A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines.

A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler-Clarke reaction with formic acid-d2 and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.

Mechanistic investigations on Pinnick oxidation: a density functional theory study.

A computational study on Pinnick oxidation of aldehydes into carboxylic acids using density functional theory (DFT) calculations has been evaluated with the (SMD)-M06-2X/aug-pVDZ level of theory, leading to an important understanding of the reaction mechanism that agrees with the experimental observations and explaining the substantial role of acid in driving the reaction. The DFT results elucidated that the first reaction step (FRS) proceeds in a manner where chlorous acid reacts with the aldehyde group through a distorted six-membered ring transition state to give a hydroxyallyl chlorite intermediate that undergoes a pericyclic fragmentation to release the carboxylic acid as a second reaction step (SRS). 1H NMR experiments and simulations showed that hydrogen bonding between carbonyl and t-butanol is unlikely to occur. Additionally, it was found that the FRS is a rate-determining and thermoneutral step, whereas SRS is highly exergonic with a low energetic barrier due to the Cl(III) → Cl(II) reduction. Frontier molecular orbital analysis, intrinsic reaction coordinate, molecular dynamics and distortion/interaction analysis further supported the proposed mechanism.

Electrochemical Deprotection of para-Methoxybenzyl Ethers in a Flow Electrolysis Cell.

Electrochemical deprotection of p-methoxybenzyl (PMB) ethers was performed in an undivided electrochemical flow reactor in MeOH solution, leading to the unmasked alcohol and p-methoxybenzaldehyde dimethyl acetal as a byproduct. The electrochemical method removes the need for chemical oxidants, and added electrolyte (BF4NEt4) can be recovered and reused. The method was applied to 17 substrates with high conversions in a single pass, yields up to 92%, and up to 7.5 g h-1 productivity. The PMB protecting group was also selectively removed in the presence of some other common alcohol protecting groups.

trans-2-Tritylcyclohexanol as a chiral auxiliary in permanganate-mediated oxidative cyclization of 2-methylenehept-5-enoates: application to the synthesis of trans-(+)-linalool oxide.

The permanganate-mediated oxidative cyclization of a series of 2-methylenehept-5-eneoates bearing different chiral auxiliaries was investigated, leading to the discovery of trans-2-tritylcyclohexanol (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼97:3). Chiral resolution of (±)-TTC, prepared in one step from cyclohexene oxide, afforded (-)-(1S,2R)-TTC (er >99:1), which was applied to the synthesis of (+)-trans-(2S,5S)-linalool oxide.

A Markovian decision model for beef cattle replacement that considers spring and fall calving.

In certain production environments, beef cows are mated during a breeding season that starts in early summer. Cows found not to be pregnant at the end of the breeding season could either be culled or retained and remated the following summer. Alternatively, nonpregnant cows could be mated in the winter. This option would result in having both a spring and a fall calving herd. The purpose of our study was to determine the optimal replacement policy (maximizing long-run average net returns) for a specific production environment by determining for each age of cow, reproductive status (nonpregnant or pregnant), and season of pregnancy checking (spring or fall) whether the cow should be retained to the next breeding season (summer or winter) or be replaced by a pregnant heifer. The problem was formulated as a Markovian decision process and the optimal policy was found by linear programming. The optimal policy was one in which nonpregnant cows were always culled and replaced by heifers in the summer breeding herd, resulting in spring calving only.

Markov chains as a shortcut method to estimate age distributions in herds of beef cattle under different culling strategies.

Markov chains were used to estimate the age distribution at equilibrium and average age in herds of beef cattle and the age distribution and average age of culled cows. These estimates are essential in systems simulation and economic analyses of beef production alternatives because the biological input and output from a beef production system depend on the age structure of the cows in the system. Ten sets of data on age-specific probabilities of culling for different reasons were found in the literature and used in simulation of different culling strategies. Three different culling strategies were simulated using these data. In addition to culling on maximum age, culling was either based on health alone, health and reproductive failure in one year (not pregnant) or health and reproductive failure in two consecutive years (not pregnant twice). The average herd age in the data sets reviewed under the actual culling strategies ranged from 4.58 to 6.73 yr and the average age of culled cows ranged from 5.41 to 9.94 yr. Description of the culling process as a Markov chain enables calculations of the age distribution at equilibrium by simple matrix operations, an advantage over the methods presently used. The scarcity of estimated age-specific probabilities of health and reproductive failure points to the need for more population analyses of beef cattle.

Pulmonary function in heterozygotes for alpha,-antitrypsin deficiency: a case-control study.

In this paper we present the initial cross-sectional data from a prospective study of lung aging in heterozygotes for alpha 1-antitrypsin deficiency. Using a case-control design, our cases included 37 heterozygotes for alpha 1-antitrypsin deficiency, protease inhibitor phenotypes MZ and MS, selected because they were parents of children with homozygous alpha 1-antitrypsin deficiency identified in a statewide newborn screening program between 1971 and 1974. All of the heterozygotes were less than 40 yr of age. Our control subjects were selected from a random sample of a working population participating in a longitudinal study of lung aging, using a 2:1 match of control subjects to cases, matching age, sex, ethnic origin, and smoking. Using a respiratory symptom questionnaire, spirometry, and the single-breath N2 test, we found no significant difference between heterozygotes and control subjects in terms of respiratory symptoms or pulmonary function data. We conclude that to 40 yr of age, the heterozygous phenotype (Pi MZ and MS) is not a risk factor for impairment of pulmonary function.