Unsubstituted compounds

Auto-association of A-4-thiazoline-2-thione and 4-alkyl derivatives has been deduced from infrared spectra of diluted solutions in carbon tetrachloride (58. 77). Results are interpretated (77) in terms of an equilibrium between monomer and cyclic dimer. The association constants are strongly dependent on the electronic and steric effects of the alkyl substituents in the 4- and 5-positions, respectively. This behavior is well shown if one compares the results for the unsubstituted compound (K - 1200 M" ,). 4-methyl-A-4-thiazoline-2-thione K = 2200 M ). and 5-methyl-4-r-butyl-A-4-thiazoline-2-thione K=120 M ) (58). 

Most of the 5-unsubstituted compounds are particularly reactive, and special care must be taken during their synthesis (386). Thus the synthesis of 2-phenyl-/i-2 thia2oline-4-one has been claimed several times, and... 

The names choline and betaine are retained for unsubstituted compounds. 

Pyridazines with a hydroxy group at an a- or y-position to a ring nitrogen atom, i.e. 3-and 4-hydroxypyridazines (4) and (5), exist predominantly in the oxo form. This conclusion is based on spectroscopic evidence from UV spectra of unsubstituted compounds and their A-methyl and O-methyl derivatives in alkaline, neutral and acidic solutions. In some instances, as for example for 6-oxo-l,6-dihydropyridazine-3-carboxamide, there is also evidence from X-ray analysis <54AX199, 63AX318). Maleic hydrazide and substituted maleic hydrazides exist in the monohydroxymonooxo form (6). 

The thiones are readily desulfurized with Raney nickel to give the corresponding unsubstituted compounds in bicyclic systems in the 2-, 4- and 7-positions, and in tricyclic systems such as (95). The 2-methylthio derivatives may be similarly desulfurized. Thione groups in the 4-position, but not the 2-position, in pyrido-[2,3- f ]- and -[3,2- f]-pyrimidines may be replaced directly with ammonia or amines. 

Thiol groups in the 2-, 3- and 6-positions have been desulfurized with Raney nickel under the usual conditions to give the corresponding unsubstituted compounds. 

Data taken from <71pmhi3i297), which contains references to the original literature. Simple alkyl- and aryl-imidazoles. iV-Unsubstituted compounds are IV-acylated prior to injection. 

In these papers the carboxylic acid to be protected was a stable, unsubstituted compound. Harsh conditions wei acceptable for both formation and cleavage of the amide. 

The relative stability of the anions derived from cyclopropene and cyclopentadiene by deprotonation is just the reverse of the situation for the cations. Cyclopentadiene is one of the most acidic hydrocarbons known, with a of 16.0. The plCs of triphenylcyclo-propene and trimethylcyclopropene have been estimated as 50 and 62, respectively, from electrochemical cycles. The unsubstituted compound would be expected to fall somewhere in between and thus must be about 40 powers of 10 less acidic than cyclopentadiene. MP2/6-31(d,p) and B3LYP calculations indicate a small destabilization, relative to the cyclopropyl anion. Thus, the six-7c-electron cyclopentadienide ion is enormously stabilized relative to the four-7c-electron cyclopropenide ion, in agreement with the Hixckel rule. 

Agnello and Laubach suggested that the dehydrogenation of A" -3-ketones to A -3-ketones by chloranil proceeds through the A -enol, which suffers hydride loss from C-7. The failure of 7a-methyl-A -3-ketones to undergo dehydrogenation while the 7/5-isomers do so readily indicates that specific removal of the 7a (axial) hydrogen probably occurs in unsubstituted compounds. ... 

In these papers, the carboxylic acid to be protected was a stable, unsubstituted compound. Harsh conditions were acceptable for both formation and cleavage of the amide. Typically, a simple secondary amide is very difficult to cleave. As the pKa of the conjugate acid of an amide decreases, the rate of hydrolysis of amides derived from these amines increases. The dimethylamide of a cephalosporin was prepared as follows using 2,2 -dipyridyl disulfide. ... 

The Pictet-Spengler reaction is an acid-catalyzed intramolecular cyclization of an intermediate imine of 2-arylethylamine, formed by condensation with a carbonyl compound, to give 1,2,3,4-tetrahydroisoquinoline derivatives. This condensation reaction has been studied under acid-catalyzed and superacid-catalyzed conditions, and a linear correlation had been found between the rate of the reaction and the acidity of the reaction medium. Substrates with electron-donating substituents on the aromatic ring cyclize faster than the corresponding unsubstituted compounds, supporting the idea that the cyclization process is involved in the rate-determining step of the reaction. 

Thiation was most frequently carried out in pyridine - for unsubstituted compounds which are considerably polar, this is a prerequisite. The less polar iV-alkylated derivatives can be thiated in toluene or xylene for thiation of 6-azathymine, tetralin was also used. ... 

A related reaction is the acylation of yA disuhstituted benzyl ketones to isobenzopyrylium salts the unsubstituted compounds yield 4-pyrones as shown in Section II,D,3,a. Another related acylation converts unsaturated esters into 2-p3U ones, e.g., ethyl, jS-dimethyl-acrylate into 4,6-dimethyl-2-pyrone. ... 

To make p and sp dimensionless, Akjk was correlated with a, where Jifc is the force constant difference and is the force constant of the unsubstituted compound. 

The first reaction series to be considered are the basicities of the various quinolines. Baciocchi and Illuminati have demonstrated that the pK values of quinolines substituted in the B-ring follow the Hammett equation well if ApK, i.e., the difference between the pK values of substituted and unsubstituted compounds, is plotted against a, the quinoline points fall on the same line as the pyridine points, as shown in Fig. 5, so that the p-values for the two series are identical. 

These investigations have served to establish the correctness of the structure of the 1,2,3,4-thiatriazole ring system. The unsubstituted compound is, however, unknown, and not many derivatives have been described to date. Tables I-IV contain to our knowledge all the 1,2,3,4-thiatriazoles so far described. The number of possible deriva-... 

Alkylamino-l,2,3,4-thiatriazoles react in the same way as the unsubstituted compound. The compounds obtained have also been formulated as thiocyanoamines, RNHNCS. ... 

Lieber et have come to the same conclusion by an investigation of the ultraviolet spectra and dipole moments of 5-amino-, 5-methyl-amino-, and 5-dimethylamino-l, 2,3,4-thiatriazole. The dimethylamino derivative, in which no tautomerism is possible, shows the same characteristic absorption near 250 m/A as the unsubstituted compound and the monomethyl derivative. The dipole moments of the three compounds differ very little. These moments are quite large (5.8 Debye), showing that ionic resonance forms of type 9 contribute considerably to the structure of these compounds. 

It seems reasonable to assume that in regard to their formation and decomposition the derivatives of phenylpentazole correspond roughly to the unsubstituted compound (see Table V). The rate data for m-and p-substituted phenylpentazoles conform to the Hammett equation with p= -f-1.01. Finally, the high rate of decomposition and... 

More recent work has shown that the 2-unsubstituted compound 40 (R = H, R = Pr ) is an effective formyl anion equivalent which reacts at C2 and undergoes both 1,4-addition to a,(3-unsaturated carbonyl compounds and 1,2-addition to aldehydes (93TL3907 96T4719). 

The infrared spectra of the crystalline compounds have been reported by several investigators. Carpino - found that 4,4-disubsti-tuted pyrazol-5-ones exibit an absorption band in the 5.63-5.84p, (1780-1710 cnrM region of the spectrum but that both the unsubstituted compounds and the compounds monosubstitutcd in the 4-position did not show this absorption band, which led him to conclude that the latter two types of compounds must exist in the NH or OH form. In 1959, American investigators reached similar conclusions for the... 

With / -substituted dienophiles, which are much less reactive than the unsubstituted compounds, reactions were performed at room temperature (Scheme 7.4). The observed enantioselectivities of 93% and 94% ee, for dienophiles with a pri-... 

Dimethyl-2,l,3-benzoselenadiazole was brominated on the methyl groups by NBS (87CB1593), but halogenation of the unsubstituted compound occurred, as with the sulfur analogue, at the 4(7)-position initially. Polybromination can occur (64JGU3063). 

Studies of chlorination and bromination of 2//-cyclopenta[reactivity differences dependent on substituents and halogenation conditions. In monochlorination the unsubstituted compound was more reactive than its 2-methyl and 2-phenyl derivatives, the reactivity ratio being 7.1 1.7 1 [78H(11)155]. Chlorination occurred most readily in the 5- and 7-positions of the cyclopentadienyl moiety, but once all three positions had been substituted, NCS attacked the methyl group... 

Fluorinated alkyls and aryls, generally more stable than the unsubstituted compounds, have been widely studied. 

Gore et al.426 have used chloroform as a solvent for acetylation catalysed by aluminium chloride and at 45-55 °C find that a 2-methoxy substituent in naphthalene increases the reactivity of the 1 position 1.72 times, of the 6 position 3.8 times, and of the 8 position, 0.9 times the former and latter of these results indicate a considerable steric effect. Likewise, a 2-bromo substituent caused the reactivity of the 6 and 8 positions to be 0.63 and 0.58 times that of the corresponding positions in the unsubstituted compound. At 20-25 °C the relative reactivities of some polycyclics were as follows427 1-naphthyl, 1.0 3-phenanthryl 0.64 9-phenanthryl, 0.02 1-phenanthryl, 0.29 2-naphthyl, 0.28 2-phenanthryl, 0.12 4-phenanthryl, 0.0085. Some of these results seem to be due to steric hindrance, and the large difference in reactivity of naphthalene and biphenyl seems erroneous. 

Finally, Kimoto434 has measured the relative reactivities of a series of substituted diphenyl ethers (4-XC6H4OPh) in acetylation as follows (X = ) MeO, 1,166 Me, 687 Cl, 121 H, 90.5 Ac, 35 N02, 1.3. The greater reactivity of the chloro- relative to the unsubstituted compound seems erroneous. 

The symbol k or K is the rate or equilibrium constant, respectively, for a side-chain reaction of a meta- or para-substituted benzene derivative, and k° or K° denotes the statistical quantity (intercept term) approximating to k or K for the parent or unsubstituted compound. The substituent constant a measures the polar (electronic) effect of replacing H by a given substituent (in the meta- or para-position) and is, in principle, independent of the nature of the reaction. The reaction constant p depends on the nature of... 

Combinations of non-selective and/or single-selective relaxation-rates, or both, with n.0.e. values may conveniently be performed with reliable results, especially when other methods seem impractical. However, these experiments are time-consuming, as they entail the determination of a rather large number of experimental values. Moreover, the n.O.e. parameters carry their own systematic and random errors, which are magnified in the calculation of interproton distances. The deuterium-substitution method requires specific deuteration at a strategic position, which, in many cases, may be inconvenient or impractical. Also, this technique is valid only when the relaxation rates obtained after deuterium substitution are at least 5% enhanced, relative to the relaxation rates of the unsubstituted compound, and it requires that, for a meaningful experiment, the following condition " be satisfied. 

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