Secondary Carbamates Research Articles

Speciation in CO2-loaded aqueous solutions of sixteen triacetoneamine-derivates (EvAs) and elucidation of structure-property relationships

The speciation in CO2-loaded aqueous solutions of 16 different derivates of triacetoneamine (EvAs) was investigated in a comprehensive NMR-spectroscopic study. About 350 experiments were carried out for CO2-loadings up to 3 moles CO2 per mole amine, temperatures between 20 °C and 100 °C, and a mass fraction of EvA in the unloaded solvent of 0.1 g/g. The observed CO2-containing species were primary and secondary carbamates, alkylcarbonate, (bi)carbonate, and molecular CO2. Some EvAs can form zwitterions with a ring structure, which have an important influence on the speciation. From the comprehensive set of data, relationships between the chemical structure of the EvAs and the observed speciation in aqueous solution were established. These results were related to application properties of the EvAs that were taken from previous work. Based on the findings, some general guidelines for the design of new amines were derived and applied for proposing new amines for CO2-absorption.

Insights into the Mechanisms and Chemoselectivities of Carbamates and Amides in Reactions Involving Rh(II)-Azavinylcarbene: A Computational Study.

Reactions involving Rh(II)-azavinylcarbenes (Rh(II)-AVCs) to synthesize nitrogen-containing compounds have attracted significant research interest. Despite the importance of these reactions, controlling the chemoselectivities in the reactions involving Rh(II)-AVC remains a challenge. To understand the mechanisms and factors controlling the chemoselectivities between N-H and C═O groups of carbamates and amides in reactions involving Rh(II)-AVC, computational studies were employed. The results reveal that not only the greater nucleophilicity of the N-H group than that of the carbonyl group, but also the presence of H-bonding interactions, could favor the addition of the N-H group of primary carbamates to Rh(II)-AVC. However, for secondary carbamates and amides, they could undergo either chemoselective N-H or C═O addition. Secondary carbamates with less steric hindrance, such as oxazolidinone, prefer the N-H addition mode. However, a switch in chemoselectivity (preference for the C═O addition) was revealed for the sterically hindered secondary carbamates/amides. In addition, a possible O-H addition pathway via the keto-enol tautomerization for isatin and isatoic anhydride was disregarded due to the energetically demanding barrier. Instead, a pathway involving the chemoselective C═O addition, formal [3 + 2] cycloaddition, followed by ring opening was proposed. The origins of the chemoselectivity and the factors responsible were addressed.

Phosphazene/triisobutylaluminum-promoted anionic ring-opening polymerization of 1,2-epoxybutane initiated by secondary carbamates

The deprotonation of secondary carbamates bytBuP2in the presence of a Lewis acid allowed initiating the polymerization of 1,2-epoxybutane.

Construction of multiple, contiguous quaternary stereocenters in acyclic molecules by lithiation-borylation.

Lithiation of carbamates followed by borylation provides a powerful method for the homologation of boron reagents. However, when applied to hindered systems (secondary carbamates with tBu-boronic esters) for the construction of two quaternary centers, this methodology fails. Instead, using mixed boranes (tBuBMe2), the synthesis of adjacent quaternary stereogenic centers with full stereocontrol was successful. The process can be repeated two or three times in one pot leading to carbon chains bearing multiple contiguous quaternary stereogenic centers. The boranes were converted into tertiary alcohols or C-tertiary amines using chloramine. The origin of the high selectivity for alkyl over Me group migration was determined computationally.

ChemInform Abstract: Synthesis of Sulfones from Organozinc Reagents, DABSO, and Alkyl Halides.

Organozinc reagents react with the SO2 surrogate DABSO, and the resulting zinc sulfinate salts are alkylated in situ to afford sulfones. This transformation has a broad scope and is compatible with a wide range of structural motifs of medicinal chemistry relevance including nitrile, secondary carbamates, and nitrogen-containing heterocycles.

Synthesis of Sulfones from Organozinc Reagents, DABSO, and Alkyl Halides

Organozinc reagents react with the SO2 surrogate DABSO, and the resulting zinc sulfinate salts are alkylated in situ to afford sulfones. This transformation has a broad scope and is compatible with a wide range of structural motifs of medicinal chemistry relevance including nitrile, secondary carbamates, and nitrogen-containing heterocycles.

Protonation sites and dissociation mechanisms of t‐butylcarbamates in tandem mass spectrometric assays for newborn screening

Structures of tert-butylcarbamate ions in the gas-phase and methanol solution were studied for simple secondary and tertiary carbamates as well as for carbamate-containing products and internal standards for lysosomal enzyme assays used in newborn screening of a α-galactosidase A deficiency (Fabry disease), mucopolysaccharidosis I (Hurler disease), and mucopolysaccharidosis II (Hunter disease). The protonation of simple t-butylcarbamates can occur at the carbonyl group, which is the preferred site in the gas phase. Protonation in methanol solution is more favorable if occurring at the carbamate nitrogen atom. The protonation of more complex t-butylcarbamates occurs at amide and carbamate carbonyl groups, and the ions are stabilized by intramolecular hydrogen bonding, which is affected by solvation. Tertiary carbamates containing aminophenol amide groups were calculated to have substantially greater gas-phase basicities than secondary carbamates containing coumarin amide groups. The main diagnostically important ion dissociation by elimination of 2-methylpropene (isobutylene, i-C(4)H(8)) and carbon dioxide is shown by experiment and theory to proceed in two steps. Energy-resolved collision-induced dissociation of the Hurler's disease enzymatic product ion, which is a coumarin-diamine linker-t-butylcarbamate conjugate (3a(+)), indicated separate energy thresholds for the loss of i-C(4)H(8) and CO(2). Computational investigation of the potential energy surface along two presumed reaction pathways indicated kinetic preference for the migration of a t-butyl hydrogen atom to the carbamate carbonyl resulting in the isobutylene loss. The consequent loss of CO(2) required further proton migrations that had to overcome energy barriers.

ChemInform Abstract: Synthesis and Antitumor Activity of 9-((Carbamoyloxy)alkyl) anthracyclines: A Novel Class of Anthracycline Derivatives.

A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.

Addressing Challenges in the Stereospecific Lithiation-Borylation of Carbamates

The enantioselective synthesis of chiral tertiary alcohols remains a challenge in organic synthesis. The authors have previously developed an approach based on the lithiation of chiral secondary carbamates and their subsequent reaction with organoboron reagents (V. K. Aggarwal and co-workers Nature 2008, 456, 778). In the present report the authors address factors which are important to the enantio­selectivity of the process and provide solutions to overcome the poor selectivity observed with challenging substrates.

Enantiodivergent Synthesis of Tertiary Alcohols from Secondary Carbamates

This paper described the stereo­divergent synthesis of tertiary alcohols from chiral secondary carbamates through lithiation-borylation followed by subsequent oxidation. This methodology afforded a very broad range of tertiary alcohols in high yields and high enantioselectivities. Remarkably, either enantiomer of the tertiary alcohol could be obtained with high enantioselectivity from the same enantiomer of the secondary alcohol depending on whether a borane or boronic ­ester is used.

Polyvinyl Pyridine as a Novel Solid Heterogeneous, Recyclable Catalyst for aza-Michael Reaction

Polyvinyl pyridine (PVP) is prepared by radical polymerization of 4-vinyl pyridine. PVP was used as a heterogeneous basic catalyst for the aza-Michael reaction of secondary amines and carbamates with α,β-unsaturated esters, cyanides and ketones to obtain the corresponding adducts in excellent yields (70-90%).

Secondary Allyltitanium(IV) Reagents in Aldehyde Allylation I: Extension of the Hoppe Reaction to γ-Alkoxy Secondary Allyl Carbamates

An efficient access to optically active (R)- or (S)-γ-alkoxy allyltitanium(IV) intermediates, in aldehyde allylation reactions, is described. Enantiomeric γ-alkoxy secondary allyl carbamates (R)- and (S)-14 were first prepared. Determination of their enantiomeric excess was realised on the corresponding deuterated isotopic derivatives by NMR in chiral liquid media. Subsequent aldehyde allylation reaction with propanal performed under Hoppe n-BuLi.(-)-sparteine/Ti(Oi-Pr) 4 or n-BuLi.TMEDA/Ti(Oi-Pr) 4 conditions, led to both enantiomeric homoallylic alcohols 15 or ent-15 in 90% yield, 100% ed and 80% ee.

Reactivity of N-pyridylcarbamates in basic media

New secondary aryl N-pyridylcarbamates were prepared by reaction of the aminopyridine anion with aryl chloroformates and their hydrolysis was studied over the pH range from 12 to 13.7. The pH–rate profile points to an E1cB mechanism, involving pre-equilibrium deprotonation of the nitrogen atom to form an anion that undergoes rate-limiting decomposition into pyridyl isocyanate and a phenoxide ion. Further reaction of the highly reactive isocyanate with water affords N-pyridylcarbamic acid, which spontaneously decomposes to aminopyridine and carbon dioxide. The absence of significant base catalysis and the isolation of a new product resulting from trapping of the intermediate with the base piperidine are also consistent with an elimination–addition mechanism. Finally the observed substituent effect (σ−) gives ρ 2.45 which is in accordance with a rate-determining departure of the phenoxide group from the anion intermediate formed in a pre-equilibrium step. Blocking the E1cb mechanism of the secondary carbamates by introduction of N,N-disubstitution in the substrate led to a rate-limiting decrease of ca. 106.

Synthesis and antitumor activity of 9-[(carbamoyloxy)alkyl]anthracyclines a novel class of anthracycline derivatives

A number of 4-demethoxyanthracyclines having hydroxylalkyl functions at the 9-position have previously been synthesized and shown to have potent antitumor activity. A series of carbamate derivatives of these (hydroxyalkyl)anthracyclines have now been prepared, many of which possess considerably greater efficacy in an L-1210 leukemia test system than do the parent alcohols or the known anthracyclines daunorubicin (1), doxorubicin (2), and 4-demethoxydaunorubicin (3). Phenylcarbamate 8a was more active than methyl analogue 8b, while the 4'-deoxy and 4'-epi phenylcarbamates 17 and 18 showed particularly high efficacy at optimal dose levels similar to that of doxorubicin. Secondary carbamates were more potent, with the 13R isomer 23 having significantly higher efficacy than 13S analogue 24.