Deactivation effects

The performance of immobilized reactors in continuous operation can be negatively influenced by several incidents such as enzyme/cell leakage, thermal denaturation of the enzyme, disintegration of the support, or microbial contamination. These parameters can be evaluated experimentally, and approaches can thus be designed in order to counter their negative effect on bioreactor performance. 

Predictive models for thermal denaturation of enzymes have been developed [24, 25], the most commonly used one being the exponential decay model  

For a bubble column, on the other hand, the following correlation is proposed  

---

These acylating agents are the most commonly used (246). Acid chlorides react with 5-nitro-2-aminothiazoIe (88) despite the deactivating effect of the nitro group (Scheme 61) (247), but more vigorous conditions are required (248). 

Pure dry reactants are needed to prevent catalyst deactivation effective inhibitor systems are also desirable as weU as high reaction rates, since many of the specialty monomers are less stable than the lower alkyl acrylates. The alcohol—ester azeotrope (8) should be removed rapidly from the reaction mixture and an efficient column used to minimize reactant loss to the distillate. After the reaction is completed, the catalyst may be removed and the mixture distilled to obtain the ester. The method is particularly useful for the preparation of functional monomers which caimot be prepared by direct esterification. 

Dinitrochlorobenzene can be manufactured by either dinitration of chlorobenzene in filming sulfuric acid or nitration ofy -nitrochlorobenzene with mixed acids. Further substitution on the aromatic ring is difficult because of the deactivating effect of the chlorine atom, but the chlorine is very reactive and is displaced even more readily than in the mononitrochlorobenzenes. 

As discussed in the theoretical section (4.04.1.2.1), electrophilic attack on pyrazoles takes place at C-4 in accordance with localization energies and tt-electron densities. Attack in other positions is extremely rare. This fact, added to the deactivating effect of the substituent introduced in the 4-position, explains why further electrophilic substitution is generally never observed. Indazole reacts at C-3, and reactions taking place on the fused ring will be discussed in Section 4.04.2.3.2(i). Reaction on the phenyl ring of C- and A-phenyl-pyrazoles will be discussed in Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i), respectively. The behaviour of pyrazolones is quite different owing to the existence of a non-aromatic tautomer. 

Dimethylpyrazole 1.4- Dimethyl-3-nitropyrazole The attack at the 3- and 5-positions occurs on the free base. Standard rates 1,4-dimethylpyrazole (attack at the 3-position), log /co = 3.55, l,4-dimethyl-3-nitropyrazole (attack at the 5-position), log /c = -4.73 (deactivating effect of the nitro group) 75JCS(P2)1632... 

Table 7.5 Catalytic and deactivating effects of ligands on metal-catalysed autoxidation of petroleum. (After Pedersen )...

Adivating/Deactivating Effects on Electrophilic Aromatic Substitution... 

The acetylation and formylation of 2,2 -bithienyl give monosubstitution in the 5-position, - Disubstitution is easily achieved and, in some cases, difficult to avoid as the deactivating effect of a substituent is not very strongly transmitted to the other ring. The nitration of 2,2 -bithienyl has recently been studied. ... 

The influence of other groups in a pyridine or similar ring system is more difficult to assess because no kinetic data are available. The deactivating effect of the bromine atom in the 2-position is greater than that in the 3-position, while 2,6-dibromopyridine is very slow to react with dimethyl sulfate. Esters, amides, and nitriles of nicotinic and isonicotinic acids undergo fairly easy quaternization at about... 

Alkyl Groups. In the class of non-conjugative positions, the observed order of the deactivating effect of the methyl group is meta > pros (2-chloroquinoline), and the fall-off factor is 1/1.3 in this case. The fall-off factor is near unity if the effects from the meta position and the conjugative cata positions are compared (4-chloroquinoline), which indicates that the deactivating effect orders are cata > epi and amphi > pros as predicted by the benzenoid order para > meta. 

The ortho indirect deactivating effect of the two methyl groups in 2,6-dimethyl-4-nitropyridine 1-oxide (163) necessitates a much higher temperature (about 195°, 24 hr) for nucleophilic displacement of the nitro group by chloride (12iV HCl) or bromide ions N HBr) than is required for the same reaction with 4-nitropyridine 1-oxide (110°). With 5-, 6-, or 8-methyl-4-chloroquinolines, Badey observed 2-7-fold decreases in the rate of piperidino-dechlorination relative to that of the des-methyl parent (cf. Tables VII and XI, pp. 276 and 338, respectively). 

The deactivating effect of a phenyl group relative to a CCI3 group on s-triazines is noted below,but comparison with hydrogen as a substituent does not appear to have been reported in heterocycles. 

A cyano group produces practical reactivity (methanolic CH30, 66°, < 3hr) by its presence in 2-chloro-3-cyano-6-methylpyridine, opposing the deactivating effect of a methyl group, and on other 2-chloropyridines (see references 3-6 in ref. 140). The cyano group activates 3-cyano-6,6-diphenyl-2-methoxypyrazine (168) (pre-... 

The deactivating effects of 2- and -amino groups in pyrimidine provide an interesting comparison. The 2-ethyleneimino group deactivates the 4- and 6-chlorines in 183 toward ethyleneimine in benzene at 50°, while the 4-ethyleneimino group in 184 deactivates the 6- but not the 2-chloro group. However, in contrast, 2-amino-... 

Relative reactivity of ring-positions based on positional selectivity of polychloro-azines must be regarded with caution because of the unequal activating effects of the chlorine substituents on each other. Also, it should be emphasized that one cannot use the positional selectivity in di- and tri-substitutions to assess relative reactivity of different positions. In such substitutions, the reactivity is determined by a complex combination of activating and deactivating effects which are unequal at the ring-positions (cf. Sections II, E, 1, II, E, 2,c, and II,E,2,e). 

---