides of acetylglycine and hippuric acid utilizing electrospray ionization (ESI) was conducted. Among the fragment ions observed was an unusual one, which we have determined to be a nitrilium ion having the structure CH3-C≡N⊕-Ph or Ph-C≡N⊕-Ph by loss of the full mass of glycine as a neutral fragment. A mechanism that we propose involves an initial protonation of the oxygen atom at the N-terminus, followed by cyclization to a five-membered imidazolium ring, and its subsequent collapse to the nitrilium ion. This mechanism is supported by extensive isotopic labels and considerable variation of substituents. A similar study of the amides of acyl β-alanine and acyl γ-aminobutyric acid revealed that the former furnishes the same nitrilium ion, but not the latter. Thus, a six-membered intermediate is also possible and capable of losing the full mass of β-alanine as a neutral fragment. When the size of the ring is forced to be seven-membered, this pathway is blocked. When this study was expanded to include a variety of N-acylproline amides, the nitrilium ion was observed in 100% abundance only when the acyl group was acetyl. Thus a proline effect (involvement of a strained bicyclic [3.3.0] structure) is being observed.

The proportions of products derived from competing modes of ring-opening of 1,3-di-tert-butylaziridinone and similar aziridinones by a variety of nitrogen, oxygen, sulfur and halogen nucleophiles do not agree with simple guidelines postulated in the literature for these types of aziridinones.

The treatment of a 1,2,5-thiadiazolidine 1,1-dioxide-derived phenylthiomethyl ether with sulfuryl chloride yielded an unexpected dimeric product whose structure was determined using X-ray crystallography. A plausible mechanism for the formation of this product is proposed. J. Heterocyclic Chem. (2009).

The influence of the presence and position of a single beta-alanine, gamma-aminobutyric acid, epsilon-aminocaproic acid or 4-aminomethylbenzoic acid residue on the tendency to form b(n)+ -and y(n)+ -type product ions was determined using a group of protonated tetrapeptides with general sequence XAAG, AXAG and AAXG (where X refers to the position of amino acid substitution). The hypothesis tested was that the 'alternative' amino acids would influence product ion signal intensities by inhibiting or suppressing either the nucleophilic attack or key proton transfer steps by forcing the adoption of large cyclic intermediates or blocking cyclization altogether. We found that specific b ions are diminished or eliminated completely when betaA, gammaAbu, Cap or 4AMBz residues are positioned such that they should interfere with the intramolecular nucleophilic attack step. In addition, differences in the relative proton affinities of the alternative amino acids influence the competition between complementary b(n) and y(n) ions. For both the AXAG and the XAAG series of peptides, collision-induced dissociation (CID) generated prominent b ions despite potential inhibition or suppression of intramolecular proton migration by the betaA, gammaAbu, Cap or 4AMBz residues. The prominent appearance of b ions from the AXAG and XAAG peptide is noteworthy, and suggests either that proton migration occurs through larger, 'whole' peptide cyclic intermediates or that fragmentation proceeds through a population of [M+H]+ isomers that are initially protonated at amide O atoms.

Extensive isotope labeling (2H, 13C and 15N), collision-induced dissociation (CID) and multiple-stage tandem mass spectrometry were used to investigate the elimination of H2O from a series of model, metal-cationized tripeptide methyl esters. The present results corroborate our earlier suggestion that loss of water from lithiated peptides is initiated by a nucleophilic attack from the N-terminal side upon an amide carbonyl carbon atom to form a five-membered ring as an intermediate followed by 1,2-elimination of water. We show that the nucleophilic atom is the oxygen atom of the N-terminal amide group in the fragmentation of [AcGGGOMe+Li]+ as well as [GGGOMe+Li]+. However, the subsequent fragmentation is markedly different in the two cases as a result of the absence and presence of a free amino group. In particular, extensive scrambling of protons in the α-positions of GGGOMe is observed, presumably as a consequence of intervention of the basic amino group. Copyright © 2006 John Wiley & Sons, Ltd.

We compared the tandem mass spectra of a range of native and acetylated Ag(+) cationized peptides to determine the influence of the derivatization step on the abundance of the [b(n) + 17 + Ag](+) product ions. Using tripeptides, the smallest for which the mechanisms to generate [b(2) - 1 + Ag](+) and [b(2) + 17 + Ag](+) products are both operative, we found that in most cases acetylation causes an increase in the abundance of the C-terminal rearrangement ion, [b(2) + 17 + Ag](+), relative to the rival N-terminal rearrangement ion, [b(2) - 1 + Ag](+). The presence of a free amino group to bind to the metal ion significantly influences the relative abundances of the product ions. We propose a mechanism for the formation of the [b(n) + 17 + Ag](+) that is based on the formation of a five-membered oxazolidin-5-one and tetrahedral carbon intermediate that may collapse to a peptide upon release of CO and an imine, aided by the fact that the ring formed during C-terminal rearrangement is both a hemiacylal and hemiaminal. We also identified an influence of amino acid sequence on the relative abundances of the [b(n) + 17 + Ag](+) and [b(n) - 1 + Ag](+) product ions, whereby bulky substituents located on the alpha-carbon of the amino acid to the C-terminal side of the cleavage site apparently promote the formation of the [b(n) + 17 + Ag](+) product over [b(n) - 1 + Ag](+) when the amino acid to the N-terminal side of the cleavage site is glycine. The latter ion is the favored product, however, when the bulky group is positioned on the alpha-carbon of the amino acid to the N-terminal side of the cleavage site.

The ring opening of 1,3-di-tert-butylaziridinone by tert-butylamine and aniline was investigated by using electrospray ionization and collision-induced dissociation in an ion trap mass spectrometer in conjunction with 15N labeling of the two amine nucleophiles. Using the MSn capabilities of the ion trap instrument, we were able to monitor the retention of the 15N label through successive fragmentation steps. Both amines exhibited a remarkable degree of selectivity in that they both cleaved exclusively the 1,3-bond (the alkyl–nitrogen bond). This result is in contrast to that obtained previously with methylamine, which cleaved just the opposite bond, namely, the 1,2-bond (the acyl–nitrogen bond). These contrasting results could not have been predicted by previously published guidelines. Copyright © 2001 John Wiley & Sons, Ltd.

Variable-temperature inversion transfer NMR is used to determine the kinetic and thermodynamic parameters of cis-trans isomerization of N-Ac-(3R) and (3S)-fluoroproline-OMe.

The proportions of products derived from competing modes of ring-opening of 1,3-di-tert-butylaziridinone and similar aziridinones by a variety of nitrogen, oxygen, sulfur and halogen nucleophiles do not agree with simple guidelines postulated in the literature for these types of aziridinones.

Reaction of 1,3-di-tert-butylaziridinone and other di-tert-alkylaziridinones with cyanamides produces an imidazolidinone (3 or 6) bearing the tert-alkyl substituents at positions 1 and 5 only, by selective cleavage of the acyl-nitrogen bond. Treatment of the product from the unsubstituted cyanamide (3) with HNO 2 furnishes the corresponding hydantoin (5), whereas treatment with alkyl halides and base affords another imidazolidinone (7)

The preparation of 15N-labeled tert-butylamine involves the conversion of the correspondingly labeled potassium cyanide into the 15N-labeled tert-butylformamide via the Ritter reaction in 85% yield, followed by hydrolysis with either aqueous sodium hydroxide or hydrochloric acid. The NMR spectra of the compounds provide a valuable opportunity for discussing several important topics in NMR spectroscopy, such as cis-trans isomerism due to restricted rotation and 15N coupling. Comparison of the IR spectra of the labeled and unlabeled compounds permits a forum for discussing the theory of vibrational frequencies.

The reaction of aziridinones (1a-1d) with tert-butyllithium at room temperature affords α-hydroxy imines (5ax-5dx).1 One possible pathway leading to these products involves the formation of 2 as an intermediate, followed by rearrangement to 3. In fact, under carefully controlled conditions that prevent the rearrange-of 2 to 3, α-amino ketones (4ax-4dx), which arise from the protonation of 2, can be isolated. Other α-amino ketones were synthesized in a like manner from aziridinones by treatment with a variety of alkyllithium reagents.2 Baumgarten and co-workers3 subsequently reported similar products from the reaction of phenyllithium and methyllithium with an aziridinone. In an attempt to extend this study to other organolithium reagents, especially those bearing functional groups, we have investigated the reaction of

The only pathway postulated in the literature for the isomerization of aziridinone (Ia) to iminooxirane (IIIa) involves a planar, open-chain, dipolar intermediate (IIa); however, INDO calculations suggest a possible alternative pathway in which an in-plane bending of the oxygen atom towards the alkyl carbon atom occurs rather than a stretching of the alkyl-nitrogen bond. INDO calculations also suggest that the unknown compound IIIa has the same degree of stability as Ia.

A quantum mechanical representation of a full M electron shell, employing nine Gaussians in a tripyramidal arrangement, is developed to extend the floating spherical Gaussian orbital (FSGO) method to molecules containing heavy atoms. To demonstrate the computational capabilities of the approach, a series of ab initio calculations including geometry optimizations are reported for CuH, ZnH2, GaH3, GeH4, AsH3, H2Se, and HBr. Excluding CuH, the average difference between predicted and observed equilibrium bond lengths is 0.03 A; errors in bond angles for AsH3 and HBr average to 2.6°. A set of rules for FSGO orbital exponents, analogous in form to Slater’s rules for STO’s, is deduced, and illustrations of the utility of the rules are given.

A series ofab initio calculations using the FSGO method and including geometry optimizations are reported for the lowest singlet states of KH, CaH2, ScH, ScH3, TiH4, VH3, CrH2, and MnH. Both core and valence orbital exponents are shown to vary systematically. The description of theM-shell electrons is uneven, in thatp orbitals are more accurately described than the 3s orbital. The bond angles of VH3 and CrH2 are predicted to be unexpectedly large (94.1° and 103.1°, respectively). Orbital energies, bond lengths and angles, dipole moments, and electron populations are reported for all systems.

The reaction of aziridinones with thiourea produces glycocyamidines bearing substituents at positions 1 and 5, which have been converted into hydantoins.

The nature of the bonding in the three-membered ring molecules cyclopropane, thiirane, oxirane, and aziridine has been investigated throughab initio FSGO calculations. The direct correspondence between floating spherical Gaussian orbitals and specific chemical bonds has been used to study the degree of “bond bending”. In accord with chemical intuition, it is demonstrated that the C-C ring bond becomes progressively more bent as the bond length is reduced. C-C bonds are found to be more flexible than C-N (O, S) bonds. The sizes and locations of carbon-heteroatom bond orbitals and C-H bond orbitals are also discussed.

The reaction of α-lactams (1a–1d) with tert-butyllithium at room temperature to yield α-hydroxy imines (5ax–5dx) was reported by us as the first example of a reaction between an α-lactam and an organolithium reagent.1 Subsequent investigation revealed that α-amino ketones (4ax–4dx) could be isolated from the reaction mixtures at lower temperatures under very carefully controlled conditions that prevent the rearrangement of 2 and 3.2 In fact, a variety of α-amino ketones were synthesized in this fashion,3 a result that was confirmed later by Baumgarten and co-workers.4 As part of a broader study of the reactions of a-lactams with organometallic reagents, we investigated the reactions of α-lactams with the lithium salt of 2,4,4,6-tetramethyl-5,6-dihydro-4H1,3-oxazine (6), a reagent that has been extensively used by Meyers5 for the synthesis of aldehydes. Although these reactions did not lead to aldehydes under the conditions described by Meyers, we did find them to be convenient routes to α-amino k...

α-Amino ketones are valuable intermediates in the synthesis of a variety of substances, especially that of heterocyclic compounds, and their preparation and reactions continue to attract attention.1 Often, these compounds are prepared from the corresponding ketones or their α-bromo derivatives, but such syntheses may involve interfering side reactions and consequent difficulties in the isolation of the product.2 We now report a new synthesis of α-amino ketones which is based on a highly selective cleavage of α-lactams with organolithium compounds. This reaction is in sharp contrast to that of α-lactams with alkylmagnesium halides, which is claimed to effect an insertion-type alkylation of the acyl groups,3 although this claim has not been substantiated.4

We have studied theoretically the C3v reaction path of the Cl− + CH3Cl SN2 reaction, using the ab-initio FSGO method. We find that the departure of the leaving group begins at an early stage in the reaction. This observation is significant in that Cl− is a “good” leaving group; previous theoretical investigations of SN2 mechanisms noted a late departure of the anion but involved poorer leaving groups. The calculations suggest that the transition state should be viewed as a tight “ion triplet”, Cl−[CH+3] Cl−, rather than as a carbon with five distorted covalent bonds.

A procedure for analyzing charge distributions of FSGO wavefunctions, by partitioning bonding electrons according to the location of the orbital centers, is proposed. Electron populations are given for singlet states of eighteen diatomic species, and are shown to be in excellent agreement with results obtained from virial partitioning of Hartree-Fock wavefunctions.