CYCLOHEXANECARBOXAMIDE

AC 94377. The compound l-(3-chlorophthalimide) cyclohexanecarboxamide [51971 -67-6] (Table 3) (45), also known as AC 94377, is a phthalamide that has plant growth regulating properties. It is relatively nontoxic so that its use in floricultural crops appears to be safe. It is mainly used to control stem length and stem numbers in hybrid tea roses (23). However, it has very limited use and is stiH experimental. 

In addition to the present method,2 1-amino-1-methylcyclo-hexane has been synthesized by the following procedures Ritter reaction, e.g., with 1-methylcyclohexanol (76%, 67%)3i 4 or 1-methylcyclohexene (35%,) 4 5 Hofmann reaction with 1-methyl-cyclohexanecarboxamide (80% as hydrochloride) 6 reduction of 1-methyl-l-nitrocyclohexane (63%) 6 Schmidt reaction with 1-methylcyclohexanecarboxylic acid (42%).6... 

Fig. 2.23. Determination of the proton affinity of cyclohexanecarboxamide (a) by the kinetic method, and (b) by the thermokinetic method. The horizontal lines show the indicative values ln[AH]V[BrefH] = 0 in (a) and REs according to different authors in (b). [101] Adapted from Ref. [109] by permission. IM Publications, 2003.

Requests for larger samples for field testing necessitated the examination of alternate routes to AC 94,377. One of these started with 1-amino-1-cyclohexanecarboxamide and 3-chloro-phthalic anhydride. Attempted cyclization of the intermediate phthalamic acid 4 with cold trifluoroacetic anhydride gave, albeit in low yield, the readily isolated imidazoisoindole Biological evaluation of indicated that it had very similar PGR properties to that of AC 94,377 yet was perhaps slower acting. This was attributed to the slow hydrolysis of back to AC 94,377. 

A -Substituted derivatives of cw-2-hydroxy-l-cyclopentanecarboxamide and cis- and tranj-2-hydroxy-l-cyclohexanecarboxamide 128 were transformed with a large excess of l,T-carbonyldiimidazole to oxazinediones 145 (cis, n = 1, 2 irons, n = 2 R = Me, Ph, CHjPh CHaCHaPh) in 40-90% yields. Derivatives with an unsubstituted nitrogen atom could not be isolated (85M857). 

The synthesis of oxaziridine-fused quinazolinones 277 follows a different route. Quinazolinones 274 (R = Et, nPr, n-hexyl) can readily be prepared by reacting 2-oxo-l-cyclohexanecarboxamide with aldehydes in the presence of ammonia solution. In the reaction of 274 and monoperoxyphthalic acid, the hydroxyoxaziridines 277 were formed via the presumed intermediates 275 and 276. No spectroscopic evidence was given for 277, nor was its relative configuration investigated [76JPR(318)895]. 

In the reaction of l-hydroxy-2-oxo-l-cyclohexanecarboxamide and cyan-amide, the 2-aminooxazole 282 was formed. Treatment of 282 with hydrazine yielded the semicarbazide 283, which on iodine oxidation gave the perhydro-2,4-quinazolinedione 284 (87JPR177). Although the configuration of the product was not given, the cis annelation can be deduced from the published NMR data. 

The parent compound 309 was synthesized by the reactions of cis- or rra i-2-amino-l-cyclohexanecarboxamides with ethyl orthoformate [69-JCS(C)1635 71JCS(C)238]. In principle, 309 can exist in five tautomeric forms two enol forms, one lactim form, and the IH and 3H forms, of which the two enol forms can be excluded because no cis-trans isomerization was observed. The H and 3H forms may be fixed with substituents hence, 310 and 311 with fixed tautomeric structures were prepared. The UV spectra reveal that the unsubstituted derivatives exist in 3H form, as shown for structure 309 [71JCS(C)238]. 

Copper-catalyzed amidation has also been achieved, and an example is the amidation of 5-bromopyrimidine 130 with cyclohexanecarboxamide 142 which went in 86% yield in the presence of catalytic copper iodide and a diamine ligand <2001JA7727, 2002JA7421>. 

Photoirradiation of inclusion crystals of 3-oxo-2-cyclohexanecarboxamide derivatives (69b-69d) with the optically active host compound 12b as a water suspension for 4 hr gave optically almost pure 2-aza-l, 5-dioxaspiro[3,5]nonane derivatives (70b-70d) [38], Optically pure 70b and 70c were prepared by the... 

AH2-Benzylaminoethyl)cyclohexanecarboxamide (115) and chloroacetyl chloride (116) gave l-benzyl-4-cyclohexylformyl-3,4,5,6-tetrahydro-2(l//)-pyrazinone (117) (NaOH, PhCH2Et3NCl, H20—PhH, 20 55°C, 2... 

C7H13N02 trans-2-hydroxy-1-cyclohexanecarboxamide 24947-95-3 23.64 1.0259 2 11952 C7H1406 alpha-methylglucoside 97-30-3 30.00 1.4600 1... 

C7H13N02 cis-2-hydroxy-1-cyclohexanecarboxamide 73045-98-4 23.64 1.0259 2 11953 C7H1406 methyl-b-D-galactopyranoside 1824-94-8 25.00 1.1769 2... 

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