Aliphatic yields with reactivities

Primary and secondary aliphatic and aromatic amines react readily with thiiranes to give 2-mercaptoethylamine derivatives (Scheme 76) (76RCR25, 66CRV297). The reaction fails or gives poor yields with amines which are sterically hindered e.g. N,iV-dicyclohexylamine) or whose nitrogen atom is weakly basic e.g. N,A/ -diphenylamine). Aromatic amines are less reactive and higher reaction temperatures are usually required for them. The reaction mechanism is Sn2 and substituted thiiranes are attacked preferentially at the least hindered... 

Additional acylation studies were also reported (24), (26). In the first case it is claimed that acylation of thiophene is achieved by means of HC104 and acetic anhydride affording a 65 % yield of 2-acetylthiophene. In the second paper Levine and coworkers reported that while 2,5-dimethylthiophene could be readily acetylated, 2,5-dichlorothiophene acetylated sluggishly. This is, however, readily explained, since the presence of chlorine atoms on the thiophene ring decreased its reactivity in electrophilic substitution reactions. In the case of methyl substitution, however, the 3 and 4 positions of the ring are activated toward electrophilic substitution by the inductive and hyperconjugative effects. Thus 2,5-dimethylthiophene was successfully acylated by the boron fluoride etherate method in high yield with three aliphatic anhydrides. 

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

Aromatic carboxylic acids are, in general, less reactive towards sulfur tetrafluoride than aliphatic acids. The reactivity strongly depends on the nature of the aromatic ring substituents. Benzoic, 4-methylbenzoic and particularly 4-methoxybenzoic acid (la-c) give poor yields of the respective (trifluoromethyl)benzenes 2a-c, but the yields of 2 increase with increasing electron-withdrawing power of the substituents.122 Yields of (trifluoromethyl)benzenes substantially increase, even under milder conditions, in the presence of an excess of anhydrous hydrogen fluoride.123... 

More importantly, this silver system catalyzes the intermolecular amination of hydrocarbons, as shown in Table 6.3. In addition to animating weaker benzylic C-H bonds, stronger aliphatic C-H bonds such as those in cyclohexane were also reactive. Although yields with more inert hydrocarbons were modest with the bathophenan-throline system, the discovery of the first silver-catalyzed intermolecular amination opens opportunities for further developments. This reaction favored tertiary cyclic sp3 C-H bonds over secondary cyclic sp3 C-H bonds, and showed limited success with simple linear alkanes. No conversion was observed with any aromatic C-H bonds. The compound NsNH2 was tested as the nitrene precursor with different oxidants. The use of PhI(OAc)2 as oxidant gave the expected amination product with a lower yield, while persulfate and peroxides showed no reactivity. 

Aminoethynylmetallation with reactive ketenes usually leads to mixtures of products because of competing [2 + 2]cycloadditions. Thus when only 68 are desired one will use the very common acid chlorides instead of ketenes. Stable silylated and germylated ketenes react only by [2 + 2] cycloaddition, 57). Aliphatic ketenes, isopropylidene and cyclopentylidene ketenes react more slowly and yields are low (114)156). 

Except for the abnormally low yield with lactim ethers derived from 3-carbethoxylactams with amidines depends on the stability of the reagents.120 Lactim ethers, just as aliphatic imino ethers, are labile to acidic and alkaline media, hence the yields depend on the rate of cyclization. With basic or enolizable amidines, the... 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

The following comments are made with regard to a correlation of the depolymerization product yields with the relative reactivities of aliphatic-aromatic carbon and oxygen-carbon bridge structures in coal ... 

The reactivity of bis(trifluoroacetoxy)iodobenzene (23) towards oximes is of interest as several products are formed depending on the substrate. 70 a ligand coupling mechanism may be suggested for the reaction of aliphatic ketoximes with bis(trifluoroacetoxy)iodobenzene, which gives fair yields of the stable, intensely blue 1-nitroso-l-trifluoroacetoxyalkanes.271... 

As Table 17 shows, aromatic diamines, from which polymers with good solubility in pyridine are formed, yield higher molecular weight polymers whereas polymers from 4,4 -diaminodiphenylsulfone and p-phenylenediamine are insoluble even in HMPA and display low viscosities in sulfuric acid. On the other hand, aliphatic diamines with high basicity afford polymers of low viscosities in low yields because of the retardation of polycondensation by the formation of pyridine-insoluble and un-reactive ammonium carbamate. The same also applies to the preparation of polythioureas. 

The reaction was also carried out with five-membered heterocycles, but only mercaptotriazoles 111 showed moderate reactivity for different substituents (Scheme 7.45a) [101]. In the same publication, the authors showed that mer-captobenzoxazoles and benzothiazoles (112) could also be used as starting materials for the Ugi-Smiles coupling, giving the final thioamides 113 in good yields with aliphatic aldehydes and ketones, and with lower yields in the case of aromatic aldehydes (Scheme 7.45b). 

Cu(OTf)2/t-Bu-BOX (13)-catalyzed conjugate addition of carbamates to a -hydroxy enones has been demonstrated by Palomo and coworkers (Scheme 17.50) [69]. Conjugate additions of carbamates (235) to a -hydroxy enones (29) bearing aliphatic P-substituents proceed in moderate to good yield with excellent enantioselectivity. However, enones bearing -aryl substituents lack sufficient reactivity. The impact of the a -hydroxy enone template in this methodology bears mention, as an a,P-unsaturated oxazolidinone substrate is completely unreactive under identical conditions. 

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