Neutral forms

If the thiazole under consideration reacts in its neutral form, the ring nitrogen is expected to be reactive center. Exceptions could be expected for 2-araino-4-R thiazoies with bulky R groups and for electrophilic reactants able to generate a carbocation. 

Aminothiazole in its neutral form seems to be able to react in 3 different positions according to the electrophilic center considered (Scheme 146). The question of C-5 reactivity for this neutral form remains open, however, because the observed product might also be formed from the protonated form of 2-aminothiazoles. A surprising... 

Step 3 The oxonium ion formed m step 2 loses a proton to give the tetrahedral intermediate m its neutral form This step concludes the first stage m the mechanism... 

Step 6 Deprotonation of the species formed m step 5 gives the neutral form of the ester product... 

Step 3 The product of step 2 is the conjugate acid of the tetrahedral intermediate It transfers a proton to water giving the neutral form of the tetrahedral intermediate and regenerating the acid catalyst... 

Step 3 Deprotonation of the oxonium ion to give the neutral form of the tetrahedral intermediate... 

Protonation of the carbonyl oxygen as emphasized earlier makes the carbonyl group more susceptible to nucleophilic attack A water molecule adds to the carbonyl group of the protonated ester m step 2 Loss of a proton from the resulting oxonium ion gives the neutral form of the tetrahedral intermediate m step 3 and completes the first stage of the mechanism... 

Step 5 Acidification of the reaction mixture This is performed m a separate synthetic operation to give the product m its neutral form for eventual isolation... 

In general the equilibrium represented by the sum of steps 1 to 3 is unfavorable (Two ester carbonyl groups are more stable than one ester plus one ketone carbonyl) However because the p keto ester is deprotonated under the reaction conditions the equilibrium represented by the sum of steps 1 to 4 does he to the side of products On subsequent acidification (step 5) the anion of the p keto ester is converted to its neutral form and isolated... 

Barbituric acids as their name implies are weakly acidic and are converted to then-sodium salts (sodium barbiturates) m aqueous sodium hydroxide Sometimes the drug is dispensed m its neutral form sometimes the sodium salt is used The salt is designated by appending the word sodium to the name of the barbituric acid—pentobarbital sodium for example... 

It IS necessary to keep the acidity of phenols in mind when we discuss prepara tion and reactions Reactions that produce phenols when earned out in basic solution require an acidification step to convert the phenoxide ion to the neutral form of the phenol... 

Step 3 Deprotonation of oxonium ion to give neutral form of tetrahedral intermediate OH OH... 

Step 2 Proton transfer from water to give neutral form of tetrahedral intermediate 0 --------------------OH... 

There is also evidence for stable 3,4-adducts from the X-ray analysis of 2-amino-4-ethoxy-3,4-dihydropteridinium bromide, the nucleophilic addition product of 2-aminopteridine hydrobromide and ethanol (69JCS(B)489). The pH values obtained by potentiometric titration of (16) with acid and back-titration with alkali produces a hysteresis loop, indicating an equilibrium between various molecular species such as the anhydrous neutral form and the predominantly hydrated cation. Table 1 illustrates more aspects of this anomaly. 2-Aminop-teridine, paradoxically, is a stronger base than any of its methyl derivatives each dimethyl derivative is a weaker base than either of its parent monomethyl derivatives. Thus the base strengths decrease in the order in which they are expected to increase, with only the 2-amino-4,6,7-trimethylpteridine out of order, being more basic than the 4,7-dimethyl derivative. 

Table 36 summarizes the known annular tautomerism data for azoles. The tautomeric preferences of substituted pyrazoles and imidazoles can be rationalized in terms of the differential substituent effect on the acidity of the two NFI groups in the conjugate acid, e.g. in (138 EWS = electron-withdrawing substituent) the 2-NFI is more acidic than 1-NFI and hence for the neutral form the 3-substituted pyrazole is the more stable. 

When the scheme is required to detect the ground fault as well as the phase faults, a triple-pole relay is used, eaeh pole of which is connected between the shorted terminals of the two same phase CTs and the neutral formed by shorting the other terminals of all the CTs, as shown in Figure 15.22. The setting of all the poles is kept the same. In other words, the sensitivity level remains the same for all types of faults. 

The electron affinity is defined as the energy released when an electron is added to a neutral molecule, computed as the energy difference between the neutral form and the anion. For example, the electron affinity of PH2 may be computed as ... 

Each amino acid is characterized by an isoelectric point , the pH at which it exists in neutral form. Differences in isoelectric points may be exploited to separate amino acids in what is termed an electrophoresis experiment. 

In summary, these results were interpreted to support rate-determining electrocyclization for the ring closure, starting from the all-trans iminium 11, via the cis conformation 13 of the neutral form, followed by fast proton transfer and elimination of aniline (Scheme 8.4.6). 

Our previous treatment (76AHCS1, p. 12) contained a section called Chemical Methods to Study Tautomerism where the relationship between tautomerism and reactivity was discussed. Today, nobody uses chemical methods to study tautomerism. However, a great many reactions are carried out on tautomeric heterocycles, although few papers contain new insights on that topic. Authors desiring to explain reactivity results based on tautomerism must take great care to verify that the substrate is in the neutral form AH and not as a conjugated anion A or cation HAH, which are usually devoid of tautomerism. They must also realize that most frequently the reaction path from tautomers to products in-... 

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