Tetrahydroazepines

In die case of nylon-6,6 waste recycled by ammonolysis, nylon is treated with ammonia in die presence of a phosphate catalyst. Reaction occurs at 330°C and 7 MPa. Distillation of die reaction mixture produces ammonia which is recycled and three fractions containing (a) caprolactam, (b) HMDA and aminocaproni-trile, and (c) adiponitrile. Aminocapronitrile and adiponitrile are hydrogenated to yield pure HMDA, and die caprolactam is eidier converted to aminocapronitrile by further ammonolysis or distilled to produce pure caprolactam. The HMDA produced by this process is extremely pure (>99.8).1 The main impurities are aminomediylcyclopentylaniiiie and tetrahydroazepine, which are expected to be removed more effectively in the larger distillation columns employed in the larger plants. 

The same catalyst IX was used in the RCM of a functional diene to give, in 87% yield, a tetrahydroazepine derivative which is a precursor in the synthesis of the metabolite (-)-Balanol (Equation 8.9) [44]. 

Hydrodebromination accompanies the partial reduction of the aminobromoazepine (111 X=Br) to its amidine hydrobromide (67JOC2367). Partial reduction of 2-dimethylamino-3H-azepine to the 4,5-dihydro derivative is possible with hydrogen and 5% Pd-C (73CC327). Wolff-Kishner reduction of 2,3,4,5-tetrahydro-2-phenyl-lfT-l-benzazepin-4-one proceeds normally to give the tetrahydroazepine (79JOC4213). 

The acid-catalyzed ring expansions of tertiary cyclohexylazides to tetrahydroazepines may be viewed as an intramolecular version of the Schmidt reaction and in general proceed in high yield. Unfortunately, the reaction is of little synthetic value as the imines formed are readily hydrolyzed to w-aminoketones in the strong acid media (B-67MI51600). However, the reaction is successful with 9-azido-9-phenylacridone, which on thermolysis or photolysis ring-expands to a mixture of 9-phenyliminoacridone (15-35%) and 6-phenyl-11//-dibenz[6,e]azepin-ll-one (65-85%) (76TL3141). 

A solid-state modification of the ring-closing metathesis reaction has also been reported in the preparation of the tetrahydroazepine derivative 189 <1999S138> and of the lactams 190 (e.g., 190, R1 Ph, R2 = H, R3 = NHBOC 36% overall yield) <1998TL2667>. 

Ring-closing metathesis using Gmbbs I mthenium catalyst 159 (2mol%) has also been used in the preparation of the Fischer-type chromium carbene complex 195 from the precursor 194 in near quantitative yield (Equation 23) <2001SL757>. The N-substituted tetrahydroazepine 197 could be prepared similarly in excellent yield from 196 (Equation 24) <2001JOC564>. 

An elegant traceless linker variation on the ring-closing metathesis strategy resulted in the preparation of the tetrahydroazepine 201 from the immobilized diene 200, although the yield of 201 was only moderate (Equation 26) <1998EJ02583>. 

An enantioselective synthesis of the substituted tetrahydroazepines 323 was achieved on treatment of 322 with a chiral lithium amide base (Equation 49) <1997JOC7080>. 

The bacterial translocase 1 inhibitor, A-500359C, 348 (and a methoxy analogue A-500359A), isolated from Streptomyces griseus SANK 50196, includes a tetrahydroazepin-2-one unit in its structure <2003JAN243>. 

Another type b cyclization route to substituted tetrahydroazepines involved a new and potentially versatile TBSOTf-mediated attack (using excess TBSOTf in DCM) on an acyclic A-formamido precursor further functional group modifications then provided access to an azepinol and azepinone derivative <2007SL497>. 

Ring closing metathesis mediated by Grubbs II catalyst in a type c ring construction process has been used to access stereoisomeric 1,2-disubstituted tetrahydroazepine-3-ol derivatives preparation of the required diene precursor started from an optically pure substituted aziridine carboxylate ester <2007T3321>. 

A novel, general route to 2,3,6,7-tetrahydroazepines via RCM was reported by Pearson and Aponick <01OL1327> (Scheme 24). Double-allylation of the amine a,a -dication equivalent 39, followed by in situ trapping with ClCC Ph gives rise to diene 40 which is efficiently converted to the 7-membered ring heterocycle 41 by treatment with the GMC in DCM. This process was effectively applied to a variety of substituted (2-azaallyl)stannanes. 

Ring closing metathesis using Grubbs ruthenium catalyst has also been used in a novel preparation of the Fischer-type chromium carbene complex 10 from the precursor 9 in >98% yield [01SL757], Similarly, the TV-substituted tetrahydroazepine 12 could be accessed in near quantitative yield from 11 [01JOC3564],... 

The use of bifunctional lactim ethers in the above reaction forms the new heterocyclic system pyrimido[4,5-6]tetrahydroazepine,36 37 and is a new method for the synthesis of alloxazines,42 7H-5,6-dihydro-pyrrolo[2,3-d]pyrimidines,38 39 and 8H-piperido[2,3-d]pyrimidines25, 115 (Scheme 21). 

The primarily formed azetidinone derivative 427 isomerized to the octahydropyrimido[l,2-fl]azepin-4-ones 428 above 130°C (70CB1797) Compound 429 was also obtained in the reaction of 2-amino-3//-4,5,6,7-tetrahydroazepine hydrochloride (414-HCl R = H) and the sodium salt of ethyl formylacetate (83JOC2914). 

The tetrahydroazepine congener (162) of the tetrahydropyridine isoxazole systems (161) is said to possess high affinity for the central receptor, coupled with only limited toxicity (196). 

Another tetrahydroazepine congener (163) displays higher affinity for muscarinic receptors but somewhat lower efficacy than the analogous fused piperidine compounds (161) (197) it was described as a partial agonist. Studies (198) of sulfur analogs and congeners (164-167) of the isoxazolotetrahydropyri-... 

Tetrabenzoperaza-crown-4 cyclophanes (biphenyl), table, lli Tetrabenzoperaza-crown-4 cyclophanes (miscellaneous), table, 734 Tetrabenzoperaza-crown-4 cyclophanes (tetrakis-p-phenylenyl), table, 726 Tetrabenzoperaza-crown-4 cyclophanes (tetrakis-p-xylyenyl), table, 731 Tetraethylene glycol bis(3-butenyl)-substituted, 38 chiral-substituted, 38 dichloride derivative, 179 diiodide derivative, 179, 184 tetramethyl-substituted, 38 Tetraethylenepentaamine, pertosylatcd, 49 Tetraglycolic acid, 112 Tetrahydro-l,4-diazepine, 93, 543 Tetrahydroazepine, 94 iV,A(Af iV -Tetrakis(2-hydroxyethyl)-ethylenediamine, 182... 

Chalcogenide oxidation. The oxidation and selenoxide elimination sequence is applicable to the generation of functionalized alkenes which are prone to Claisen rearrangement. Medium-sized rings including tetrahydroazepin-2-ones are accessible in this manner. ... 

Tetrahydroazepines of several structure types are efficiently prepared by ring-closure metathesis (RCM, [20]) of a,co-diene or -eneyne systems [21], e.g. the pyrrolidinoazepinone 27 from the pyrrolidine-derived a,(0-diene precursor 26 ... 

A number of natural products contain the azepine framework, e.g. the nonproteinogenic aminoacid muscaflavine 35, a yellow pigment of the fly agaric, the 2i/-azepine chalciporon 36, a pungent substance of the peppery bolete [22], and the ethano-bridged tetrahydroazepine ( )-anatoxin 37, a toxic principle of blue-green algae. 

---