Morpholino ketones

All the members of this class of compounds contain an aromatic ketone group, the most representative systems being benzoin [71], benzoin ethers [72], dialkoxy-acetophenones [73], hydroxyalkylphenones [74], benzoyloxime esters [75] and, more recently, benzoylphosphine oxides [76], a-hydroxymethylbenzoin sulfonic esters [77], sulfonyl ketones [78] and morpholino ketones [70],... 

A further interesting feature of the polymeric photoinitiators is based on the possibility of anchoring different photosensitive moieties to the same macromolecule in order to provide a synergistic effect on activity due to their interaction along the polymer chain. In this context, the synthesis of several copoly-meric photoinitiators bearing side-chain thioxanthone and hydroxyalkylphenone or morpholino ketone moieties has been reported recently [156]. In particular, the free radical copolymerization of 2-[2-(acryloyloxy)ethylthio] thioxanthone (AETX) with either [4-(2-acryloyloxyethoxy)phenyl]-2-hydroxy-2-propyl ketone (HPA) or [4-(2-acryloyloxyethylthio)phenyl]-2-(iV-morpholino)-2-propyl ketone (APMK) [poly(AETX-co-HPA) and poly(AETX-co-APMK), respectively] and of 4-[2-(methacryloyloxy)ethoxycarbonyl] thioxanthone (METX) with APMK [poly(METX-co-APMK)] has been performed. 

The formation of the amine (496) when 3)5-toluene-p-sulphonates are treated with 2-dimethylaminoethanol involves both inversion at C-3 and demethyla-tion. The reaction of androstane-16,17-ketols and 17 -acetoxy-16a,Ha-epoxide with morpholine to give a-morpholino-ketones has been thoroughly investigated and rationalised. H/5-Aminoandrosta-3,5-diene, prepared by reduction of the H-oxime, possesses some antimicrobial activity which is not enhanced by substitution of the amino-groups with 2-chloroethyl, 2-hydroxy-ethyl, or 3-aminopropyl groups similar 2-chloroethyl substituted H)5-amines have been cyclised by treatment with base to give H -aziridines. All four... 

Morpholino- and Amino-Ketones These classes of photoinitiators present a good activity [Is], The cleavage mechanisms ((10.16) and (10.17)) and the reactivity of the excited states have been fully reported [2i,30], Excellent representatives of morpholino ketones are 2-methyl- l-(4-methylthiobenzoyl)-2-morpholino-propan-1-one TMPK (10.16) and 2-methyl-l-(benzoyl)-2-morpholino-propan-l-one MPK. In amino ketones, the introduction of a morpholino moiety on a benzoyl group such as in 2-benzyl-2(diethylamino)-4,-morpholinobutyrophenone MPPK (10.17) red shifts the absorption. In both cases, efficient initiating radicals are generated. 

Energy transfer is rather seldom encountered [2j] due to the obvious difficulty to have the S triplet-state level higher than that of I. The most typical case of energy transfer is encountered between a thioxanthone derivative and a morpholino ketone derivative (10.60) the excitation moves from the thioxanthone triplet state to the morpholino ketone triplet state. With other thioxanthone derivatives, electron transfer followed by proton transfer with the amine moiety can compete to some extent [212]. The sensitized cleavage in covalently linked thioxanthone derivative/cleavable photoinitiator was recently investigated and discussed [213],... 

Although a-cleavage is the main photodecomposition product of morpholino ketones, some P-cleavage might also be taking place. Also, side reactions that can result in loss of initiating radicals can be illustrated as follows ... 

Various derivatives of thioxanthone are often used as photosensitizers with substituted morpholino ketones as energy aeeeptors. Aetually, the two materials by themselves are effieient initiators. It was shown that when eombinations of thioxanthone derivatives with morpholino ketones are irradiated with light, two types of reaetions ean take plaee. If the triplet-triplet energy transfer oeeurs when the energy level of the thioxanthone is higher than that of the morpholine ketone, eleavage of the morpholino ketone is the result ... 

On the other hand, reaetions of thioxanthones with morpholino ketones ean also results in eleetron transfers without eleavages. This is shown below... 

Furan, 3-(4-methylpentanoyl) — see Perilla ketone Furan, 2-methylthio-mass spectrometry, 4, 583 Furan, 3-morpholino-2,5-diphenyl-reaotions... 

The reaction of ketene with the enamine (113) is reported (88) to give l-morpholino-2-acetyl-l-cyclohexene i.e., the enamino ketone expected from acylation of (113). The pyrrolidine enamine (28), however, has been shown to react (73) with excess ketene to give the a-pyrone (124). On the... 

It has been reported that perfluoroisobutylene and perfluorocyclobutene undergo 1,2 cycloaddition with l-(N-morpholino)isobutylene in ether at room temperature to give the corresponding perfluorocyclobutane derivatives ]20a). Enamines of cyclic ketones produce only simple alkylation products when treated with these perfluoroolefins. 

Treatment of l-morpholino-6-iminocyclohexene with hydrazine hydrate in the presence of ketones leads to 2,3,5,6,7,8-hexahydro-l,2,4-benzotriazine 4-oxides 156. In the absence of carbonyl compounds, this reaction affords the spirobicyclo compound 157 (75S794). 

Morpholino-l-cyclohexene (Chapter 9, Section I) A Methyl vinyl ketone MCB, A... 

Methyl phenyl sulfide, see Thioanisole Methyl phenyl sulfoxide, 46, 78 from methylsulfinyl chloride and benzene with anhydrous alumi num chloride, 46, 80 Methyl vinyl ketone, reaction with 1-morpholino 1 cyclohexene, 45,... 

The thermolysis of 4-azidophenyl methyl ketone in morpholine at 170°C yields a mixture of the expected 5-acetyl-2-morpholino-3f/-azepine (33) and 6-acetyl-2-morpholino-3//-azepine (34), the product of a unique and totally unexpected thermal rearrangement of the 5-acetyl derivative.119 Similar results can be obtained in hot piperidine, whereas thermolysis of 4-azido-diphenyl ketone under similar conditions yields only the 6-benzoyl-2-(cycloalkylamino)-3//-azepines (7-18%) accompanied by much tar. 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

The synthesis of amines from oximes is exemplified by the reduction of oxime 332 to 333 (99W032453) and of bicyclic oximes (derived from ketones 3 and 23a), for instance, of oxime 387 (Scheme 87) to amine 388 that is acylated to yield potential pharmaceutical agent 390 (92BML1147). Nucleophilic substitution of chloropyridine 384 generates morpholino derivative 385 (76IJB400). 

Z)-l -Nitro-l-alkene werden in Diethylether an En-amine addiert3- u. Die Additionsreak-tion verlauft weitgehend diastereo- und enantioselektiv. Durch saure Hydrolyse kann das Amin nach der Addition abgespaltcn werden und man erhalt ein Keton. So reagiert 2-Morpholino-3,4-dihydro-naphthalin mit (Z)-2-Nitro-l-phenyl-ethen zu l-(2-Nitro-l-phe-nyl-ethyl) -2-oxo-tetralin. 

In the presence of magnesium bromide, cyclobutenecarbonitrile reacted with 1-morpholino-cy-cloalkenes to give exclusively the cycloadducts 23. Rather surprisingly, only cyclobutyl ketones 24 were obtained when cyclobutenecarbonitrile or methyl cyclobutenecarboxylate was reacted with other enamines under similar conditions.30... 

Enamines of cyclic ketones may also be used to prepare polyamides in a different type of condensation reaction (67MI11100). This polymerization involves reaction with diisocyanates (Scheme 46), with the enamine functioning as a difunctional reagent. Morpholino- and piperidino-enamines are the most effective monomers. 

From a preparative point of view, the acylation of ketones via enamines is of particular interest. In comparison with pyrrolidine and piperidine enamines, the less reactive morpholine enamines give better yields, as found by Hiinig et al.2iZ j8-Diketones are the products of acylation with an acyl halide followed by acid hydrolysis, whereas with ethyl chloroformate, /J-ketoesters are obtained.212 Hiinig and his collaborators242-247 have used the acylation of 1-morpholino-l-cyclopentene and 1-morpholino-l-cyclohexene to lengthen the chains of acids by five and six carbon atoms, respectively. The reaction may... 

The cation radical intermediates formed from the enamines may be trapped by nucleophiles other than the solvent when these nucleophiles are electrochemically less oxidizable than the enamines. Indeed, the cation radical intermediates formed from morpholino-, piperidino-and pyrrolidinoenamines are trapped by carbanions derived from active methylene compounds such as methyl acetoacetate, acetylacetone and dimethyl malonate with moderate yields (equation 2)3. The products are easily transformed to the corresponding a-substituted ketones by hydrolysis with dilute hydrochloric acid. 

Enamines 10 (RjR R2 = H,Me X = 0,S,NMe X1 = morpholino, pyrrolidino, piper-idino) were prepared by reaction of the appropriate heterocyclic ketones with the heterocyclic base144. 

Cyclopropyl ketones (19, R1 = Me, Et, cyclopentyl) have been converted to enamines (20 R2N = Me2N, Et2N, pyrrolidino, morpholino), but when R = aryl or cyclopropyl, ring opening occurs153. 

Aminomercuration of CH=CCH2OCHR1C=CR2 (R1 = H, R2 = Me, SiMe3) with morpholine (R3 = morpholino) gave enamines R2C=CCHR1OCH = CMeR3)226. Re-giospecific synthesis of terminal oxyfunctionalized methyl ketone enamines via catalytic aminomercuration of prop-2-ynyl esters and ethers has been also described227. 

The Horner-Wittig reaction has been applied to the synthesis of both aldehyde and ketone enamines. The substituted lithio aminomethylphosphonates (48, R1 = H, alkyl, aryl R2 = Me, Et, Ph R2N = MeNPh, morpholino) unite with aliphatic, aromatic and a,/ -unsaturated aldehydes or ketones to furnish the corresponding enamines235-245... 

Mannich reaction of CH(OEt)3, a ketone MeCOR [R = Et, Me2CHCH2, Ph, o-C6H4(CH2)2, p-ClC6H4, p-anisyl, 2-thienyl, 2-pyridyl, 2-furyl] and RjNH (R1 = Me, Et NRj = piperidino, morpholino) gave 33-80% of enaminones RCOCH=CHNR2 5". 

Reaction of l-morpholino-4-r-butylcyclohex-l-ene and phenyl vinyl ketone (PVK) gave the cis-fused dihydropyran (46) and the trans ketone (46a) on mild hydrolysis, indicating initial attack from the axial direction. The cis isomer (46b) can be obtained by heating 46a with acid (Scheme 30). 

Ring-fused pyridines of type 300 and 301 have been prepared by condensation of enamines with immonium salts170, and by reaction of morpholino enamines derived from a-pyridyl ketones with aromatic aldehydes and further treatment with ammonium acetate171,172, respectively. 

Vinylogous thioamides 33 (NR2 = dimethylamino or morpholino) react with benzyl chloride to give thiophenes42, while thienyl ketones are produced from a-bromo ketones43 (equation 22). 

---