Other Substitution

Other modes of ring substitution can often lead to splitting patterns more complicated than those of the aforementioned cases. In aromatic rings, coupling usually extends beyond the adjacent carbon atoms. In fact, ortho, meta, and para protons can all interact, although the last interaction para) is not usually observed. Following are typical J values for these interactions  

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FIGURE 7.65 The expanded para-disubstituted benzene AA BB pattern. 

FIGURE 7.66 The aromatic ring portion of the 60-MHz H NMR spectrum of 2,4-dinitroanisole. 

FIGURE 5.46 The 60-MHz NMR spectrum of the aromatic-ring portion of 2,4-dinitroanisole. 

FIGURE 5.48 The 300-MHz NMR spectra of the aromatic-ring portions of 2-, 3-, and 4-nitroaniiine. 

FIGURE 5.49 Expansions of the aromatic-ring-proton multiplets from the 300 MHz spectrum of 2-nitrophenol. The accompanying hydroxyl absorption (OH) is not shown. 

292 Nuclear Magnetic Resonance Spectroscopy Part Three Spin-Spin Coupling 

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Aldehydes. Formaldehyde, metaformaldehyde, acetaldehyde, paraldehyde, chloral hydrate, benzaldehyde, salicylaldehyde (and other substituted benzaldehydes). 

Methyl, ethyl, n-propyl, isopropyl, n-hutyl, benzyl, cyclohexyl esters of formic, acetic, oxalic, succinic, tartaric, citric, benzoic, salicylic (and other substituted benzoic acids), phthalic and cinnamic acids phenyl esters of acetic, benzoic and salicylic acids. 

In this modified procedure the presence of alcohol is essential otherwise no iao-thiocyanate is obtained. The process may be applied to other substituted anilines. 

The cr-complexes (iv) are thus the intermediates corresponding to the substitution process of hydrogen exchange. Those for some other substitutions have also been isolated in particular, benzylidyne trifluoride reacts with nitryl fluoride and boron trifluoride at — ioo°C to give a yellow complex. Above — 50 °C the latter decomposes to hydrogen fluoride, boron trifluoride, and an almost quantitative yield of tn-nitrobenzylidyne trifluoride. The latter is the normal product of nitrating benzylidyne trifluoride, and the complex is formulated as... 

Reactivity numbers of the most reactive positions have been used to correlate the reactivities in nitration (see below) and other substitutions of a series of polycyclic aromatic hydrocarbons, and they give somewhat better correlations than any of the other commonly used indices of reactivity. The relationship shown below, which was discussed earlier ( 7.1.1),... 

Suffice to say that anything that remotely smells like sassafras oil or licorice or any of those strong rustic spices is going to have some amphetamine precursor, maybe not safrole exactly, but definitely something. There is just no other substitute in nature for the aroma these unique compounds give. 

Carbon-hydrogen stretching vibrations with frequencies above 3000 cm are also found m arenes such as tert butylbenzene as shown m Figure 13 33 This spectrum also contains two intense bands at 760 and 700 cm which are characteristic of monosub stituted benzene rings Other substitution patterns some of which are listed m Table 13 4 give different combinations of peaks... 

Substitution of Trp by D-Trp increased the potency of somatostatin (101). Most other substitutions, however, are deleterious to biological activity. Cychc octapeptide analogues of somatostatin retain high potency one of them, CTOP, is a potent mu-opioid antagonist. 

Dibromoborane—dimethyl sulfide is a more convenient reagent. It reacts directly with alkenes and alkynes to give the corresponding alkyl- and alkenyldibromoboranes (120—123). Dibromoborane differentiates between alkenes and alkynes hydroborating internal alkynes preferentially to terminal double and triple bonds (123). Unlike other substituted boranes it is more reactive toward 1,1-disubstituted than monosubstituted alkenes (124). 

Substitution at the Alcohol Group. Acylation of the OH group by acylating agents such as acid chlorides or anhydrides is one of the important high yielding substitution reactions at the OH group of lactic acid and its functional derivatives. AUphatic, aromatic, and other substituted derivatives can be produced. 

Other substituted phenyl A/-methylcarbamates that have been used for insect control include metalkamate [8065-36-9] a 1 4 mixture of y -(l-ethylpropyl)-phenyl A[-methylcarbamate [672-04-8] and y -(l-methylbutyl)-phenyl A/-methylcarbamate [2282-34-0], rat oral LD qS 87, 170 mg/kg, used as a soil insecticide MTMC [1129-41 -5], 3-methylphenyl N-methylcarbamate (mp 76°C), rat oral LD q 268 mg/kg, used for rice pests MPMC [2425-10-7], 3,5-dimethylphenyl A/-methylcarbamate (mp 79°C), rat oral LD q 380 mg/kg, used for rice pests TBPMC [780-11-0], 3-/ l -butylphenyl A/-methylcarbamate (mp 140°C), mouse oral LD q 470 mg/kg, for rice pests and butacarb [2655-19-8], 3,5-di-/ l -butylphenyl A/-methylcarbamate (mp 98°C), rat oral LD q >4000 mg/kg, for sheep blowfly larvae control. 

Colorimetric. A sensitive method for the deterrnination of small concentrations of dissolved iron is the spectrophotometric deterrnination of the orange-red tris(1,10-phenanthroline)iron (IT) complex. Other substituted phenanthrolines can be even more sensitive. Only the inon(II) complexes of these Ligands are highly colored. The sample is first treated with an excess of reducing agent. The complexes are stable from pH 2 ndash 9 and analysis preferably is done at about pH 3.5. 

Neither benzenepentacarboxylic acid nor mellitic acid are manufactured commercially, but synthetic mellitic acid can be purchased as a laboratory chemical (99). Both can be synthesized by oxidizing the corresponding methylbenzenes or other substituted benzenes, and both are present in trace amounts after oxidation of coal or coal-like substances. 

Important commercial alkylpyridine compounds are a-picoline (2), Ppicoline (3), y-picoline (4), 2,6-lutidine (5), 3,5-lutidine (6), 5-ethyl-2-methylpyridine (7), and 2,4,6-coUidine (8). In general, the alkylpyridines serve as precursors of many other substituted pyridines used in commerce. These further substituted pyridine compounds derived from alkylpyridines are in turn often used as intermediates in the manufacture of commercially usehil final products. 

Although most nonionic organic chemicals are subject to low energy bonding mechanisms, sorption of phenyl- and other substituted-urea pesticides such as diuron to sod or sod components has been attributed to a variety of mechanisms, depending on the sorbent. The mechanisms include hydrophobic interactions, cation bridging, van der Waals forces, and charge-transfer complexes. 

Sulfonic acids may be hydrolytically cleaved, using high temperatures and pressures, to drive the reaction to completion. As would be expected, each sulfonic acid has its own unique hydrolytic desulfonation temperature. Lower alkane sulfonic acids possess excellent hydrolytic stability, as compared to aromatic sulfonic acids which ate readily hydrolyzed. Flydrolytic desulfonation finds use in the separation of isomers of xylene sulfonic acids and other substituted mono-, di-, and polysulfonic acids. 

Other substitution reactions have been described with ketones, epoxides, anhydrides, acyl haUdes, amides, and imidates, among others (4). 

Curing Systems. The most commonly used vulcanizing agent for the polyethers not containing AGE, that is, ECH and ECH—EO, is 2-mercaptoimidazoline, also called ethylenethiourea [96-45-7]. Other commercially appHed curing agents include derivatives of 2,5-dimercapto-l,3,4-thiadiazole, trithiocyanuric acid and derivatives, bisphenols, diamines, and other substituted thioureas. 

Irradiation of l//-indazoles under nonacidic conditions resulted in isomerization to benzimidazoles and also ring opening to isomeric benzonitriles. With 1-substituted benzimidazoles and sensitized irradiation, nitriles were formed, but these are only minor products with other substitution patterns 67HCA2244, 64TL2999). Irradiation of benzimidazoles leads to oxidative dimerization. 

The basicities of indazole (1.31), 1-methyl (0.42) and 2-methyl (2.02) derivatives and of eight other substituted indazoles have been measured (67BSF261 The effect of substituents in the 3-position is similar in pyrazoles and indazoles with Api values as follows Me, 0.80 and 0.86 Cl, -3.01 and -2.98 Br, -2.85 and -2.82, respectively. A nitro group in the homocycle has an expected base-weakening effect of -2 pK units, whether it is at the 5- or the 6-position. 

Fused benzene rings are treated as substituents. Thus quinoline, for example, is considered as a substituted pyridine, albeit a very special and important one, and treated alongside other substituted pyridines in the discussion of its structure, reactivity and synthesis. Reactions of quinoline at positions 1-4 are considered as reactions at ring atoms, whilst reactions at positions 5-8 are regarded as reactions of the substituent . 

Cyclopentadiene, b.p. 40°, is obtained by heating commercial 85% dicyclopentadiene (e.g., from Matheson, Coleman and Bell Company, Norwood, Ohio) under a short column (M in. diameter X 8-12 in. length) filled with glass helices. The distilled cyclopentadiene is collected in a receiver which is maintained at Dry Ice temperature until the cyclopentadiene is used. Methylcyclopentadiene and other substituted cyclopentadienes such as indene may also be employed for the synthesis of the correspondingly substituted ferrocenes. In these cases, the reaction of the hydrocarbon with sodium is much slower than with cyclopentadiene, and refluxing for several hours is required to complete the reaction. 

The general mechanistic framework outlined in this section must be elaborated by other details to fully describe the mechanisms of the individual electrophilic substitutions. The question of the identity of the active electrophile in each reaction is important. We have discussed the case of nitration, in which, under many circumstances, the electrophile is the nitronium ion. Similar questions arise in most of the other substitution reactions. 

A considerable number of examples will be found in the text in which halo-genated and other substituted olefins are produced. Their modes of fonnation do not usually differ in principle from the corresponding unsubstituted case. However, some special methods have been used, for example, the direct preparation of halo olefins from ketones with phosphorous hahdes, or via hydrazones. 

Other substituted cyclohexanes are similar- to methylcyclohexane. Two chair confonnations exist in rapid equilibrium, and the one in which the substituent is equatorial is more stable. The relative fflnounts of the two confor-rnations depend on the effective size of the substituent. The size of a substituent, in the context of cyclohexane confor-rnations, is related to the degree of branching at the atom connected to the ring. A single... 

Ti(0-/-Pr)4, i-BuMgCl, THF, rt, 69-97% yield. Methallyl and other substituted allyl ethers are not cleaved, but ester groups are partially removed, as expected. ... 

The DMB carbamate can also be introduced through the 4-nitrophenyl carbonate. " It has been prepared from an isocyanate and 3, 5 -dimethoxybenzoin. The synthesis of a number of other substituted benzoins as possible protective groups has been described. ... 

The effects of substituents in the thiophene nucleus on the reactions discussed in the foregoing and on other substitution reactions will be given in Sections IV and V. The reactivity of the functional groups will be discussed in Section VI. 

It is thus apparent that the selectivity of a reagent toward thiophene and benzene can differ appreciably, and this difference in selectivity is also strongly noticeable in the proportions of 2- and 3-isomers formed. Although in certain reactions no 3-isomer has been detected, appreciable amounts have been found in other reactions. Thus 0.3% of the 3-isomer has been found in the chlorination of thiophene.- Earlier results indicated that 5-10% 3-nitrothiophene is formed in the nitration of thiophene and a recent gas-chromatographic analysis by Ostman shows that the mononitrothiophene fraction contains as much as 16% of the 3-isomer. It appears that gas-chromatographic analysis should be very useful for the detection of small amounts of 3-isomers in other substitution reactions. However, from routine analyses of IR spectra, it appears to the present author that the amount of 3-isomers formed in acylation, formylation, and bromina-tion of thiophene are certainly less than a few per cent. 

The quaternization of pyrazine compounds has not been extensively studied, and, therefore, a detailed discussion of the effect of substituents is not possible. Recently Cheeseman has shown, from spectroscopic evidence, that 2-amino- and 2-diethylamino-pyrazine (50, Y = NH2 and NEt2) quatemize at N-4, although protonation occurs at position-1. Other substituted pyrazines from which quaternary salts of structure 51 are formed include 2-chloro- and 2-... 

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