Alkylation and Acylation

Friedel-Crafts reactions are almost unknown in pyridine and azine chemistry. Direct electrophilic alkylation in the pyrimidine 5-position can be carried out on pyrimidines with at least two strongly donating groups, and more readily with three such groups. Thus, a-haloketones and a-bromocarboxylic esters can be used for direct alkylation of 6-aminouracils (118), for example in the formation of (119). The 5-position can also act as the nucleophile for Michael additions (e.g. 118 — 120, where a subsequent elimination occurs) (92AHC(55)129). For similar reactions in barbituric acids see (85AHC(38)229). 

Treatment of pyrazole with 1-bromoadamantane affords either 4-(l-adamantyl)pyrazole (273) 94TL183,94H(37)1623 or 3(5)-(l-adamantyl)pyrazole (271) 94CL2079 (see Section 3.01.12.1) depending on the experimental conditions (heating in a sealed tube or heating in a microwave oven). The x-ray structure of 4-(l-adamantyl)pyrazole was determined 94H(37)1623 . 

Progress has been made in the experimental procedures for the formylation of pyrazoles (Vilsmeir-Haack reaction) at their 4 position 93JHC957, 94CPB237). For instance, 4/f-pyrazolo[l,5-a]indoles are formylated under milder eonditions than pyrazoles 94CPB237 . 

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In each case the configuration around the boron changes from trigonal planar to tetrahedral on adduct formation. Because of this ability to form additional compounds, boron trifluoride is an important catalyst and is used in many organic reactions, notably polymerisation, esterification, and Friedel-Crafts acylation and alkylations. 

Reactions. The CF O— group exerts predominant para orientation in electrophilic substitution reactions such as nitration, halogenation, acylation, and alkylation (350). 

Uses. The largest usage of PCl is to produce phosphonic acid, H PO, which in reaction with iminodiacetic acid and formaldehyde forms a glyphosate intermediate that is decarboxymethylated to glyphosate, an effective nonselective herbicide (see Herbicides). Phosphoms trichloride is also a convenient chlorinating reagent for producing various acyl and alkyl chlorides. 

Acid-catalyzed hydrogen exchange Halogenation Acylation and alkylation Mercuration Diazo coupling Nitrosation... 

Correlations with o in carboxylic acid derivative reactions have been most successful for variations in the acyl portion, R in RCOX. Variation in the alkyl portion of esters, R in RCOOR, has not led to many good correlations, although use of relative rates of alkaline and acidic reactions, as in the defining relation, can generate linear correlations. The failure to achieve satisfactory correlations with cr for such substrates may be a consequence of the different steric effects of substituents in the acyl and alkyl locations. It has been shown that solvolysis rates of some acetates are related to the pA", of the leaving group, that is, of the parent alcohol. The pK of alcohols has been correlated with but this relationship... 

Those derivatives that result by the action of acylating and alkylating reagents, such as A -acetylcotarnine (9b), A-benzoylcotarnine (9c), or cotarnmethin methyliodide (19) can only be derived from... 

Besides acylation and alkylation reactions, typical carbonyl reactions, such as reduction and substitution, are known. Thus, the oxo group in position 3 of 8 is attacked by sodium cyanide, resulting in the cyanohydrin in 55% yield. Subsequent dehydration with p-toluene-sulfonic acid and acetylation in position 5 gives 1-benzothiepin 12.90... 

CAUTION All azides, particularly low molecular weight acyl and alkyl azides, are explosive, and great care should be taken while preparing and handling these materials. In addition, hydrazoic acid, which is liberated from unbuffered aqueous solutions of sodium azide, is highly toxic and all operations involving its use should be carried out in an efficient fume hood. 

Soedjak HS, A Butler (1990) Charactarization of vanadium bromoperoxidase from Macrocystis and Fucus reactivity of bromoperoxidase towards acyl and alkyl peroxides and bromination of amines. Biochemistry 29 7974-7981. 

Liquid-solid reactions (Friedel-Crafts acylations and alkylations, Grignard reactions) 1-5 50-250 250 250... 

Titanium-mediated intramolecular Friedel-Crafts acylation and alkylation are important methods for construction of fused-ring systems (Scheme 29).107 As well as aromatics, olefin units also react in the same way.108 Alkylation of electron-rich olefins such as enol ethers or silyl enol ethers proceeds effectively in the presence of TiCl4.109... 

Thioacetals eliminate to vinylsulfides in the presence of CuOTf (Scheme 46).192 Cu1 and Cu11 triflates are mild Lewis acids for Friedel-Crafts acylation and alkylation reactions. CuOTf effectively catalyzes the reaction of anisole with selenoesters.193,194 Copper(II) sulfate promotes epoxide ring opening reactions in the presence of pyridine,195 with retention of configuration being observed. Cu(OTf)2 is a catalyst for the ring opening of aziridine by aniline.196... 

Among the wide variety of organic reactions in which zeolites have been employed as catalysts, may be emphasized the transformations of aromatic hydrocarbons of importance in petrochemistry, and in the synthesis of intermediates for pharmaceutical or fragrance products.5 In particular, Friede 1-Crafts acylation and alkylation over zeolites have been widely used for the synthesis of fine chemicals.6 Insights into the mechanism of aromatic acylation over zeolites have been disclosed.7 The production of ethylbenzene from benzene and ethylene, catalyzed by HZSM-5 zeolite and developed by the Mobil-Badger Company, was the first commercialized industrial process for aromatic alkylation over zeolites.8 Other typical examples of zeolite-mediated Friedel-Crafts reactions are the regioselective formation of p-xylene by alkylation of toluene with methanol over HZSM-5,9 or the regioselective p-acylation of toluene with acetic anhydride over HBEA zeolites.10 In both transformations, the p-isomers are obtained in nearly quantitative yield. 

Figure 1.10 Sulfhydryl groups may undergo a number of additional reactions, including acylation and alkylation. Thiols also may participate in redox reactions, which generate reversible disulfide linkages.

The method of action of the aluminium chloride is not yet clearly understood. Since with acyl and alkyl chlorides it forms complex addition products which can be isolated, it is possible that in these products the bond between the chlorine and the rest of the organic molecule is loosened, and that so the additive power is increased. It is also possible, however, that the aluminium chloride increases the reactivity of the hydrocarbon by combining with it. 

More than 25 different substituted urea herbicides are currently commercially available [30, 173]. The most important are phenylureas and Cycluron, which has the aromatic nucleus replaced by a saturated hydrocarbon moiety. Benzthiazuron and Methabenzthiazuron are more recent selective herbiddes of the class, with the aromatic moiety replaced by a heterocyclic ring system. With the exception of Fenuron, substituted ureas (i.e., Diuron, Fluometuron, Fig. 10, Table 3) exhibit low water solubilities, which decrease with increasing molecular volume of the compound. The majority of the phenylureas have relatively low vapor pressures and are, therefore, not very volatile. These compounds show electron-donor properties and thus they are able to form charge transfer complexes by interaction with suitable electron acceptor molecules. Hydrolysis, acylation, and alkylation reactions are also possible with these compounds. 

As lipophilic anchors, we chose modifications with long acyl and alkyl chains, preferably of similar chain lengths as the phospholipids to allow optimal alignment with the phospholipids molecules of the liposome bilayers. 

The branching of the polymer is shown schematically in (25). The distribution of amino groups in 25% primary, 50% secondary, and 25% tertiary. The primary amines occur on the outside of the molecule and are easily substituted by acylation and alkylation. 

A reaction in which an electrophile participates in het-erolytic substitution of another molecular entity that supplies both of the bonding electrons. In the case of aromatic electrophilic substitution (AES), one electrophile (typically a proton) is substituted by another electron-deficient species. AES reactions include halogenation (which is often catalyzed by the presence of a Lewis acid salt such as ferric chloride or aluminum chloride), nitration, and so-called Friedel-Crafts acylation and alkylation reactions. On the basis of the extensive literature on AES reactions, one can readily rationalize how this process leads to the synthesis of many substituted aromatic compounds. This is accomplished by considering how the transition states structurally resemble the carbonium ion intermediates in an AES reaction. 

Besides confirming that chain propagation involves 1,2 insertion, the simultaneous observation of acyl and alkyl intermediates in the flow cell has shown that both intermediates are relatively long-lived species under catalytic conditions and have also comparable lifetimes in the presence of both CO and styrene [6b]. 

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