How does organic structure determine organic reactivity? The effect of ortho-dimethyl groups on the nucleophilic substitution and alkene-forming elimination reactions of ring-substituted cumyl derivatives

1999 ◽  
Vol 77 (5-6) ◽  
pp. 922-933 ◽  
Author(s):  
Tina L Amyes ◽  
Tadeusz Mizerski ◽  
John P Richard
Keyword(s):  
Rate Constant ◽  
Nucleophilic Addition ◽  
Substituent Effects ◽  
Fold Increase ◽  
Methyl Groups ◽  
Diffusion Limited ◽  
Azide Ion ◽  
Brønsted Base ◽  
High Concentrations ◽  
Ortho Substituent

The addition of a pair of ortho-methyl groups to ring-substituted cumyl derivatives to give the corresponding 2,6-dimethylcumyl derivatives X-1-Y leads to modest (<5-fold) changes in the observed rate constant for reaction in 50:50 (v:v) trifluoroethanol-water (I = 0.50, NaClO4). The reactions of X-1-Y proceed by a stepwise mechanism through the liberated 2,6-dimethylcumyl carbocations X-2 that partition between nucleophilic addition of solvent and deprotonation to give good yields ([Formula: see text] 67%) of the corresponding 2-(2,6-dimethylaryl)propenes X-3. The carbocations X-2 are also trapped by nucleophilic addition of azide ion to give good yields ([Formula: see text] 68% at [N3-] = 0.50 M) of the corresponding 2,6-dimethylcumyl azides X-1-N3. In the presence of high concentrations of azide ion there are constant limiting yields of the alkenes X-3, which shows that X-2 also undergo significant reactions with azide ion as a Brønsted base. The product rate constant ratios for partitioning of the 2,4,6-trimethylcumyl carbocation Me-2 between reaction with azide ion as a Lewis and a Brønsted base, kaz/kB, the nucleophilic addition of azide ion and solvent, kaz/ks (M-1), and deprotonation by solvent, kaz/ke (M-1), were combined with (kaz + kB) = 5 × 109 M-1 s-1 for the diffusion-limited reaction of azide ion to give absolute rate constants for the reactions of Me-2. The data show that the addition of a pair of ortho-methyl groups to the 4-methylcumyl carbocation to give the sterically hindered Me-2 results in a 70-fold decrease in the rate constant for nucleophilic addition of solvent to the benzylic carbon, but a 60-fold increase in the rate constant for deprotonation of the carbocation by solvent.Key words: carbocation, ortho-substituent effects, steric effects, solvolysis, elimination.

Kinetic study of hydrolysis of benzoates. part xxvii. ortho substituent effect in alkaline hydrolysis of phenyl esters of substituted benzoic acids in aqueous Bu4NBr

2009 ◽  
Vol 74 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Vilve Nummert ◽  
Mare Piirsalu ◽  
Signe Vahur ◽  
Oksana Travnikova ◽  
Ilmar A. Koppel
Keyword(s):  
Alkaline Hydrolysis ◽  
Rate Constants ◽  
Pure Water ◽  
Substituent Effects ◽  
Benzoic Acids ◽  
Resonance Effects ◽  
The Media ◽  
Substituted Benzoic Acids ◽  
Hydrolysis Of ◽  
Ortho Substituent

The second-order rate constants k (in dm3 mol–1 s–1) for alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5, have been measured spectrophotometrically in aqueous 0.5 and 2.25 M Bu4NBr at 25 °C. The substituent effects for para and meta derivatives were described using the Hammett relationship. For the ortho derivatives the Charton equation was used. For ortho-substituted esters two steric scales were involved: the EsB and the Charton steric (υ) constants. When going from pure water to aqueous 0.5 and 2.25 M Bu4NBr, the meta and para polar effects, the ortho inductive and resonance effects in alkaline hydrolysis of phenyl esters of substituted benzoic acids, became stronger nearly to the same extent as found for alkaline hydrolysis of C6H5CO2C6H4-X. The steric term of ortho-substituted esters was almost independent of the media considered. The rate constants of alkaline hydrolysis of ortho-, meta- and para-substituted phenyl benzoates (X-C6H4CO2C6H5, C6H5CO2C6H4-X) and alkyl benzoates, C6H5CO2R, in water, 0.5 and 2.25 M Bu4NBr were correlated with the corresponding IR stretching frequencies of carbonyl group, (ΔνCO)X.

scholarly journals THE RATE OF BACTERICIDAL ACTION OF PENICILLIN IN VITRO AS A FUNCTION OF ITS CONCENTRATION, AND ITS PARADOXICALLY REDUCED ACTIVITY AT HIGH CONCENTRATIONS AGAINST CERTAIN ORGANISMS

1948 ◽  
Vol 88 (1) ◽  
pp. 99-131 ◽  
Author(s):  
Harry Eagle ◽  
A. D. Musselman
Keyword(s):  
Bacterial Species ◽  
Fold Increase ◽  
Bactericidal Effect ◽  
Penicillin G ◽  
Bacterial Suspension ◽  
Maximal Effect ◽  
Maximal Rate ◽  
Effective Level ◽  
High Concentrations

1. The concentrations of penicillin G which (a) reduced the net rate of multiplication, (b) exerted a net bactericidal effect, and (c) killed the organisms at a maximal rate, have been defined for a total of 41 strains of α- and ß-hemolytic streptococci, Staphylococcus aureus and Staphylococcus albus, Diplococcus pneumoniae, and the Reiter treponoma. 2. The concentration which killed the organisms at a maximal rate was 2 to 20 times the minimal effective level ("sensitivity" as ordinarily defined). With some organisms, even a 32,000-fold increase beyond this maximally effective level did not further increase the rate of its bactericidal effect. However, with approximately half the strains here studied (all 4 strains of group B ß-hemolytic streptococci, 4 of 5 group C strains, 5 of 7 strains of Streptococcus fecalis, 2 of 4 other α-hemolytic streptococci, and 4 of 9 strains of staphylococci), when the concentration of penicillin was increased beyond that optimal level, the rate at which the organisms died was paradoxically reduced rather than increased, so that the maximal effect was obtained only within a relatively narrow optimal zone. 3. There were marked differences between bacterial species, and occasionally between different strains of the same species, not only with respect to the effective concentrations of penicillin, but also with respect to the maximal rate at which they could be killed by the drug in any concentration. Although there was a rough correlation between these two factors, there were many exceptions; individual strains affected only by high concentrations of penicillin might nevertheless be killed rapidly, while strains sensitive to minute concentrations might be killed only slowly. 4. Within the same bacterial suspension, individual organisms varied only to a minor degree with respect to the effective concentrations of penicillin. They varied strikingly, however, in their resistance to penicillin as measured by the times required to kill varying proportions of the cells.

scholarly journals Thunderstorm outflows preceding epidemics of asthma during spring and summer

Thorax ◽  
2001 ◽  
Vol 56 (6) ◽  
pp. 468-471
Author(s):  
G B Marks ◽  
J R Colquhoun ◽  
S T Girgis ◽  
M Hjelmroos Koski ◽  
A B A Treloar ◽  
...  
Keyword(s):  
Pollen Grains ◽  
Ground Level ◽  
Fold Increase ◽  
Underlying Mechanism ◽  
Detailed Examination ◽  
Asthma Exacerbations ◽  
Eastern Australia ◽  
The Difference ◽  
High Concentrations ◽  
Thunderstorm Outflow

BACKGROUNDA study was undertaken to assess the importance of thunderstorms as a cause of epidemics of asthma exacerbations and to investigate the underlying mechanism.METHODSA case control study was performed in six towns in south eastern Australia. Epidemic case days (n = 48) and a random sample of control days (n = 191) were identified by reference to the difference between the observed and expected number of emergency department attendances for asthma. The occurrence of thunderstorms, their associated outflows and cold fronts were ascertained, blind to case status, for each of these days. In addition, the relation of hourly pollen counts to automatic weather station data was examined in detail for the period around one severe epidemic of asthma exacerbations. The main outcome measure was the number of epidemics of asthma exacerbations.RESULTSThunderstorm outflows were detected on 33% of epidemic days and only 3% of control days (odds ratio 15.0, 95% confidence interval 6.0 to 37.6). The association was strongest in late spring and summer. Detailed examination of one severe epidemic showed that its onset coincided with the arrival of the thunderstorm outflow and a 4–12 fold increase in the ambient concentration of grass pollen grains.CONCLUSIONSThese findings are consistent with the hypothesis that some epidemics of exacerbations of asthma are caused by high concentrations of allergenic particles produced by an outflow of colder air, associated with the downdraught from a thunderstorm, sweeping up pollen grains and particles and then concentrating them in a shallow band of air at ground level. This is a common cause of exacerbations of asthma during the pollen season.

scholarly journals The effect of copper excess on iron metabolism in sheep

1978 ◽  
Vol 170 (1) ◽  
pp. 137-143 ◽  
Author(s):  
E C Theil ◽  
K T Calvert
Keyword(s):  
Iron Metabolism ◽  
Iron Concentration ◽  
Transferrin Saturation ◽  
Fold Increase ◽  
Copper Treatment ◽  
Excess Copper ◽  
High Concentrations ◽  
Copper Excess ◽  
Effect Of Copper ◽  
Haemoglobin Content

Sheep were treated with large amounts of copper (20 mg of CuSO4,5H2O/kg body wt. per day) for 9 weeks to examine the effect of copper excess on iron metabolism. In addition to confirming that massive haemolysis and accumulation of copper occurs in the liver, kidney and plasma after 7 weeks of exposure to excess copper, it was observed that excess copper produced an increased plasma iron concentration and transferrin saturation within 1 week. Further, iron preferentially accumulated in the spleen between 4 and 6 weeks of copper treatment, producing 3-fold increases in the iron content of both the ferritin and non-ferritin fractions. A 3-4 fold increase was also observed in the amount of ferritin that could be isolated from the spleen. The copper treatment had little or no effect on the concentration of iron in the liver and bone marrow. The following properties of erythrocytes were also unaffected by copper treatment: size, haemoglobin content and pyruvate kinase activity, although the erythrocyte concentration of copper increased after 6 weeks. Copper accumulated in the spleen between 6 and 9 weeks, probably owing to the phagocytosis of erythrocytes containing high concentrations of copper. The data suggest that copper excess influences iron metabolism, initially by causing a compensated haemolytic anaemia, and later by interfering with re-utilization of iron from ferritin in the reticuloendothelial cells of the spleen.

Ortho-Substituent Effects on Diphenylurea Packing Motifs

2017 ◽  
Vol 17 (10) ◽  
pp. 5065-5072 ◽  
Author(s):  
Marina A. Solomos ◽  
Taylor A. Watts ◽  
Jennifer A. Swift
Keyword(s):  
Substituent Effects ◽  
Ortho Substituent

scholarly journals A Predictive Model for Additions to N-Alkyl Pyridiniums

2020 ◽  
Author(s):  
Brian Knight ◽  
Zachary Tolchin ◽  
Joel Smith
Keyword(s):  
Predictive Model ◽  
Insecticidal Activity ◽  
Nucleophilic Addition ◽  
Substituent Effects ◽  
Reactive Component ◽  
Tricyclic Compound

Disclosed in this communication is a thorough study on the dearomative addition of organomagnesium nucleophiles to <i>N</i>-alkyl pyridinium electrophiles. The regiochemical outcomes have observable and predictable trends associated with the substituent patterns on the pyridinium electrophile. Often, the substituent effects can be either additive, giving high selectivities, or ablative, giving competing outcomes. Additionally, the nature of the organometallic nucleophilic component was also investigated for its role in the regioselective outcome. The effects of either reactive component are important to both the overall reactivity and site of nucleophilic addition. The utility of these observed trends is demonstrated in a concise, dearomative synthesis of a tricyclic compound shown to have insecticidal activity.

Abstract TP94: Mesenchymal Stromal Cells Behave Differently When Exposed to Medications Commonly Prescribed to Stroke Patients

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Nikunj Satani ◽  
Bing Yang ◽  
Duyen M Nghiem ◽  
Xiaopei Xi ◽  
Adrian P Gee ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
High Glucose ◽  
Fold Increase ◽  
Stroke Recovery ◽  
Stroke Patients ◽  
Healthy Humans ◽  
Tnf Α ◽  
High Concentrations ◽  
And Function

Background: As a promising investigational therapy for stroke recovery, mesenchymal stromal cells (MSCs) are in various stages of clinical trials. MSCs may promote recovery through cytokine release and immunomodulation. Stroke patients typically are treated with antiplatelets and medications for hypertension and hyperlipidemia. We explored the effect of commonly prescribed drugs at physiological concentrations on MSCs. Methods: Clinical grade bone marrow MSCs from healthy donor at passage 2 were thawed and re-suspended in serum free media. Monocytes (Mo) were isolated from peripheral blood of healthy humans. MSCs and Mo were cultured alone as well as in co-culture and exposed to simvastatin, atenolol, losartan, captopril, or aspirin. They were also exposed to high glucose (upto 40mM) to simulate hyperglycemia. At 24 hours of incubation, media was collected and TNF-α concentration was measured, as an index of immunomodulation of Mo by MSCs. Cell viability was also measured (using MTT assay and flow cytometry). Results: There were significant effects of all drugs on viability of MSCs but with no impact on Mo. More importantly, Losartan (dose independent), Simvastatin and Atenolol (dose-dependent) reduced the viability of MSCs even at the pharmacologically relevant concentrations (Fig 1). High glucose had no effect on viability of MSCs or Mo. TNF-α secretion from co-culture of MSCs and Mo at 24 hours showed differences at very high doses of aspirin (2-fold increase), atenolol (0.5 fold decrease), and glucose (0.5 fold decrease) (data not shown). However, these high concentrations are unlikely to be achieved pharmacologically in plasma of patients treated with these drugs. Conclusion: Exposure of MSCs to clinically relevant drugs can alter their viability and function. Our results suggest that stroke trials involving use of intravenous MSCs should consider the differential impact of commonly prescribed medications on MSCs function.

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